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VOL 5 | ISSUE 10
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FEBRUARY 2019
FUTUREMEDICINEINDIA.COM
STARTING TO
FORGET
THE SPECTRE OF ALZHEIMER’S LOOMS LARGE OVER
INDIA’S FAST-EXPANDING POPULATION OF THE AGED
CASE REPORT EDUCATION RESEARCH ONCO SURGERY
A HARROWING
SWALLOW
INTERNSHIP
FOR FOREIGN
GRADUATES
FLUID DIAGNOSIS
FOR DEMENTIA
NOVEL SURGICAL
OPTIONS FOR
BREAST CANCER

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editor’s note
editor’s note
FEBRUARY 2019 / Vol. 5 / Issue 10
Founder AUGUST & 2018 Editor / Vol: 5 / Issue: 4
CH Unnikrishnan
Executive Editor
S Harachand
Science Editor
Dr Rajanikant Vangala
Consulting Editors
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Dear Doctor,
We are glad you are enjoying the knowledge journey with us, as evidenced by
your encouraging feedback. We are also happy to know that the topics that we
choose to discuss in each of our editions have been helpful in your daily practice.
In
Dear
this
Doctor
edition, we want to touch your mind with the sad story of India’s
growing cases of dementia in the elderly and the greater dilemma of it
remaining We know as you a hidden are busy. problem. It is always The rapid reassuring growth that of the the elderly trust population and faith of will
soon hundreds increase of the patients burden in of your Alzheimer’s healing touch Disease, keeps the most you busy common in this cause noble of
dementia. profession. Unfortunately, In the hectic the practice, issue is yet it’s to quite be addressed natural that adequately you might by miss either
the out community on some or of government the latest developments agencies. in emerging medicine. In this era
To of make innovation, things medical worse, currently science is available getting disease redefined management almost by the options day. are Old
limited technologies and researchers are being are replaced still scrambling by the for new better in the remedies. blink of Thankfully,
eye. Robots
several and artificial drugs are intelligence now clinical are taking trials as over part a of good the search part of for the novel procedures, treatments
for while Alzheimer’s genomics disease and globally molecular and science many of unveil them the are mysteries in advanced of life stages. further.
Prevention We are fortunate studies are to also have looking such breakthroughs to identify the link as they between help lifestyle specialists and like
dementia. you rise Several above the clinical expectations trials are also of today’s underway informed around patient. the world to test
the effect of adopting healthier lifestyle habits to prevent cognitive decline,
Alzheimer’s Similarly, and it is also other a dementias. time when India is witnessing revolutionary growth in
It healthcare is time for industry, the community especially to be in alert the private to this sector, dilemmatic wherein situation an increasing and to
invest number in research of doctors and identify are taking risks up contributing multiple roles to the of clinician, diseases researcher of the ageing and
brain. entrepreneur. We hope our This deeply requires researched expansion cover of your story, focus analysing to a the wider current canvas. situation In
and this emerging context, remedies, it becomes will important help you become how a busy extra professional vigilant about like this you critical can
challenge. keep pace with these latest developments in a quick and easy way.
In this edition, we also touch upon medical education. The State Medical
Councils At Future have Medicine, jointly proposed which is mandatory conceived internship and crafted for by medical a team graduates of senior
who journalists, qualify abroad. scientists If implemented, and doctors, doctors our aim who is to complete help you their do just graduation that. We
from
are
foreign
equipped
countries
to bring
will
you
have
the
to
latest
do a one-year
from the
internship
science of
in
care
India
from
before
across
practicing
the world
here.
in an interesting and convenient way, supplemented by the best
I
of
am
views
sure
and
an insightful
analyses
interview
from the
with
masters
Prof.
in
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each field. We
Nair,
present
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you this
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and
knowledge
a world renowned
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medico-literary
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author,
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touching
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upon
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of
practice of neurology and the changing aspects of medical profession will also
care seamlessly. Come, let’s join hands in this information journey.
add value to your read.
Happy CH Unnikrishnan
reading
editor@futuremedicineindia.com
C H Unnikrishnan
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www.futuremedicineindia.com futuremedicineindia FutureMedIndia
AUGUST 2018/ FUTURE MEDICINE / 3

