March 2019 digital v1

abravelab

₹ 250.00

VOL 5 | ISSUE 11

PAGES 100

MARCH 2019

FUTUREMEDICINEINDIA.COM

No 1

INFECTIOUS

KILLER AGAIN

TUBERCULOSIS IS BACK TO THE FORE DUE TO MICROBIAL

RESISTANCE AND A WANT OF NOVEL DRUG REGIMENS

TECHNOLOGY CASE REPORT STRAIGHT TALK SCIENTIFIC REPORT

NGS BREAKS NEW

GROUND IN TB CARE

WHEN PARKINSON’S

STRIKES EARLY

NOBEL LAUREATE

PROF ADA E YONATH

GENETIC TARGET

FOR CRC


The vastness of the sky inside

9 of the Top 10 Hospitals Ranked by U.S. News & World Report 2018-19

feature Sky Factory Luminous SkyCeilings.

The most sought-after feature

in any architecture is a visual

connection to nature. When

building design or location

precludes this life-supporting

feature, a biophilic illusion of

nature restores this essential

wellness benefit.

Generate Wellness

Our therapeutic installations engage and

relax patients, dramatically altering clinical

interiors and facilitating medical treatments

and procedures.

Evidence-based

Illusions of Nature

Neural research on Sky Factory’s Open Sky

Compositions has received international

recognition for its exceptional quality and

practice-based application.

APPLICATIONS

IMAGING & ONCOLOGY ENVIRONMENTS, PATIENT & EMERGENCY

ROOMS, TREATMENT ROOMS, RECEPTION & WAITING ROOMS...

www.skyfactoryindia.com

EXCLUSIVE INDIAN PARTNER

UNIT NO. G-157, DREAMS MALL,

L.B.S. MARG, BHANDUP (W), MUMBAI - 400078

TELEPHONE: +91 22 21660060

MOBILE: +91 98211 43366


editor’s note

editor’s note

March 2019 / Vol. 5 / Issue 11

Founder AUGUST & 2018 Editor / Vol: 5 / Issue: 4

CH Unnikrishnan

Executive Editor

S Harachand

Science Editor

Dr Rajanikant Vangala

Consulting Editors

Dr Founder Shivanee & Editor Shah

Jeetha CH Unnikrishnan D’Silva

Dr

Executive

Sumit

Editor

Ghoshal

Copy S Harachand Editor

Sreejiraj Eluvangal

Science Editor

Curator-cum-Correspondent

Dr Rajanikant Vangala

Divya Choyikutty

Photo Copy Editor Editor

Umesh Sreejiraj Eluvangal Goswami

Design Consulting Editors

Gopakumar Dr Shivanee Shah K

Advisory Dr Sumit Ghoshal Board

Dr

Photo

Devi

Editor

Shetty

Dr B S Ajaikumar

Umesh Goswami

Dr Shashank Joshi

Dr Illustrator Prof. Arumugam S

Dr Mathewkutty I C Verma J Mattam

Dr N K Warrier

Dr Advisory Indira Board Hinduja

Dr Devi Sekar Shetty Seshagiri

Mr Dr B Rajesh S Ajaikumar R Nair

Knowledge

Dr Shashank Joshi

Partner

SGRF Dr Prof. Arumugam S

Dr I C Varma

National Business Head

Shiny

Dr N K Warrier

Thomas

Phone: Dr Sekar +91 Seshagiri 9821435120

e-mail: Knowledge shiny@futuremedicineindia.com

Partner

Manager- SGRF Business Development

Jyotsna Budhiraja

Business Head

Phone: +91 8586094582

e-mail: Tushar Kanchan jyotsna@futuremedicineindia.com

Chief Circulation Consultant & Subscription Manager

(Circulation S Sanjeev Nair and Market Development)

Rajesh

Design &

A

Graphics

Shah (MediaCafe)

Phone: +91 9594 625 231

e-mail:

Blackboard

rajesh@futuremedicineindia.com

Kochi

Circulation Editorial Offices Executive

Sandesh BANGALOREChennamkulath

Phone: Ground Floor, +91 9061969996

JP Tower, Whitefield, Bangaluru.

e-mail: MUMBAI subscribe@futuremedicineindia.com

Editorial M9B, Press Enclave, OfficesPrateeksha Nagar, Sion East Mumbai.

BANGALORE

KOCHI

Ground 3Rd Floor, Floor, Kurian JP Towers, Classic, Banerji Corporate Road Block,

EPIP Ernakulam Zone, - 682 Whitefield, 018. Bengaluru - 560066

MUMBAI

Printed and Published by

5 101, Wework Zenia, Central Circle,

Ravi DeeCee, DC Books

Hiranandani Business Park, Off. Ghodbunder Road,

Thane, Printed at Mumbai, MH- 400 607.

KOCHI Spenta Multimedia Pvt Ltd.

3rd Lower Floor, Parel Kurian (W), Mumbai Towers, 400 013. Banerji Road

Ernakulam - 682 018

Printed and Published by

Ravi The publishers DeeCee, regret DC that Books they cannot accept liability for errors or omissions

Printed contained in at this publication, however caused. The opinions and views contained

Spenta in this publication Multimedia are not necessarily Pvt Ltd. those of the publishers. Readers are advised

Ambernath to seek specialist advice (West), before Thane acting on 421 information 505. contained in this publication,

which is provided for general use and may not be appropriate for the readers’

The

particular

publishers

circumstances.

regret that

The

they

ownership

cannot

of

accept

trademarks

liability

is acknowledged.

for errors or omissions

No part of

contained this publication in this or publication, any part of however the contents caused. thereof The opinions may be reproduced, and views contained stored in in a

this retrieval publication system are or transmitted not necessarily in any those form of without the publishers. the permission Readers of are the advised publishers to

seek in writing. specialist An exemption advice before is hereby acting granted on information extracts contained used for in the this purpose publication, of fair

which is provided for general use and may not be appropriate for the readers’

particular

review.

circumstances. The ownership of trademarks is acknowledged. No part of

this publication or any part of the contents thereof may be reproduced, stored in a

retrieval Printed and system Published or transmitted by Ravi in Dee any Cee, form DC without Books, the D C permission Kizhakkemuri of the Edam, publishers Good

in Shephered writing. An Street, exemption Kottayam, is hereby Kerala granted on behalf for extracts of NextGen used Science for the purpose Media Pvt. of Ltd, fair

review. printed at Spenta Multimedia Pvt, Lower Parel (West), Mumbai-400 013,India and

Printed published and at Published DC Books, by D C Ravi Kizhakkemuri Dee Cee, DC Edam, Books, Good D C Shephered Kizhakkemuri Street, Edam, Kottayam, Good

Shephered Street, Kottayam, Kerala on behalf of NextGen Science Media Pvt. Ltd,

Kerala

printed at Spenta Multimedia Pvt, Lower Parel (West), Mumbai-400 013,India and

published at DC Books, D C Kizhakkemuri Edam, Good Shephered Street, Kottayam,

Kerala © 2018 NextGen Science Media Pvt. Ltd, RNI Number KERENG/2012/44529

© 2018 NextGen Science Media Pvt. Ltd, RNI Number KERENG/2012/44529

Dear Doctor,

We say with much pride that technology is changing the paradigm in

today’s Dear medicine. Doctor We also get much excited about the stories of newgeneration

techniques like gene sequencing and editing, 3D printing, deep

learning We know and you artificial are busy. intelligence, It is always which reassuring are revolutionizing that the trust the way and we faith do of

diagnosis hundreds and of treatments patients in today. your Certainly, healing touch these keeps are great you achievements

busy in this noble

of the profession. brave new In the scientific hectic world practice, that it’s need quite to be natural acknowledged that you might and miss

accepted. out on some of the latest developments in emerging medicine. In this era

But, of innovation, the same medical time, we science tend to is getting forget a redefined sad reality: almost Millions by of the people day. Old

are technologies still dying due are to being simple replaced infections by in the many new parts in the of the blink world of an including eye. Robots

India. and This artificial is because intelligence the last are antibiotics taking over that a we good invented part of sixty the years procedures,

ago while are becoming genomics less and effective molecular and science the microbes unveil the that mysteries we successfully of life further.

countered We are decades fortunate ago to have are getting such breakthroughs stronger and have as they started help fighting specialists back like

more you aggressively. rise above the Tuberculosis expectations is back of today’s the fore informed as the patient. No.1 infective

disease that kills people even in this era of genomic medicine. The most

unfortunate

Similarly, it

part

is also

is that

a time

this is

when

despite

India

the

is

scientific

witnessing

community’s

revolutionary

best

growth in

efforts to find novel pathways for developing new antibiotics. Our cover

healthcare industry, especially in the private sector, wherein an increasing

story in this edition tries to get to the depths of this glaring contradiction.

number of doctors are taking up multiple roles of clinician, researcher and

Serendipitously, we also met Prof Ada E Yonath, the chemistry Nobel

entrepreneur. This requires expansion of your focus to a wider canvas. In

Laureate whose pioneering work on ribosomes and their structure and

this context, it becomes important how a busy professional like you can

functions opened up a whole new avenue for developing new and more

keep pace with these latest developments in a quick and easy way.

effective antibiotics. You can read more about the encounter in Straight

Talk.

Inside, At Future you’ll Medicine, also find which a beautifully is conceived illustrated and story crafted on by India a team generously of senior

honouring journalists, its great scientists clinicians and doctors, with the our nation’s aim highest is to help honour, you do as just well that. We

as are US-based equipped genomics to bring scientist you the Dr latest Amitabha from Chaudhuri’s the science well of care explained from across

scientific the world report in an on interesting the alarming and growth convenient of inherited way, supplemented colorectal cancer by and the best

new of generation views and treatments. analyses from the masters in each field. We present you this

specialised knowledge vehicle that plugs you into the emerging world of

Happy care seamlessly. reading Come, let’s join hands in this information journey.

CH Unnikrishnan

editor@futuremedicineindia.com

C H Unnikrishnan

editor@futuremedicineindia.com

www.futuremedicineindia.com futuremedicineindia FutureMedIndia

AUGUST 2018/ FUTURE MEDICINE / 3


TECHNOLOGY CASE REPORT ORTHOPAEDICS SCIENTIFIC REPORT

Vol 5 Issue 11

March 2019

₹ 250.00

VOL 5 | ISSUE 11

PAGES 100

MARCH 2019

FUTUREMEDICINEINDIA.COM

No 1

INFECTIOUS

KILLER AGAIN

TUBERCULOSIS IS BACK TO THE FORE DUE TO MICROBIAL

RESISTANCE AND A WANT OF NOVEL DRUG REGIMENS

NGS BREAKS NEW

GROUND IN TB CARE

WHEN PARKINSON’S

STRIKES EARLY

CHALLENGES OF

SKELETAL TB

GENETIC TARGET

FOR CRC

30

TECHNOLOGY

NGS BREAKS

NEW PATH

IN TB CARE

REGULAR FEATURES

06 Letters

08 News updates

14 Policy

32 Drug approvals

56 Research snippets

60 Hospital news

62 Scientific report

66 Cosmetic surgery

68 Public health

70 Devices&gadgets

74 Pharma

80 Research

82 Products

85 Guidelines

92 Events

96 Calendar

98 Holy grail

Columns

16 THE CATALYST

Muralidharan Nair

48 THE CELLVIEW

Dr Rajani Kanth Vangala

46

CASE REPORT

FIGHTING OFF

SWINE FLU

Swine flu can be one of

the most severe acute

respiratory distress syndromes

36

STRAIGHT TALK

“EVERYBODY HAS

TO DEVELOP THE

WAY THEY ARE.

TAKING ADVICE

IS LIKE COPYING

SOMEONE”

Prof Ada E Yonath


50

ORTHOPAEDICS

SKELETAL

TUBERCULOSIS

THE CHALLENGES

Occurrence of

osteoarticular

tuberculosis recorded

a rising trend among

extrapulmonary TB

world over

18

COVER STORY

WAR TO END

A SCOURGE

India is battling to eliminate

TB by 2025 — to vanquish an

infectious malady that has been

haunting humanity for ages

40

EDUCATION

MBBS INTERNS

MAY SOON GET

UNIFORM STIPEND

MCI BOG’s decision is

seen as a move to end the

discrimination

faced by medical interns in

the country

76

A strong pipeline

of novel drugs will

ensure that we are

well-prepared to

treat any form of

the disease, which

will be essential to

meeting global and

national targets for

TB eradication.

Dr Mel Spigelman

President and CEO

Global Alliance for TB

Drug Development

(TB Alliance)

FRONTIER LIFELINE

NUTRIGENETICS

CLINIC


CASE REPORT EDUCATION RESEARCH ONCO SURGERY

letters to the editor

A HARROWING

SWALLOW

INTERNSHIP

FOR FOREIGN

GRADUATES?

Eye opener

FLUID DIAGNOSIS

FOR DEMENTIA

₹ 250.00

VOL 5 | ISSUE 10

PAGES 100

FEBRUARY 2019

FUTUREMEDICINEINDIA.COM

STARTING TO

FORGET

THE SPECTRE OF ALZHEIMER’S LOOMS LARGE OVER

INDIA’S FAST-EXPANDING POPULATION OF THE AGED

NOVEL SURGICAL

OPTIONS FOR

BREAST CANCER

Dear Editor,

The cover story ‘Starting to

Forget’ in the February issue

was an eye opener. When

read, frankly, even we medical

students felt so less informed

about this complex disease.

Our curriculum as of now

touches just a tip of what

you have covered in this story

about AD.We realise that we

are taught only the basics of

this neurodegenerative disease

and the world has advanced

so much in understanding

its vast intricacies, though

uncertainties still prevail in the

treatment regime.

Sabu Varghese and

Anil Kothari

Nagpur.

Unique experience

Dear sir,

The ‘First & Most Unique’

series in Future Medicine truly

brings interesting and curious

things that gets introduced or

uniquely exists in the country’s

medical arena. The style of

best narration and pictorial

expression adapted in this

series actually makes me feel

as if I have seen or visited

the place. Congratulations for

introducing such an amazing

column, which I am sure, other

readers too would enjoy the

same way.

Sarita Mehra

Researcher

Jaipur

Well brought out

Hi,

Read the latest issue of Future

Medicine. Really informative

and well brought out. Wish

you all success for the same.

Thanks & regards

Dr DB Anantha Narayana

Managing Trustee, Delhi

Pharmaceutical Trust,

and Former Head, Naturals

Research for Foods, Unilever

Research Centre, Bangalore.

Top class

Hello,

Seen copies of Future

Medicine. Top class production

quality and great compilation

of articles. Congrats.

MG Arun

Executive Editor

India Today,

Mumbai.

Very useful

Dear Editor,

The article about ‘Fluid

diagnosis for dementia’ was

really informative. Grateful

for bringing out such a very

useful but at the same not

easily available information to

the medical professionals

like me.

Dr Sukumar Acharya

Vadodara, Gujarat.

& GET 20 %

NOW

Please send me my subscription of FUTURE MEDICINE for (Select your plan)

SUBSCRIBE

One year Rs. 2,400/- Two years Rs. 4,800/- Three years Rs. 7,200/-

OFF

NAME

ADDRESS

CITY

POSTAL CODE

E-MAIL

PHONE

Fill complete details and send it along with the cheque/DD in favour of ‘NEXTGEN SCIENCE MEDIA (P.) LTD.’ to Future Medicine,

5th floor, Wework Zenia, Zenia Building, Hiranandani Business Park, Off. Ghodbunder Road, Thane, Mumbai, MH- 400 607

For NEFT/RTGS : Account No. 50200032001372, IFSC:- HDFC0000684 Name: NextGen Science Media Pvt Ltd, HDFC Bank Ltd,

Kakkanad Branch, Cochin • For more details call - 9594 625 231 or mail - subscribe@futuremedicineindia.com


A medical science and news magazine for every new-age

clinician. It empowers doctors with the most relevant updates,

trends, case studies, expert views, knowledge exchange,

hospital management and latest breakthroughs in medical

science. To be relevant in the future of care, subscribe today.

20%

20%

Rs. 2,400/-

Rs. 4,800/-

Rs. 7,200/-

AUGUST 2018/ FUTURE MEDICINE / 59


news updates

India to regulate more

med devices as drugs

The health ministry

has notified eight

more medical equipment,

including all implantable

devices, as “drugs”

effective from April 1,

2020.

This step will enable

the regulation of some of

the widely used medical

devices along the lines of

pharmaceutical products

to ensure their quality and

safety.

The notified list

includes all implantable

medical devices, CT

scan equipment, MRI

equipment, defibrillators,

dialysis machine, PET

equipment, X-ray machine

and bone marrow cell

separator.

This is in addition

to the 27 categories of

devices that were notified

as drugs till last year,

including blood pressure

monitoring devices,

digital thermometers and

glucometers that were

notified in December

2018.

The decision was

taken after consultation

with the Drugs Technical

Advisory Board, according

to the ministry. A Gazette

notification was issued to

this effect.

The move is lauded by

healthcare NGOs saying

that the decision would

help ensure the quality of

the diagnostic equipment

as well as the safety of

the patients. Majority

of medical devices are

unregulated in India, as

there is no regulatory

framework for medical

devices, currently.

Odisha approves

DACP scheme

Odisha has approved a

new Dynamic Assured

Career Progression (DACP) for

government doctors working

in the eastern Indian state.

The scheme assures

promotion for all government

doctors.

“As per the new provision,

all the Odisha Medical and

Health Services (OMHS) cadre

officers will get three assured

promotions after 7, 14 and 21

years of continuous service

from their entry-level,” a

notification issued by the

Chief Minister’s Office stated.

This will encourage the

members and bring about

greater commitment and

dedication, the statement

read.

Around 2000 of the total

3600 doctors in the state are

likely to benefit from the new

DACP scheme, reports said.

Doctors have been

protesting the proposed

OMHS Cadre Rules, 2018

alleging that the new rules

are aimed at regulating

the method of recruitment,

promotion and condition of

service of medical officers.

The central government

started DACP in 2008.

Subsequently, nearly 15

state governments have

implemented it.

AstraZeneca,

NASSCOM to

promote NCD

care

D

rug major AstraZeneca

has joined hands with

the National Association

of Software and Services

Companies (NASSCOM)

IoT Centre of Excellence

to set up an accelerator

programme to support Indian

start-ups for developing

innovative solutions to noncommunicable

diseases

(NCDs) care in India.

AstraZeneca and

NASSCOM will incubate

start-ups in bringing new

concepts that can help in

the management of noncommunicable

diseases

(NCDs).

The two organizations

have signed a memorandum

of understanding (MoU) to

start an incubation centre in

Bengaluru, recently.

Start-ups will have access

to NASSCOM’s innovation

labs, development resources,

cloud services and mentoring

support, including the

opportunity to showcase

their innovations in national

and global platforms. This

opportunity

will be open for

companies or

individuals who

are working in

therapeutic areas

like diabetes,

cardiovascular,

8 / FUTURE MEDICINE / March 2019


India and Norway extend

cooperation on child health

The governments of

India and Norway have

extended cooperation within

the health sector for a period

of three years starting from

2018 to 2020.

A memorandum of

understanding (MoU) between

the Norwegian Ministry of

Foreign Affairs, Government of

Norway and Ministry of Health

and Family Welfare, India has

been signed to this effect,

recently.

The extension of the

Norway India Partnership

Initiative (NIPI) will include

areas related to maternal,

newborn, child health etc. The

cooperation will continue to

focus on innovative, catalytic

and strategic support.

The best practices in

maternal and new-born child

health carried out under the

National Health Mission and

NIPI shall be shared for global

dissemination and learning.

In the recent World Health

Assembly, Family Participatory

Care, an initiative of NIPI was

showcased as an India case

study.

Norway and India had

agreed in 2006 to collaborate

towards achieving Millennium

Development Goals 4 (MDG 4)

to reduce child mortality.

cancer and respiratory

medicine.

SC frees Saridon

from list of

banned FDCs

The Supreme Court of India

has exempted Saridon

from the list of banned fixeddose

combinations (FDCs) in

the country.

FDCs contain more than

two active ingredients in a

fixed proportion.

Saridon, which

is a combination of

propyphenazone, paracetamol

and caffeine, is a popular

analgesic brand promoted by

Piramal Enterprises Limited

(PEL), Mumbai

PEL had challenged the

ban of Saridon in the SC

listing it under the irrational

combination of drugs. In

September 2018, SC allowed

the company to continue

manufacturing, distribution

and sale of the FDC through

an interim order staying the

ban.

Now with the lifting of the

ban, Saridon will be available

across the country.

Last year, India’s health

ministry slapped a ban on

over 300 FDCs as an

expert committee set up of

for the purpose concluded

that there was no therapeutic

justification for such

combinations.

Saridon is one of the

leading brands in India›s

analgesics market, which

is estimated to be worth

around Rs 2,050 crores as of

December 2018.

Haryana revises

NPA to stop

private practice

The government of

Haryana has decided to

increase the non-practicing

allowance (NPA) for medical

officers to 20% of the basic

pay, in accordance with the

recommendations of the 7th

Pay Commission. The revised

NPA will be implemented with

retrospective effect from May

1, 2018.

The decision is expected

to benefit 272 medical

PRIVATE

PRACTICE

officers, assistant medical

officer, senior medical officer,

dental surgeon and director of

ESI healthcare department.

Medical officers who will

be eligible for NPA include

government employees

posted against a clinical post,

reports said.

NPA is aimed at

prohibiting the private

practice of government

medical officers in public

interest and the allowance

would be admissible only in

such cases and circumstances.

The total pay combined with

NPA should not exceed Rs

2,24,550 per month.

The government medical

March 2019 / FUTURE MEDICINE / 9


officers have been demanding

to revise the NPA as

recommended by the 7th Pay

Commission.

Kareena to lead

Serum’s vaccine

campaign

Serum Institute of India,

the vaccine maker, has

roped in the Bollywood

actress Kareena Kapoor Khan

to spread awareness on the

importance of vaccination and

immunisation across India.

Kareena is the campaign

ambassador for Swasth

Immunised India – a

nationwide vaccination and

immunisation campaign.

Serum has joined hands with

Network 18 for the campaign

that will focus on the need for

childhood immunisation.

Kareena will be advocating

the urgency and the need for

vaccination in the nation-wide

campaign lasting for a year.

The awareness campaign

comes at a time when the

number of non-vaccinators is

increasing the world over.

According to the figures

available with the ministry

of health, India has a

vaccination cover of about

70 percent. The country was

able to successfully eradicate

smallpox and polio through

intensive immunisation efforts.

However, the diphtheria

outbreak in some regions

of the country again turned

the spotlight on possible

vaccination gaps.

Serum Institute of India

is now the world’s largest

vaccine manufacturer by the

number of doses produced

and sold globally. The Punebased

company’s portfolio

includes vaccines for polio,

diphtheria, tetanus, pertussis,

Hib, BCG, hepatitis B, measles,

mumps and rubella. It is

estimated that about 65%

of the children in the world

receive at least one vaccine

manufactured by Serum.

UK surcharge

unfair: Indian

doctors

Indian doctors and

healthcare professionals

in the UK are campaigning

against an “unfair” doubling of

a health surcharge slapped on

professionals from outside the

European Union (EU) living

and working in Britain.

UK increased the

“Immigration Health

Surcharge”, which was

introduced in April 2015, to

GBP 400 from GBP 200 per

year from December last

year.

The surcharge

was applicable

to all in the UK

on a work,

study or

family visa for

longer than six

months. The hike

was imposed as part

of raising additional funds

for the country’s state-funded

National Health Service (NHS).

The payment is made at

the time of the immigration

application. The person

is required to pay the fee

annually until he or she is

granted indefinite leave to

remain (ILR) in the UK or

returns to their home country

at the end of their visa period.

Clinicians wishing to

work in the UK were already

facing burdensome processes

relating to regulation and

immigration, and this

surcharge was only going to

see UK losing out on quality

healthcare professionals from

non-EU countries, said a letter

sent to UK home secretary

from the British Association

of Physicians of Indian Origin

(BAPIO) seeking a rethink on

the surcharge.

MCI BOG nod for 2 super specialties in paediatrics

Medical Council of India

Board of governors

(MCI BOG) has given

recognition to DM in

paediatric neurology course

from the next academic year

onwards.

The new super specialty

course in paediatric neurology

has been included in the Post

Graduate Medical Education

Regulations, 2000 via an

official notification in the

Gazette of India.

According to the

notification, doctors qualified

in MD in paediatrics or MD

in general medicine can join

DM (Paediatric Neurology)

programme.

All India Institute of

Medical Sciences (AIIMS),

New Delhi had approached

the court seeking to start

the super specialty course.

Currently, the department

of paediatrics, AIIMS, New

Delhi offers one seat for DM

(Paediatric Neurology).

Also, the BOG has

given its go-ahead to the

inclusion of M Ch in paediatric

orthopaedics in the Post

Graduate Medical Education

Regulations, 2000.

The prior requirement

or feeder qualification for

M Ch (Paediatric

Orthopaedics) will be MS in

orthopaedics.

10 / FUTURE MEDICINE / March 2019


INDIA HONOURS ITS

ASHOK LAXMANRAO KUKADE

A Physician,

author and

founder of

Vivekananda

Hospital and

Research Centre,

He has been

honoured for his

commendable

service to the

needy in the

backward,

drought-prone

region of Latur,

Maharashtra.

MAMMEN CHANDY

Pioneer in

developing

the field of

haematology and

bone marrow

transplantation in

India. Dr Chandy

is currently

director at Tata

Medical Centre,

Kolkata and is

chair of Human

Genome Task

Force, India.

The profession of care has been well

recognised with the nation’s highest

honour this time. The number of

Padma Awards bestowed on members

from the field of medicine was one of the

highest in 2019. 15 doctors, who have

contributed immensely to the field, have

been honoured with Padma Awards this

year in recognition of their invaluable

service to the suffering lot as well as their

contribution to the profession in terms of

research and innovation.

JAGAT RAM

TSERING NORBOO

Director of

PGIMER

Chandigarh.

He developed

innovative

paediatric

cataract surgery

to cure an earlier

incurable birth

defect.

SMITA AND RAVINDRA KOLHE

Husband and wife doctor duo who

worked for the uplift of the poor tribals

helping to eradicate malnutrition from

one of Maharashtra’s poorest regions of

Melghat.

Consultant

Physician

Mahabodhi

Karuna Charitable

Hospital

Choglamsa.

He has treated

several patients

in the difficult

terrain, from

remote areas of

Ladakh for over

50 years and

is specialised

in high altitude

medicine.

12 / FUTURE MEDICINE / March 2019


GREAT CLINICIANS

SHYAMA PRASAD MUKHERJEE SHADAB MOHAMMAD PRATAB SINGH HARDIA

Ranchi-based

doctor who

is known for

charging minimal

consultation

fee for medical

treatment.

The 83-yearold

doctor

has helped

provide quality

health care to

many poor in

Jharkhand.

Professor

and Head of

Department

of Oral and

Maxillofacial

Surgery at King

George’s Medical

University,

Lucknow.

80-year old

ophthalmologist

from Indore

specialised

in cataract

surgeries and

myopia, provides

free services to

the poor patients

SANDEEP GULERIA RAMASWAMI VENKATASWAMI OMESH KUMAR BHARTI

Senior consultant

surgeon at

Indraprastha

Apollo Hospitals

and professor

at AIIMS. He led

the team which

conducted the

first successful

cadaver renal

transplant in

India.

Pioneer of hand

and reconstructive

surgery helping

millions of people,

whose arms

got severed in

accidents. Founder

of Institute for

Research and

Rehabilitation

of Hand and

Department of

Plastic Surgery

at Government

SMCH, Chennai.

Epidemiologist

who developed

low-cost antirabies

treatment

protocol at

1/10th of the

prevailing costaccepted

as part

of WHO protocol

globally.

ILIAS ALI R V RAMANI SUDAM KATE

Pioneer of

laprascopic

surgery in the

North East.

He developed

no scalpel

vasectomy and

popularised

family planning.

Founder of

Sankara Eye

Foundation

working on

80:20 model

for providing

affordable

eyecare services

across the

nation.

Indian social

activists doctor

known for his

pioneering

work in the

field of sicklecell

anaemia in

India. He has

helped diagnose

and treat over

3000 sickle cell

patients from

the rural tribal

communities of

Maharashtra,

Gujarat and MP.

March 2019 / FUTURE MEDICINE / 13


policy

GUIDELINES FOR NANO

DRUGS

The draft guidelines look at easing the evaluation process of nanotech-based

medicines in India

The Department of Biotechnology

(DBT) and Indian Society of

Nano Medicine has come out

with guidelines for evaluation of

nanopharmaceuticals in India.

The guidelines are being framed

in the backdrop of growing research

and development and usage of

nanomedicine in the country. According

to reports, the nanomedicine market

in the country is estimated to grow

to around $1.6 billion in 10-15 years.

Considering the growth of healthcare

market in the country, which is

expected to be in the top three among

world healthcare markets by 2020, the

need of the hour is to set standards for

nano pharmaceuticals.

The guidelines aim to ensure

quality, safety and efficacy as well as

to encourage the commercialisation

of nanotechnology-based innovation

with high benefit to risk ratio, says the

document.

DBT has given special emphasis

to promoting nanobiotechnology that

have applications in various sectors of

life sciences. It has been funding R&D

in this area since 2007, and various

scientists and stakeholders have felt

the need to have specific guidelines

for the evaluation of products in

various sectors of biological sciences

developed through interventions of

nanotechnology.

Nano pharmaceuticals is an

emerging field that combines

nanotechnology with pharmaceutical

and biomedical science to improve

efficacy and safety profile via targeted

drug delivery. Alteration into nanoscale

for drug delivery may significantly alter

the pharmacokinetic, biodistribution

and toxicokinetic parameters of

conventional/traditional drugs,

raising various concerns related to

quality, safety and efficacy of nano

pharmaceutical products, says the

guideline. Considering the complexity

of nanomaterial behaviour in the

SPECIFIC SCIENTIFIC

EVIDENCE IS REQUIRED

FOR APPROVAL OF ANY

NANO PHARMACEUTICAL

AND STRATEGIES FOR

PHARMACOVIGILANCE

biological environment, certain degree

of uncertainty may be inherent to such

system.

Charting the course

There are no uniform, internationally

acceptable guidelines for

nanopharmaceuticals. The usual

consensus for evaluation of quality,

safety and efficacy of nanotechnologybased

products is to have a ‘case

by case approach’, taking into

consideration of the physical, chemical

and biological characteristics of the

nanoparticle used and the route of

administration, the indication for which

the product is intended to be used and

other related aspects.

These guidelines apply to

nanopharmaceuticals in the form of

a finished formulation as well as an

API of a new molecule or an already

approved molecule with altered

dimensions, properties or phenomenon

associated with the application

of nanotechnology intended to

be used for diagnosis, treatment,

mitigation or prevention of diseases

in human beings. In the guidelines,

nanopharmaceuticals have

been classified according to

their degradability, organicity,

function and status of

approval. Accordingly, the safety and

efficacy data requirements have been

described.

Specific scientific evidence

required for approval of any nano

pharmaceutical and the strategies for

pharmacovigilance of such products

has also been incorporated in these

guidelines. Each application should

be considered on its own merit of

the data submitted using scientific

judgment and logical argument. For

the new generation of nanomaterials,

the development of methods for safety

testing and risk assessment, and a

better availability of quality data on

nanomaterials for regulatory purposes

are essential.

The guidelines define nano

pharmaceutical as a pharmaceutical

preparation containing nanomaterials

intended for internal or external

application on the body for the

purpose of therapeutics, diagnostics

and any other health benefit. These

are the products that contain materials

in the size scale range of 1 to 100nm

14 / FUTURE MEDICINE / March 2019


in at least one dimension. However,

if the particle size is >100nm and

10%.

Less stringent?

The guidelines also stipulate various

steps for the development of a

March 2019 / FUTURE MEDICINE / 15


column

the catalyst

An OYO model for

hospital beds!

An aggregator model like that of OYO is a possibility to

leverage the capacity utilisation agenda of providers

MURALIDHARAN NAIR

The healthcare industry has entered a

phase which will be characterised by

unprecedented opportunities for the

growth for affordable healthcare service

offerings. Even while the government aspires

to strengthen the public delivery system, it is

certain that much of the emerging demand

will have to be met by the private sector.

At the same time, it will not be wrong to

say that, barring a few exceptions, quality

affordable care models do not exist in India.

One of the key reasons for this has been the

intrinsic belief by the incumbent class that

we are highly cost-effective compared to the

global context, which, in my view, has little

relevance as a justification. However, things

are poised to change, given the irreversibility

of public demand, policy direction and a shift

in payer profile to the institutional from the

individual. Given this context, the following

could emerge as the key imperatives and

responses from industry in the times to

come:

1. Adopting design to cost method: In my

observation, one key reason for despair

among providers with the emerging price

expectations of mass healthcare schemes is

rooted in their approach to find a solution

through what I call a performance-plus

model, i.e., an incremental improvement over

the current state. However, what they need is

a holistic approach that aims to redesign

the capex and opex model to achieve the

target cost of delivery. This is called the

Design-to-Cost approach, which has been

prevalent for long in the manufacturing

and automotive industries. This will entail

fixing the total cost of delivery first and then

evolving an optimal cost structure of fixed

and variable costs. It will be based on firstprinciple

analysis (not accepted industry

norms) to rationalise layout design, human

resource, material consumption and medical

technology, formulary design, backed by

an unrelenting focus on buying efficiency

and commercial excellence, and clinical

excellence.

2. Volume will be King: Economies of scale

and asset sweating will be a critical enabler

for managing efficiency. Capacity planning

and dynamic pricing models (driven by

available capacities), akin to the hospitality

industry, will become increasingly relevant for

healthcare industry. The economic unit size

for a multi-speciality tertiary care hospital

will move closer to 1,000 beds from the

current levels of 250-300 beds, even though

capacity phasing during ramp up will have to

be planned with much greater care than is

typically done at present.

3. OYO model for hospital beds: The kind of

efficiency that will be needed in the future

will not lend itself to the high quantum

of unutilised capacities that exists on an

average, even for well-managed hospitals,

owing to demand variability. It is quite likely

that we will witness in the not-so-distant

future a capacity aggregator model like

OYO, which will possibly be an intermediary

between patients and providers and payers

to best leverage the capacity utilisation

agenda of the providers for optimum

benefit to patients and payers. This is not

as impractical as it may seem at first glance.

Barring a small percentage (less than 10

percent) of procedures, clinician stickiness

will come down further within

the mass healthcare space as the credibility

of empanelled hospitals gain ground with

time.

The author has long-standing association with

EY India but the views are strictly personal.

16 / FUTURE MEDICINE / March 2019


cover story

18 / FUTURE MEDICINE / March 2019


WAR TO

END

A SCOURGE

India is battling to eliminate TB by 2025 —

to vanquish an infectious malady that has

been haunting humanity for ages

S HARACHAND

In the year 1821, John Keats, one of the most celebrated

English poets, died of consumption at the age of 25.

Centuries later, that ‘consumptive disease’ still takes a

toll of millions of lives the world over in a more lethal form,

despite tremendous strides made by modern medicine to

curb diseases caused by bacterial infectious agents.

The history of tuberculosis is, perhaps, as old as

humanity itself. Though mankind survived the onslaught

of many a foul contagion that threatened to wipe it out

through the ages, tuberculosis (TB) turned out to be a

particularly resilient adversary.

March 2019 / FUTURE MEDICINE / 19


TB is one of the top 10 causes of death today and the

leading cause of death from a single infectious agent. More

people die from TB than HIV. In 2017, the infection caused

nearly 1.3 million deaths, excluding the 300,000 HIV-positive

people who lost their lives to TB that year, according to WHO

estimates. Ten million people developed the disease during

the year, including 1 million children.

India has the world’s highest burden of TB, accounting for

27 percent of all cases and over 30 percent of all TB-related

deaths.

Recognised as the leading infectious killer, TB is now

getting unprecedented attention in India. Signalling an

increased commitment, the health ministry has announced

an ambitious nationwide campaign to end TB by 2025, five

years ahead of UN’s Sustainable Development Goals. The

National Strategic Plan (NSP) for TB elimination 2017-25, with

an estimated cost of Rs 16,649 crore, banks on public-private

partnership to ensure that every TB patient has access to

quality diagnosis, treatment and support. The NSP provides

goals and strategies for the country’s response to the disease

during the period.

Missing millions and gaps in reporting

Home to a quarter of the 8.6 million cases of TB that

occur worldwide, India also has the dubious distinction of

Novel additions

No new antibiotic has been developed to

fight tuberculosis for several decades. The

emergence of more lethal drug-resistant strains

of Mycobacterium tuberculosis is now forcing

a change in the status quo. The urgency to

address MDR TB prompted a fast-track approval

of some of these treatments well before the

availability of their safety and efficacy data from

phase 3 programmes.

Bedaquiline

The first drug to treat TB in more than forty

years, bedaquiline was approved in 2012 by the

US FDA as a part of the accelerated approval for

use in MDR and XDR TB.

In the following year,. the WHO gave a

conditional recommendation to use bedaquiline

(BDQ) in MDR TB patients where other standard

regimens cannot be designed.

The drug belongs to a new class of drugs

called the diarylquinolines which blocks the

proton pump for ATP synthase of mycobacteria.

Data from clinical studies have shown an

increased risk of death with BDQ treatment.

Johnson & Johnson, the maker of the medicine,

also warns of QT prolongation with the use of

the drug.

Phase 3 studies are ongoing to assess the

safety and efficacy of BDQ.

BDQ was introduced at six sites in 5 Indian

states under Conditional Access Programme

(CAP) in March 2016. In the absence of phase 3

data, the Drug Controller General of India (DCGI)

approved the use of BDQ under RNTCP through

conditional access.

900 patients have been initiated on a BDQcontaining

regimen at 21 sites as of the end of

2017. The programme will expand the usage

of BDQ to all states as per their preparedness,

according to TB India Report 2018.

Delamanid

Delamanid belongs to a new class of TB drugs

called nitroimidazoles. In 2014, the WHO issued

interim policy guidance on the use of delamanid

(DLM) in MDR-TB regimen in adult patients with

pulmonary TB. The drug received approval in

Europe, Japan and South Korea in the same

year. The WHO extended the use of DLM to

children aged 6-17 years in 2016, following a

review of data from a 6-month safety, efficacy

and pharmacokinetic trial of paediatric patients.

These data were also considered to be of

very low certainty based on GRADE evidence

assessment.

In mid-October 2017, Otsuka Pharmaceutical

announced the final results of Trial 213 to

the public during the annual UNION World

20 / FUTURE MEDICINE / March 2019


in anti-TB armamentarium

Conference on Lung Health in Mexico.

The phase 3, multicentre, randomized,

double-blind, placebo-controlled clinical

trial compared two regimens for the

treatment of MDR-TB in adult pulmonary

TB patients.

The trial data found that the longer

MDR-TB regimen, used as the optimised

background regimen, had an overall

treatment success rate of 81%, much

higher than the global value of 54%

reported to WHO.

Studies to evaluate the efficacy of DLM

in children with MDR TB (Otsuka 233) and

paediatric MDR TB HIV patients (Otsuka

232) are underway.

National TB programmes and other

stakeholders are advised to only add

DLM to a longer MDR-TB regimen when it

cannot be composed according to WHO

recommendations. When an effective and

well-tolerated longer MDR-TB regimen can

be otherwise composed, the addition of

delamanid can be avoided.

In August 2017, DCGI issued permission

to import formulations of DLM (50 mg)

tablets to treat pulmonary MDR-TB in adult

patients. Accordingly, the guidelines were

prepared for use of 400 courses of DLM in

7 states.

Rifapentine

Rifapentine, a rifamycin antibiotic, inhibits

RNA polymerase in MTB. The drug was

approved by the US FDA in combination

with isoniazid (INH) for the treatment

of latent TB infection (LTBI) in patients

two years of age and older at high risk

of progression to TB disease in 2014,

following a priority review.

Weekly regimen of rifapentine with

isoniazid for three months has been

found effective in the prevention of active

tuberculosis

India’s health ministry may allow the

import of rifapentine for the treatment

of LTBI, waiving off the local clinical trials

requirement, otherwise mandatory for

all new drugs to be introduced in India,

reports said.

Pretomanid

Pretomanid is an experimental bicyclic

nitroimidazole-like molecule currently

undergoing phase 3 trials. The compound

was shown efficacious at doses of 100–

200 mg daily in studies conducted on

adult patients with pulmonary TB. Also,

no evidence of mutagenicity has been

detected in genotoxicity studies and no

significant cytochrome P450 interactions.

This compound has been developed by TB

Alliance.

Trials explore new strategies to tackle TB

Clinical trials of several novel drug regimens are currently underway as part of efforts to tackle

drug resistance and stop TB infection in its tracks

STREAM (Standardised Treatment Regimen

of Anti-Tuberculosis Drugs for Patients with

MDR TB) is an ongoing study supported

by USAID. It is a multi-centre international

randomized control trial to evaluate

shortened regimens for patients with MDR

TB.

STREAM Stage 1 is phase 3 study which

compares the standard WHO MDR-

TB regimen with a 9-month, modified

Bangladesh Regimen. The study has been

completed and results are pending.

STREAM Stage 2 aims to compare 6 and

9-month bedaquiline-containing regimen

against the WHO and Bangladesh regimen

in a phase 3 study.

NeXT (New Treatment Regimen for Patients

with Multi-drug Resistant Tuberculosis), an

open-label RCT of a 6-9-month, injectionfree

regimen containing bedaquiline,

linezolid, levofloxacin, ethionamide/high

dose isoniazid and pyrazinamide, is currently

in phase 3.

NiX-TB, a phase 3 study of bedaquiline,

pretomanid and linezolid in patients with

XDR-TB and MDR-TB for 6 months, with an

option of 9 months, has been completed.

TB-PRACTECAL (Pragmatic Clinical Trial

for a More Effective Concise and Less Toxic

MDR-TB Treatment Regimen(s)) is a multicentre,

open label, multi-arm, randomized,

controlled, phase 2-3 trial evaluating short

treatment regimens containing bedaquiline

and pretomanid in combination with

existing and re-purposed anti-TB drugs

for the treatment of biologically confirmed

pulmonary MDR-TB.

IMPAACT 2005 is a phase1/2 study to

evaluate the pharmacokinetics, safety and

tolerability of DLM in combination with

optimised multidrug background regimen

(OBR) for MDR-TB in HIV-infected and

HIV-uninfected children with MDR-TB. It is

currently enrolling non-US participants in

Botswana, India, South Africa and Tanzania.

endTB is a phase 3, randomized, controlled,

open-label, non-inferiority, multi-country

trial evaluating the efficacy and safety of

new combination regimens for MDR-TB

treatment.

DELIBERATE is evaluating the drug-drug

interactions and combined QT effects of

bedaquiline and delamanid in a phase 2

programme.

DRAMATIC is a proposed investigational

regimen combining two new drugs, BDQ

and DLM, with three anti-TB agents of

known potency, linezolid (LZD), levofloxacin

(LFX), and clofazimine (CF), to provide a

shorter, better-tolerated and more effective

MDR-TB treatment regimen for persons with

fluoroquinolone-susceptible MDR-TB.

March 2019 / FUTURE MEDICINE / 21


“TB Alliance looks to

dramatically shorten the

duration of TB therapy”

Mel Spigelman is the President

Dr and Chief Executive Officer of the

Global Alliance for TB Drug Development

(TB Alliance). He is a leader in

developing a regimen-based paradigm

of TB drug development – a faster

and more efficient approach, which is

emerging as the gold standard within

the TB drug research field. A recipient

of the American Cancer Society’s Clinical

Oncology Career Development Award

(1985-1988), Dr Spigelman is presently

the Co-Chair of the Working Group

on New Drugs of the WHO Stop TB

Partnership. Edited excerpts from an

interview with FM

Can you kindly brief us on the

current status of TB Alliance’s TB

clinical programmes?

TB Alliance is conducting three latestage

clinical trials to evaluate new drug

regimens for various forms of TB. Two

of the trials, known as Nix-TB and ZeNix,

are evaluating three-drug (bedaquiline+

pretomanid+ linezolid), six-month

regimens for the most resistant cases

of TB, including XDR-TB. Another trial,

Dr Mel Spigelman

called SimpliciTB, is evaluating a fourdrug

– bedaquiline + pretomanid+

moxifloxacin+ pyrazinamide - regimen

to treat both drug-sensitive TB in four

months and multidrug-resistant TB in

six, respectively.

What are the latest drug regimens

to tackle MDR/XDR TB?

The World Health Organization

recently released new treatment

guidelines for treating drug-resistant TB.

Currently, the recommended treatment

duration ranges from about 9 to 20

months. For the longer treatment

regimens, WHO no longer prioritises the

use of injectable drugs in the treatment

of drug-resistant TB. There are multiple

different regimens in a variety of clinical

trials, including STREAM, TB-PRACTECAL,

endTB and NeXT in addition to the trials

sponsored by TB Alliance.

Multi-drug resistance poses a

formidable challenge to bring TB

pandemic under control. How does

TB Alliance strategize to deal with this

growing threat?

Our strategy is to develop novel

TB drug regimens that are shorter,

safer, more effective and affordable.

Treatments with those characteristics

could both cure people with drugresistant

TB and prevent resistance from

emerging in the first place. A strong

pipeline of novel drugs will ensure that

we are well-prepared to treat any form

of the disease, which will be essential to

meeting global and national targets for

TB eradication.

In what ways does TB Alliance

address the question of affordability of

the new TB regimens in the developing

harbouring about a third of the ‘missing 3

million TB cases’ that do not get diagnosed

or notified. India, along with Indonesia and

Nigeria, accounts for 80% of the global

shortfall in the reporting of TB cases.

A study reported in The Lancet in 2016

found that prescriptions and drug sales

exceeded the number of cases recorded in the

national registry by almost 2 million, clearly

indicating improper reporting from the private

sector. This failure in reporting continues

to hamper an effective implementation of

eradication strategies.

The scenario is

expected to change

as the reporting of

TB has been made

compulsory

Dr George Mothy

Justin

Pulmonologist

As much as 60-70% of patients access

private health care providers as the first

point of care, including for TB, according to

National Sample Survey Office. The majority

of the patients take prescriptions from private

hospitals due to the dysfunctional public

sector.

“A ubiquitous private sector and low

notification rates have been one of the

major impediments in getting a sense of the

magnitude of the TB challenge,” points out Dr

Sameer Kumta, Senior Programme Officer, TB,

Gates Foundation, India.

22 / FUTURE MEDICINE / March 2019


world where TB is a major

healthcare problem?

In line with our “AAA” mandate,

we are committed to ensuring that

all drugs and regimens we work

on will be affordable, available and

adopted around the world. We derisk

the research and development

of our work through the financial

support from our donors, which

lowers the bar for our commercial

partners to get involved. We also

ensure that all molecules in which

we invest can be manufactured at a

very reasonable cost of production.

In addition, we will give royaltyfree

licenses to our products to

multiple, high-quality manufacturers

in the developing world to generate

generic competition. Through generic

competition, as we have seen in many

fields, prices can be reduced to their

lowest sustainable levels.

One of the stated goals of TB

Alliance is making ultra-short, simple

treatment regimens for battling

TB. How far has the organization

succeeded in achieving this

objective?

We have developed the largest

single portfolio of potential new TB

therapeutics ever assembled. Our goal

is to discover or partner with others

on multiple new chemical entities

that do not have cross-resistance

with presently available anti-TB drugs,

and which can be given together in

regimens that are safe enough to be

used in all TB patients and effective

enough to dramatically shorten the

duration of TB therapy. We now have

multiple new drug candidates in our

pipeline that, in combination with

those of other organisations, have

the potential to deliver a very short

treatment for virtually all patients with

active TB.

What is TB Alliance’s most crucial

therapeutic intervention in TB

management?

Children with TB have long been

the neglected of the neglected,

with an estimated 1 million children

developing TB each year. To date,

we have seen major progress in the

global uptake of child-friendly TB

medicines introduced by TB Alliance

and our partners, with

over 900,000 treatment courses

ordered by 88 countries and counting

since becoming available at the end

of 2015. These new formulations of

first-line treatment, which are

available in India, come in WHOapproved

doses and are designed

to be easy for children to take:

fruit flavoured for palatability and

dissolvable in water. Looking ahead,

we hope to introduce novel TB drug

regimens that are shorter, safer,

effective and affordable, suitable for

every person with TB.

Most Indians prefer seeking care from the private sector

first, resulting in under-reporting of TB, he adds.

India declared TB a notifiable disease way back in 2012.

However, the reporting of the disease is abysmally low from

the private health care sector in the northern regions of the

country where the incidence of TB is very high.

“The scenario is expected to change as the reporting of

TB has been made compulsory,” says Dr George Mothy Justin,

Head of the Department, Respiratory Medicine, Medical Trust

Hospital, Kochi, India.

Last year, India made non-reporting of TB a punishable

offence. Failure to report TB cases can now invite punishment

under relevant sections of Indian Penal Code.

INDIA TARGETS TO

END TB BY 2025

India has set an ambitious target to

eliminate TB by 2025. The goal is to

end the country’s leading infectious

disease five years ahead of the global

target of 2030.

The government has announced

the National Strategic Plan (NSP), with

an estimated cost of Rs 16,649 (USD

2,485 million), to ensure access to

diagnosis, treatment and support for

all TB patients.

The new scheme looks to expand

public-private partnership models

and use information technology tools

for monitoring the programme and

treatment adherence. Community

engagement is the hallmark of the

programme and it is becoming a

social movement, according to the

Union health minister JP Nadda.

The new NSP adopts a multipronged

approach, which aims

to detect all TB patients, with

an emphasis on reaching TB

patients seeking care from private

providers, and undiagnosed TB

in high-risk populations. It aims

to treat all patients irrespective of

where they seek care, adopting a

patient-centric approach and to

prevent the emergence of TB in

susceptible population groups and

build empowered instaitutions and

human resources to streamline

implementation, Nadda said.

The implementation of NSP will be

a combined effort of all stakeholders

working towards the same goals. A

restructured Central TB Department

(CTD) at the ministry of health will

oversee the implementation of the

plan by coordinating the work of the

National TB Control Board. State TB

cells will continue to oversee the work

at state and district levels.

March 2019 / FUTURE MEDICINE / 23


NOTIFY ON NIKSHAY:

INDIAN MEDICAL

ASSOCIATION

E

ven though India declared TB a

notifiable disease in the year 2012,

the level of notification has not risen to

expectations. All medical practitioners

in the country have to notify their TB

patients to the government registry.

However, a review of the state-wise

notification data from 2018 showed

that the percentage of notification from

the private health sector in the Indian

states of Uttar Pradesh, Maharashtra,

Bihar Rajasthan, Gujarat, Madhya

Pradesh is a mere 28%. Among these

six states, Bihar is leading in private

notification at 40%, according to the

Indian Medical Association (IMA), which

carried out the survey.

IMA, the umbrella organisation

of Indian clinicians, has recently

urged private doctors to notify every

tuberculosis patient and register them

on Nikshay, a web-enabled application

developed by India’s health ministry.

Nikshay is an online tool which aims

to create a database of all TB patients

for monitoring and research purposes.

Notification allows access to free drugs

and diagnostic tests, nutritional and

patient-centric support that ensures

patients adhere to the treatment and

incentives.

Doctors in the private sector have a

huge role to play in reporting TB cases

and adhering to the Standards for TB

Care in India (STCI). STCI needs to be

followed uniformly across the private

sector.

With the largest burden of

tuberculosis in the world, the Indian

government is working towards a TBfree

India by 2025. Notification of every

TB patient is the single most important

intervention to meet the government’s

vision of a TB-free India.

India accounts for

a quarter of the 8.6

million cases of TB

that occur worldwide.

India also accounts for

a third of the ‘missing

3 million TB cases’ that

do not get diagnosed or

notified.

Leading pulmonologists like Dr George are sceptical

whether India would be able to bring down its numbers

within the stipulated timelines, considering the slow pace

of diagnosis and unusually protracted treatment regimens

practiced in India’s TB hotspots.

Treating latent TB: A daunting task

Also, at 40%, the proportion of people with latent TB is

higher in India owing to poor diagnosis and ineffective

treatment. People with latent TB infection (LTBI) do not

show any symptoms nor do they infect others. The infection,

however, won’t go away unless treated along the lines of

active TB.

The WHO recommends treating only those with active

diseases in high-burden countries like India, a stand criticised

by many TB experts. Targeting LTBI, along with the active

disease, is important to eliminate TB, they assert.

Recent reports indicate that the government is

considering to bring all LTBI patients too under the purview

of treatment. Treating asymptomatic TB patients would

be a daunting task in India as the numbers can be huge.

Policymakers plan to tackle the enormous LTBI population in

a phased manner, targeting the high-risk group with priority

to achieve the goal.

Among those included in the high-risk group and

identified to receive LTBI treatment by the NSP are those

on long-term corticosteroids, immunosuppressants, the HIVinfected

and juvenile contacts of sputum-positive index cases.

Since children are more susceptible to develop severe

forms of disseminated TB, those above six years of age, who

are in close contact of TB patients, will be evaluated. After

excluding active TB cases, they will be given 10 mg/kg of

isoniazid (INH) administered daily for a minimum period of six

months irrespective of their BCG or nutritional status.

INH preventive therapy will also be considered for all HIV

infected children, all tuberculin skin test (TST) positives who

24 / FUTURE MEDICINE / March 2019


BATTLE FOR BEDAQUILINE

Bedaquiline is the first anti-TB drug

developed in over four decades.

The cost of the treatment goes up to

$30,000 for a six-month course.

A diarylquinoline

antimycobacterial agent, bedaquiline’s

cure rates for patients have been

reported at over 80%.

The drug also has fewer sideeffects

compared to the old anti-TB

injectable drugs which can even

cause deafness.

By 2016, at least 35 countries

have introduced shorter regimens

for treatment of MDR/RR-TB and 89

countries and territories had started

using bedaquiline, shows WHO Global

TB Report 2017.

Nevertheless, the drug still

remains out of reach for most lowand

middle-income countries. To

date, only 25,000 people around the

world have received bedaquiline and

two-thirds of these patients have

been in South Africa. South Africa

is among those small number of

countries which have negotiated a

greatly reduced price of $400 from

Johnson & Johnson, the maker of the

drug.

The drug maker Johnson &

Johnson, in its latest filing, seeks

extended patent protection to

bedquiline in India. The company›s

current patent expires in 2023. If

granted, the drug will enjoy exclusive

marketing rights till 2027.

Since India is considered the hub

of generic medicines of the world, the

additional patent could further delay

the availability of low-priced versions

of this life-saving medicine and will

also indirectly impact many countries

in the world, say those opposing the

patent in India.

Activists demanded J&J to

slash the price for the blockbuster

tuberculosis drug at the opening of

49th Union World Conference on

Lung Health in the Netherlands in

October last year.

There is a greater chance

of curing MDR-TB patients who

otherwise look at an abysmal curerate

of 50 percent, but this can only

happen if J&J cuts the price for

bedaquiline to a dollar a day, they

maintained.

J&J said in a statement that

their new price of $400 per course

is “genuinely a special effort that we

set to encourage rapid scale-up of

bedaquiline in countries with a high

TB burden”.

Controversies over pricing have

the potential to further damage an

already fragile environment for TB

research and development.

Since its approval as part of

USFDA’s Fast Track accelerated

approval process in 2012, J&J

has donated 60,000 bedaquiline

treatments to patients in such

high-TB-burden countries as China,

India and South Africa, the company

said.

In 2017, J&J formed a

collaboration with India’s Institute

of Microbial Technology (IMTech),

focused on discovering safer, more

effective oral treatments and multidrug

regimens for MDR-TB.

J&J has tied up with the

International Union Against

Tuberculosis and Lung Disease

to include bedaquiline in the STREAM

study, a multicentre international trial

to evaluate the medicine in patients

with MDR-TB. Final study results are

expected as early as 2023.

are receiving immunosuppressive therapy and a child born to

a mother who was diagnosed to have TB during pregnancy.

The health ministry is likely to allow the import of

rifapentine for the treatment of LTBI, waiving off the local

clinical trials requirement that is mandatory for all new drugs

introduced in India, according to reports.

A weekly regimen of rifapentine with isoniazid for three

months has been found effective in the prevention of active

tuberculosis

But the implementation of treating LTBI can still be

challenging as people without any obvious symptoms have to

adhere to a months-long regimen of multiple pills which often

have undesirable side-effects.

“If you start checking, you will come to know that a good

proportion of the Indian population has asymptomatic TB.

We have systems in place to rapidly detect the disease with

nearly 100% accuracy. And we have effective medicines

to treat even MDR TB. But the question is, will everybody

detected with asymptomatic, latent TB be willing to follow

the treatment course,” asks Dr Sunil Nair, Assistant Professor,

Pulmonary Medicine, Medical College, Trivandrum. Places like

Kerala have brought down TB cases dramatically through

effective intervention. The situation, however, is not so in

other parts of the country, where the infection is more

rampant.

Unlike earlier days, we now have GeneXpert machines

March 2019 / FUTURE MEDICINE / 25


in place to quickly diagnose TB in every

district. Soon the facility will be brought to

the taluk level. Nevertheless, the availability

of the diagnostic facility doesn’t mean that

everybody goes for testing. If one tests

positive for diabetes, he wouldn’t hesitate

to share the status with his friends. It is not

usually the case with TB. In many cases, the

person wouldn’t share the information with

even his family members. Tuberculosis, like

HIV, still has a lot of stigmas. People may

not go forward to test TB as eagerly as they

go for other diseases, comments Dr Nair.

Challenge of drug resistant TB

While the increasing number of deaths

are attributed to delayed diagnosis and

inadequate treatment, the emergence of

multi-drug resistant strains presents the

most formidable challenge to the efforts

of containing TB. Again, India tops the list

of the three countries which account for

nearly half of the world’s cases of MDR/

RR TB. There are around 1.5 lakh cases of

MDR TB in India. Of this, nearly 12% are in

Mumbai, which is considered the epicentre

of the MDR TB. Unlike drug-sensitive TB, the

success rate for curing MDR-TB is only 33

percent.

Even though, drugs to treat MDR TB

is currently available, not all Indian clinics

have access to these novel treatments. Both

bedaquiline and delamanid — novel anti-TB

drugs — were introduced in India through

a conditional access programme and

included in the Revised National TB Control

Programme (RNTCP). Their availability is

limited to a handful of patients from select

cities.

For instance, the 400 doses of

delamanid that India received from Otsuka

Pharma as part of a phase 3 programme

were rolled out in seven states in November

last year. High costs remain a major barrier

to patients accessing these treatments,

which are yet to come out with their safety

and efficacy data from phase 3 trials.