CASE REPORT EDUCATION RESEARCH ONCO SURGERY
Vol 5 Issue 10
February 2019
₹ 250.00
VOL 5 | ISSUE 10
PAGES 100
FEBRUARY 2019
FUTUREMEDICINEINDIA.COM
A HARROWING
SWALLOW
INTERNSHIP
FOR FOREIGN
GRADUATES?
STARTING TO
FORGET
THE SPECTRE OF ALZHEIMER’S LOOMS LARGE OVER
INDIA’S FAST-EXPANDING POPULATION OF THE AGED
FLUID DIAGNOSIS
FOR DEMENTIA
NOVEL SURGICAL
OPTIONS FOR
BREAST CANCER
40
CASE REPORT
CYST OR
CYSTICERCUS?
REGULAR FEATURES
06 Letters
08 News updates
28 Research
30 Drug approvals
48 Research snippets
58 Onco surgery
60 Hospital news
62 Policy
68 Devices&gadgets
78 Guidelines
90 Events
96 Calendar
97 Book review
98 Holy grail
Columns
14 THE CATALYST
Muralidharan Nair
52 THE CELLVIEW
Dr Rajani Kanth Vangala
12
EDUCATION
MANDATORY
INTERNSHIP
FOR FOREIGN
GRADUATES?
State medical councils moot
mandatory internship for
medical graduates
who qualify abroad
36
STRAIGHT TALK
“EVERYTHING
CAN BE
MADE A STORY”
Prof K Rajasekharan Nair
Eminent neurologist and
renowned writer

66
EXOTICA
THE MIND-BODY
CONNECTION
IN CANCER
Currently, there is
not enough scientific
evidence to support
the theory that one’s
attitude alone can
directly impact cancer
progression
16
COVER STORY
STARTING TO
FORGET
India faces yet another
healthcare challenge
- Alzheimer’s - as the
country’s elderly
population grows fast
54
DISEASE
INDIA’S
CANCER
BURDEN
Cancers contributed 5% of
the total disabilities and 8.3%
of all deaths in India in 2016,
shows a state-wise study
74
It is currently not
known if the classic
pathologies of
amyloid and tau
represent valid
drug targets and if
these targets alone
are enough to
treat Alzheimer’s
disease.
Dr Howard Fillit
Chief Science Officer
Alzheimer’s Drug
Discovery Foundation
New York
MERIL’S
MYVAL

ORTHOPAEDICS POLICY SPECIALTIES CASE REPORT
letters to the editor
THE BRAVE
NEW WORLD
OF IMAGING
AI, DEEP LEARNING AND BIG DATA USHER IN
A NEW ERA OF MEDICAL IMAGING
ADVANCED
ORTHO IMAGING
CONSUMER BILL:
DOCTORS
DISMAYED
IR: SPEARHEAD
OF LESS-INVASIVE
MEDICINE?
FACTS ON
FANCONI
Great case studies
₹ 250.00
VOL 5 | ISSUE 9
PAGES 100
JANUARY 2019
FUTUREMEDICINEINDIA.COM
Dear Sir,
I found few articles related
to our work by Dr Shivanee
Shah, on Non-functional
platelets, Metabolic Defects,
Dilemma of Diarrhoea & Falling
Neutrophils. These articles
reconfirm the critical nature of
our work and how this is going
to be an important part of
treatment going forward.
All the very best.
Arvind K Agrawal
CFO, Ajanta Pharma Limited
Mumbai
Kudos
Dear Editor,
The magazine (Future
Medicine) has really come
out well. You and your team
deserve congratulations.
Overall presentation and
get up of the magazine is
of high quality.
Kudos once again.
Sreedharan Nair
Director External Relations
Family Planning
Association of India
New Delhi
Fabulous work
Hello,
After returning to Istanbul,
I had the chance to
review your magazine.
I could not drop it from my
hand for an hour and
wanted to read
out all stuff. It is fabulous.
All the article are very
fresh update of the market,
it is a magazine not only
for doctors, It is also for
companies and individuals.
Very good job.
One news attracted my
attention in your January
edition, page 59. It mentions
about number of beds in the
hospital reached 21,551 in
2019. Is that all the beds in all
hospitals in India? It should be
more than that I guess.
Saygilarimla/Best Regards
Mustafa Karamizrak
General Manager
Meril Tibbi Cihazla san. Tic AS.
Atasehir, Istanbul.
Dear Mr Karamizrak,
Thank you for your feedback.
On your query on hospital
beds, would like to inform
you that this number
—21,551 doesn’t include the
government hospital beds,
which is around 14,00,000.
This report in page 58 &
59 are about India’s private
hospital industry. However,
the overall patient: hospital
bed ratio at 0.9 per thousand
patient is still far below in
India as compared to other
developing and developed
countries. —Editor
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hospital management and latest breakthroughs in medical
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AUGUST 2018/ FUTURE MEDICINE / 59