Even with the latest treatment,

India is achieving a cure rate of only around

47% on average at the national level.

India-wide, around 15-20% of MDR TB

patients die. There are very few diseases

with such a high mortality rate. Many

cancers have a better cure rate. This makes

The government

has backed

the NSP with a

historic resource

commitment of

Rs 12,000 crores

over three years,

while it increased

investment in

research and

development to

$6 million.

Dr Sameer Kumta

Senior Programme

Officer, TB

Gates Foundation

India

CHALLENGE OF TUBERCULOSIS

16,00,000

died of tuberculosis infection in 2017

TB kills

someone every

18

seconds

India accounts

for 27% of all TB

cases in the world

and 30% of all TBrelated

death

Uttar Pradesh

3,29,092

Gujarat

1,23,665

Maharashtra

1,50,293

Madhyapradesh

1,19,117

10,00,000

children get sick with TB

each year

Rajasthan

1,35,428

Bihar

1,03,255

26 / FUTURE MEDICINE / March 2019


TREATMENT

SUCCESS RATE

83%

54%

30%

TB MDR-TB XDR-TB

SOURCE: WHO

WHO REMOVES INJECTABLE DRUGS

FROM MDR REGIMENS

The WHO has revamped the treatment

guidelines for MDR and rifampicinresistant

(RR-TB) even as multi-drug

resistance poses a threat to the End TB

Strategy.

The guidance, based on a review of

the recent evidence on priority questions

in MDR/RR-TB treatment, was formulated

by the Guideline Development Group

(GDG).

“The new WHO recommendations,

based on the most recent available

evidence, signal an important departure

from previous approaches to treat

MDR/RR-TB. Injectable agents are no

longer among the priority medicines

when designing longer MDR-TB

regimens. Fully oral regimens should thus

become the preferred option for most

patients,” stated Dr Tereza

Kasaeva, Director of WHO’s Global TB

Programme.

The evidence included the recently

completed phase 3 trials of delamanid

(Otsuka’s Trial 213) and the standardised

9-12-month shorter MDR-TB regimen

(STREAM Stage 1), as well as individual

data for 13,100 patients treated with

longer MDR-TB regimens in 40 countries

and over 2,600 patients treated with

the shorter MDR-TB regimen from 15

countries. Additional trial data from

patients under 18 years of age allowed

a review of recommendations for the

use of bedaquiline and delamanid in

children.

Fluoroquinolones (levofloxacin or

moxifloxacin), bedaquiline and linezolid

are strongly recommended for use in

longer regimens, which are completed

with other medicines ranked by their

relative balance of effectiveness to

potential toxicity.

The shorter MDR-TB regimen may be

offered to eligible patients who agree to

a briefer treatment. Shorter regimens for

MDR may, however, be less effective than

an individualized longer regimen and

that requires a daily injectable agent for

at least four months. Regimens that vary

substantially from the recommended

composition and duration like the

FLUOROQUINOLONES

(LEVOFLOXACIN OR

MOXIFLOXACIN), BEDAQUILINE

AND LINEZOLID ARE

STRONGLY RECOMMENDED

FOR USE IN LONGER

REGIMENS

standardized 9-12-month shorter MDR-

TB regimen in which the injectable

agent is replaced by bedaquiline can

be explored under operational research

conditions.

The recommendations apply

generally to children and adults, to

people living with HIV (PLHIV) and to

MDR/RR-TB patients who have additional

resistance to fluoroquinolones or other

agents.

Bedaquiline may now be given to

children aged 6 years and more and

delamanid from 3 years of age.

Supportive measures to improve

diagnostics and other programmatic

components will be critical. Ahead

of enrolment on MDR-TB treatment,

all patients should be appropriately

counselled to enable participatory

decision-making. Patient-centred support

for medication adherence and active TB

drug safety monitoring and management

(aDSM) are essential for anyone starting

an MDR-TB regimen.

March 2019 / FUTURE MEDICINE / 27


IDRI’S TB VACCINE ENTERS PHASE 2 TRIALS

An experimental vaccine, called

ID93, developed by scientists at the

Infectious Disease Research Institute

(IDRI) in Seattle, has advanced to phase

2 clinical testing.

The TB vaccine candidate combines

ID93, a fusion of 4 mycobacterium

tuberculosis antigens with diverse roles

in pathogenesis, with the adjuvant

GLA-SE, a synthetic toll-like receptor

4 (TLR4) agonist, formulated in a

squalene oil and water nano-emulsion

that has a significant safety track

record.

“The four antigens representing

different families of mycobacterium

tuberculosis (MTB) proteins have

been shown to be recognised in

MTB-exposed individuals. RV1813 is a

conserved hypothetical protein that

is upregulated under hypoxic growth

and predicted to be localised in the

outer membrane. RV2608 (PPE42) is a

probable outer membrane-associated

PPE (pro-pro-glu motif-containing)

protein. RV3619 (ESXV) and RV3620

(ESXW) are secreted proteins belonging

to the ESAT-6 family of virulence

factors,» says Rhea Coler, Senior. Vice

President, Preclinical & Translational

Science at IDRI.

Explaining the role of the adjuvant,

Rhea Coler

STUDIES HAVE SHOWN

THAT ID93+GLA-SE

IS EFFICACIOUS

PROPHYLACTICALLY

AS WELL AS

THERAPEUTICALLY

Coler said, GLA-SE skews the immune

response to a TH1 type immune

response with induction of CD4+ T

cells. Human immune correlates of

protection against TB have not yet

been identified. T-helper 1 (TH1) type

cellular immunity is known to be crucial

for controlling MTB infection and thus

vaccine strategies aim to elicit these

subsets.

Recently, studies have shown

evidence that antibodies may also

contribute to controlling disease in

latently infected individuals.

Pre-clinical studies using mice,

guinea pigs and non-human primates,

have shown that ID93+GLA-SE is

efficacious prophylactically as well as

therapeutically. The vaccine significantly

improved TB treatment outcomes

over antibiotics alone and allowed the

duration of antibiotic treatment to be

reduced by 30%.

Therapeutic efficacy of ID93+GLA-

SE is associated with enhanced TH1

responses, improved MTB clearance,

and reduced pulmonary inflammation.

“In mice and humans, we have

observed immune responses 6-12

months after immunization,’’ Coler

adds.

As a part of the efforts to make

the vaccine affordable for those who

need it, IDRI is planning to transfer the

technology involved in the production

of the vaccine to 3 different facilities in

Africa and Asia.

TB a big challenge.

TB kills more than 1,400 people every day, or around

480,000 Indians every year, as per official estimates.

India accounts for nearly 10% of the global burden of HIVassociated

TB. According to the India TB Report 2018, 87,000

HIV-associated TB patients are being diagnosed annually. HIV

prevalence among incident TB patients is estimated to be

4%. The mortality in TB/HIV co-infected patients is very high

and 12,000 people die every year from this condition.

Prevention as centrepiece?

Alongside free diagnosis and treatment, the NSP provides

an incentive for nutritional support. “In India, undernutrition

is a driver of TB,” comments Dr Sameer. Undernutrition and

TB have a bidirectional relationship. While undernutrition

increases the risk of TB, contracting the disease increases

the risk of malnutrition, thereby culminating in an intercausal

cycle for the two diseases.

India has practically doubled the budget to meet the

target of eliminating TB by 2025. “The government has

backed the NSP with a historic resource commitment of Rs

12,000 crores over three years, while it increased investment

in research and development to $6 million,” comments Dr

Sameer.

Some experts are of the opinion that the current budget

allocation may still be way below the actual requirement.

Considering the enormity and the urgency of the situation,

both the regular, drug-susceptible TB as well as the drugresistant

TB need additional expenditure.

In order to achieve the target of ending TB by 2025, India

needs to reduce new TB cases by 10 percent every year. But

recent reports indicate that the country is nowhere near the

number. Moreover, India needs to pay more attention to a

preventive strategy. The goals can’t be translated to reality

until prevention becomes the centrepiece of India’s TB policy,

warn experts.

28 / FUTURE MEDICINE / March 2019


technology

NGS BREAKS NEW PATH

IN TB CARE

Integration of NextGen Sequencing can reduce the Mycobacterium tuberculosis

disease burden

DR RAJANI KANTH VANGALA

In order to have an effective

treatment for tuberculosis (TB),

there is an urgent need to modify

the current treatment regime, which

includes low efficacy, high toxicity and

long duration drugs, and consumes

significant resources. In 2015 alone,

there have been 10.4 million TB

infections and 1.8 million deaths,

making TB one of the top 9 killers in

the world, higher than HIV/AIDS. This

unsatisfactory situation is mainly due

to the development of drug resistant

TB, which is immune to isoniazid and

rifampicin. The three different types of

resistance include multi-drug resistance

(MDR), extensive drug-resistance

(XDR) and totally drug-resistance

(TDR), based on the exact strain of

Mycobacterium tuberculosis responsible

for the infection.

At the same time, there has

been the emergence of “offlabel”

repurposed drugs such as

oxazolidinones, carbapenems and

clofazimine, which are being used to

treat highly-resistant TB cases. The

identification of the type of infection

and proper diagnosis have been found

to be the most important factor that

determines the clinical outcome

in such cases, even as drug-resistant

strains are becoming a major global

challenge. This challenge can only

be addressed by genetic analysis to

understand its complex biology and the

mechanisms of drug-resistance.

In this respect, one of the most

important technological advances is

whole-genome sequencing (WGS),

which was first reported by Cloe et

al in 1998, sequencing the M.

tuberculosis strain H37Rv. This

has significantly improved our

understanding of the bacterial strain

30 / FUTURE MEDICINE / March 2019


about its physiology, metabolism, and

pathogenicity.

Diagnosing resistance

The advent of NextGen Sequencing

(NGS) technologies, combined with

bioinformatics tools, has enabled

the establishment of new platforms

for better diagnosis and potential

therapeutic approaches. Generation

of large-scale genomic data in less

time and at a lower cost (Metzker,

2010) has led to its use in various

clinical scenarios, such as drug

susceptibility, diagnosis and genetic

diversity (Satta et al., 2017). Zhang

et al (2013) analyzed 161 clinical

isolates in China and Casali et al

(2014) analyzed 1000 M. tuberculosis

genomes using WGS technology,

leading to the identification of 28

intergenic regions (IGRs) associated

with drug resistance, 10 IGR single

nucleotide polymorphisms (SNPs), 72

new genes and 11 non-synonymous

SNPs. Several other uncharacterized

genes, intergenic regions and SNPs

were also reported to be associated

with drug resistance phenotypes by

other research groups (Anderson et

al., 2014; Ali et al., 2015; Pankhurst

et al., 2016). Further improvements,

like the use of direct clinical samples

or biospecimens, without the need

for costly infrastructure has also

changed the ease with which data

can be generated. NGS can now be

directly applied to clinical isolates using

tabletop machines without the need for

too much pre-processing and in very

short times.

The quality and depth of the

complete genome sequence provided

by NGS has helped in the development

of MDR/XDR-TB diagnostics. It has also

helped in comparative genomic analysis

to understand genomic diversity

and the evolution of drug-resistant

pathogens (Liu et al., 2014). Some of

the recent NGS-based studies focusing

on the evolution of XDR M. tuberculosis

have shown that a single patient can

have both a susceptible ancestor for

fluoroquinolones as well as resistant

bacteria (Zhang et al. 2016). One of

the most important limiting steps yet

in NGS is cumbersome bioinformatics

and data inconsistencies about

correlations between gene mutations

and phenotypic drug susceptibility test

(DST). However, the emergence of a

new generation of sequencing, enabling

long reads of up to 100kb (Lee et al

2016), has resulted in a reduction of

fragment assemblies. Presently there

are three third-generation technology

platforms, namely Pacific Biosciences

(PacBio) Single Molecule Real Time

(SMRT) sequencing, Illumina Tru-seq

Synthetic Long-Read technology and

Oxford Nanopore Technologies’ MinION.

These technologies are now making

whole-genome sequencing much

faster and simpler. In addition, recent

publications have generated data on

mythelomes that suggest that MTases

activities, which are up-regulated,

contribute to genome modifications

and mutations leading to the evolution

of drug resistance in MDR-TB clinical

isolates (Leung et al., 2017).

THE QUALITY AND DEPTH

OF THE COMPLETE GENOME

SEQUENCE PROVIDED BY

NGS HAS HELPED IN THE

DEVELOPMENT OF

MDR/XDR-TB DIAGNOSTICS

Enabling faster detection

Some of the important challenges

which need urgent attention include,

DNA extraction, the need for culture

for WGS, understanding the molecular

mechanisms of drug resistance and

large-scale data analysis. Starting

with DNA extraction, there are many

technologies in this arena, and an

evaluation of these will help in selecting

the best. For example, Nextera DNA

Flex / Nextera XT / Nextera mate

Pair work on an Illumina platform

with as low as 1ng of DNA. The

new concept of DNA isolation from

saliva without culturing has gained

a lot of momentum as it reduces

the time required and gives faster

results. However, this also comes

with its own difficulties in removing

human DNA and other potential

contaminants. Furthermore, this gets

more complicated due to the use of

nonspecific primers. Some of the new

technologies which are picking up this

challenge are differential lysis protocol

followed by DNA extraction using a

NucleoSpin tissue-kit or Illumina MiSeq

sequencer with 87% success rate

(Doughty et al 2014), SureSelectXT

target enrichment system (Agilent

Technologies) with 83% success (Brown

et al., 2015). Further developments are

required to evolve these technologies

for lower cost and improved diagnosis.

As we are still at a nascent stage of

understanding the evolution of drugresistant

phenotypes using NGS, tools

for automated pipeline, like Mykrobe

Predictor TB, TB Profiler, CASTB,

PhyResSE and KvarQ, are enabling

faster detection of drug resistance

and lineage-specific mutations from

raw, whole genome sequence of M.

tuberculosis.

The future of M. tuberculosis

management will not only depend

on NGS technologies but also in

developing direct DNA isolation

for sequencing, along with better

bioinformatics. Such developments

might help us finally realize the goals

of the StopTB partnership and reduce

disease burden.

March 2019 / FUTURE MEDICINE / 31


drug approvals

Priority review for

upadacitinib to treat RA

AbbVie said the US FDA has

accepted upadacitinib for

priority review for the treatment

of adult patients with moderate

to severe rheumatoid arthritis.

Upadacitinib is an

investigational once-daily oral

JAK1-selective inhibitor being

studied for multiple immunemediated

diseases.

The new drug application

is supported by data from the

global upadacitinib SELECT

phase 3 rheumatoid arthritis

programme evaluating more

than 4,000 patients with

moderate to severe rheumatoid

arthritis across five of six phases

3 studies. In all SELECT phase

3 studies, upadacitinib met all

primary and ranked secondary

endpoints.

Upadacitinib is also under

review by the European

Medicines Agency for the same

indication.

The SELECT phase

3 rheumatoid arthritis

programme evaluates more

than 4,900 patients with

moderate to severe rheumatoid

arthritis in six studies, five of

which support a regulatory

submission for upadacitinib.

Ropeginterferon

for polycythaemia

in EU

PharmaEssentia announced

that the European

Commission (EC) has approved

ropeginterferon alfa-2b

(Besremi) as monotherapy

in adults for the treatment

of polycythaemia vera

(PV) without symptomatic

splenomegaly.

The EU market

authorization makes

ropeginterferon alfa-2b the

first and the only approved

treatment for PV, independent

of previous hydroxyurea

exposure, based on phase III

clinical data.

Ropeginterferon alfa-2b

will be available as a solution

for injection in a pre-filled pen

in two dosage strengths of 250

microgram/0.5 ml and 500

microgram /0.5 ml.

Ropeginterferon alfa-

2b is a novel, long-acting,

predominately single isomer

mono-pegylated proline

interferon with improved

pharmacokinetic properties.

It is administered once

every 2 weeks, or once every

4 weeks during long-term

maintenance, and is the first

interferon approved for PV.

Turoctocog alfa

for haemophilia A

treatment

The US FDA has approved

turoctocog alfa pegol,

N8-GP (Esperoct) for the

treatment of adults and

children with haemophilia A.

Turoctocog alfa pegol

is indicated for use in

adults and children with

haemophilia A (congenital

factor VIII deficiency) for

routine prophylaxis to reduce

the frequency of bleeding

episodes, Novo Nordisk

announced.

The approval is based on

the results from the clinical

programme conducted in

270 previously treated people

(PTPs) with severe haemophilia

A and more than 5 years of

clinical exposure. Turoctocog

alfa was shown to provide

effective routine prophylaxis in

people with severe haemophilia

A through a simple, fixed

dosing regimen of one injection

every 4 days in adults and

adolescents or every 3-4 days

in children.

Turoctocog alfa is an

extended half-life factor VIII

molecule for replacement

therapy, which provides a 1.6-

fold half-life prolongation in

adults/adolescents and a 1.9-

fold half-life prolongation in

children, compared to standard

half-life factor VIII products.

Polatuzumab

combo for B-cell

lymphoma

Polatuzumab vedotin

in combination with

bendamustine plus rituximab

(BR) has been granted priority

review by the US FDA for the

32 / FUTURE MEDICINE / March 2019


treatment of people with

relapsed or refractory (R/R)

diffuse large B-cell lymphoma

(DLBCL).

The GO29365, a global,

phase Ib/II randomized study,

showed that polatuzumab

vedotin plus BR improved

median overall survival

compared to BR alone in

people with R/R DLBCL not

eligible for a hematopoietic

stem cell transplant. The

study also showed that 40

percent of people treated with

polatuzumab vedotin plus BR

achieved a complete response

(CR), while only 18 percent of

people treated with BR alone

achieved a CR.

Polatuzumab is developed

by Genentech, a member of

the Roche Group.

Renexus to treat

macular disease

The US FDA has granted

Fast Track designation

for NT-501 or Renexus for

the treatment of macular

telangiectasia type 2

(MacTel), Neurotech

Pharmaceuticals said.

Renexus is a novel

cell-based drug delivery

system. Human-derived

cells encapsulated in a

semipermeable hollow fibre

membrane device release

US FDA panel okays esketamine

nasal spray for depression

The Janssen

Pharmaceutical

Companies of Johnson

& Johnson announced

that the US Food and

Drug Administration (FDA)

recommended the use

of esketamine (Spravato)

for treatment resistant

depression.

The

psychopharmacologic

drug advisory committee

and drug safety and risk

management advisory

committee of US FDA jointly

voted that data support

the favorable benefit-risk

profile of esketamine nasal

spray CIII for adults living

with treatment-resistant

depression.

Esketamine is thought

to work differently than

currently approved therapies

for major depressive

disorder (MDD). If approved,

esketamine would provide

the first new mechanism of

action in 30 years to treat

this debilitating mental

illness.

ciliary neurotrophic factor

(CNTF) demonstrated to

reduce photoreceptor cell loss

in animal models of retinal

degeneration.

The implanted Renexus

device results in sustained

The committees based

their support on the safety

and efficacy data from five

phase 3 studies in patients

with treatment-resistant

depression: three short-term

studies; one maintenance

of effect study; and one

long-term safety study. In

addition, the esketamine

research programme

provided supportive data

from three Phase 2 studies

and 19 phase 1 studies in

patients with treatmentresistant

depression and

healthy volunteers.

Esketamine is a

glutamate receptor

modulator, thought to help

restore synaptic connections

in brain cells in people

with the major depressive

disorder.

The US FDA has granted

Breakthrough Therapy

Designations for esketaine

for treatment-resistant

depression and for a second

indication, major depressive

disorder with imminent risk

for suicide.

delivery of CNTF localized to

the retina, the light-sensing

tissue in the back of the

eye. MacTel is a rare macular

degenerative disease typically

diagnosed in middle age.

Patients rarely experience total

vision loss, but the disease

nonetheless has a significant

impact, through visual loss, on

a patient’s quality of life.

Based on the positive

phase 2 results, two parallel

phase 3 studies were initiated.

Macular telangiectasia

(MacTel), or idiopathic

juxtafoveal macular

telangiectasia, is a rare

neurodegenerative disease

with characteristic alterations

of the retinal vasculature and

localized retinal degeneration.

Triclabendazole

to treat

fascioliasis

N

ovartis said triclabendazole

(Egaten) has won approval

from the US FDA for the

treatment of fascioliasis in

patients six years of age and

older.

Triclabendazole is

currently the only medicine

for fascioliasis recommended

by the WHO and is on the

WHO Model List of Essential

Medicines.

Fascioliasis, commonly

known as liver fluke infestation,

is a neglected tropical disease

that infects 2.4 million people

worldwide, with an additional

180 million at risk of infection.

It is caused by two species

March 2019 / FUTURE MEDICINE / 33


of parasitic flatworms or

trematodes that mainly affect

the liver (Fasciola hepatica

or Fasciola gigantica). Both

species can infect humans

following ingestion of larvae in

contaminated water or food

(mainly raw or undercooked

vegetation). The larvae mature

into adult worms in the biliary

tract. No continent is free from

fascioliasis; human cases have

been reported from more than

70 countries worldwide.

Orphan drug

designation for

cryptococcosis

medicine

Orphan drug

designation has

been granted to a lead

drug candidate, APX001

for the treatment of

cryptococcosis, said Amplyx.

APX001 had previously

received orphan drug

designation for the treatment

of invasive candidiasis,

invasive aspergillosis,

coccidioidomycosis, and rare

mold infections caused by

Scedosporium spp., Fusarium

spp., and Mucorales fungi

(including Mucor spp., and

Rhizopus spp.).

APX001A, the active moiety

of APX001, inhibits the highly

conserved fungal enzyme Gwt1,

compromising growth of major

fungal pathogens.

APX001 is currently in

Oral dapagliflozin for type-1 diabetes

EMA has recommended a new indication for

dapagliflozin (Forxiga) for use as an oral adjunct

treatment to insulin in adults with type-1 diabetes

(T1D).

Dapagliflozin, a selective sodium glucose

cotransporter-2 (SGLT2) inhibitor, is the first oral

medicine to receive a positive recommendation

from the EMA for use in T1D as an adjunct to

insulin in patients, AstraZeneca said.

The DEPICT clinical programme

consists of two trials, DEPICT-1 and -2,

with the primary efficacy endpoint at

24 weeks and a long-term extension up

to 52 weeks. Both trials demonstrated

that dapagliflozin, when given as an oral

adjunct to adjustable insulin in adults with

inadequately-controlled T1D, showed

significant reductions from baseline in

HbA1c, weight and total daily insulin

dose at 24 and 52 weeks, vs. placebo,

at both 5mg and 10mg doses.

Dapagliflozin is also under

regulatory review in the US and

Japan for use as an adjunct

treatment to insulin in adults

with T1D.

phase 2 clinical trial evaluating

the efficacy and safety of both

IV and oral APX001 for the

first-line treatment of patients

with fungal infections.

Cryptococcosis is an

infectious disease of the

lungs or central nervous

system caused by the

fungus Cryptococcus (either

Cryptococcus neoformans or

Cryptococcus gattii), which

is typically found in the

environment and inhaled.

Brain infections due to the

fungus Cryptococcus are called

cryptococcal meningitis.

Split-dosing

regimen of

daratumumab

The US FDA has approved

a split-dosing regimen

for daratumumab (Darzalex)

providing healthcare

professionals and patients with

multiple myeloma an option to

split the first infusion over two

consecutive days.

The US FDA approval

is based on data from the

phase 1b Equuleus clinical

study, which demonstrated

daratumumab pharmacokinetic

concentrations were

comparable at the end of

weekly dosing, regardless of

whether the first dose was

administered as a split infusion

or as a single infusion.

Daratumumab is the first

CD38-directed antibody to

receive regulatory approval to

treat multiple myeloma. In the

US, Darzalex (daratumumab)

first received FDA approval

in November 2015 as a

monotherapy for patients with

multiple myeloma who have

received at least three prior

lines of therapy, including a

proteasome inhibitor (PI) and

an immunomodulatory agent,

or who are double refractory to

a PI and an immunomodulatory

agent, Janssen said.

Benralizumab for

HES get orphan

drug tag

The US FDA has granted

Orphan Drug designation

benralizumab (Fasenra) for the

treatment of hypereosinophilic

syndrome (HES).

HES is a group of rare,

potentially fatal disorders

characterised by high numbers

of eosinophils in blood and

tissues, which can cause

34 / FUTURE MEDICINE / March 2019


progressive damage to any

organ in the body.

Benralizumab is a

monoclonal antibody that binds

directly to IL-5 receptor on

eosinophils and attracts natural

killer cells to induce rapid and

near-complete depletion of

eosinophils via apoptosis.

Benralizumab was

developed by AstraZeneca with

MedImmune.

Dacomitinib to

treat NSCLC

in Europe

The Committee for Medicinal

Products for Human Use

(CHMP) of the European

Medicines Agency (EMA) has

adopted a positive opinion

recommending dacomitinib

45 mg (Vizimpro) for the firstline

treatment advanced or

metastatic non-small cell lung

cancer (NSCLC) with epidermal

growth factor receptor (EGFR)-

activating mutations, according

to Pfizer.

Dacomitinib is an oral,

once-daily, irreversible panhuman

epidermal growth

factor receptor kinase inhibitor.

Dacomitinib was approved

by the US FDA in 2018 for the

first-line treatment of patients

with metastatic NSCLC with

EGFR exon 19 deletion or

exon 21 L858R substitution

mutations as detected by an

FDA-approved test. It was also

recently approved in Japan for

EGFR gene mutation-positive,

inoperable or recurrent NSCLC

The Marketing

Authorization Application

(MAA) for dacomitinib

was based on results from

ARCHER 1050, a randomized,

multicentre, multinational,

open-label, phase 3 study

conducted in patients with

locally advanced unresectable,

or metastatic NSCLC harbouring

EGFR exon 19 deletion or

exon 21 L858R substitution

mutations, an Eastern

Cooperative Oncology Group

(ECOG) performance status of

0 or 1; with no prior therapy for

metastatic disease or recurrent

disease with a minimum of

12 months disease-free after

completion of systemic therapy.

Pexidartinib to

treat TGCT gets

priority review

Daiichi Sankyo said

pexidartinib for the

treatment of tenosynovial giant

cell tumour (TGCT) has been

granted priority review by US

FDA.

TGCT, also referred to

as pigmented villonodular

synovitis (PVNS) or giant cell

tumour of the tendon sheath

(GCT-TS), is a non-malignant

tumour of the joint or tendon

sheath, which can be locally

aggressive and debilitating in

some patients. There are no

currently approved systemic

therapies for TGCT.

The NDA is based on results

of the pivotal phase 3 ENLIVEN

study of oral pexidartinib, the

first placebo-controlled study

of a systemic investigational

therapy in patients with TGCT.

Pexidartinib is an

investigational oral small

molecule that potently inhibits

CSF1R (colony stimulating

factor-1 receptor), which is

a primary growth driver of

abnormal cells in the synovium

that cause TGCT. Pexidartinib

also inhibits c-kit and FLT3-ITD.

Nanobody drug

for aTTP

The US FDA cleared

caplacizumab-yhdp

(Cablivi), an anti-vWF

Ospemifene for vaginal

dryness

The US FDA has expanded

use of ospemifene

(Osphena) to include

treatment of moderate to

severe vaginal dryness due

to menopause.

Vaginal dryness and

itching are symptoms of

vulvar and vaginal atrophy.

Ospemifene is an

oestrogen receptor

nanobody, in combination

with plasma exchange and

immunosuppression for

the treatment of acquired

thrombotic thrombocytopenic

purpura (aTTP) in adults.

Caplacizumab is the

first FDA approved therapy

specifically indicated for the

treatment of aTTP.

Caplacizumab targets von

Willebrand factor (vWF), a

protein in the blood involved

in hemostasis. It is designed to

inhibit the interaction between

vWF and platelets.

agonist/antagonist with

tissue selective effects.

It is available in 60 mg

tablets which were initially

approved in 2013 to

treat moderate to severe

dyspareunia due to

menopause.

The approval has been

on the basis of safety

and efficacy data from

a confirmatory phase

3 randomized, doubleblind,

placebo-controlled

multicentre study evaluating

ospemifene in patients with

moderate to severe vaginal

dryness.

The data showed that

treatment with ospemifene

led to a statistically

significant improvement

in self-reported, most

bothersome symptom of

vaginal dryness as well as

a statistically significant

increase in the proportion

of superficial cells and a

corresponding statistically

significant decrease in the

proportion of parabasal cells

on a vaginal smear; mean

reduction in vaginal pH

between baseline and week

12 was also statistically

significant.

Caplacizumab is Sanofi›s

first Nanobody-based medicine

to receive approval in the US.

Nanobodies are a novel

class of proprietary therapeutic

proteins based on singledomain

antibody fragments

that contain the unique

structural and functional

properties of naturallyoccurring

heavy chain only

antibodies.

The treatment received

FDA Fast Track designation and

was evaluated under Priority

Review.

March 2019 / FUTURE MEDICINE / 35


straight talk

“EVERYBODY HAS TO

DEVELOP THE WAY THEY

ARE. TAKING ADVICE IS LIKE

COPYING SOMEONE”

Less focus on basic science and limited

support for discovery research are the

two issues the scientific community as

well as governments all over the world

should be seriously worried about

today. Big pharmaceutical companies

ignoring the serious threat of microbial

resistance to existing antibiotics and

not thinking about developing new

ones is another dangerous trend that

the world is facing at present, says

PROF ADA E YONATH.

The Chemistry Nobel Laureate, who

was in India in February to deliver the

keynote address at the International

Conference on Advanced Chemical and

Structural Biology - 2019 in Chennai,

spoke to Future Medicine at length

in an exclusive interview with Editor

C H UNNIKRISHNAN. Edited excerpts:

One of the key objectives of your path-breaking work on

ribosomes was to help the development of new antibiotics.

But, has it really resulted in the introduction of any in the

market, especially in a situation where the existing ones are

becoming less effective due to bacterial resistance?

There are quite a few in the development stage across

the globe, targeting ribosomes. But, in general, it seems that

many of the big companies do not think that antibiotics are a

profitable business for them. It is very unfortunate, and I wish

they would think beyond profit and would take up more such

projects and introduce them in the market quicker, considering

the urgent need to save human life as antimicrobial resistance

is a crucial health issue now.

Why can’t big pharmaceutical companies, who often talk

eloquently about philanthropy and social responsibility,

work on these novel pathways, including your discovery, to

develop new products that help combat this serious issue?

There were several companies that showed interest in

developing new products targeting proteins. Nothing much

has happened so far as hardly anyone really worked to take it

up. I know that the investment that is required to develop new

drugs is high and that’s why they found it not profitable. I do

not know if there are other reasons as well. One should ask

them (the industry).

You have been very vocal about the imminent health crisis

that can manifest if there are no new antibiotics developed

against multi-drug resistant bugs quickly. Do you think

governments and not-for-profit organisations should step in?

I don’t think governments can get into the business of

product development and production, though it can facilitate

and support research. It is the industry that should take them

up. But, as you rightly said, one thing is sure that the crisis of

drug resistant bacteria is going to be big in the world if there

are no new antibiotics that enter the market soon.

After your path-breaking work on identifying the ribosome

structure and crystallising them, are there more research or

36 / FUTURE MEDICINE / March 2019


Prof Ada E Yonath

PHOTO: UMESH GOSWAMI

March 2019 / FUTURE MEDICINE / 37


slug

progressive work on the same happening to

take it forward?

Not on the same, but yes, there are

many good works happening around. The

researchers are thinking in different ways and

are exploring new mechanisms to target the

ribosome, among others and also to find out

different factors that cause natural mutation

within the bacteria that gives them resistance.

There aren’t anything in the same way, which

I know; though we don›t think ours was the

best. We are also exploring further.

Multi-drug resistant tuberculosis is a

very serious medical challenge in India and

also in many other Asian countries. How

do we explain the resistance mechanism in

I think there is

scope for exploring

new antibiotics

for treating

drug-resistant

tuberculosis,

targeting

ribosomes.

tuberculosis, where drugs are not targeting

ribosomes?

There are also some tuberculosis drugs

targeting ribosomes of late. But, most of

the existing drugs target cell walls, cell

cycles and checkpoint controls and other

pathways. Although we have not focused

on tuberculosis as such so far, I think there

is scope for exploring new antibiotics for

treating drug-resistant tuberculosis, targeting

ribosomes.

How do bugs continue to develop

resistance to more and more antibiotics?

It is part of the natural survival

[mechanism] of organisms. As I said before,

there are natural mutations that take place

38 / FUTURE MEDICINE / March 2019


Nobel Laureate Prof. Ada E Yonath

shared the world’s most coveted

prize in chemistry with Dr Thomas Steitz

and Prof. Venkataraman Ramakrishnan

in 2009. Her pioneering work on

ribosomal crystallography helped in the

precise identification of the structure

and functions of ribosomes and it

opened up immense possibilities of

targeting ribosomes for developing

new antibiotics. The first Israeli woman

to win a Nobel Prize, Prof Yonath

accepted her postdoctoral positions

at Carnegie Mellon University in 1969

and MIT in 1970. She was also group

leader with Heinz-Gunter Wittmann at

the Max-Planck Institute for Molecular

Genetics in Berlin. She was the visiting

professor at the University of Chicago

in 1977-78 and then headed one of the

Max-Planck Institute’s research unit at

DESY in Hamburg, Germany in parallel to

her research activities at the Weizmann

Institute.

Yonath focuses on the mechanisms

underlying protein biosynthesis by

ribosomal crystallography, a research

line she pioneered over twenty years

ago despite considerable skepticism on

the part of the international scientific

community. Ribosomes translate RNA

into protein, and because they have

PROF ADA E YONATH

slightly different structures in microbes

when compared to eukaryotes such

as human cells, they are often a target

for antibiotics. In 2000 and 2001, she

determined the complete high-resolution

structures of both ribosomal subunits

and discovered within the otherwise

asymmetric ribosome, the universal

symmetrical region that provides

the framework and navigates the

process of polypeptide polymerisation.

Consequently, she showed that the

ribosome is a ribozyme that places

its substrates in stereochemistry

suitable for peptide bond formation

and for substrate-mediated catalysis.

In 1993, she visualised the path taken

by the nascent proteins, namely the

ribosomal tunnel, and recently revealed

the dynamic elements enabling its

involvement in elongation arrest, gating,

intra-cellular regulation and nascent

chain trafficking into their folding space.

Additionally, Yonath elucidated the

modes of action of over twenty different

antibiotics targeting the ribosome,

illuminated mechanisms of drug

resistance and synergism, deciphered

the structural basis for antibiotic

selectivity and showed how it plays a key

role in clinical usefulness and therapeutic

effectiveness, thus paving the way for

structure-based drug design.

For enabling ribosomal crystallography,

Yonath introduced a novel technique—

cryo bio-crystallography, which became

routine in structural biology and allowed

intricate projects otherwise considered

formidable.

At the Weizmann Institute, Yonath

is the incumbent of the Martin S. and

Helen Kimmel Professorial Chair. She

is also a member of the United States

National Academy of Sciences, the

American Academy of Arts and Sciences,

the Israel Academy of Sciences and

Humanities, the European Molecular

Organisation and the European Academy

of Sciences and Art. In 2014, Prof.

Yonath was named a member of the

Pontifical Academy of Sciences by Pope

Francis. Her other awards and honours

include the Israel Prize (2002), Harvey

Prize (2002), Massry Prize (2004),

Paul Karrer Gold Medal (2004), Horvitz

Prize (2005), Wolf Prize in Chemistry

(2006), Rothschild Prize in Life Sciences

(2006), The EMET Prize for Art, Science

and Culture in life sciences (2006), Paul

Ehrlich and Ludwig Darmstaeder Prize

(2007), Albert Einstein World Award of

Science (2008), Wilhelm Exner Medal

(2010) and Honorary Doctorates from

several universities.

within the living organisms as a process of getting adapted to

their living environment and there is constant fight that takes

place between one and the other for survival.

Do you think Indian scientists could have achieved more

had the government been more supportive and encouraging

in research and development here?

I don’t know about the support system in India. So, I

can’t comment on that. But I can say that Indian scientists

have been doing well in many areas. There is good science

done in India, which may not be in antibiotics or new drug

development. But it is cleverer in many other areas. Also, there

are good Indian scientists outside the country who are brilliant

and much more capable than others.

The problem that I really see now everywhere is a lack

of support for basic science. Original discoveries should

be encouraged by governments and other systems. Basic

science that tries to understand what is not

understood so far brings real changes in

the society and that should be the focus of

research.

I know that your best advice to young

and aspiring scientists is not to seek advice.

Could you elaborate on this?

Because everybody has to develop the

way they are. Let the young minds grow with

what he or she is really passionate about. It

is the self-curiosity that leads one to discover

new things and that is the kind of research

that the world is looking for and will help

it progress. Taking advice is like copying

someone else, and it will not work the same

way for the other or result in anything new.

March 2019 / FUTURE MEDICINE / 39


education

MBBS INTERNS MAY SOON

GET UNIFORM STIPEND

MCI BOG’s decision is seen as a move to end the discrimination

faced by medical interns in the country

UNIFORM STIPEND

In a significant move, the Medical

Council of India (MCI) Board of

Governors has sought suggestions

from stakeholders on the demand for

a uniform stipend for MBBS interns

across the country. The move is likely

to benefit thousands of medical

interns, particularly those in private

medical colleges. In order to introduce

uniform stipend for medical interns,

the Graduate Medical Education (GME)

Regulations 1997 will be amended.

The Board of Governors (BOG)

issued a public notice in this

regard on January 25, 2019. The

stakeholders were requested to give

their suggestions within 15 days. The

notice says, “All candidates pursuing

compulsory rotation internship at

the institution from which the

MBBS course was completed

shall be paid stipend on par

with the stipend being paid

to the interns of the state

government medical

institution/ central

government medical

institution in the state/

union territory where the

₹23,500

Central government

medical colleges

₹20,000

West Bengal, Delhi,

Chhattisgarh, Odisha,

Assam and Kerala etc.

₹6,000

Maharashtra

40 / FUTURE MEDICINE / March 2019


institution is located.” It further said,

“All concerned are requested to give

their comments/ suggestions within 15

days to bring the above amendment in

regulations for payment of stipend to

interns.”

A long-time demand

Students of private medical colleges

have been demanding stipend on

par with students of state and central

government medical institutions for

quite some time. At present, students

of many of the private medical colleges

are being paid a meagre amount as

stipend. There were also cases of

interns not being paid. There have

been many incidents of MBBS interns

resorting to protests for a reasonable

stipend.

In many states, MBBS interns of

state-run medical colleges are also

being paid very less. They have been

demanding an increase in stipend for

a long time. In Maharashtra, medical

interns are currently being paid a

stipend of Rs 6,000 per month. But

in states like West Bengal, Delhi,

Chhattisgarh, Odisha, Assam and

Kerala, medical interns are being paid a

monthly stipend of Rs 20,000 or more.

Recently, Union Ministry of

Health and Family Welfare

had increased the stipend

of MBBS interns at central

government medical

colleges to Rs 23,500

from Rs 17,000.

Medical interns of

various states have

been conducting

continuous protests,

demanding a

hike in their

THERE ARE APPREHENSIONS

THAT THE MOVE DOESN’T

PROVIDE MUCH RELIEF TO

MEDICAL INTERNS IN PRIVATE

MEDICAL COLLEGES

stipend. Last year, medical interns in

Maharashtra staged an indefinite strike

demanding a 40 per cent increase in

stipend. Students under government

quota in two private medical colleges

in Karnataka had also staged protests

last year against the non-payment of

stipend. In Andhra Pradesh, medical

interns of S.V. Ruia Government Medical

College recently boycotted their duty

as they had not been paid stipend for

several months. The present move of

the BOG is aimed at bringing an end to

the discrimination faced by medical

interns in the country.

Burden to fall on students?

Welcoming the move, Mohamed

Asif Patel, Joint Secretary, Grant

Government Medical College, Mumbai,

said, “It will benefit medical interns

across the country. The job interns

do across the country is the same

and therefore the stipend should also

be uniform. The interns are working

more than 60 hours in a week. In

Maharashtra, medical interns are paid

just Rs 6,000.” He added that the

move will benefit medical interns in

private medical colleges too, provided

clear guidelines are set by the MCI.

However, there are apprehensions

that the move doesn’t provide much

relief to medical interns in private

medical colleges as they are likely

to charge stipend amount as part of

the course fee. Commenting on the

development, Dr P A Fazal Gafoor

MD, Director, MES Academy of Medical

Sciences, said, “It should be inbuilt in

the fee. If it is made mandatory, the

increased stipend will be inbuilt in

the fee of students from next batch

onwards. The house surgency stipend is

also included in the course. If increased,

it will fall on the students.”

March 2019 / FUTURE MEDICINE / 41


case reports

WHEN PARKINSON’S

STRIKES EARLY

Parkinson’s disease is often misdiagnosed or missed in young adults

Josh (name changed) is a 30-year-old man, who was

healthy, happily married, regularly went to the gym and

had a good job and a relatively stress-free life. For the

past several months, however, he seemed to have become

lethargic and withdrawn, and appeared unhappy and

depressed to his family members. He also had mild stiffness on

the left side of the body. While this did not impact his lifestyle

and exercise regimen, he had become slower than normal.

Josh underwent a complete evaluation, including routine blood

workup, metabolic profile and was also tested for possible

infections. Results from all the tests were normal. Josh was still

not convinced and wanted to know why he was feeling this

way.

Josh then consulted Dr. Anil Venkitachalam, a consultant

neurologist and a specialist in movement disorders at Nanavati

Hospital, Mumbai, for further assessment. Dr. Venkitachalam

examined him and noticed a difference in his left arm swing,

but there were no other obvious problems. However, the

slowness on left side, together with a lack of emotions and

underlying depression, was indicative of early Parkinson’s

disease.

Even though Parkinson’s disease is commonly associated

with tremors involving one of the hands, it is

also associated with slowness of movement.

The slowness of movement can be subtle,

where one may simply stop swinging the

arm while walking, or speech may become

slurred. Until a few years ago, the only way to

diagnose Parkinson’s was by identifying the

four key symptoms that included slowness,

tremor, rigidity and postural instability.

However, there are many who do not present

with these symptoms and often the disease is

EVEN THOUGH PD IS COMMONLY

ASSOCIATED WITH TREMORS

INVOLVING ONE OF THE HANDS,

IT IS ALSO ASSOCIATED WITH

SLOWNESS OF MOVEMENT

42 / FUTURE MEDICINE / March 2019


misdiagnosed. It is therefore important to confirm the disease

with a more quantitative test. The DaT scan or dopamine

transporter scan is a single photon emission computerized

tomography (SPECT) imaging technique that determines the

levels of the dopamine transporter in the striatum. SPECT

visualizes the radiolabeled isotope that binds to the dopamine

transporter, effectively quantifying the transporter levels. These

transporters are important for the reuptake of dopamine at the

synaptic cleft and have been shown to be reduced by 50-70%

in patients with Parkinson’s disease. Josh was confirmed to

have Parkinson’s disease after having an abnormal DaT scan.

There is no known cause for Parkinson’s disease. It

is believed that there are multifactorial reasons for the

degeneration of dopaminergic neurons, which ultimately

affects overall bodily movements. In addition to tremors

and slowness of movement, patients with Parkinson’s often

experience depression and pain, and may have disorders

related to sleeping, eating, urination and constipation.

Over the past 2 decades, significant research has been

done on the disease. While there is no known cure at this

time, there are several drugs in the market to symptomatically

manage the disease. Research has focused on refining the

existing treatment options, developing new surgical equipment

for advanced interventional therapy, improving physician

skill sets and so on. The current gold standard for treating

Parkinson’s disease is the oral administration of carbidopalevodopa.

Levodopa is a natural chemical that can cross the

blood brain barrier with the help of carbidopa, and then

get converted to dopamine. Other drugs include dopamine

agonists that mimic dopamine. However, these are not as

effective as carbidopa-levodopa.

With Josh being so young, it was a challenge for him

and his family to accept that he was diagnosed with such a

degenerative disorder with no known cure. He was started

on an oral medication with dopamine agonists that increase

dopamine levels in the brain, along with a recommendation

for vigorous lifestyle changes, including increased physical

activities like cardiovascular exercises, healthy diet to include

more fiber and fluids, and stress reduction. This treatment has

thus far been effective for Josh. However, he has a long journey

ahead with Parkinson’s disease. As the disease progresses, his

symptoms are likely to change, and oral medication will likely

become ineffective. As per Dr. Venkitachalam, oral medications

are suitable for the first 5-7 years of the disease, when the

symptoms are relatively stable and well controlled. After that,

treatment will most likely need to be changed as the side

effects of the drugs kick in and the absorption of dopamine

from the gastrointestinal tract decreases.

In cases where symptoms of Parkinson’s disease kick in

early in life, oral medications would need to be eventually

replaced with other advanced therapy options. These may

need to be considered for Josh. The deep brain stimulation

surgery involves implanting electrodes in the brain connected

to a pacemaker that sends electrical pulses to specific areas

within the brain. This treatment is effective for

patients who demonstrate a good response

to levodopa. Alternatively, for patients who

experience fluctuations in plasma levodopa

levels upon oral intake of carbidopa-levodopa,

transdermal patches of dopamine agonists

and infusion therapies such as apomorphine

and levodopa- carbidopa intestinal gel are

available.

Patients must be closely monitored, and

regular visits to the treating neurophysician

every 3-4 months is advised. Associated

symptoms should be treated, and the

drug choices/doses adjusted, based on

disease progression. As both motor and

non-motor symptoms are associated with

Parkinson’s Disease, often, falls and fractures

IN CASES WHERE SYMPTOMS OF

PD KICK IN EARLY IN LIFE, ORAL

MEDICATIONS WOULD NEED

TO BE EVENTUALLY REPLACED

WITH OTHER ADVANCED

THERAPY OPTIONS

add to the disability in these patients and

multidisciplinary treatment may be needed

during the course of the disease.

Even though Parkinson’s Disease is

classically thought to be a disease that affects

the elderly and tremors in the hand are often

the most common symptom that is noticed,

in Josh’s case, there was no tremor and he

was really young. Dr. Venkitachalam stresses

that often Parkinson’s disease is misdiagnosed

or missed in young adults as the symptoms

are not looked at collectively. “It is important

to consider Parkinson’s disease beyond age

and tremors, and look for additional clinical

clues such as depression, constipation, pain,

slowness and lethargy. It is also important to

remember that Parkinson’s disease is the only

neurodegenerative disorder where treatment

is available. Early diagnosis and treatment can

help an affected patient have a normal quality

of life.”

DR SHIVANEE SHAH

March 2019 / FUTURE MEDICINE / 43


case reports

RECREATING THE IMPOSSIBLE;

REGENERATING HOPE

How abdominal fat turns saviour to help regrow irreparably lost tissue

Pulak Pal (name changed) was working

in his hairpin manufacturing factory when he

42-year-old

accidentally put his hands into a machine and

the fingers of his right hand got crushed. Pulak’s right

middle finger got a deep gash, the thumb was completely

crushed and worst of all, the index finger got severed at

the base. The injury was so severe that all nearby hospitals

advised amputation of the fingers. However, Pulak’s family

did not give up and eventually took him to Apollo Gleneagles

Hospitals, Kolkata.

His case was forwarded to Dr. Srinjoy Saha, Consultant,

Plastic, Aesthetic, Reconstructive & Burns Surgery. Dr. Saha

methodically carried out the initial investigations to assess the

extent of damage. He asked for all necessary investigations and

a pre-anesthetic check to determine if Pulak could be taken

up for early surgery. While the X-ray showed multiple fractures

and crushed bones in the hand, advanced examinations of the

fingers revealed poor blood circulation with about 80% of the

tissue already dead or dying and only about 20% still healthy.

Based on these findings, Dr. Saha discussed various treatment

options available with the patient and his family during the

initial consultation. He said Pulak could either amputate

the fingers like the other doctors in previous hospitals had

suggested, or he could try to save them using stem cells

present inside abdominal fat. However, there would be no

guarantee of saving the fingers and the process would be

cumbersome for at least a 3-week period. Faced with a choice

between a 3-week hardship or a lifetime of loss, Pulak and his

family decided to save his fingers and give the new option of

regenerative medicine a try.

Regenerative medicine is the science of replacing,

engineering, or regenerating human cells, tissues, or organs

to restore or establish normal form and function. It is an

exciting new way of treatment, utilizing the body’s own cells

to heal damaged tissues and form new ones. Stem cells have

an enormous capacity to self-renew and differentiate into

multiple cell types. Stems cells used to be harvested from

foetal sources such as amniotic fluid or the umbilical cord.

Today they can be harvested from adult tissues such as bone

marrow and more recently, from adipose tissues or body fat.

Adipose tissue-derived stem cells (ADSCs) are relatively easy to

harvest by subcutaneous lipo-aspiration and can be induced

to differentiate into different cell types as needed in the

laboratory.

In this particular case involving massive

bone and soft-tissue damage, however, lipoaspirated

cells would not work. More than

just cells were required to regenerate the

fingers, since the soft tissue of the fingers

and its blood supply was also missing.

Abdominal fat has been found to have a

well-defined structure with a rich network

of blood vessels, lymphatics, stem cells

and macrophages, among others. Dr. Saha

combined the principles of plastic surgery

and regenerative medicine to try a novel

technique using flaps made up entirely of

abdominal fat. Such a flap would provide

stem cells, along with the required blood

supply and the necessary infection-resistance

to the fractured and crushed finger bones.

MORE THAN JUST CELLS WERE

REQUIRED TO REGENERATE THE

FINGERS, SINCE THE SOFT TISSUE

OF THE FINGERS AND ITS BLOOD

SUPPLY WAS ALSO MISSING

He made two incisions in the subcutaneous

component of the abdomen, creating two

tunnels through the abdominal fat in which

he placed the thumb and the index finger.

The patient was discharged a day after the

surgery and spent time at home while his

thumb and index finger regenerated within

his abdomen. “Pulak was a very cooperative

patient. Such placement is difficult to bear for

a day, let alone for the 3 weeks that it took for

complete regeneration”, remarked Dr. Saha.

After 3 weeks, the fingers were separated from

the abdomen. The fingers were covered with

abdominal fatty tissue, which had developed

new blood supply from the base of the fingers.

44 / FUTURE MEDICINE / March 2019


Excess fat was trimmed away until a healthy

layer of soft-tissue remained around the bones

of the fingers, such that the thickness of the

newly reconstructed fingers matched that of

the other fingers. Dr. Saha covered these softtissues

partially with abdominal skin taken as

flaps. He performed one more surgery where

he covered the remaining raw areas of the

fingers with skin grafts harvested from the

thigh. Reconstruction of the thumb and index

finger was finally complete. During this entire

period of treatment, Pulak was required to

visit the hospital for a day only to perform his

surgeries; and was on minimal medications

including antibiotics and pain killers, that too

for a limited time. Within 6 months from his

injury, Pulak regained complete movement and

control of all fingers of his working right hand,

and easily performed all necessary hand and

finger movements. Outside of work, Pulak is

passionate about playing carrom. “I am even

able to play and win carrom tournaments

again, besides performing all my routine work,”

exclaims an elated Pulak.

The regenerative procedure faced several

stiff challenges. Finger bones were fractured,

crushed and lost at places. Ensuring coverage

and survival of the finger bones without

bone death or new infection was an uphill

task. Pulak’s crushed soft tissues had been

found to be infected with multi-drug resistant

Klebsiella during admission. Ensuring adequate

control and limiting the read of infection was

also a difficult challenge. Abdominal fat, with

its inherent structure, vascularity, stem cell

potential and infection-fighting capability, can

do wonders. This case is a perfect example

of how the “abdominal fat pad flap” improves

vascularity, protects from infections, and allows

for regeneration of lost tissue. Dr. Saha has

now achieved successful regeneration of finger

tissue in six patients. He credits his success to

his patients, saying that “the patient is the real

hero as he must be willing to spend 3 weeks

with his fingers inserted in his abdomen, and

then perform physiotherapy religiously to gain

adequate hand function”. Dr. Saha is excited

with the success of this technique and hopes

that more and more plastic surgeons will get

involved in successfully saving fingers instead

of amputating them.

DR SHIVANEE SHAH

March 2019 / FUTURE MEDICINE / 45


case reports

FIGHTING OFF SWINE FLU

Swine flu can be one of the most severe acute respiratory distress syndromes

Elbualy Mohamed Ali, a Kenyan national,

was visiting New Delhi to support a

close relative who was undergoing

treatment for a cancerous condition. Much

to his dismay, during his stay as a caregiver,

Ali quite suddenly developed high fever,

severe breathlessness and persistent cough.

A concerned Kenyan acquaintance of Ali

referred him to Dr Sudha Kansal, a senior

consultant in the Department of Respiratory

Medicine, Critical Care and Sleep Medicine

at the Indraprastha Apollo Hospital in New

Delhi.

During preliminary examination, Dr

Kansal thought that Ali’s condition was due

PRIMARY INVESTIGATIVE

CHEST X-RAY INDICATED

BILATERAL CHEST OPACITIES

AND CONFIRMED A CHEST

INFECTION

to community-acquired pneumonia with

respiratory failure and suspected obstructive

sleep apnoea. In addition, Ali was also a

known hypertensive and a type II diabetic.

Primary investigative chest X-ray indicated

bilateral chest opacities and confirmed a

chest infection. To further determine the

causative agent, blood culture, sputum

culture, complete blood counts and kidney

and liver function tests were carried out.

Simultaneously, Ali was placed on a noninvasive

ventilator to facilitate his breathing

and started on injection azithromycin and

ceftriaxone.

Though a diagnosis of communityacquired

pneumonia was relatively apparent

because of the sudden onset of fever and

quickly deteriorating respiratory symptoms,

atypical pneumonia, possibly due to a viral

46 / FUTURE MEDICINE / March 2019


or mycoplasma etiology was also considered. Much

to everybody’s surprise, the throat swab RT-PCR turned

out to be positive for swine flu. This diagnosis required

immediate action. Within 18 hours of being admitted, Ali

was started on the anti-viral tablet, oseltamivir, a well-known

antiviral agent used to treat influenza type A virus, including

swine flu.

In spite of the prompt diagnosis and quick treatment,

Ali’s condition started deteriorating and his oxygenation

level was not improving with the noninvasive ventilator.

Since these were concerning signs, he was intubated and

subsequently moved to prone ventilation support due to

severe hypoxia. However, this was not effective either and

his blood oxygenation levels remained low. His condition

continued to worsen, and a decision was taken to move

him back to a supine position, and Veno-venous

Extracorporeal Membrane Oxygenation (ECMO) support

was initiated. As the name suggests, ECMO is an

extracorporeal technique that allows the exchange of

blood gases to occur outside the body through a specially

designed equipment. It is used in children and adults with

cardiac and respiratory failure when blood carbon dioxide

levels need to be reduced and blood oxygenation needs

to be normalized after failing mechanical ventilation, while

allowing the lungs to rest to recover from the injury caused

due to infection, trauma etc.

The ECMO support comes with its own set of challenges.

For patients on ECMO, it is necessary that the blood

flows at an appropriate rate for the exchange of gases to

occur. Patients are put on anticoagulants such as heparin

to prevent clotting of the circuit, which requires close

monitoring of blood clotting time. Due to the use of

heparin, there is always the impending danger of internal

bleeding which can sometimes be fatal, especially if it

occurs in the brain. It has been observed that about 20-

30% of patients on ECMO may have internal bleeding due to

heparin.

While Ali’s activated clotting time was being closely

monitored, he developed significant gastrointestinal

bleeding. His heparin levels were therefore re-titrated and

blood products were transfused to prevent further bleeding.

As he also had multiple episodes of generalized seizures

while on ECMO, Ali was immediately started on antiepileptic

drugs. Seizures might have been precipitated by conditions

such as metabolic encephalopathy as no focal deficit,

suggesting a brain bleed, was noticed. A brain CT scan

would have been ideal to determine bleeding in the brain;

however, this could not be done as the patient could not

be moved to CT scan department due to ongoing ECMO. Ali

was kept on minimum sedation so that he could be closely

monitored, and his neurological status could be continuously

assessed.

Ali’s condition slowly recovered after being on ECMO

support for 8 days. He was then weaned off the ECMO over

two days and maintained on ventilator

support. However, by now, Ali had

developed critical illness myo-neuropathy

and was very weak. A tracheostomy was

needed to assist his breathing and slowly

the ventilator support was stopped after

3 days. After this, he gradually recovered.

Intensive chest physiotherapy and

limb therapy were started. Wheelchair

mobilisation was done. He had to undergo

considerable physiotherapy to regain his

strength before he could be discharged.

It was a difficult journey for both the

patient and the medical team, especially

since Ali’s condition deteriorated so rapidly,

with the ventilator being ineffectual and him

developing multiple generalized seizures

IT WAS A DIFFICULT JOURNEY

FOR BOTH THE PATIENT AND

THE MEDICAL TEAM, ESPECIALLY

SINCE THE PATIENT’S CONDITION

DETERIORATED SO RAPIDLY,

WITH THE VENTILATOR BEING

INEFFECTUAL

and GI bleeding. However, Ali

was one of the lucky severe swine flu

infected patients who survived and

eventually regained his strength to normalcy.

Dr Kansal would like to specially thank Dr

Rajesh Chawla, Dr Mukesh Goel, the entire

ICU team, and the perfusionist for their

tireless efforts in bringing Ali back to health.

Dr Kansal mentions that in the past

season, they had 20 swine flu patients

who required ventilator support, 5 of who

had to be given ECMO, and of these, only 2

survived. She stresses that “swine flu can be

one of the most severe ARDS, that must be

diagnosed early on. If the patient does not

start improving with mechanical ventilation,

ECMO therapy should be considered”. While

ECMO can be expensive, early treatment is

imperative, although there is no guarantee

that it will work for everyone.

DR SHIVANEE SHAH

March 2019 / FUTURE MEDICINE / 47


column

the cellview

Taking the lead

India can play a major role in world TB space by developing

supplementary technologies

DR RAJANI KANTH

VANGALA

The author is medical

scientist and former

director of SGRF,

Bangalore

The very fact that the sequencing

costs are coming down should make

multidrug-resistant Mycobacterium

tuberculosis (MDR-TB) more manageable.

However, that is not the case. Development

of novel technologies and a reduction

in costs and infrastructure barriers are

important to the reduction of disease burden

and better management. It is high time

that India embraces this fact and develops

research capabilities in two very important

aspects of tuberculosis diagnostics. The first

tool is a biospecimen/sputum collection

system, which will enable direct, wholegenome

sequencing, and the second is

building robust bioinformatics capabilities for

improved data analysis.