news updates
India exempts new drugs
from price control for 5 years
The government of India has decided
to exempt innovative medicines
developed by foreign companies from
price control for five years.
The Centre has brought necessary
amendments to the Drugs (Price
Control) Order (DPCO), which sets
the rules for regulating the prices of
medicines through a National List
of Essential Medicines, known as
Schedule-I.
As per a notification issued by the
Ministry of Chemicals and Fertilisers,
new drugs patented under the Indian
Patent Act of 1970 are exempted
from price regulation for a period of
five years from the date of
commencement of its commercial
marketing by the manufacturer in the
country.
Prior to this amendment, the
exemption for five years was available
only to those new drugs which
were patented in India, but were
not produced elsewhere and were
developed through indigenous research
and development.
The amendment allows any
new drug to get the exemption if
it is patented in India under Indian
Patents Act, 1970 and developed and
manufactured by any patentee across
the globe.
The move is expected to enable
access to novel medicines, especially
orphan drugs for treating rare diseases
in India.
The WHO defines rare disease as
a lifelong disorder with a prevalence
of one or less per 1,000 population.
India, however, is yet to have a
standard definition for rare diseases. It
is estimated that one in 20 Indians is
affected by one of the 7,000 diseases
listed as rare diseases, if we go by
the definition that rare disorders are
those that affect less than one in 2,500
people in India.
docprime.com
expands to more
places
docprime.com, a free online
consultation platform,
will be expanded to 12 major
states of India, the company
announced.
Online services of the
portal will now be available in
Andhra Pradesh, Telangana,
Karnataka, Tamil Nadu,
Gujarat, Maharashtra, Punjab,
Madya Pradesh, West Bengal,
Uttar Pradesh, Rajasthan and
Chhatisgarh.
docprime.com, which
already has a strong presence
new drugs
PRICE
CONTROL
8 / FUTURE MEDICINE / FEBRUARY 2019