Historically, tuberculosis detection has

relied heavily on microscopy as the first-line

diagnosis, which often fails in the detection

of drug-resistant genotypes of the bacterium.

Traditional, culture-based diagnosis of TB

typically takes several weeks, owing to the

slow growth rate of M. tuberculosis. Some

technical advances have resulted in liquid

culture and an automated detection system

called mycobacteria growth indicator tube

(MGIT), which takes less than a fortnight

(Pfyffer et al., 1997). India, with increasing

infections of TB, can very much take the

lead in supplementing these technologies

by conducting large-scale, genome-wide

studies, in collaboration with companies or

research groups focusing on biospecimen

collection systems. Some of the tools

developed in this direction are SureSelelctXT

target enrichment, MolYsis Basic5 kit

(Molzym, Germany) and NucleoSpin Tissue-

Kit (Machery-Nagel, Duren, Germany).

Any NGS workflow will not be complete

without sequence data analysis, which

requires expertise in information technology

and clinical-data analytical capabilities -

both of which are already possessed by the

Indian scientific community, both commercial

and academic. In the past few years, there

has been an explosion of bioinformatics

platforms for both expert and non-expert

analysis and the interpretation of MTB

NGS data. The majority of existing tools

provide cloud-based WGS pipeline to start

processing from the raw sequence. There are

two important data consortiums, namely

ReseqTB and CRyPTIC, which have

accumulated large datasets and maintain

genomic and phenotypic data. New

advancements have resulted in several

WGS tools, of which Mykrobe predictor is

currently compatible with both Illumina and

Oxford Nanopore WGS data. However, there

is still a large gap in improving data quality

assessment (control parameters like base

score, quality score etc), which are presently

done by platforms like FastQC. There are

additional steps needed, like trimming and

combination of multiple sequencing files.

Easy-to-use, web-based tools, like Galaxy

Cloudman and Cloud Virtual Resources,

can facilitate user better outcomes. There

is also a need to work on providing more

computational space for data storage and

on developing a tailored analytical software

collection for customization. Another

important area where there is a large gap

is NGS data reporting, including sequence

variants (single nucleotide polymorphism –

SNPs), deletions, insertions and structural

variants.

These opportunities are some of the

important aspects that will need large-scale

collaborations for improved clinical research.

India can play a major role in emerging as a

leader in managing TB, not just here, but for

the world at large.

48 / FUTURE MEDICINE / March 2019


orthopaedics

SKELETAL TUBERCULOSIS

THE CHALLENGES

Occurrence of osteoarticular tuberculosis recorded a rising trend among

extrapulmonary TB world over

DR VINOD KUMAR B P

Mycobacterium tuberculosis is

an organism that causes multisystemic

involvement. Although

pulmonary tuberculosis is the major

manifestation of the disease, multifocal

and extra pulmonary tuberculosis has

gained medical attention since the

emergence of HIV. In the late 1980s,

the world was on its way to control

tuberculosis. However, an increase in

the incidence of diabetes mellitus, HIV

etc. led to a comeback of tuberculosis.

The world experienced a rising trend

in the occurrence of extra-pulmonary

tuberculosis crossing all socioeconomic

barriers. Lymphadenopathy

and tuberculosis of the spine account

for the lion’s share of extra pulmonary

tuberculosis. Then comes tuberculosis

of the hip, the knee and the foot, in

that order. In the foot, the decreasing

order of occurrence are calcaneum,

talus, 1st metatarsal and naviculum.

The evolution of MDR and XDR TB

have led to further challenges in the

management of tuberculosis. XDR –TB

is a rare type of multi drug resistant

TB that is resistant to isoniazid and

rifampicin, plus fluoroquinolones and

at least one of three injectable second

line drugs such as amikacin, kanamycin

or capreomycin.

X- ray misses early lesions, and

any obvious bony destruction may not

be apparent for up to 3 months from

the time of occurrence of the disease.

The advantage of X- ray is that it can

be taken in vertical as well as a loadbearing

position, as against MRI. Even

though MRI is the gold standard in the

diagnosis, its over-sensitivity is an issue.

However, it is quite efficient in early

diagnosis, assessing the progression

and finding out the skip-lesions.

CT scan is the choice in occipitocervical

and sacroiliac TB lesions

and in defining the extent of bony

destruction.

50 / FUTURE MEDICINE / March 2019


Diagnosing extra-pulmonary TB

Tuberculosis is the ninth leading cause

of death as far as the global burden

of diseases is concerned. In 2016, an

estimated 1.3 million TB deaths were

reported among HIV-negative people

(1.7 million in 2000) and an additional

374,000 deaths were seen among

HIV-positive people. (Global incidence

– 10,400,000, Indian incidence –

2,790,000, Indian Deaths - 435,000.)

The revised national tuberculosis control

programme suggests a daily regime,

instead of the DOTS regime.

If you suspect extra pulmonary

tuberculosis in a patient and if the

disease tissue is available, it is advisable

to do a CBNAAT (Cartridge Based

Nucleic Acid Amplification Test). CBNAAT

is a polymerase chain reaction which

also detects rifampicin resistance as it

targets an rpoB gene of mycobacterium.

Another test, MGIT (Micobacteria Growth

Indicator Tube) is also preferred. It is a

test to isolate mycobacterium from all

types of clinical specimens, pulmonary

as well as extra pulmonary, except

those from blood and urine. After the

processed specimen is inoculated, the

MGIT tube is monitored until positive

or till the end of the testing protocol.

If MTB is detected, we may start anti-

TB drugs after evaluation for drug

resistance and liver and kidney function

tests.

Spinal tuberculosis

The other major developments are in

the management of spinal tuberculosis.

• A course of 6 to 12 months of ATT

instead of the old practice of 18-24

months.

• Hong Kong operation, the “Middle

Path Regime’’ of a great Indian

orthopaedic surgeon, Prof. Tuli, and

the newer “Millennium Doctrine’’ based

on the cardinal principles for the

management of spinal tuberculosis.

• Nonsurgical treatments that yield

good results as elective surgeries in

spinal instability, para-spinal abscess

CHART TO DIAGNOSE

EXTRA PULMONARY TUBERCULOSIS

CBNAAT

Tissue +

MTB

CULTURE OF MTB IN

CLINICAL SPECIMENS USING

TB MGIT, THE CURRENT

GOLD STANDARD, IS MORE

SENSITIVE THAN SMEAR

BIOPSY

and spinal cord compression in place of

surgical intervention.

• Posterior surgical approaches which

are less morbid to the patients and

more surgeon-friendly gaining more

acceptance than anterior approaches

that better anterior reconstruction and

neurological decompression.

Culture of MTB in clinical specimens

using TB MGIT, the current gold

standard, is more sensitive than smear

biopsy. The drawback is a longer

incubation period of 10-14 days. If

it turns out to be MDR TB, it would

have caused more destruction by the

time the results are in. Newer, ultrafast

modalities of GeneXpert test and

Line Probe Assay have revolutionized

Extra Pulmonary Tuberculosis

MGIT

No MTB

High Clinical Suspicion

Other Tests

ATT MTB+ D/D

the management of tuberculosis. The

Xpert MTB RIF Assay detects DNA

of mycobacterium and rifampicin

resistance in 2 hours. LPA also detects

resistance to isoniazid, quinolones and

second-line injectables, thus detecting

MDR as wells as XDR TB in 48 hrs.

These tests are to be done on biopsy

specimens in addition to TB MGIT

culture and histopathology.

The emergence of MDR and atypical

lesions made biopsy and culture

mandatory procedures. The biopsy

specimen should be from granulation

tissue rather than from an abscess

to make a prompt diagnosis. Biopsy

with a 11 G needle instead of fine

needle aspiration cytology is advised

in the present practice to diagnose

tuberculosis.

Here, I am describing a case

which was really challenging for me to

manage: An 80-year-old grandma came

with complaints of inability to walk and

back pain in a devastated condition

at our OP clinic. Clinically, she had loss

of sleep and appetite, chills and fever

due to UTI, a neurogenic bladder and

extensor plantar response. She was

posted for surgical decompression and

March 2019 / FUTURE MEDICINE / 51


instrumentation at another hospital for

‘? Tuberculosis/Tumour spine’. Clinical

examination, blood investigation,

Mantoux test, X-ray evaluation,

ultrasound evaluation and MRI scan

had revealed left renal calculus,

cystitis / pyelonephritis, destruction

at D6/7, end plate destruction and

normal pedicles. It was clinically and

radiologically diagnosed as tuberculosis

of the spine.

The grandma and her bystanders

were not willing for any type of surgery,

even a CT guided biopsy. After getting

well informed consent, ATT was started.

A therapeutic trial of ATT based on

clinical and radiological evidence is

legitimate only in a population setting

treating large numbers of tuberculosis

cases under a national programme.

After starting ATT (DOTS regime), she

was mobilized in wheel chair with the

help of spinal brace and rehabilitation

within two weeks of starting the

treatment.

Another challenge is in getting

to the end point of treatment. Back

pain can persist due to mechanical

causes as well as deformity even after

a healed status. MRI may show soft

tissue image and sterile abscess after

complete eradication of infection. Also,

a late onset paraplegia (a delayed

presentation of old healed TB spine)

with progressive neurology and a highgrade

kyphosis also poses challenges to

the orthopedic surgeon.

Follow up Assessment

Hematological findings on 11/4/2016

showed ESR-60; Total Count -10300

polymorphs- 63 lymphocytes- 30

eosinophil- 7, HB-9.5, LFT/RFT-normal,

GRBS-117, urine - severe UTI, uric acid-

6.5, Mantoux test – positive 14 mms.

X-ray showed: D6/7, end plate disease

with pedicle intact.

Catheterized since there was

neurogenic bladder and UTI.

21.7.2016: Hemetologically -

HB=10.4, ESR-20

23.9.2016: HB- 11.8

26/5/2016: Catheter removal done.

Her urination became normal.

X-ray AP and lateral view: TB spine showing end plate destruction at D6/7

MRI T1 & T2 weighted images: End plate destruction with soft tissue swelling.

After 9 months of ATT: The follow up x-ray showed definite evidence of healing.

Clinically, she walks well, no physical illness, increase in appetite and weight gain.

She lives with good physical status in accordance with her age.

X- Ray of thoracic spine AP and lateral view: 6 months follow up

2 years’ follow up: Patient has no fresh complaint.

52 / FUTURE MEDICINE / March 2019


TUBERCULOSIS OF HIP

A 38-year-old gentle man

presented with severe hip

pain, true shortening, all

movements painfully restricted.

ESR was at 70, Mantoux test

positive, CBNAAT test positive,

Histopathology also positive. He

was on bed rest with traction for

2 months and on ATT. Now he is

undergoing ATT.

X-ray pelvis showing both hips

with destruction of right hip

(head of femur and acetabulum).

TUBERCULOSIS OF THE KNEE

32-year-old gentleman, welder by

profession, presented with right knee

pain since 3 yrs. According to his words

the complaint started after a hit to his

knee with an iron bar while working.

In the last one-year period he could

do work only for 4 months (the other

8 months were spent on treatment

from various other health facilities). His

personal history revealed that he has

no diabetes, jaundice, hypertension,

recurrent fever or HIV. The complaint

stated as a sudden onset of pain 3 years

back following hit to an iron rod, with

a swelling disproportionate to the pain.

Now presented with swelling around

right knee. O/E: Patient walks with

antalgic gait, horse shoe swelling around

knee with increased temperature,

patellar tap was present along with

synovial thickening. Fixed flexion

deformity of 20 degrees then flexion

possible up to 90 degrees but with pain.

Clinically a diagnosis of chronic synovitis

was made. The case is interesting for its

3-year duration, and the MRI report of

pigmented villo-nodular synovitis.

THE CASE IS INTERESTING

FOR ITS 3-YEAR DURATION,

AND THE MRI REPORT OF

PIGMENTED VILLO-NODULAR

SYNOVITIS

Investigations

HB: 11.7, TC-4200, P-69%, L-23%, E-6%,

M-2%. ESR-80. RBS: 143mgs, HBS

Ag, HCV, HIV – negative X-ray showed

osteoporosis.

MRI report indicated synovial

thickening, 2 punched out lesions at

Biopsy result of synovectomy specimen.

the femoral condyles, pigmented villo

nodular synovitis to be considered. After

proper preoperative checkup partial

synovectomy and biopsy done under

spinal anesthesia.

Medial para- patellar incision,

synovium was thickened with increase in

vascularity. Synovial fluid sent for culture

and sensitivity - the result after 72 hours

was sterile. Drain removed after 24

hours; collection was 50 ml only. Wound

inspection done on 3rd day which was

clean. Patient was discharged on 3rd

day. Suture removal was done after 14

days. Quadriceps exercises started from

second day onwards. The biopsy report

came after 2 weeks and it was a typical

March 2019 / FUTURE MEDICINE / 53


tuberculous granuloma. Liver function test

and renal function test was normal. He was

registered in government DOTS regime.

By 2 months, the pain and swelling

disappeared. By 6 months, ESR become

25. Completed chemotherapy by 9 months.

Rejoined in his company at Ernakulam after 7

months post op.

2yrs follow up

Patient has no complaints. On examination

terminal 10 degrees of flexion limited.

Otherwise healthy.

Differential diagnosis

1. Tuberculosis. 2. Pigmented villo-nodular

synovitis 3. Rheumatoid arthritis 4. Seronegative

arthropathy.

Tuberculosis of the knee causes triple

dislocation due to hamstring spasm and

contracture. These are flexion, posterior

dislocation, lateral rotation and adduction of

tibia. In advance cases in adults, arthrodesis

is done by using Charnley’s compression

arthrodesis. Other causes of triple deformity

are polio and rheumatoid arthritis. DOTS

treatment was for 6 months with 2 months

of four-drug regime and 4 months two-drug

regime. At my request, the medical officer

in charge of DOTs programme extended

treatment up to 9 months

X-ray AP and lateral view of right knee showing

peri articular osteoporosis

The author is additional

professor in Orthopedics,

Govt. Medical College,

Kollam, India.

TUBERCULOSIS OF CALCANEUM

Biopsy result of curetted specimen from calcaneus

Radiological and clinical photograph of a healed lesion tuberculosis of calcaneum

at 6 months

Tuberculosis affecting this bone

is a rare occurrence even though

infections are not uncommon

in calcaneum, especially in

compound injuries. Co-morbid

conditions like diabetes, arterial

diseases, smoking, alcoholism

etc. are other contributing

factors.

A 35-year-old gentleman

presented with a non-healing

ulcer at the lateral aspect of

foot. Two years back, he had

a swelling at the same region;

for which he underwent an

incision and drainage (I &D) in

a local hospital. At that time the

ulcer was healed in 2 weeks.

The 2nd recurrence occurred

after 8 months, but at that time

there was no ulcer, only pain,

which was cured by NSAIDs

and footwear modification

(micronized rubber shoes).

Now he presented with a nonhealing

ulcer at the lateral aspect

of foot at the same region of

I&D. It started 1 month back

with a swelling at the lateral

aspect of the foot. An I&D was

done at a local hospital for the

same. Culture and sensitivity

of pus yielded heavy growth of

coagulase positive staphylococci

sensitive to cloxacillin and

gentamicin. X-ray showed a

lytic lesion at the antero-lateral

portion of the calcaneum.

With the help of C-Arm,

we identified the lytic lesion,

thorough debridement was

done, and the specimen was

sent for histopathology. The lytic

space was filled with vancomycin

impregnated purified Ca SO4

(Stimulan). Suture removal was

done at 10 days post operatively,

then a below-knee plaster cast

was given.

After 6 weeks it was

converted to a walking cast for

six more weeks and then he was

allowed full weight bearing.

The case was managed with

the DOTS regime protocol. Follow

up X-ray and clinical picture at 3

months shows well healed scar

and consolidating lesion.

54 / FUTURE MEDICINE / March 2019


AUGUST 2018/ FUTURE MEDICINE / 85


esearch snippets

Fibrinogen induces spine

elimination in Alzheimer’s

Mario Merlini et al unveiled

the role of the blood-clotting

protein fibrinogen in blood in

causing the characteristic cognitive

decline of Alzheimer’s disease.

Cerebrovascular alterations are a

key feature of Alzheimer’s disease

(AD) pathogenesis. The researchers

used state-of-the-art imaging

technology to produce the first

three-dimensional volume images

of Alzheimer’s disease. The images

of the brains of patients with

Alzheimer’s disease and mouse

models were studied. The bloodprotein

fibrinogen was seen to leak

from the blood into the brain, where

it activated the brain’s immune

cells triggering them to destroy

neuronal synapses. Fibrinogen then

induces spine elimination leading

to cognitive deficits mediated by

CD11b-CD18 microglia activation.

Fibrinogen-induced spine elimination

was prevented by inhibiting

reactive oxygen species (ROS)

generation or by genetic elimination

of CD11b. In the mouse models,

this genetic elimination showed

to reduce neuroinflammation,

synaptic deficits and cognitive

decline. The research thus unveils

that fibrinogen-induced spine

elimination and cognitive decline

via CD11b leads to cerebrovascular

damage with immune-mediated

neurodegeneration and may have

important implications in AD and

related conditions.

Source: Neuron Feb 5,t 2019 DOI: https://doi.

org/10.1016/j.neuron.2019.01.014

Ovarian cyst surgery

often unnecessary

Wouter Froyman et al shows

evidence promoting a watchful

waiting approach towards non-cancerous

ovarian cyst. The researchers performed

a two-year study involving 1919 women

from 10 different countries, including

the UK, Belgium, Sweden and Italy, who

were diagnosed with non-cancerous

ovarian cysts. The average age of the

women in the study was 48, and the

average size of the cyst was 4cm. Out of

the 1919 women in the trial, 20 percent

had cysts that disappeared of their

own accord, and 16 percent underwent

surgery. Overall, in 80 percent of cases

either the cyst resolved or did not need

intervention. Only 12 women were

subsequently diagnosed with ovarian

cancer, making the risk of cancer 0.4

percent. The rate of other complications,

such as ovarian twisting or cyst rupture

was 0.4 percent and 0.2 percent

respectively. The researchers suggest

that the risk of malignancy and acute

complications is low if adnexal masses

with benign ultrasound morphology are

managed conservatively, invasive surgical

procedures can be avoided.

Source: The Lancet Oncology February 05, 2019

https://doi.org/10.1016/S1470-2045(18)30837-4

Oral delivery of insulin

via ingestible capsule

A

bramson et al. developed an

ingestible drug delivery vehicle that

can be used for oral administration

of insulin. The capsule is designed

to be able to self-reorient from any

starting position so as to attach to

the gastric wall. This ingestible selforienting

millimeter-scale applicator

(SOMA) autonomously positions itself

with the gastrointestinal tissue. Within

the capsule, a needle is attached to a

compressed spring that is held in place

by a disk made of sugar which gets

dissolved on reaching the stomach.

It then deploys its needles fabricated

from active pharmaceutical ingredients

directly through the gastric mucosa while

avoiding perforation and delivers the

active pharmaceutical ingredient. The

approach successfully provided active

insulin delivery in pigs and rat models.

56 / FUTURE MEDICINE / March 2019


The study demonstrates a less invasive

method of drug delivery which can be

used to deliver insulin and other protein

drugs.

Source: Science 08 Feb 2019: Vol. 363, Issue

6427, pp. 611-615 DOI: 10.1126/science.

aau2277 http://science.sciencemag.org/

content/363/6427/611

Gut microbiome may

alter symptoms of

schizophrenia

Peng Zheng et al have found that

people with schizophrenia have

a significant difference in their gut

microbiomes compared to people

without the disorder which may be

linked to the altered neurologic function.

The researchers collected stool samples

from 53 schizophrenia patients who

were taking medication, five samples

from schizophrenia patients who were

not taking medication and from 69

people who did not have schizophrenia.

Gene sequencing of the samples

was done to isolate gut microbiome

bacteria. They divided the bacteria they

found into operational taxonomic units

(OTUs). Out of 854 OTUs, they found

56 that appeared only in schizophrenia

patients and 64 that appeared only

in the control group. They also noted

that the gut microbiomes of the

schizophrenia patients had overall lower

diversity than the control group. The

study also reported the presence of a

smaller subset of bacteria that were

clearly different between schizophrenia

patients and those without the disorder.

On introducing samples of the subset

from the schizophrenia patients into

the microbiomes of healthy mice, the

mice displayed behaviour changes. The

research reveals a plausible link between

schizophrenia microbiome which may

alter neurochemistry and neurologic

function in ways that may be relevant to

schizophrenia pathology.

Source: Science Advances 06 Feb 2019: Vol. 5, no.

2, eaau8317 DOI: 10.1126/sciadv.aau8317 http://

advances.sciencemag.org/content/5/2/eaau8317

Binge-watching of

TV shows raises

colorectal cancer risk

Long H Nguyen et al shows sedentary

behavior as a contributory factor to

the dramatic rise in colorectal cancer

(CRC) among people under the age

of 50. The study specifically looked at

TV viewing time and increased risk of

young-onset CRC, after adjusting for

putative risk factors, including obesity

and physical activity. The study subjected

89,278 American women between 25

and 42 years at the start of the study,

in 1991. The research documented 118

incident cases of young-onset CRC

over 22 years of follow-up. The study

found that in women with 7.1–14 hours

of TV watching per week had a multivariable

relative risk (RR) of 1.12, which

further increased for greater than 14

e-cigarette chemical

flavourings may

impair lung function

Hae-Ryung Park et al found

evidence suggesting the

potentially harmful effect of

two chemicals used to flavour

e-cigarettes on human lungs.

Diacetyl and 2,3-pentanedion,

widely used to flavour electronic

cigarettes, were found to impair

the function of cilia in the human

airway by inducing transcriptomic

changes. Researchers identified that

RNA-Sequencing of primary normal

human bronchial epithelial (NHBE)

cells showed a total of 163 and 568

differentially expressed genes in

cells that were exposed to diacetyl

and 2,3-pentanedione, respectively.

The cells were cultured at an airliquid

interface (ALI) to mimic

the in vivo airway characteristics.

The expression of multiple genes

involved in cilia biogenesis was

also found to be significantly

downregulated in reverse

transcription polymerase chain

reaction (RT-PCR) test of NHBE

cells. These flavouring substances

commonly used as food flavouring

substances are not proven safe for

inhalation apart from consumption.

The study sheds new light on the

likely adverse effect of e-cigarettes

on the lungs.

Source: Scientific Reports volume 9, Article

number: 1400 (2019) https://www.nature.

com/articles/s41598-018-37913-9

March 2019 / FUTURE MEDICINE / 57


hours per week. This association was

observed among participants without

a CRC family history and was more

pronounced for rectal cancer. Overweight

or obese participants were pronounced

to be more susceptible. Researchers

suggest further studies to be conducted

to elucidate the underlying biological

mechanism that may explain this

phenomenon.

Biomarkers open new gateways

towards precision medicine for pain

Niculescu et al open door towards

precision medicine for pain,

with the objective to determine

the severity of a patient’s suffering.

The study tracked hundreds of

participants to identify biomarkers

that can help determine the severity

of a patient’s pain. The researchers

were able to find a handful of genes

that correlated to pain state and of

future emergency department (ED)

visits for pain. The genes which the

scientists were able to correlate with

pain were MFAP3, GNG7, CNTN1,

LY9, CCDC144B, and GBP1. Using

bioinformatic drug repurposing

analyses, they were able to find

novel drug compounds that would

selectively target these genes and

could be used to not only measure

pain level but also inform the drug

discovery process to use these

genetic biomarkers to create more

personalized treatments for pain.

MFAP3, which had no prior evidence

in the literature for involvement

in pain, showed the most robust

empirical evidence acting as a strong

predictor for pain in the independent

cohorts. The breakthrough research

could help overcome the massive

negative impact of untreated pain

on quality of life, helping determine

the appropriateness of treatment,

and the severe addiction gateway

potential of existing opioid-based

pain medications.

Source:MolecularPsychiatry(2019) https://

www.nature.com/articles/s41380-018-0345-

5#Sec23

Source: JNCI Cancer Spectrum, Volume 2, Issue 4,

1 November 2018, pky073,https://doi.org/10.1093/

jncics/pky073

Transplanted β cells

rapidly restore glucose

tolerance in mice

Leonardo Velazco-Cruz et al

demonstrated a breakthrough study

by converting human pluripotent stem

cells (hPSCs) into stem cell-derived

β cells (SC-β cells) as a promising

alternative source for diabetes cell

replacement therapy. The researchers

developed functioning healthy SC-β

cells in vitro using an enriched serumfree

media. On transplanting them into

mice, the cells began to produce insulin

and respond to blood sugar within

days. Researchers introduced a new

differentiation strategy which focused

on modulating transforming growth

factor β (TGF-β) signaling. This helps

in controlling cellular cluster size, and

express β cell markers and undergo GSIS

(glucose stimulated-insulin secretion).

The capacity of these cells to undergo

GSIS with dynamic insulin release makes

them a promising cell source for diabetes

cellular therapy. This study provides

insights into the role of TGF-β signaling

in functional maturation where TGF-β

inhibition has been shown to promote

the replication of the cells. This helped

protect against stress-induced loss of the

phenotype and reduced apoptosis in a

mouse model, which give hope

for developing a potential cure for

treating type 1 diabetes in the near

future.

Source: Stem Cell Reports | VOLUME 12, ISSUE

2, P351-365, FEBRUARY 12, 2019 DOI: 10.1016/j.

stemcr.2018.12.012

—Compiled by Divya Choyikutty

58 / FUTURE MEDICINE / March 2019


hospital news

Apollo Hospitals honoured with

postal stamp

Governor of Tamil Nadu released a postal

stamp commemorating the pioneering

efforts of the chairman of Apollo Hospitals, Dr

Pratap C Reddy’s in preventive healthcare in

India, recently.

Since its establishment in 1983, Apollo

Hospitals pioneered innumerable initiatives in

healthcare management.

“Dr Reddy and Apollo are synonymous

with healthcare excellence in the world.

They excel in end to end healthcare of

consumers from 140 plus countries and have

many firsts including the recent launch of

South East Asia’s first ever Proton Cancer Care

Therapy centre. Preventive Care was

first pioneered in India by Dr Pratap Reddy

and today I am happy to commend his

dedication to disease prevention through this

special stamp,” Banwarilal Purohit,

the governor of Tamil Nadu, said on the

occasion.

Apollo’s Preventive Healthcare initiatives

have been working tirelessly for almost four

decades to ensure that Dr Pratap Reddy’s

dream is realised, said Preetha Reddy, Vice

Chairperson of Apollo Hospitals in a statement.

“We take pride in having touched 20 million

lives through our preventive healthcare

endeavours. It is a very significant moment for

the entire Apollo family as a special preventive

healthcare commemorative stamp is being

released, in recognition of our efforts,” she

said.

New hospital in Lucknow

President Ram Nath Kovind inaugurated

the Apollomedics Super Specialty hospital

in Lucknow. It is the 72nd hospital of Apollo

Hospitals Enterprise, Asia’s largest hospital

chain, which has a total bed capacity of

10000 across India. The group also runs

3500 pharmacies, over 90 primary care and

diagnostics clinics, and more than 160 Apollo

Munich Insurance branches.

Dr S Natarajan

elected

president of

AIOS

S Natarajan, chairman

Dr and managing director,

Aditya Jyot Eye Hospital,

Mumbai has been elected

as president of All India

Ophthalmological Society.

Established in the year

1930, AIOS has continuously

grown over the years and

currently has over 20,000

life members. The key

objectives of the society are

cultivation and promotion

of the study and practice of

ophthalmic sciences, research

and manpower development

with a view to render service

to the community and to

promote social contacts

among ophthalmologists of

the country.

Max sells controlling stake in Max Bupa to True North

The Board of Max India on Tuesday

approved the sale of its 51% stake in

Max Bupa Health Insurance Company

(Max Bupa), to the leading Private Equity

firm True North. The all cash transaction

values Max Bupa at an enterprise value of

Rs 1,001 crore and is subject to requisite

regulatory approvals. Bupa, the existing

joint venture partner in Max Bupa, remains

committed to the joint venture and will

continue to play an active role in the

company as before through its Board

positions and knowledge exchange

initiatives.

At the conclusion of the transaction,

True North will nominate

directors on Max Bupa’s

Board, while Max India’s

nominated directors

will step down. The use

of the Max brand will

be phased out over a

period of two years and

replaced with a suitable

name. The Bupa brand

name will continue as

before.

True North

Analjit Singh

Founder &

Chairman

Max Group

(formerly known as India Value Fund

Advisors) is an active investor in Indian

assets. It has built deep knowledge and

skills in the Indian market, investing in

more than 40 Indian businesses over the

last 19 years through its 6 investment

funds with a combined corpus of over US$

2.8 billion. Over the years, True North has

made productive investments across the

financial services and healthcare sector, to

the tune of Rs 5,700 crore.

The transaction will lead to a cash

inflow of Rs 511 crore for Max India. The

company intends to utilize the proceeds to

invest in both existing and new business

opportunities which are currently under

evaluation.

60 / FUTURE MEDICINE / March 2019


scientific report

TARGETING GENETIC BASIS OF

CRC WITH NOVEL THERAPIES

Identifying high-risk patients carrying known disease through genetic testing

should be part of colorectal cancer screening

CORAL MIRIAM MAGDALENE AND

AMIT CHAUDHURI

Colorectal cancer (CRC) is the third

most common cancer with an

estimated global incidence of

1.8 million. In India, the incidence and

prevalence of the disease is 27,605 and

53,700 respectively with a mortality

of 19,548 (https://www.uicc.org/newglobal-cancer-data-globocan-2018).

Although the incidence rates of CRCs

are lower in India compared to the

Western countries, the mortality rates

are higher due to their late-stage

presentation and lack of effective

therapies. The risk factors for developing

CRC, include age, gender, race, family

history, inheritance, and inflammatory

bowel disease. Lifestyle factors which

attribute to this burden include physical

inactivity, obesity, a diet low in fruits

and fibres, smoking and alcohol

consumption. More than 90% of the

CRCs occur in people who are 50

years older in Western countries, but in

India, there is a mounting incidence of

younger people presenting with latestage

disease.

In general, about 75% of the CRCs

are sporadic while 25% are familial.

Among the familial, the vast majority

is familial adenomatous polyposis

(FAP), an autosomal dominant disease

caused by the loss-of-function (LOF)

mutation in the adenomatous polyposis

coli (APC) gene on chromosome 5q21.

A less prevalent familial CRC is Lynch

syndrome (LS), an autosomal dominant

disease also known as Hereditary nonpolyposis

CRC caused by mutations in

one of the DNA mismatch repair (MMR)

genes, such as MSH2, MSH6, MLH1, and

PMS2. In India, the prevalence of familial

colorectal cancer is 10-15% (Maharaj,

Shukla et al. 2014). This could be a gross

underestimation because of lack of

systematic genetic screening, cost of the

test and strong social stigma. In a recent

study, we identified several FAP and

Lynch syndrome families who would

normally not undergo genetic testing

FAP, AN AUTOSOMAL

DOMINANT DISEASE CAUSED

BY THE LOSS-OF-FUNCTION

(LOF) MUTATION IN THE

ADENOMATOUS POLYPOSIS

COLI (APC) GENE ON

CHROMOSOME 5Q21

but for our research initiative (Majumder,

Shah et al. 2018, Majumder, Shah et al.

2018).

The common symptoms of CRC are

altered bowel habits, rectal bleeding,

constipation, diarrhea, unexplained

weight loss, etc. with rectal bleeding

being the most important symptom

(Loh, Majid et al. 2013). Colorectal

cancer is treated based on the

presentation stage of the disease and

the age of the patient. Surgery is still

the mainstay of treatment for a locally

advanced tumourr that is resectable.

Adjuvant chemotherapy or radiation

therapy is decided depending on

the stage and clearance of resection

margins. In the case of nodes positive

stage III and IV cancers, where surgery

is not feasible, chemotherapy is used as

the first line of treatment. Improvements

in surgery and combination

chemotherapies in the last 20 years

have doubled the 5-year survival of

CRCs, yet the global mortality remains

at ~50%. As discussed below, colorectal

cancer serves as a poster-child of our

understanding of the molecular basis of

carcinogenesis, which is applicable to all

cancers in general.

Accumulation of mutations

Bert Vogelstein and his team from

John Hopkins University studied

familial colorectal cancer in the 80s

and 90s to reveal for the first time

the mechanism of cancer progression

occurring by stepwise accumulation of

mutations in oncogenes and tumour

suppressor genes. Oncogenes, such

as RAS, BRAF, PI3K endow cancer

cells to divide incessantly and survive

indefinitely creating a dependence

of cancer cells to their presence,

referred to as genetic addiction.

Mutations resulting in the activation

of oncogenes (gain-of-function) are

therefore a hallmark of cancer. By

contrast, tumour suppressor genes,

such as APC (adenomatous polyposis

coli), TP53, TGF-β (transforming growth

factor-β) prevent cells from growing

aberrantly and typically lose their

function (loss-of-function), which is

the second hallmark. Vogelstein’s

work demonstrated how mutations

62 / FUTURE MEDICINE / March 2019


BENIGN TO

MALIGNANT

Sequential mutations in

KRAS, TGF-β and PT53

transform pre-malignant

colonic epithelial cells to

become cancerous

Shedded

dead cells

Low

Villus

Colon cancer progression

Colonic

crypts

Normal

epithelium

Dysplastic

epithelium

Early

adenoma

Late

adenoma

Carcinoma &

Metastasis

High

Paneth

cells

Wnt

Signaling

APC

KRAS TGF-β PT53

Normal Colon Benign pre-malignant Malignant

in oncogenes and tumour suppressor

genes occur in a sequential pattern to

transform normal colon epithelial cells

into colorectal cancer (see figure). The

mechanistic basis for the two-hit model

of cancer initiation gained scientific

acceptance through these studies, in

which the transformation of healthy

epithelial cells requires at least two

hits, one that takes out the function

of a tumour suppressor gene, and

the other that activates oncogenes.

Over 80% of sporadic CRC is caused

by the inactivation of APC resulting in

colon cancer cell survival. The second

hit is the activation of RAS oncogene

that results in cellular transformation

and formation of adenoma. Additional

mutations in TP53 pushes the cells to

become an adenocarcinoma.

The genetic foundation emerging out of

these studies has a profound impact on

cancer treatment and the development

of novel therapies. Successful targeted

therapies inhibiting the function of

overexpressed genes, such as HER2

in breast cancer, or EGFR in colorectal

cancer or gain of function mutations in

EGFR (epidermal growth factor receptor)

in non-small-cell lung cancer, or BRAF

March 2019 / FUTURE MEDICINE / 63


FAMILY PEDIGREE OF LYNCH SYNDROME

The proband (II.2) indicated by a black arrow, was diagnosed with a relapsed colorectal cancer.

The heterozygous germline MLH1 mutation was found in the proband and his brother (II.6)

who was also diagnosed with colorectal cancer and had undergone surgery. All other family

members lacked the MLH1 germline mutation.

MLH1 gene mutation

in melanoma are grounded on the

concept of driver mutations and genetic

addiction. Metastatic CRCs are treated

with monoclonal antibodies that starve

the tumour of nutrients and oxygen

by preventing the growth of blood

vessels, such as Avastin or Zaltrap

that bind VEGF (vascular endothelial

growth factor), or Cyramza, which

binds VEGF receptor-2 (VEGFR2). A

subset of colorectal cancer patients

overexpressing EGFR protein is treated

with monoclonal antibodies Erbitux

or Vectibix that block EGFR signalling.

In 2018, a novel inhibitor targeting

neurotrophin receptor (NTRK) fusions,

Vitrakvi was approved for all solid

tumours that express these fusions

including CRC. Overall, NTRK fusions

are rare in cancers; however, the

presence of this fusion in colon

cancer can be treated. The use of

EGFR monoclonal antibodies Erbitux

or Vectibix to treat colon cancer in

India is limited, however, published

reports indicate superior overall

survival of Vectibix compared to

Erbitux in combination with Folfox in

metastatic colorectal cancer with wildtype

KRAS (Pathak, S et al. 2018). The

anti-angiogenic therapies or targeted

therapies have extended limited

benefit and new therapies are needed

to treat this deadly disease.

diagnosed with colorectal cancer.

A slash through the shape indicates a deceased member. Roman numerals indicate generations.

Cancer immunotherapy has

produced long-term benefit and has

given a new lease of life to 15-20% of

patients with terminal disease, who had

exhausted all therapies. The therapy

boosts patients’ immune system by

targeting a group of receptors called

checkpoint control proteins. The three

checkpoint control proteins currently

targeted by monoclonal antibodies

are cytotoxic T-lymphocyte associated

protein-4, CTLA-4 (targeted by Yervoy),

programmed cell-death protein-1, PD-1

(targeted by Opdivo and Keytruda)

and programmed cell-death proteinligand-1,

PD-L1 (targeted by Tecentriq

and Imfinzi). In colorectal cancer, Opdivo

and Keytruda have been approved

to treat 10-15% of tumours with

microsatellite instability (MSI) phenotype.

These tumours carry a high number of

mutations and show an overall response

of over 70% to checkpoint inhibition.

The correlation between high tumour

mutation burden (TMB) first reported

in colon cancer has been reproduced

in other cancer types qualifying this

feature as a critical biomarker of patient

selection (Le, Durham et al. 2017). In

India, the incidence of MSI ranges from

5-10% (Maharaj, Shukla et al. 2014).

However, the prohibitively high cost of

checkpoint inhibitor antibodies will have

limited utility in India.

Checkpoint inhibitors

Use of high TMB as a biomarker of

patient selection has left over 75%

of colorectal cancers and 70% of all

cancers untreatable with checkpoint

blockade therapy. To expand the utility

of these powerful therapies into other

cancers, the field is actively pursuing

discovery of novel biomarkers for

patient selection, combining checkpoint

inhibitors with other therapies to make

tumours more immunogenic and

sensitizing them to immune-mediated

attack. There is also a concerted effort

from the industry to develop vaccines

against tumour-specific neoantigens

to induce an immunological response.

Limited results from ongoing clinical

trials in melanoma and ovarian cancer

suggest that vaccines can skew the

immunological balance towards a more

inflammatory phenotype permissive to

T cell-mediated killing of tumour cells

(Ott, Hu et al. 2017, Tanyi, Bobisse et al.

2018).

We have shown in two recent

studies that in familial colorectal

cancer - familial adenomatous coli

(FAP) and Lynch syndrome, cancerspecific

mutations are immunogenic

and an interventional approach with

vaccines may be feasible (Majumder,

Shah et al. 2018, Majumder, Shah et al.

2018). The progression of colon cancer

through an intermediate polyp-stage is

an ideal intervention point for vaccine

therapy since the immune system is not

tolerized to the neoantigens that appear

during polyp development. Further

research is required to identify whether

neoantigens in polyps are private, or

shared between patients, whether

multiple polyps in the same individual

have a similar mutational profile, and

what fraction of the mutations are

immunogenic. In addition, clinical use

of vaccines will rely on good delivery

mechanisms and use of optimal

adjuvants if the delivery route is through

peptides.

In conclusion, our understanding

of the molecular mechanisms of colon

cancer carcinogenesis has exploded

in recent years with the use of next

64 / FUTURE MEDICINE / March 2019


GENETIC SCREENING FOR COLON CANCER PREVENTION

DR SHIVANEE SHAH

old Jignesh was

suffering from weight loss

52-year

and changes in bowel

movement. A similar incident in his

brother had already been diagnosed

as cancer. Jignesh did not want to take

any chances and got a PET scan and

an endoscopy mediated biopsy done.

Biopsy results came out to be positive

for colon cancer and Jignesh consulted

Dr Rakshit Shah, consultant surgical

oncologist, at the Kailash Cancer Hospital

and Research Centre (KCHRC), Goraj,

Gujarat. D. Shah reviewed the family

history and endoscopy results carefully.

Based on the endoscopy results showing

the presence of >100 polyps in the

colon and the biopsy results, Dr Shah

performed a colectomy. In the meantime,

because of the family history and the

extent of polyps, Dr Shah strongly

suspected Jignesh to have Familial

Adenomatous Polyposis (FAP).

FAP is an autosomal dominant

disorder that is caused due to a

mutation in the adenomatous polyposis

coli (APC) gene. The APC protein is a

tumour suppressor gene and carriers

with a mutation in the APC gene

resulting in an inactive APC protein are at

an almost 100% risk of colon cancer by

the age of 40.

To confirm the diagnosis and to

test other family members, Dr Shah

counselled Jignesh and 26 of his family

members to agree to undergo genetic

testing. A total of 10 family members

carried the mutation in the APC gene. 6

members were diagnosed with polyps,

3 of which were diagnosed with cancer

and all 6 immediately underwent

prophylactic colectomy. 4 members

were younger and did not have polyps

as yet. However, they have a strong

predisposition of getting polyps and

colon cancer later and are advised

to undergo regular colonoscopies to

monitor the generation of polyps.

Colon cancer can also be triggered

due to mutations in the DNA mismatch

repair genes MLH1, MSH2, MSH6, and

PMS2 or EPCAM gene which results in

inactive MSH2 protein. These mutations

result in the Lynch syndrome or

hereditary nonpolyposis colorectal cancer

(HNPCC). Patients with Lynch syndrome

also have an increased risk of developing

colorectal cancer. Aneesh was one such

In these cases, family

history is very important

and the entire family should

be counselled for genetic

testing to ensure adequate

surveillance

Dr Rakshit Shah

Consultant surgical oncologist

patient who had come to Dr Shah with a

relapsed case of colorectal cancer. After

genetic testing, he had a mutation in the

MLH1 gene. His family members were

also counselled and underwent genetic

testing. However, of the 13 members

tested, only Aneesh and his brother

were positive and the remaining family

members were relieved to have been

tested negative.

As per Dr Shah, some of the major

challenges in getting patients to undergo

genetic testing is the cost factor or the

worry regarding social stigma. For these

cases, the testing was done for free by

MedGenome Labs, Bangalore. Further,

because of the existing family history,

these families willingly agreed for the

testing.

Once operated, there is no need to

undergo further treatment. However,

colectomies may result in liquid stools

with an increase in frequency of bowel

movements per day. While this may

not seem very enticing to someone to

undergo prophylactic surgery, Dr Shah

strongly advocates that “prevention is

better than cure.” He advices that in such

cases, family history is very important

and the entire family should be

counselled for genetic testing to ensure

adequate surveillance and prophylactic

therapy.

Currently, there are no targeted

therapies to block the tumour-promoting

changes that happen in FAP and Lynch

syndrome patients. However, there is

some hope that boosting the immune

system of individuals after colectomy

may prevent or delay the progression to

full-blown colon cancer.

generations sequencing technology and

advanced data analysis tools. A range

of novel targetable driver mutations,

including gene fusions have been

reported in these studies (Seshagiri,

Stawiski et al. 2012, Dienstmann,

Vermeulen et al. 2017). In India,

colorectal cancer is usually detected

at an advanced stage with limited

treatment options. Identifying high-risk

patients carrying known

risk alleles through genetic testing

should be part of colorectal cancer

screening awareness programmes.

MSIhi tumours stand to benefit the

most by checkpoint blockade therapy.

Finally, vaccines should be considered in

neoadjuvant setting to delay recurrence

or in familial cancer after surgical

removal of polyps.

The authors are with MedGenome Inc.,

Foster City California

March 2019 / FUTURE MEDICINE / 65


cosmetic surgery

BREAST IMPLANTS CARRY

LYMPHOMA RISK: US FDA

The world’s leading drug regulator finds an increasing number of unique cases

of implant-associated large cell lymphoma

Binita Ashar, MD, of the FDA’s

Centre for Devices and

Radiological Health issued a

statement on known risk of lymphoma

from breast implants.

One of the most important roles

we have as a public health agency is

educating patients and health care

providers about both the benefits and

risks of medical products, including

breast implants.

I know there are many choices of

breast implants available to patients,

including the size, implant fill and

surface texture. We want to provide

patients with the most up-to-date

information about the variety of breast

implants available so that patients

and providers can have thorough and

thoughtful discussions weighing the

benefits and risks of different products.

We also want to be transparent in

sharing the information we regularly

gather and analyse in a way that

provides important context to help

inform these discussions.

Today, we are providing an update

regarding the number of cases of breast

implant-associated anaplastic large cell

lymphoma (BIA-ALCL), a type of non-

Hodgkin’s lymphoma and a known risk

from breast implants. In 2011, the FDA

was the first public health agency in

the world to communicate about the

risks of BIA-ALCL, warning women that

the available information at the time

indicated that there is a risk for women

with breast implants for developing this

disease. Since then, we have regularly

updated the information available on

our website regarding known BIA-ALCL

cases, including deaths and known risks.

We hope that this information

prompts providers and patients to have

important, informed conversations

about breast implants and the risk of

BIA-ALCL. At the same time, we remain

committed to working in partnership

with all stakeholders to continue to

study, understand and provide updates

about this important public health issue.

Today, the agency is providing an

updated number of medical device

reports (MDRs), also known as adverse

event reports. After thorough data

analysis, we are reporting that, as

of September 2018, the agency has

received a total of 660 total medical

device reports regarding BIA-ALCL cases

since 2010. Of the 660 MDRs, our indepth

analysis suggests that there are

457 unique cases of BIA-ALCL, including

9 patient deaths.

We understand that the information

presented shows an increase of 246

new MDRs since last year. Given

the agency’s continued efforts to

communicate with stakeholders

about BIA-ALCL risks and our work

66 / FUTURE MEDICINE / March 2019


to encourage patients and providers

to file MDRs with the agency, these

types of increases in the MDRs are

to be expected and may include

past cases that were not previously

reported to the FDA. The increased

number of MDRs contributes to our

evolving understanding of BIA-ALCL

and represents a more thorough and

comprehensive analysis.

The number of unique cases is

lower than the total number of reports

because the FDA’s medical device

reporting system allows patients,

providers and manufacturers to each file

their own reports even if it’s about the

same case, which can lead to duplicative

reports of BIA-ALCL. Through our review

of each report, our team of experts

works to remove duplicative information

and analyse the data provided to help

better understand what these reports

may or may not tell us about the

benefits and risks of the device. For

example, our analysis of these reports

is better when there is a wide range of

information provided concerning the

breast implant texture and implant fill,

and other helpful details like a patient’s

age, how long a patient has been

implanted, and time from implantation

to diagnosis. This information

helps us understand how and why

this lymphoma may be occurring.

Unfortunately, not every report provides

thorough information about each case,

including what type of breast implant

(e.g., surface texture) the patient

received, which makes it more difficult

to know if any particular breast implant

characteristic is associated with BIA-

ALCL or if higher reports of BIA-ALCL

are simply due to a higher implantation

rate of a particular manufacturer. In

the interest of transparency, on our

webpage, we provide a breakdown

of the data and an analysis of that

information that was provided to the

agency.

For patients, we know the

information regarding breast implants

can be overwhelming, which is why

we are committed to continuing our

efforts to provide up-to-date publicly

IT IS DIFFICULT TO KNOW IF

ANY PARTICULAR BREAST

IMPLANT CHARACTERISTIC IS

ASSOCIATED WITH BIA-ALCL

available resources to help understand

the known benefits and risks of

implants. We encourage patients to

review our website and read specific

device labelling, including patient

labelling information, for any product

they may consider implanting. Choosing

to obtain a breast implant is a very

personal decision that patients and

their providers should make based on

individual needs and with the most

complete information about products.

We are also aware that our

counterparts in different countries

are taking certain actions or may be

reporting different information about

breast implant safety than the FDA.

The different devices approved in each

country, availability of products, variation

in market share, extent of medical

device adverse event reporting, and

availability of information regarding the

total number of implants sold differs

from country to country. This makes

it difficult for the regulatory bodies of

different countries to compare data and

determine risk rates on a global scale.

We recognize the limitations of

medical device reports, which is why

we review other sources of information,

including medical literature and

the Patient Registry and Outcomes

for Breast Implants and Anaplastic

Large Cell Lymphoma Aetiology and

Epidemiology (PROFILEdisclaimer

icon). PROFILE collects real-world

data regarding patients who have a

confirmed diagnosis of BIA-ALCL.

In addition to updating our medical

device reports, we are issuing a Letter

to Health Care Providers to encourage

those who regularly treat patients,

including primary care physicians and

gynaecologists, to learn about BIA-ALCL

in patients with breast implants. We

want to ensure that all providers who

treat patients with breast implants have

information regarding identification,

diagnosis and treatment. Patients are

more likely to seek routine care from

primary care physicians, gynaecologists

and others besides their treating plastic

surgeon.

Dr. Binita Ashar is a general surgeon and

the director of the Division of Surgical

Devices in the FDA’s Center for Devices and

Radiological Health.

March 2019 / FUTURE MEDICINE / 67


public health

MEASLES IN EUROPE

WHO URGES EU NATIONS TO ADDRESS IMMUNISATION GAPS

Measles killed 72 children and adults in the European region in 2018

In light of measles data for the year

2018 showing a rising number of

deaths from the viral infection, the

WHO has urged European countries to

target their interventions to those places

and groups where immunization gaps

persist.

More children in the WHO European

region are being vaccinated against

measles than ever before; but progress

has been uneven between and within

countries, leaving increasing clusters of

susceptible individuals unprotected, and

resulting in a record number of people

affected by the virus in 2018.

Measles killed 72 children and

adults in the European region in 2018.

According to the WHO’s monthly country

reports for January to December 2018

(received as of 01 February 2019),

82 596 people in 47 of 53 countries

contracted measles. In countries

reporting hospitalisation data, nearly

2/3 (61%) of measles cases were

hospitalized. The total number of people

infected with the virus in 2018 was the

highest this decade: 3 times the total

reported in 2017 and 15 times the

record low number of people affected

in 2016.

The surge in measles cases in 2018

followed a year in which the European

region achieved its highest ever

estimated coverage for the second dose

of measles vaccination (90% in 2017).

More children in the region received the

full two-dose series on time, according

to their countries’ immunisation

schedules, in 2017 than in any year since

THE SURGE IN MEASLES

CASES IN 2018 FOLLOWED

A YEAR IN WHICH THE EU

ACHIEVED ITS HIGHEST

EVER ESTIMATED COVERAGE

FOR THE SECOND DOSE OF

MEASLES VACCINATION

WHO started collecting data on the

second dose in 2000. Coverage with the

first dose of the vaccine also increased

slightly to 95%, the highest level since

2013. However, progress in the region,

based on achievements at the national

level, can mask gaps at subnational

levels, which are often not recognised

until outbreaks occur.

“The picture for 2018 makes it

clear that the current pace of progress

in raising immunization rates will be

insufficient to stop measles circulation.

While data indicate exceptionally high

immunization coverage at regional

level, they also reflect a record number

affected and killed by the disease. This

means that gaps at local level still offer

an open door to the virus,” stated Dr

Zsuzsanna Jakab, in a WHO release.

Increasing susceptibility

While immunization coverage has

improved overall in the region, many

people remain susceptible.

Estimated coverage with the second

68 / FUTURE MEDICINE / March 2019


dose of measles vaccine was below the

95% threshold to prevent circulation

(that is, to achieve “herd immunity”) in

34 countries of the region in 2017.

Subnational coverage rates point

to disparities even within countries.

Suboptimal coverage for either dose sets

the stage for transmission in the future.

The European Vaccine Action Plan

2015–2020 (EVAP) lays out a strategy

endorsed by all 53 member states to

eliminate both measles and rubella.

Most importantly, at least 95% of

every population needs to be immune,

through two doses of vaccination or

prior exposure to the virus, to ensure

community protection for everyone

– including babies too young to be

vaccinated and others who cannot be

immunized due to existing diseases and

medical conditions.

“In adopting EVAP, all countries in the

European region agreed that elimination

of measles and rubella is possible and

is also a cost-effective way to protect

people of all ages from avoidable

suffering and death,” according to

Dr Nedret Emiroglu, Director of the

Division of Health Emergencies and

Communicable Diseases, WHO Regional

Office for Europe.

Forty-three European countries

interrupted transmission of endemic

measles for at least 12 months as of

the end of 2017. Some of them, also

managed to limit the spread of the

virus following importation to very few

cases in 2017 and 2018, showing that

elimination of the disease is well within

reach for the whole Region. “Progress

in achieving high national coverage is

commendable. However, it cannot make

us blind to the people and places that

are still being missed. It is here that we

must now concentrate increased efforts.

We should never become complacent

about our successes but continue to

strive to reach the final mile. Together

we can make this happen,” concludes Dr

Emiroglu.

Suboptimal coverage

Many factors contribute to suboptimal

immunization coverage and the spread

of measles. To prevent outbreaks and

eliminate measles, countries need to

sustain high national and subnational

immunization coverage with two doses

of measles-containing vaccine, as well

as identify and address all pockets

of underimmunization among their

populations.

FORTY-THREE EU COUNTRIES

INTERRUPTED TRANSMISSION

OF ENDEMIC MEASLES FOR AT

LEAST 12 MONTHS AS OF THE

END OF 2017

The regional office continues to

work with countries in the region to

enhance their immunization and disease

surveillance systems. This includes

building capacities and providing

guidance to:

• ensure that all population groups

have equitable access to vaccination

services and that these are convenient

SPURT IN NUMBERS

Measles cases and MCV1 & MCV2 coverage

in the WHO European Region, 2009-2018

Number of measles cases

90000

80000

70000

60000

50000

40000

30000

20000

10000

0

94

73

7884

93

80

30604

• identify who has been missed in the

past and reach them with the vaccines

they need

• ensure that health workers are

vaccinated to prevent transmission in

health facilities and that they

have sufficient technical knowledge

about vaccines and the immune

system to feel confident in

recommending vaccination to their

patient

• strengthen trust in vaccines and

health authorities

• secure access to a timely and

affordable supply of vaccines

• improve outbreak detection and

response

• listen and respond to people’s

concerns and respond to any health

event that could be potentially related

to vaccine safety.

Most of the countries struggling

with suboptimal immunization coverage

against measles in the Region are

middle-income countries. The regional

office is working with these countries

to implement a coordinated strategy to

address targeted programme areas, the

WHO said.

2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

Measles cases

94

83

33254

95

83

26788

95

89

32857

Data sources : 1. Measles cases - monthly aggregated and case-based data reported by Member States to WHO/Europe

or via ECDC/TESS by as of 01 Feb 2019. 2. MCV1 and MCV2 coverage - WHO/UNICEF Estimates of National Immunization

Coverage (WUENIC) as of 08 Nov 2018.

MCV1 = first dose of measled - containing vaccine; MCV2 = second dose of measles-containing vaccine

Year

94

89

18869

MCV1 coverage

94

89

28413

93

88

5273

95

90

25863

MCV2 coverage

82596

100

90

80

70

60

50

% Coverage

March 2019 / FUTURE MEDICINE / 69


devices&gadgets

Interoperable insulin pump

gets US FDA nod

DBS for epilepsy

therapy launched

M

edtronic has launched

Deep Brain Stimulation

(DBS) for medically-refractory

epilepsy in the US.

DBS therapy uses a

surgically implanted medical

device for epilepsy. It delivers

controlled electrical pulses to

a target in the brain called

the anterior nucleus of the

thalamus (ANT), which is

part of a network involved in

seizures.

Recently, the US FDA

granted pre-market approval

for Medtronic DBS therapy

for epilepsy as an adjunctive

treatment for reducing the

frequency of partial-onset

seizures in individuals 18

years of age or older who are

refractory, or drug-resistant,

to three or more antiepileptic

medications.

The approval was based

on results from the SANTE

(Stimulation of the Anterior

Nucleus of the Thalamus

in Epilepsy) trial, wherein

patients had a median seizure

frequency reduction of 75

percent at seven years postimplant.

Similar to a cardiac

pacemaker, it delivers electrical

stimulation to precisely

targeted areas of the brain as

adjunctive treatment for several

neurological disorders.

In addition to medically

refractory epilepsy, DBS

therapy is currently approved

in many locations around the

world, including the US and

Europe, for the treatment

The US FDA approved

Tandem Diabetes

Care’s t: Slim X2 insulin

pump with interoperable

technology for delivering

insulin under the skin.

Referred to as an

alternate controller enabled

(ACE) infusion pump, it

allows patients to tailor

diabetes management

to their individual device

preferences.

The interoperable t:

Slim X2 pump works by

delivering insulin under

of the disabling symptoms

of essential tremor and

recent and longer-standing

Parkinson’s disease. The device

is also useful to treat chronic

intractable primary dystonia

and severe, treatment-resistant

obsessive-compulsive disorder,

the company said.

Intravitreal

implant to treat

uveitis launched

Fluocinolone acetonide

intravitreal implant (Yutiq)

the skin at set or variable

rates. It can be digitally

connected to automatically

communicate with and

receive drug dosing

commands from other

diabetes management

devices, such as AID

systems. AID systems

typically consist of a pump,

CGM, and software to

control the system.

The t: Slim X2 insulin

pump was reviewed

through the de novo

pathway

has been launched in the US,

EyePoint Pharmaceuticals,

Inc said. Yutiq is a three-year

micro-insert for the treatment

of chronic non-infectious

uveitis affecting the posterior

segment of the eye.

The company has also

launched EyePoint

Assist, a programme

to ensure access to

Yutiq for eligible

patients.

One microinsert

of Yutiq

has the ability

to deliver up

to three years of

The FDA reviewed

interoperable t: Slim X2

pump performance data

demonstrating that the

device can dose insulin

accurately and reliably and

at the rates and volumes

programmed by the user.

The FDA also assessed

the ability of the pump to

communicate with external

devices with appropriate

reliability, cybersecurity and

fail-safe modes, Tandem

said

fluocinolone acetonide, a

commonly used steroid,

with continuous dosing that

avoids the peaks and valleys

of local corticosteroids, the

current standard of care, the

company said.

Yutiq utilizes Durasert

drug delivery technology

and is an intravitreal

micro-insert

containing

0.18 mg of

fluocinolone

acetonide,

designed to

release consistently

for up to 36 months.

70 / FUTURE MEDICINE / March 2019


Robotic catheter

for lung biopsy

gets clearance

The US FDA cleared the

Ion endoluminal system

to enable minimally invasive

biopsy in the peripheral lung,

Intuitive Surgical said.

The Ion system uses

an ultra-thin articulating

robotic catheter that can

move 180 degrees

in all directions. The

outer diameter of the

catheter is 3.5 mm,

which physicians can

navigate through small

and tortuous airways to

reach nodules in any airway

segment within the lung.

The Ion system’s flexible

biopsy needle

can also pass

through very

tight bends

via Ion’s catheter

to collect tissue in

the peripheral lung.

The catheter’s 2mm

working channel can

also accommodate

other biopsy tools, such

as biopsy forceps or

cytology brushes, if

necessary.