in Delhi and NCR, will extend
services to a total of 34
cities of the country with the
expansion.
The platform
allows patients to book
appointments with over
20,000 doctors and 5,000
diagnostic labs at discounted
rates across the country.
The company also plans
to expand to 100 cities with
1,00,000 doctors and 20,000
labs in 2019, reports said,
quoting top company officials.
docprime.com features
cashless transactions that
allow the customers to pay
directly at the time of booking
an appointment and no extra
charge is levied after the
consultation. Customers can
also reschedule bookings and
avail 100% refund in case of
cancellation.
PMC exempts
credit hours
for CME
T
he Punjab Medical
Council (PMC) has given
a one-time exemption of the
mandatory credit hours of the
Continuous Medical Education
(CME) that are necessary for
registration renewal.
The MCI, in February
1997, had recommended 30
credit hours per year, or 150
credit hours per five years, for
renewal of licenses.
PMC guidelines mandate
that all the doctors registered
under the state medical
council have to acquire 50
hours of credit within 5 years
for CME accreditation.
4,677 Jan Aushadhi outlets
functional, says minister
There are 4,677 Pradhan
Mantri Bhartiya Jan
Aushadhi Pariyojana
(PMBJP) currently
functional across the
country, according to the
government.
As on 31.12.2018,
4,677 PMBJP Kendras
are functional in 35 states
and union territories
of the country, stated
Mansukh Mandaviya, Union
Minister for Chemicals and
Fertilizers, in parliament,
recently.
PMBJP was launched
by the Department of
Pharmaceuticals, Ministry
of Chemicals and Fertilizers,
Government of India with
an objective of making
available unbranded
generic medicines at
affordable prices to all.
Unbranded generic
medicines worth Rs 417
crore of MRP have been
sold through PMBJP
Kendras since the inception
of the scheme till the end
of December 2018. This
sale is roughly equivalent
to the sale of Rs 2,085
“All members unanimously
decided that up to 31.03.2019,
renewal of registration of
all doctors who have not
renewed their registrations
irrespective of time lapse are
being given an exemption
crore of the branded
medicines. Thus, PMBJP
has resulted in the saving
of approximately Rs 1,668
crore to the citizens of
the country, Mandaviya
informed Rajya Sabha, the
upper house of the Indian
parliament.
PMBJP product
basket covers more
than 800 medicines
and 154 surgicals and
consumable across 23
major therapeutic groups
such as anti-infectives,antidiabetics,
cardiovasculars,
anti-cancers, gastrointestinal
medicines, etc.
The minister said the
maximum retail price of
medicine sold through
PMBJP outlets is fixed in
such a way that it is at least
50% below the average
MRP of corresponding
top three brands of
that medicine. In order
to ensure the quality of
medicines sold through
PMBJP Kendras, the
drugs are procured only
from WHO-GMP certified
manufacturers.
of CME credit hours on the
recommendation of Punjab
Medical Council,” says a notice
issued by PMC.
The organization
requested all medical
practitioners who have not
renewed their registration
till date to apply for renewal
even without CME hours up to
31st March.
Th exemption is only up
to the stated period and after
the expiry of the period, the
mandatory clause of CME
hours will be applicable, the
notification says.
PGs in Punjab get
10 credit hours per year,
whereas in other states,
the postgraduate medical
professionals will get only four
credit hours per year.
Reports show that medical
practitioners in Karnataka
need six credit hours per year,
while it is 30 CME credit hours
per year in Gujarat.
HIV undetectable =
untransmittable:
NIH
Clinical evidence has
firmly established
the HIV Undetectable =
Untransmittable (U=U)
concept as scientifically sound,
say officials from the National
Institutes of Health (NIH), US.
U=U means that people
living with HIV who achieve
and maintain an undetectable
viral load by taking and
adhering to antiretroviral
therapy (ART) as prescribed
cannot sexually transmit the
virus to others.
Officials from NIH’s
National Institute of Allergy
and Infectious Diseases
(NIAID) summarise results
from large clinical trials and
cohort studies validating
FEBRUARY 2019 / FUTURE MEDICINE / 9

New autism bill passed
New legislation on autism,
which is scheduled to
be enacted in the country,
is expected to help people
suffering from the condition
live independently.
The Indian parliament
passed the National Trust
for Welfare of Persons with
Autism, Cerebral Palsy, Mental
Retardation and Multiple
Disabilities (Amendment) Bill,
2018. The law amends the
principal Act enacted in 1999.
The new law allows setting
up of a national trust to
enable persons with disability
to live independently by
promoting measures for their
protection in case of death of
their parents.
The bill also includes
procedures for appointment
of guardians and trustees, and
facilitating equal opportunities
in society, agency reports said.
Under the principal Act,
the chairperson and members
of the board of the national
trust could hold office for
three years from the date
of their appointment or
until their successors were
appointed, whichever was
longer. The new bill amends
this provision to fix the tenure
of the chairperson and board
members to three years. Also,
the government will initiate
the process for appointment
of the chairperson or any
member of the board at least
six months prior to the expiry
of their tenure.
U=U. The landmark NIHfunded
HPTN 052 clinical trial
showed that no linked HIV
transmissions occurred among
HIV serodifferent heterosexual
couples when the partner
living with HIV had a durably
suppressed viral load.
Subsequent
studies confirmed these
findings and extended them
to male-male couples, NIH
observed in a commentary in
JAMA.
Validation of the HIV
treatment as a prevention
strategy and acceptance
of the U=U concept as
scientifically sound have
numerous behavioural, social
and legal implications, the
NIAID officials note. U=U
can help control the HIV
pandemic by preventing
HIV transmission, and it can
reduce the stigma that many
people with HIV face.
HIV prevention method
determines the success
of U=U as it depends on
achieving and maintaining
an undetectable viral load by
taking ART daily as prescribed.
Stigma biggest
barrier to ending
leprosy: WHO
Discrimination, stigma and
prejudice are the biggest
barriers to ending leprosy,
says the WHO.
India accounts for
more half of the estimated
2,00,000 cases reported
every year, though the
number of leprosy cases has
steadily declined worldwide.
Leprosy is detected in
significant numbers in the
WHO South-East Asia Region,
Brazil, sub-Saharan Africa and
the Pacific.
WHO’s Global Leprosy
Strategy 2016-2020 outlines
policies that promote inclusion
and keeps the ending of
leprosy-related discrimination,
stigma and prejudice at the
front and centre of all leprosy
programmes.
It is often the disability
and deformity that fuels
leprosy-related discrimination,
stigma, and prejudice, even
though the disease needn’t
cause the disabilities which
are often equated with it. The
percentage of patients that
present with these symptoms
is down to 6%, demonstrating
the disease is being
diagnosed earlier than ever.
Given the fact that the
disease is 100% curable when
detected early, the human
rights of persons affected by
leprosy must be prioritised,
besides empowering people
with leprosy to be agents of
social change, it said. There is
also a need to promote access
to purpose-built social and
financial support for persons
affected by leprosy.
In recent years India,
along with other countries
in the region and beyond,
has repealed legislation that
discriminates against persons
affected by leprosy: In 2016,
for example, it repealed the
draconian colonial-era Lepers
Act, and recently repealed
a law allowing leprosy as
legitimate grounds for divorce.
Both initiatives are to be
commended, WHO notes.
10 / FUTURE MEDICINE / FEBRUARY 2019