The system’s fibre optic

shape sensor technology

provides the physician

with the precise location

and shape information of

the catheter throughout

the navigation and biopsy

process.

The Ion system easily

integrate into existing lung

nodule biopsy workflows,

as well as existing imaging

technology, including

fluoroscopy, radialendobronchial

ultrasound, and

cone-beam CT.

Bone loss

treatment device

gets approvals

NuVasive received 510(k)

clearance from the US FDA

as well as European CE mark

approval for its Precice Bone

Transport System for use in

segmental bone loss treatment

in the tibia and femur resulting

from trauma or infection.

The Precice Bone

Transport System includes

an implantable, magnetic

intramedullary nail with a dual

slot designed to support the

transport of an intercalary

bone segment to facilitate

healthy regeneration. Following

implantation, an external

remote controller is used

to precisely move the bone

segment up to 10 centimetres

based on the specific needs of

each patient.

It provides an all-internal

solution compared to

traditional external fixation

systems which require patients

to wear an external device for

an extended period of time,

with the potential for increased

pain and risk of infection.

Indications for the Precice

Bone Transport System include

treatment of acute bone

defects up to 10 centimeters.

The stainless-steel device

provides the strength and

stability needed to treat more

complex segmental defects

due to trauma or infection

including infected non-unions,

segmental defect and chronic

bone infections.

Neuromodulator

to treat bladder

wins CE mark

S

timRouter Neuromodulation

System developed by

Bioness has received CE Mark

Approval in Europe for the

treatment of overactive bladder

(OAB).

In the US, the StimRouter

currently has FDA approval for

the treatment of chronic pain

of a peripheral nerve origin as

US FDA clears DR 800 imaging system

Agfa NV has received FDA

510(k) clearance for its DR 800

multipurpose imaging system with

tomosynthesis.

Tomosynthesis is used to synthesize

tomographic slices from a single

tomographic sweep.

The DR 800 includes Agfa’s

tomosynthesis algorithms for iterative

reconstruction, which deliver images

with less noise and fewer artefacts.

These algorithms also enable faster

image reconstruction overcoming the

usual slow iterative reconstruction

process.

The DR 800 comes standard with

Dynamic MUSICA, for both static and

dynamic images. This image processing

software enhances noise suppression,

offers superb brightness control, reduces

veiling glare, and plays a significant role

in enabling potential dose reduction.

The MUSICA Digital TomoSynthesis

software powers the tomosynthesis

reconstruction, automatically

presenting images with

optimal contrast

and providing

consistent image

quality across the

individual slices and

images.

March 2019 / FUTURE MEDICINE / 71


Philips launches cardio

imaging system

Royal Philips has launched

IntelliSpace Cardiovascular

4.1, its next-generation

cardiovascular image and

information management

system.

The new version builds on

the existing paediatric reporting

capabilities, recognizing the

important and unique nature

of the paediatric environment.

Clinicians can now complete

their workflows more efficiently

in a web browser, while

integration with Philips Forcare

enables the sharing of patient

data between health systems

and hospitals. IntelliSpace

Cardiovascular 4.1 aggregates

patient information into one

solution to provide a holistic

view to facilitate betterinformed

decision-making.

The addition of the webbased

paediatric module to

IntelliSpace Cardiovascular

4.1 provides a complete echo

solution that aggregates data

into one system. The paediatric

module also includes new

z-score packages, which are

a common way to chart serial

measurements in paediatric

cardiology practices.

an adjunct to other non-drug

therapeutic options.

Bioness is, currently,

enrolling patients for a US FDA

IDE study to support the use of

the system for the treatment of

OAB in the US.

Unlike traditional

treatments that include

invasive sacral nerve

stimulation systems and

externalized percutaneous

needle stimulation procedures

requiring frequent clinic visits,

the StimRouter provides

patients with a minimally

invasive, permanent treatment

that puts the patient in control

of their therapy at home.

The StimRouter procedure

requires only one small incision

and is completed in about 30

minutes while the patient is

awake under local anaesthesia.

A hand-held remote allows

patients to control their

symptoms by delivering gentle

stimulating pulses to the tibial

nerve to reduce the chronic

urge to urinate.

Kiran launches

colour doppler in

India

Kiran Medical Systems has

launched SonoRad V9 Color

Doppler in India.

SonoRad V9 can be used

for a wide range of clinical

applications.

SonoRad V9 comes

with features like 38 cm

depth penetration, 4D, real

skin imaging, tomographic

ultrasound imaging, panoramic

imaging, real-time doppler

auto-trace, anatomical

M-mode with special 3 cursors,

advanced ergonomics with

omni-directional mechanic

arm and 19” LED Monitor with

170-degree wide view.

It supports wide variety

of probes to suit major

applications like obstretics/

gynaecology and radiology.

SonoRad V9 supports

cardiology features like TDI

as well and CW/PW/HPRF

is available with supporting

probe.

US FDA okays

AdvantageRib

System

SIG Medical said the US

FDA has granted 510(k)

clearance for its enhanced

AdvantageRib System,

K183317.

This product marks the

third rib fracture 510k that SIG

Medical is commercializing.

The latest 510k features

new implants to treat

patients along the

entire

spectrum of bone quality

and modifications to existing

implants to improve surgeon

experience.

AdvantageRib, in a limited

market release, has been

utilized in over 50 rib fractures

with the first patient treated

nearly 2 years ago.

SIG Medical plans to

make AdvantageRib available

nationwide. The US full market

launch is slated to occur at

the 2019 Chest Wall Injury

Society (CWIS) Annual Meeting

where the leading experts

gather to focus on operative

care of patients with chest wall

injuries.

72 / FUTURE MEDICINE / March 2019


pharma

ADVANCED WOUND THERAPY

India will be potentially a huge market for wound care products

KAYAPAN SATYA DHARSHAN

The state of Indian pharma Industry

is wider and larger in all aspects

compared to Indonesian pharma

industry. India has its own technologies

and expertise which is being widely

acknowledged in SE Asia. The wound

care market in India has seen a huge

upsurge in recent years due to growing

incidences of untreated chronic, acute,

cancer radiotherapy and burn wounds

coupled with the largely ineffective

traditional methods of treating them.

Rising prevalence of diabetes and

cancer, attempts to lower the duration

of hospital stay in order to reduce the

healthcare expenses and the growing

inclination towards products that

enhance therapeutic outcomes are also

driving the demand for advanced wound

care products. Traditional methods of

wound treatment are still being mostly

followed and now India is covering the

wound care market in higher growth

rate.

Advanced wound care products are

designed to cure and treat complex

wounds, such as diabetic foot ulcers,

venous ulcers, and pressure ulcers.

Advanced wound management is based

on the principle of moisture therapy. In

advanced wound management, moisture

is provided to the wound site to allow

cells to heal and repair naturally. The

rising incidence of hard-to-heal wounds

and their growing adoption (due to their

high efficacy) are driving the growth of

this product segment.

MARKET DYNAMICS

Drivers

• Growing prevalence of diabetes

• Rapid growth in the geriatric

population

• Developments and innovations in

wound care products

• Increasing funding for wound care

research

• Awareness programs for wound care

treatment and management

Restraints

• High cost of advanced wound care

products

• Risk associated with wound care

products

Opportunities

• Emerging economies

• Increasing research in the field of

advanced wound care

• Potential application of stem cell

therapy in wound care

• Growing popularity of active wound

care products

Challenges

• Increasing number of acquisitions

• Survival of new entrants and small

players

Developments and innovations in

wound care products drives the

global wound care market

The development of new products

is another major factor driving the

growth of the wound care market.

The continuous development of

new products provides end users

with advanced options for wound

treatment (especially in the case of

hard-to-heal wounds).

Target Audience

• Wound care product manufacturers

• Wound care associations

• Research and consulting firms

• Distributors of wound care devices

• Contract manufacturers of wound care

products

• Healthcare institutes (hospitals,

medical schools, diagnostic centres,

and outpatient clinics)

• Research institutes

• Venture capitalists

• Insurance providers (payers)

• Government bodies

By wound type, the market is

classified into chronic wounds and

acute wounds. The chronic wounds

segment is estimated to account for

the largest share of the global wound

care market. The large share of this

segment can be attributed to the

rising incidence of diabetic foot ulcers,

pressure ulcers, and other types of

chronic wounds.

The author is Founder and

Chairman of Dermozone,

an Indonesia based

wound care and skincare

products company.

74 / FUTURE MEDICINE / March 2019


FRONTIER LIFELINE

NUTRIGENETICS CLINIC

Nutrigenetics clinic offers personalised diet after

assessing the gene-diet interaction status from

patients’ DNA samples

NARRATION: C H UNNIKRISHNAN

PHOTO: UMESH GOSWAMI

She is cute and brilliant. The

15-year-old Tess Katungi’s

favourite food is fried chicken

and finger chips. It›s her second visit to

Chennai›s well-known heart specialty

hospital, Frontier Lifeline Hospital,

and most of the doctors and staff

members at this hospital have already

become her friends as she has been

here with her mother for some days

now after a successful open-heart

surgery. Her first visit to this hospital

76 / FUTURE MEDICINE / March 2019


was almost six months ago to consult

the chief surgeon Dr K M Cherian after

she was diagnosed with a type of

congenital heart disease in Uganda,

her home nation.

Tess’s surgery was a great success.

She needs to have physiotherapy and

a couple of post-surgery check-ups

now at the hospital, and she will be

back at her school in Kampala in the

next few weeks.

But what makes Tess most happy is

that she can again have her favourite

food, chicken, which had been a strict

no-no for her since she was diagnosed

with the heart disease at a Kampala

hospital last year.

“Her nutrigenetic assessment

allows her to include chicken in her

diet, though there are a few more

things we are adding to her diet with a

personalised diet plan that will

keep her well and healthy, now as well

as in future, with no recurring health

issues,” says Tess’s dietitian at Frontier

Lifeline Hospital, which started the

country’s first nutrigenetics clinic fully

integrated with a specialty hospital

setup.

Nutrigenetics, which evaluates and

analyse gene-diet interaction status

from patients’ DNA samples to deliver

a personalised DNA-DIET, helps to

enhance treatment outcome as well as

boost and maintain desired immunity

levels to prevent diseases in future.

Pioneering Concept

Many of us still do not have much

idea about genetics in India. Thus, the

biggest challenge that this Chennai

nutrigenetics centre had to undertake

was to create awareness.

“Through genetic counselling, we

give basic introduction about the

subjects of genetics and nutrigenetics.

We explain the process involved and

what all one can expect to see as the

outcome. We also collate the incidence

of genetic diseases through family

history and the patent’s current lifestyle,

including his or her BMI and

medical history,” says Beula Daniel,

Chief Dietitian and Head - Nutrigenetics

Clinic, Frontier Lifeline Hospital.

The patients enrolled in the

clinic for nutrigenetic assessment

are also asked to do a blood test

that measures levels of lipids or

fats, including cholesterol and

triglycerides. These data would be

utilised for assessing the individual’s

current health portfolio, added

Beula Daniel.

In recent times, with the

With the technology

advancements,

especially in the area

of genomics and DNA

testing, we aim to offer

the individuals modified

nutrition based on

their genetic character

and a personalized

diet plan achieved

through informed diet

counselling.

Dr. KM Cherian

Founder and CEO

Frontier Lifeline Hospital

March 2019 / FUTURE MEDICINE / 77


slug

advancement of molecular tools,

the two branches of nutritional

genomics — namely Nutrigenetics and

Nutrigenomics — have become the

front-runners in the field of nutritional

research. Both these concepts stem

from the fact that the genetic makeup

of every individual is different. In other

words, no two individuals react exactly

the same way to a food substance,

and at the same time, no single food

substance has exactly the same impact

on the gene expression patterns of

two individuals.

According to Dr C N Ramchand,

Scientific Advisor for Frontier Lifeline

Nutrigenetics Clinic and an Adjunct

Professor, Faculty of Science,

Engineering and Technology at

Swinburne University of Technology,

Australia, Nutrigenetics aims to

identify genetic susceptibility to

diseases and the ways in which very

small difference in our genes can alter

the effects that nutrient intake has

on the body. By understanding and

analysing these variations, specific

dietary and disease prevention advice

can be given, based on personal

genetic makeup.

For example, Apolipoprotein A1

(ApoA1) plays an important role in

serum cholesterol metabolism. Studies

clearly indicate that a polymorphism

close to the ApoA1 gene determines

NUTRIGENETICS AIMS TO

IDENTIFY GENETIC

SUSCEPTIBILITY TO DISEASES

AND THE WAYS IN WHICH

VERY SMALL DIFFERENCE IN

OUR GENES CAN ALTER THE

EFFECTS THAT NUTRIENT

INTAKE HAS ON THE BODY

how polyunsaturated fatty acid (PUFA)

intake affects plasma HDL cholesterol

levels. In this context, it would make

sense for some people to consume

higher amounts of PUFAs than others,

depending on genotype, to reduce

the risk associated with cardiovascular

disease (CVD).

More specifically, Eicosapentaenoic

acid (EPA) is a PUFA which is abundant

in fish oils and is prescribed as a dietary

supplement to prevent CVD.

On the other hand, Nutrigenomics

initially concerned itself with the effects

of nutrients on the expression of an

individual’s genetic makeup.

Of late, this definition has been

broadened to encompass nutritional

factors that protect the genome

from damage. Thus, nutrigenomics is

concerned with the impact of dietary

components on the genome, proteome

and metabolome, added

Dr Ramchand.

Hospital Integrated Functioning

While several technology providers

have recently entered this novel

healthcare segment in the country,

most of them still cater to the

consumer as service aggregators and

are not attached with a hospital where

all the assessment and treatment

components are integrated for better

patient outcome.

In this context, the Frontier Lifeline

initiative is unique.

“After the enrolment, we first collect

the recommended volume of blood

sample for DNA isolation (around 3-5

ml). While the nutrigenetics report

would take 45 to 60 days, including

shipping of samples, processing and

the design of diet plans, once the

genetic interpretation is delivered,

the patients would be referred to the

inhouse cardiologist, physiotherapist

and dietitian.” said Ramya Koshi,

Genetics Counsellor at the clinic.

The assigned cardiologist would

assess the patients’ lifestyle record

and genetic results to recommend

any medical advice. Simultaneously,

the hospital’s physiotherapist would

recommend physical activities which

would be beneficial according to

78 / FUTURE MEDICINE / March 2019


the patent’s genetic result and the

dietitian would assess his or her

current lifestyle and food intake

pattern to recommend a personalised

diet plan as per the genetic result,

evaluating the nutrition requirement.

This first, integrated centre in

nutrigenetics also offers health

supplement products made in-house,

on a case to case basis, if required.

“Our food and nutrition department

has formulated and introduced

multigrain, multiprotein and golden

milk mix from 36 grains and other

natural sources. These products are

helping diabetic and cardiovascular

patients by reducing bad cholesterol,

normalising glucose levels and

boosting antioxidants and immunity

levels,” added Koshi.

The improvements from these

recommendations could be assessed

after 6 months with a blood test and

BMI analysis, she added.

Trend Setting

While patients suffering from

cardiovascular diseases, obesity,

hypertension and diabetes can do

the test to find the right diet, healthy

individuals of any age group can also

enroll in such clinics as nutrigenetics is

emerging as a trend towards precision

diet. More importantly, individuals

having a strong family history of

genetic diseases can test themselves

Through genetic

counselling, we give

basic introduction

about the subjects

of genetics and

nutrigenetics. We

explain the process

involved and what

all one can expect to

see as the outcome.

Beula Daniel

Chief Dietitian and Head

Nutrigenetics Clinic

Frontier Lifeline Hospital

to prevent the onset of such

diseases by enrolling for a genetic

diet plan.

For instance, dietary components

can selectively activate or deactivate

gene expression by inducing

changes in DNA methylation, histone

modifications and alteration in

microRNA (miRNA) expression,

without any change in the DNA

sequence (called as ‘epigenetic

regulation’). The best and most

well-studied example is Curcumin

(diferuloylmethane), a component

of the golden spice Curcuma longa,

commonly known as turmeric. It has

been determined to induce epigenetic

changes, thereby preventing various

kinds of cancer. Hence, it is quite

vivid that approaching a disease

condition with a molecular vision

definitely helps in an adjuvant

treatment modality in addition or

conjunction with the mainstream

therapy for a given condition. Also,

gaining knowledge about the genetic

makeup of every healthy individual

will undoubtedly help in preventing

diseases through the prescription

of a customized diet regimen, says

Dr Ramchand.

This is part of a series that features India’s

First & Most Unique institutions, facilities,

technologies, products etc in the medical

and healthcare space.

March 2019 / FUTURE MEDICINE / 79


esearch

COMBATING MALARIA: THE GENOMIC WAY

Genome-wide analysis of the malarial parasite provides clues on potential drug targets

ANIKET PRATAPNENI

New methods of treatment and

prevention have emerged to treat

malaria from the growing field

of genetics. The first of these methods

involves targeting the Plasmodium

genome. By conducting genome-wide

analyses, researchers have been able

to identify core genes of the malarial

parasite that offer targets for new drugs.

One of the most important of these

studies – and possibly indicative of the

future course of the disease treatment

– was conducted at the University of

Melbourne. The researchers used genetic

analysis and basic biology to discover

what could be an instrumental chink in

malaria’s armour of mutability.

Atovaquone is an anti-malarial

drug that was not under use for fear

of the development and spread of

resistance. However, the study showed

that although malaria parasites can

develop resistance to atovaquone, but

they cannot spread it. The mutation that

makes it possible to resist atovaquone

also render it impossible for the parasite

to survive the subsequent step of its life

cycle – entering a mosquito. And since

malaria cannot be transferred from one

person to another, the atovaquoneresistant

parasite cannot spread. This

illuminates a new strategy for managing

drug resistance. The mutation pathway

that results in this genetic quandary can

be targeted by drug developers while

creating new drugs.

‘Partner’ drugs

Researchers at the Wellcome Sanger

Institute and the University of South

Florida used a new, specialized

technique – piggyBac-transposon

insertional mutagenesis – to inactivate

random Plasmodium falciparum genes

and incorporated a newly developed

sequencing tool to identify the relative

importance of each gene in terms of

survival. They found that around fifty

percent (over 2,600 out of 5,400) of

the genes were essential for its growth

and propagation in erythrocytes – a list

of 2,600 targets for drug developers.

In addition, approximately 1,000 of

those 2,600 targets are common to all

Plasmodium species, and although their

exact functions are currently unknown,

their status as integral genes make them

DRUGS TARGETING GENES

WOULD BE EXTREMELY

EFFECTIVE AS ‘PARTNER’

DRUGS, WORKING IN TANDEM

WITH ARTEMISININ

potential targets for anti-malarial drugs.

Many of these genes were also found to

be involved in a proteasome pathway

that is responsible for degrading proteins

in the cell, which is thought to be

linked to artemisinin resistance. Thus,

drugs targeting these genes would be

extremely effective as ‘partner’ drugs,

working in tandem with artemisinin.

Extinction by gene drive?

The second of these new methods

involves targeting the Anopheles

genome. In a recent study, genetic

engineers used CRISPR/Cas9 to render

a population of Anopheles gambiae

mosquitos – Africa’s primary malariaspreading

mosquito species – incapable

of producing offspring within twelve

generations. Based on the results of

further trials using this tool, it could

be the first to be able to eliminate

an entire species of disease-carrying

mosquitos. The tool used to create

such a groundbreaking effect was a

gene drive. These use the CRISPR/Cas9

‘scissor’ enzyme to insert themselves

into an organism’s genome at specific

loci. This gene drive in particular exploits

a recessive Anopheles gene called

doublesex. If a female mosquito inherits

two copies of the broken doublesex

gene, it develops like a male, which

are incapable of biting – and therefore

infecting – humans. Any mosquito that

inherits only one copy of the exploited

gene will develop normally. The gene

drive was designed to circumvent the

natural laws of inheritance. Normally,

if a parent carries two different alleles

of a gene, the offspring will have a

50% chance of inheriting either one.

However, with the doublesex gene

drive, more than 95% of the offspring

inherited the exploited gene, allowing

it to spread through the population

much faster. Once all the members of

a generation carried two copies of the

gene drive – which took between 8 and

12 generations in the study – none of

the mosquitos were capable of laying

eggs or biting, forcing the population to

die out without biting other organisms.

The gene drive creates the prospect of

causing the extinction of malaria-carrying

species, which could eventually result in

the extinction of malaria itself.

Author is a student at

TISB, Bangalore. He

interned at Professor

Bobby Kasthuri’s lab at

the University of Chicago

and will be pursuing

undergraduate studies

in the field of molecular

biology.

80 / FUTURE MEDICINE / March 2019


Ultrasound

All-in-one imaging.

Complete solution.

Breast cancer is the most common cancer among women, early detection is key

to saving lives. Introducing eL18-4, a single probe solution for breast assessment.

It allows clinicians to effectively assess, monitor and treat breasts diseases;

PureWave crystal technology on

eL18-4 enables transducer to achieve

superb clinical performance across

various patients including technically

difficult patients.

Complete Elastography solutions for

rapid assessment of whole array of

breasts lesions with enhanced

confidence.

Anatomical intelligence facilitates

breast exam while preserving superb

image quality.

Assess

Monitor

Treat

New precision biopsy capabilities

reduce needle blind zone and

ensures enhanced display of needle

reflections.

For more information, please visit:

www.philips.co.in/healthcare or call 1800-419-8844 (Toll Free)


products

DALETHYNE: NEW HOPE

IN WOUND CARE!

Dalethyne derivatives allow unhindered execution of the healing process

Wound and skin care is one of

the fast-emerging markets in

India for innovative products

not only from within the country but

also from outside. These areas of care,

which saw several new releases in the

recent past, has seen the launch of

an innovative series from Indonesia,

giving new hope for clinicians who

treat unsolved chronic and acute burn

wounds. These products, developed

around the key ingredient—dalethyne

and its derivatives, work on the

basis of their interaction with the

proteins that regulate wound healing in

the human body.

According to the innovator, PT

Dermazone Pratama Indonesia,

dalethyne is a breakthrough in

medicinal science. Obtained from a

process of fatty acid segregation of

extra virgin olive oil, dalethyne has

proven with anti-microbial, fungicidal

and antiviral qualities with deep-skin

penetration.

Kayapan Satya Darshan, the

inventor of dalethyne and the

founder and chairman of Dermazone

Pratama, said that these molecules —

synthesized in-house — were docked

with various proteins involved in the

process of wound healing and the

binding energies of the molecules were

calculated by the prediction of their Ki

values.

“Dalethyne derivatives exhibited

sufficient propensity to inhibit the

inflammation-causing agents and at the

same time allow unhindered execution

of the healing process,” he said in an

interview with Future Medicine.

“It has proven anti-microbial,

fungicidal and antiviral quality

with deep skin-penetrable quality.

Investigations have revealed that

82 / FUTURE MEDICINE / March 2019


dalethyne reduces inflammation and

accelerates wound healing,” he added.

A research paper* published in

Science PG in 2018 validates the

docking methodology of dalethyne

saying: “The binding interactions of

the molecules thus calculated were

compared with that of the native

ligand.”

The report states that, in the

normal wound healing process,

platelet activation after the wound

appearance causes the release of a

pro-inflammation cytokine such as

TNF-α and IL-1β, which will activate the

macrophage.

“The wound will also activate

MMP-9 and COX-2. The further

release of IL-1β and IL-6 will inhibit

the fibroblast production, keratinocyte

proliferation and migration; which

will delay the epithelization and

granulation process. The inhibition of

the fibroblast proliferation will cause

a decrease of FGF-2 synthesis and

therefore will also decrease the TGF- β1

expression regulation. This process will

cause a decrease of endothelial cell

proliferation and thus will delay the

neoangiogenesis and vasculogenesis.

At the same time, these phenomena

will delay the wound healing process. In

the present work, dalethyne derivatives

have been predicted to have the ability

to suppress the inflammation-causing

agent, such as MMP-9 and COX-2.

It could also lessen the increased

oxidative stress and modulate the

expression of the growth factors (FGF-2

and TGF-β1) and inflammation mediator

(IL-1β and IL-6), which helps to fix the

wound healing process. In the purview

of the pharmacology involved in the

wound healing process, it was observed

that the dalethyne derivatives showed

effective interactions with the amino

acid residues present in the active site

of the proteins, MMP-9 and COX-2. This

accounted for the conducive inhibitory

effects of these molecules towards the

respective receptors,” the report said.

Moreover, the simple structure of

the dalethyne derivatives resembling

the native ligand attributed to the

inability to these molecules to bind with

the proteins involved in the process of

cell proliferation and re-epithelization.

From these observations, it can thus be

inferred that the dalethyne derivatives

exhibited sufficient propensity to inhibit

the inflammation-causing agents and

at the same time allow unhindered

execution of healing process, the paper

cited.

“The results thus provide an insight

Investigations have

revealed that dalethyne

successfully reduces

inflammation and

accelerates wound healing.

Kayapan Satya Darshan

Founder and Chairman

Dermazone Pratama

for the structure of the dalethyne

derivatives that would facilitate their

activity as wound healing agents.

Subsequently, the in-house synthesized

molecules can be suitably formulated

into a pharmaceutical dosage form

that can be efficiently used for

the treatment of different types of

wounds,” Science PG paper concluded.

“Investigations have revealed

that dalethyne successfully reduces

inflammation and accelerates wound

healing. It has been patented in several

countries under my name and this

patent is certified as a Novel Innovation

Patent in Geneva,” Satya Darshan

confirms.

The Jakarta-based company, which

has also introduced a range of nonprescription

products, including acne

wax, face wash and face scrub along

with a series of baby care products.

It has appointed Delhi-based Alniche

Life Sciences, a specialty healthcare

company, to handle its marketing and

sales of its wound care products. The

company is also in talks with Indian

companies to market its consumer

health products.

* Kayapan Satya Dharshan. Docking Studies

for Assessment of Wound Healing Potential of

Dalethyne Derivatives: An in-silico Approach.

Computational Biology and Bioinformatics.

Vol. 6, No. 2, 2018, pp. 36-50. doi: 10.11648/j.

cbb.20180602.12

March 2019 / FUTURE MEDICINE / 83


guidelines

ASBrS RECOMMENDS GENETIC

TESTING FOR ALL PEOPLE

WITH BREAST CANCER

All patients with a

diagnosis of breast

cancer should undergo

expanded panel testing,

proposes the new

consensus guideline

by American Society of

Breast Surgeons

American Society of Breast

Surgeons (ASBrS) has released

Consensus Guideline on

Genetic Testing for Hereditary Breast

Cancer in February 2019. Literature

review included large datasets, basic

science publications, and recent

updated national guidelines.

Recommendations:

1. Breast surgeons, genetic

counsellors, and other medical

professionals knowledgeable in

genetic testing can provide patient

education and counselling and make

recommendations to their patients

regarding genetic testing and arrange

testing

When the patient’s history and/or

test results are complex, referral to a

certified genetic counsellor or genetics

professional may be useful. Genetic

testing is increasingly provided through

multi-gene panels. There are a wide

variety of panels available, with different

genes on different panels. There is

March 2019 / FUTURE MEDICINE / 85


a lack of consensus among experts

regarding which genes should be tested

in different clinical scenarios. There is

also variation in the degree of consensus

regarding the understanding of risk and

appropriate clinical management of

mutations in some genes.

2. Genetic testing should be made

available to all patients with a personal

history of breast cancer

Recent data support that genetic

testing should be offered to each

patient with breast cancer (newly

diagnosed or with a personal history).

If genetic testing is performed, such

testing should include BRCA1/BRCA2

and PALB2, with other genes as

appropriate for the clinical scenario and

family history. For patients with newly

diagnosed breast cancer, identification

of a mutation may impact local

treatment recommendations (surgery

and potentially radiation) and systemic

therapy. Additionally, family members

may subsequently be offered testing

and tailored risk reduction strategies.

3. Patients who had genetic testing

previously may benefit from updated

testing

Every patient being seen by a

breast surgeon, who had genetic

testing in the past and no pathogenic

variant was identified, should be

re-evaluated and updated testing

considered. In particular, a patient

who had negative germline BRCA1

and 2 testing, who is from a family

with no pathogenic variants, should

be considered for additional testing.

Genetic testing performed prior to

2014 most likely would not have had

PALB2 or other potentially relevant

genes included and may not have

included testing for large genomic

rearrangements in BRCA1 or BRCA2.

4. Genetic testing should be made

available to patients without a history

of breast cancer who meet NCCN

guidelines

Unaffected patients should be

informed that testing an affected

relative first, whenever possible, is

more informative than undergoing

testing themselves. When it is not

feasible to test the affected relative

first, then the unaffected family

member should be considered for

testing if they are interested, with

careful pre-test counselling to explain

the limited value of “uninformative

negative” results. It is also reasonable

to order a multi-gene panel if the

family history is incomplete (i.e., a case

of adoption, the patient is uncertain

of the exact type of cancer affecting

family members, among others) or

other cancers are found in the family

history.

5. Variants of uncertain significance

are DNA sequences that are NOT

clinically actionable

This type of result needs to be

considered as inconclusive, and the

patient should be managed based on

their risk factors and not influenced by

this result.

Summary of data reviewed

The National Cancer Institute estimates

for 2018 were that more than 266,000

new cases of invasive breast cancer

would be diagnosed in the US, and

more than 40,000 patients would die

from the disease. Approximately 10%

of breast cancers are associated with

a pathogenic germline variant in one

of several different genes. More than

50% of pathogenic germline variants

are mutations in the BRCA1 and BRCA2

genes. Using genetic testing to identify

patients who are at increased risk to

develop breast cancer enables patients

to take steps to reduce this risk. There

are several risk management strategies

available for individuals at increased

risk (e.g., chemoprevention along with

enhanced screening; risk-reducing

surgeries).

Unfortunately, in the current state of

medical practice, a significant number

of pathogenic mutation carriers remain

undetected and undiagnosed. These

are largely women with “moderate

86 / FUTURE MEDICINE / March 2019


BREAST

CANCER IN US

Every patient being seen by

a breast surgeon, who had

genetic testing in the past and

no pathogenic variant was

identified, should be

re-evaluated and updated

testing considered

266,000

new cases of invasive

breast cancer would be

diagnosed

40,000

patients would die

from the disease

SOURCE: THE NATIONAL CANCER INSTITUTE

penetrance” mutations, but even

women with BRCA1 or 2 mutations may

not be identified. There is an unmet

challenge to improve our identification

and diagnosis of patients who have an

inherited increased lifetime risk of breast

cancer.

Access to genetic counselling and

testing

There are fewer barriers to genetic

testing now than previously, and testing

is less costly and being offered by more

labs. The indications for who should

be offered testing are ever increasing -

each guideline update casting a wider

net, and there is more public awareness.

However, some barriers remain - one

of which is the limited availability of

genetic counselling nationwide for

patients and their family members.

Increased access to testing would likely

lead to more patients pursuing testing

and improving rates of identification of

gene carriers. Breast surgeons are well

positioned to be a resource for patients

who may benefit from testing. Breast

surgeons can identify individuals who

are suitable for testing, inform patients

of the risks and benefits, provide

access to genetic testing, and also

discuss risk management strategies for

those patients who test positive. For

patients with less common mutations,

strong consideration should be given

to consultation with cancer genetics

specialists.

Hereditary breast cancer

syndromes

Hereditary mutations to be considered

include BRCA 1&2, PALB2, and other

hereditary breast cancer syndromes,

which include but are not limited

to Li-Fraumeni syndrome (TP53

pathogenic variant), Cowden syndrome

(PTEN pathogenic variant), Hereditary

diffuse gastric cancer syndrome (CDH1

pathogenic variant), and Peutz-Jegher

syndrome (STK11 pathogenic variant).

Impact of genetic testing results on

management recommendations

10%

breast cancers are

associated with a

pathogenic germline

variant in one of several

different genes

Identification of patients with

pathogenic variants in these genes can

influence patient management in terms

of high-risk screening and risk reduction

as well as therapeutic options related

to surgery, radiation, and systemic

therapies. For example, identifying that

a breast cancer patient has a BRCA1

pathogenic variant provides that patient

the opportunity to learn of her elevated

risk for contralateral breast cancer as

well as of ovarian cancer and to make

educated decisions to reduce those

risks.

Studies are underway to determine

whether these patients also might

benefit from PARP inhibitors being

included in their adjuvant therapy

regimen. Another example is that

radiation is relatively contraindicated

in patients with TP53 pathogenic

variants (associated with Li-Fraumeni

Syndrome) due to their increased risk of

developing radiation-induced secondary

malignancies. Identifying a patient who

has a pathogenic variant that indicates

high hereditary breast cancer risk

can have a profound impact on that

patient’s health and management.

Additionally, it has a potential

impact on that patient’s family

members who should be counselled

to consider testing for the mutation

identified in the family, the result of

which can guide their risk of breast

cancer development and consideration

of risk management strategies. The

genetic testing information should be

considered together with the details of

each patient’s case including age, family

history, medical history, and contributing

risk factors, as well as careful review

of existing management guidelines. It

is important to understand that risk

of development of breast and other

cancers and risk management guidelines

vary both by the mutated gene and

the penetrance of the specific genetic

mutation. Additionally, not all pathogenic

variants identified are medically

actionable. Just because a hereditary

pathogenic mutation that predisposes

to breast cancer is identified does not

mean that the risk-reducing mastectomy

March 2019 / FUTURE MEDICINE / 87


is indicated.

Risk-reducing mastectomy can be

considered in BRCA1, BRCA 2, PTEN,

and TP53. Consideration may also be

appropriate for patients with mutations

in other genes when combined with

a significant family history of breast

cancer. Patients with BRCA1 or BRCA2

pathogenic variants should consider

risk-reducing bilateral salpingooophorectomy

after child-bearing or

between the ages of 35-40 to reduce

ovarian and fallopian tube cancer risk.

Women with BRCA1 should consider

oophorectomy between ages 35-40,

while BRCA2 carriers should consider

it between ages 40-45. Prophylactic

oophorectomy in premenopausal

women with BRCA2 pathogenic variants

has also been shown to reduce the risk

of breast cancer by about 50%. There

is also breast cancer risk reduction from

RRSO in BRCA1 patients but to a lesser

degree.

For patients with mutations in

ATM, CDH1, CHEK2, NBN, NF1, PALB2,

and STK11, enhanced screening is

recommended; however, currently, the

data are not sufficient to support riskreducing

mastectomy in the absence

of other factors such as a strong family

history. There are substantial gaps in

our ability to predict individual risks

associated with mutations in some of

these genes. Risk is modulated by age,

family history, and in some cases, the

specific mutation in a particular gene.

For the aforementioned syndromes, the

guidelines broadly support considering

mammography with tomosynthesis and

breast MRI with and without contrast for

annual screening due to the elevated

risk for breast cancer.

For BARD1, MSH2, MLH1, MSH6,

PMS2, EPCAM, BRIP1, RAD51C, RAD51D,

there are some data suggesting an

elevated lifetime risk of breast cancer;

however, there is insufficient evidence to

support the change in breast cancer risk

management based on the presence

of a mutation alone. Mutations in

these genes may be associated with

an increased risk of gynaecological

cancers, which may warrant specific

management. MSH2, MLH1, MSH6, and

PMS2 are associated with the Lynch

Syndrome, a multi-organ predisposition

syndrome that requires multidisciplinary

management. The list of actionable

genes and recommendations for

screening and risk management

continually evolves as additional

information becomes available.

Limitations of genetic testing

Health care providers and patients

need to know that genetic testing

is one of several tools for assessing

breast cancer risk. Not every genetic

test yields a straightforward answer

with clear guidance on how to proceed

for optimal care. Patients should be

made aware that negative test results

do not necessarily mean they are not

IT IS CRITICAL TO LOOK

BROADLY AT THE PATIENTS’

OTHER CONTRIBUTING

FACTORS, SOME OF WHICH

ARE: AGE, MEDICAL HISTORY,

LIFESTYLE, EXPOSURES, AND

FAMILY HISTORY

at increased risk for developing breast

cancer. Many factors contribute to a

patient’s lifetime risk of breast cancer,

and genetic testing is an effort to

better define one of these elements

(the measurable inherited risk). When

counselling patients about their lifetime

risk of breast cancer, it is critical to

look broadly at the patients’ other

contributing factors, some of which are:

age, medical history, lifestyle, exposures,

and family history.

For patients who test positive for

a pathogenic variant, it is important

to gain a detailed understanding of

that variant when advising on risk

management strategies – details such as

the penetrance of the cancer risk among

carriers (how likely is the patient to

actually develop breast cancer).

Penetrance varies among the

identified hereditary cancer syndromes.

In other words, not all carriers of

pathogenic genetic variants will develop

breast cancer, and the level of risk varies

with the gene affected and likely the

variant as well. For example, some types

of CHEK2 and ATM variants have low

penetrance while other types are more

highly penetrant. Just because a patient

test positive for a hereditary breast

cancer syndrome does not mean that

the patient will develop breast cancer.

It is important to note that these

calculators are constrained by the

limitations of the studies that provide

the underlying odds ratios used to

generate the absolute risk estimates and

do not account for modification of those

odds ratios by age, mutation position,

family history, or polygenic background

risk.

Pre-and post-test counselling

Before testing, patients need to

be made aware of the implications

that the test result can have (pretest

counselling); and when results

become available, patients should be

reminded of these implications and

be provided the appropriate clinical

context for the results to make informed

decisions (post-test counselling). All

genetic testing should be performed

in the setting of informed consent.

The American College of Surgeons

Commission on Cancer accreditation

program mandates that cancer risk

assessment, counselling, and genetic

testing services be provided to patients

by a physician who does risk assessment

regularly and/or is qualified to do testing

or a qualified genetic professional either

on site or by referral.

A systematic review of the literature

indicates that pre-test counselling,

whether by a geneticist, breast

surgeon, oncology nurse, or other

medical professional with expertise and

experience in cancer genetics reduces

distress, improves risk perception

accuracy, and improves follow through

for testing.

Breast surgeons who are

88 / FUTURE MEDICINE / March 2019


Current rates of

identifying a VUS with

newer multi-gene panel

testing is reported to be

between

6.7-41.7%

knowledgeable in cancer genetics

can initiate and guide genetic testing

for their patients. Pre-test counselling

should include discussion of the types of

results (true positive = pathogenic, true

negative = benign (although without a

known positive in a family, it may also be

inconclusive as well), and inconclusive =

variant of uncertain significance (VUS)).

Other potential issues of testing should

also be reviewed, such as inconclusive

results, misperception of true risk, and

discrimination.

Patients

need to

know there are

limitations to this

testing including noninformative

results or negative

tests as well as the reality of the

evolving science. It is important to

educate patients on the benefits of

testing as a vehicle to knowing better

their individual risk and empowerment

to consider interventions to manage or

reduce that risk. It can be helpful to set

expectations for when the test results

will be available.

Post-test counselling is important

regardless of the actual result. The

current best practice is for all patients

who undergo genetic testing to have

some form of post-test counselling.

By NCCN guidelines, this can occur

in person or remotely. This allows for

patients’ questions to be answered and

for a thorough debriefing. If a result is

negative or non-informative (such as a

variant of uncertain significance – VUS)

then the patient’s other risk factors for

breast cancer (age, medical history,

family history, etc.) need to be evaluated

to formulate the appropriate risk

management plan.

Depending on the level of risk for

breast cancer, strategies to manage

that risk can be discussed, including

enhanced screening imaging (annual

mammogram and breast MRI);

chemoprevention (endocrine therapy

to lower risk); lifestyle modification with

respect to obesity, tobacco use, and

alcohol consumption; and exogenous

hormone use among others.

For patients who test positive for

a pathogenic variant, a clear review of

the state of evidence for that specific

syndrome is imperative. To make

educated decisions, patients need

to know about the spectrum of risk

management strategies. Ultimately, a

customized plan for the patient is the

goal with their informed consent. In this

discussion, a frank statement of the level

of risk reduction for each intervention

is needed. For example, risk-reducing

mastectomy and reconstruction in a

BRCA1-positive 35-year-old patient

leads to much greater risk reduction for

breast cancer mortality than that same

intervention in a 65-year-old patient.

The surgeon should discuss these

issues and refer to other specialists

(such as gynaecologic oncologists,

gastroenterologists, etc.) for other

organs at risk as appropriate. For

90 / FUTURE MEDICINE / March 2019


complex

scenarios, referral to

a genetics professional

is recommended.

Multi-gene panel testing

Genetic testing has expanded in scope

and availability since 2013 when the

U.S. Supreme Court ruling in Association

for Molecular Pathology v. Myriad

Genetics, Inc. increased the testing

options. Increased competition has

helped to lower the cost. Improvements

in technology, like next-generation

sequencing, has made testing for more

than one gene at a time a reality. which

can improve the cost-effectiveness and

efficiency of testing.

While BRCA1 and BRCA2 remain

the most likely genes to be mutated in

a family with high breast and ovarian

cancer risk, panel testing can allow

for more comprehensive coverage of

less common syndromes that can also

confer hereditary cancer risk. Numerous

recent studies have shown that panel

testing can significantly increase the

rate of detection of pathogenic variants,

with the most frequently identified

pathogenic variants (outside of BRCA1

and BRCA2) being in PALB2, CHEK2,

and ATM.

There is a comparatively limited

understanding of individual breast

cancer risk associated with mutations

in genes other than BRCA1 and BRCA2.

However, the presence of mutations

in PALB2, ATM, truncating mutations

in CHEK2, and possibly other genes

are likely to be associated with lifetime

breast cancer risks of greater than

20% and therefore, in the US, at least

support a decision for enhanced

surveillance with annual mammography

with tomosynthesis and breast MRI

with contrast. Mutations in other

genes may also reach this threshold,

although the rarity of such mutations

and the possibility of subtype-specific

predisposition make risk estimation

more challenging. A multi-gene panel

may include genes with varying degrees

of evidentiary support and “actionability.”

This testing method is optimal when

the individual genes included are

clinically valid and comprehensively

address the details of each patient’s

case. Panel testing can be considered

for patients who qualify for hereditary

breast cancer testing to more efficiently

and cost-effectively evaluate genes that

confer risk and impact management

recommendations.

When genetic testing is being

recommended based on phenotypic

syndromes (for example three or more

close family members affected by

breast cancer at any age) then multigene

panel testing is likely to be more

efficient in evaluating patients. In fact,

THE PRESENCE OF MUTATIONS

IN PALB2, ATM, TRUNCATING

MUTATIONS IN CHEK2, AND

POSSIBLY OTHER GENES ARE

LIKELY TO BE ASSOCIATED

WITH LIFETIME BREAST

CANCER RISKS

the most recent NCCN guidelines allow

that panel testing will largely replace

sequential gene sequencing (i.e., the

older approach of evaluating BRCA

pathogenic variants first, then selecting

additional genes if BRCA tests are

negative).1 Insurance companies are

urged to incorporate the advantages

of panel testing into their algorithms

to allow hereditary cancer syndrome

testing for patients at high risk.

Surgeons, genetic counsellors, and

other health care professionals who

order panel testing for breast cancer

patients or their family members should

at a minimum test the breast cancer

genes that are clinically actionable given

the current state of medical evidence.

Testing of additional genes can also

be performed at the discretion of the

ordering physician or as directed by the

family history.

Variant of uncertain significance

Variants of uncertain significance are

DNA sequences that are not clinically

actionable. This type of result needs

to be considered as inconclusive. For

example, a patient who receives a

genetic testing result of “BRCA1 variant

of uncertain significance” should not

be recommended for a change in

management based on that test result

alone. No clinical treatment plan or risk

management plan should be influenced

by a VUS. These are DNA sequences

about which the lab is still accruing data

for definitive classification as to benign

or pathogenic.

The vast majority are re-classified

as benign when enough data are

collected. Usually, it takes several years

for the reclassification to take place. The

American College of Medical Genetics

has published guidelines for reporting

DNA sequence variations. The rate of

identifying VUSs can be high when

new syndromes are identified but

that rate decreases as data regarding

those genes and the VUSs are accrued.

Current rates of identifying a VUS with

newer multi-gene panel testing is

reported to be between 6.7-41.7%.

There are still VUSs identified with

BRCA1/2 testing. However, the rates

are generally much lower, ranging from

2-5%, now that testing of these two

syndromes has been available for more

than 20 years. In general, patients with

VUSs should be managed based on

their family history, medical history, age,

and other factors that influence breast

cancer risk. No weight should be given

to the VUS found, and co-segregation

among affected family members is not

conclusive evidence of pathogenicity.

This statement was developed by

the panel members on February 10,

2019.

—Courtesy: American Society of Breast

Surgeons

March 2019 / FUTURE MEDICINE / 91


events

ICACSB-2019 calls for innovation

in biopharmaceuticals

The three-day meet re-emphasizes the need for developing

new drugs and antibiotics

FM BUREAU, CHENNAI

Bacterial resistance to existing

antibiotics is a severe problem

in the field of medicine at

present. Structural studies on

ribosomes from multi-resistant

bacteria and comparisons to previous

ribosome structures revealed novel

structural motifs, essential for protein

biosynthesis. These are not located

in the primary ribosomal active sites,

hence there is no effective mechanism

for their modification, which leads to

resistance to antibiotics. These findings

prompted the design of antibiotics

with desired structures that can be

optimized in terms of their chemical

properties, toxicity, cellular penetration

IN ORDER TO OVERCOME THE

PROBLEM OF BACTERIAL

RESISTANCE, ANTIBIOTICS

NEED TO BE MODIFIED AND

NEW DRUG DISCOVERY

PURSUED

and species-specificity, said Israeli

Nobel Laureate Prof. Ada E Yonath,

reiterating her views on the urgent

need for quick and specific efforts on

the development of new antibiotics.

She was delivering her keynote

address at the 5th International

Conference of Advanced Chemical and

Structural Biology organised by PRIST

Deemed University.

Echoing similar views, Prof TP

Singh, Department of Biophysics, All

India Institute of Medical Science, New

Delhi, said that in order to overcome

the problem of bacterial resistance,

antibiotics need to be modified and

new drug discovery pursued.

Delivering his keynote lecture on

the topic — Protein Antibiotics as New

Generation Weapons Against Invading

Microbes — Singh added: “Here we

propose an entirely new concept of

introducing innate immune proteins

from different species. It has been

well known that the proteins of the

innate immune system provide the

first line of defence against infecting

microbes. These proteins recognize the

conserved motifs that are present on

92 / FUTURE MEDICINE / March 2019


the cell walls of bacteria.”

The three-day conference, which

consisted of six plenary sessions, five

keynote addresses, 15 short lectures

and 117 posters, brought together

several scientists from countries that

were hitherto unrepresented in the

conference.

Senior scientists from premium

research institutions in countries such

as Israel, South Korea, Japan, France,

China, Singapore, Sweden, Germany,

USA and India participated in the

conference.

“The objective was to effectively

spread the message of chemical

and biological science researchers

all over the world. It also offers new

networking opportunities amongst

scientists and young research scholars

from all over the world to create an

immense outreach for academic

circles and research industries,”

informed Dr Dhurairajan Senthilnathan

from Center for Computational

Chemistry, PRIST University, and

convener, ICACSB.

Presenting a plenary lecture on

Noncanonical DNAs: Structure, function

and modulation, Kyeong Kyu Kim from

Department of Molecular Biology,

Sungkyunkwan University School of

Medicine, South Korea, said that most

DNA in the genome is considered

to be present as B-form, but new

evidence suggests that DNA structures

are highly polymorphic. “Therefore,

We propose an

entirely new concept

of introducing innate

immune proteins from

different species.

Prof TP Singh

Department of Biophysics

AIIMS, New Delhi

many sequence-specific noncanonical

DNA or non-B DNA conformations

transiently exist in the genome,

often in response to changes in the

cellular environment or when bound

to proteins, and thus their presence

or mutation is relevant to various

diseases, including tumours.”

Keeping abreast of advancements

in chemical and structural biology

is key to making significant inroads

to attack problems that have an

interdisciplinary nature, and provides

a research base for advancing

biopharmaceutical research. The

innovations and research in this field

are already impacting the society

positively and hence we could expect

more innovations that will contribute

to the sustainability of human beings

in this century, said Dr N Ethirajalu, vice

chancellor, PRIST University.

March 2019 / FUTURE MEDICINE / 93


ADVERTORIAL

Magnetom Lumina3 Tesla (3T)

magnetic resonance imaging

The Magnetom Lumina is a new 3 Tesla

(3T) magnetic resonance imaging (MRI)

system that features BioMatrix patient

personalization technology which

significantly improves productivity while

ensuring consistent quality.

The Food and Drug Administration

(FDA) has cleared the Magnetom

Lumina 3 Tesla (3T) magnetic resonance

imaging (MRI) scanner from Siemens

Healthineers.

The system has a wide, 70-cm bore and

GO technologies powered by artificial

intelligence (AI), which accelerate the

entire MRI workflow. For example, a

whole spine exam can be performed

up to 20 percent faster compared to a

conventional system.

Tim 4G and Dot (Day Optimizing

Throughput) engines support

standardized, highly reproducible

scan procedures. To further facilitate

workflow efficiency, the system features

an optional dockable table. Additionally,

new Turbo Suite acceleration packages

can further reduce scan time on routine

musculoskeletal (MSK) examinations

of various parts of the body by up to 50

percent.

The Magntom Lumina will also

offer the optional Innovision in-bore

infotainment system, which is designed

to move with the scanner table to not

only create the illusion of an enlarged

bore, but also to provide a unique video

experience with excellent sound quality.

The optional audio/video system provides

entertainment for patients, which is

particularly beneficial when working with

children and impatient adults.

FEATURES

New Turbo Suite: Turbo Suite enables

dramatic reductions in exam times by

exploiting advanced accelerated imaging

techniques.

GO technologies & BioMatrix

technology: GO and BioMatrix

technologies, both supported by

AI, further boost efficiency through

automation by reducing numerous timeconsuming

workflow steps.

Dot Engines: Eight available Dot

engines—covering routine scans from

head to toe— ensure consistent exams

between patients and across time.

BioMatrix Tuners: BioMatrix tuners

overcome variations by automatically

adjusting to the individual patient.

Syngo Virtual Cockpit: Syngo MR XA

software platform and game-changing

syngo Virtual Cockpit3 provide the right

tools to achieve consistency across your

entire MR system fleet.

Innovision: Innovision, a revolutionary

in-bore, infotainment and noise

cancellation solution, enhances the

patient exam experience.

Coil portfolio: The Tim 4G coil portfolio

with its lightweight, breathable coils

supports patient comfort and simplifies

set-up times by easily adapting to

anatomy. Free-breathing and accelerated

exams help reduce patient stress and

get them back to their daily routine

faster.

New 3Tesla magnet and other

Innovative service offerings

The system enables for a wide clinical

application by delivering productivity

gains and reproducible results.

This is a sponsored article. FM editorial holds no responsibility for the information therein.

94 / FUTURE MEDICINE / March 2019


calendar

Upcoming conferences

MARCH

1-2 GASTROENTEROLOGY

ISTH–ILBS Symposium on

Coagulopathy in Liver Disease

2019

New Delhi

1-3 GYNECOLOGY

ISAR Conference

Mumbai

2-3 GASTROENTEROLOGY

ISTH–ILBS Symposium on

Coagulopathy in Liver Disease

2019

New Delhi

2-3 HEPATOLOGY

Master Class in Liver Disease

Edition (MCLD)

Chennai

8-10 NEUROLOGY

ISAR Conference

New Delhi

8-10 DIABETES

International Diabetes Summit

(IDC)

Pune

8-10 NEUROLOGY

Joint Annual Conference of

Indian Epilepsy Society and

Indian Epilepsy Association

New Delhi

9-10 GYNECOLOGY

India Fertility Show-2019

Bangalore

9-11 IMMUNODEFICIENCY

DISEASES

International Conference on

Primary Immunodeficiency

Diseases

Mumbai

11-12 CARDIOLOGY

ICCA Stroke 2019 - Acute Stroke

Interventions and Carotid

Stenting

New Delhi

16-17 NEUROSURGERY

Indo Japan Neurosurgical

Meeting (IJNM)

Secunderabad

24-25 EDUCATION & TRAINING

International Conference on

Medical & Health Science

(ICMHS)

Pune

28-29 EDUCATION & TRAINING

28-

Mar 3

International Conference on

Medical & Health Science

(ICMHS)

Panjim

CARDIOLOGY

India Live Conference

Mumbai

APRIL

4-6 SPINE CONGRESS

Spine Congress

New Delhi

5-7 ORTHOPEDICS

3rd Annual Jaipur Shoulder

Knee Course (JSKC)

Jaipur

7 HEALTHTECH

Hitcon South Gujarat

Surat

19-20 WELLNESS AND

HEALTHCARE

National Conference on

Healthcare Management

(Symhealth)

Pune

27-28 GYNAECOLOGY

Hysterectomy Summit

Mumbai

26 HEALTHTECH

Futuristic Healthcare Summit

(FHS)

Bengaluru

29-30 MEDICAL T RAINING

International Conference on

Medical & Health Science

(ICMHS)

Chennai

MAY

3-5 MED EQUIPMENT

MEDIKO India (MEDIKA)

Hyderabad

23 CLINICAL TRIAL

Annual Clinical Trials Summit

(Clinical Trials Asia)

Mumbai

26-11 PHYSICAL THERAPY

FM UQ: Functional Mobilization

Upper Quadrant

New Delhi

23-24 CLINICAL GENETICS

CRO/Sponsor Summit 2019

Hyderabad

31-2 NEUROLOGY

Asian And Oceanian Myology

Center Meeting (AOMC Meeting)

Mumbai

JUNE

7-9 GYNAECOLOGY

Annual Conference of the Indian

Association of Gynaecological

Endoscopists

Ahmedabad

8-9 OPHTHALMOLOGY

28-30 EXPO

National Conference on

Community Ophthalmology

Chennai

India Med Expo (IME)

Bengaluru

JULY

4-7 ANAESTHESIOLOGY

9th National Conference of

the Academy of Regional

Anaesthesia of India

Coimbatore

5-6 MICROBIOLOGY

World Congress on Microbial

Infectious Diseases

Goa

5-7 DERMATOLOGY

Dermatology and Allied

Specialites Summit (DAAS)

New Delhi

5-7 DERMATOLOGY

Dermatology and Allied

Specialites Summit (DAAS)

New Delhi

AUGUST

3-4 OPHTHALMOLOGY

Ophthall (OPH)

Hyderabad

3-4 SURGERY

World Congress & Summit on

Surgery

New Delhi

3-5 OPHTHALMOLOGY

India International Optical &

Ophthalmology Expo (IIOO

EXPO)

Hyderabad

9-11 CARDIOLOGY

Echo Nagpur Summit

Nagpur

The announced dates of the conferences may change

96 / FUTURE MEDICINE / March 2019


YOU CAN’T FIND PATIENTS’ FEAR,

ANXIETY AND PAIN IN ANY LAB REPORT

PROF K RAJASEKHARAN NAIR

Eminent neurologist and well-known writer

As a medical teacher who had his initial medical

training in the early 1960s, and then taught

post- and post-postgraduate medical students

throughout his teaching career, I have seen implausible

advances in imaging technologies, electrophysiological

studies, investigative and therapeutic tools and the

entry of molecular and genetic engineering in medicine.

In the bargain, good old clinical medicine with a

stethoscope, a knee hammer, a tuning fork and pins and

needles has gradually withered away. But the rituals

of using these instruments are continued, to pretend

that clinical medicine methods are still practiced. In

many large hospitals, the medical history of patients is

taken by the junior-most doctors or the nurses who are

overburdened by their routine work. They stick to the

protocols of history-taking given in each specialty.

The patients are in awe of these protocols and they

forget to tell their problems. The youngsters have

forgotten the usefulness and the palliative nature of

haptics as no one now teaches how to touch or feel

the patients. Nor do they realize that a compassionate

hearing can have a curative effect and that a kind touch

can alleviate pain.

For them, after all, clinical medicine is dead already.

Is it really so?

In the final count, medicine is, as it always was, a

deep transaction narrowed down to two - the patient

and the doctor: One trying to comfort and heal, and

the other seeking the same. The plethora of lab results,

imaging reports and histopathological studies mean

very little to the patient who sits across the table of

the doctor or lies down on the hospital bed diseased,

desolate and depressed. His fears, anxiety, anger and

sadness are not reflected in any of the reports which his

doctor received from his labs. He is not really bothered

whether his brain tumour is glioblastoma multiforme or

a glioma grade 2.

He prays and expects his doctor would tell him

that he would recover soon. Soothing words could be

placebos as well.

These days, it is mandatory that all relevant

investigations are prescribed, and new treatment

technologies used, to treat ailments. They certainly help

to arrive at correct conclusions and definite diagnoses.

But patients should never be told about their ailments

and the treatment planned in a rough manner. After

all, like placebos which please the people, there are

nocebos too (which bring pain, distress and anguish)

both in drugs and dialogues.

Why can’t we at least show some humaneness and

empathy even if the patient has a fatal illness?

The doctors too will become patients one day or the

other, and then only, will they know the anxiety, the fear

of mortality and the terrible unpleasantness of the pills

given, cuttings done and inexorable bills they accrue for

the diseases.

98 / FUTURE MEDICINE / March 2019


Sep 30 th - Oct 2 nd , 2019 - Mumbai, India

REGISTRATIONS OPEN

Early bird ends on

15 th June, 2019

Abstract submission

ends on 1 st July, 2019

NextGen Genomics, Biology, Bioinformatics and Technologies (NGBT) Conference is an international

meeting organized by SciGenom Research Foundation (SGRF), a not-for-profit organization working to

promote Science, Research and Education in India and rest of Asia.

HIGHLIGHTS

• Learn about cutting edge developments in

genomics, biology, bioinformatics, drug

discovery, plant and animal sciences

• Network with scientists of global repute

• Meet national and international genomics,

biology and technology companies

• Interact with leaders from drug industry

• Explore collaboration opportunities

• Scholarship opportunities for students to support

their participation at the meeting

KEY FOCUS AREA

• Genomics technologies

• Population genomics

• Clinical/Medical genomics

• NIPT/Liquid biopsy

• Precision (personalized) medicine

• Cancer genomics

• CRISPR/CAS9

• Gene editing

• Signal transduction

• Cancer immunology

• Biomarkers

• Drug discovery

• Metagenomics

• Plant genomics/sciences

• Agriculture genomics/sciences

• Veterinary genomics/sciences

• Wildlife genomics/conservation

100+

Speakers

Ms. Ms. Kamalika Das Das

+91- 8374 27 4074

800+

Delegates

ngbt2019@sgrf.org

300+

Posters

www.sgrfconferences.org

100+

Scholarships & Awards


RNI Number KERENG/2012/44529

More magazines by this user
Similar magazines