education
MANDATORY INTERNSHIP
FOR FOREIGN GRADUATES?
State medical councils moot mandatory internship for
medical graduates who qualify abroad
Doctors who
complete their
graduation from the
foreign countries may have
to do a one-year mandatory
internship in India for practicing
in the country, as state medical
councils are planning to take up the
matter with the union health ministry
and Medical Council of India (MCI). A
decision in this regard was taken in
a meeting of state medical councils
hosted by the Maharashtra Medical
Council.
The meeting held in Mumbai was
attended by representatives of 22
state medical councils. Speaking to
Future Medicine, Dr Shivkumar Utture,
President, Maharashtra Medical Council,
said: “Making internship mandatory for
foreign medical graduates was one of
the topics in the meeting and many of
the state medical councils agreed on
the same. As the decision has to be
taken at the national level now, we are
planning to hold a meeting with MCI
Board of Directors. It may take a long
time to get it done, but the process has
already started.”
Emphasizing on the need to make
internship mandatory for foreign
medical graduates, Dr Utture said the
type of diseases differs from country
to country, as does ethics. “If the
medical professional is not exposed to
diseases, then he
won’t gain practical
knowledge. The
doctor can gain
practical knowledge if
the internship is made
mandatory for foreign
medical graduates before
practising in India. If the doctor
is not exposed to ethics and the
type of patients he is dealing with,
then it will be a loss to the doctor
and for the patient.” He added that
by doing an internship in India, the
medical professional can gain the kind
of practical knowledge required to
practice in this country.
Need for orientation
Agreeing with Dr Utture,
Dr Jayakrishnan AV, Chairman of the
Kerala chapter of IMA Hospital Board
of India, said that though the medicos
learn theory, they get the actual
orientation during house surgency. “The
system existing in India is different from
other countries. Also, the syllabus of
MBBS in India is more comprehensive
than [those in] other countries and
here, the training period is longer.”
Medical professionals who obtain
their degree from countries such
as Mauritius have been doing their
one-year internship in India. But in
case of countries such as China,
they undergo internship in the
respective country. “Everyone
should be made to do
their internship in
India,” said Dr Utture.
Commenting on the development,
Dr A Najeerul Ameen, President, All
India Foreign Medical Graduates
Association, said: “Students who
are pursuing medical graduation in
countries such as Russia and China are
already doing their internship in India.
After doing the internship, foreign
medical graduates should be allowed
12 / FUTURE MEDICINE / FEBRUARY 2019

to directly practice medicine. It will
benefit both society and the graduates.
By allowing foreign medical graduates
to do their internship in India, services
of more doctors can be made available
in hospitals. Also, such candidates need
to wait two to three years to clear the
Foreign Medical Graduate Examination
(FMGE).”
Steep rise in outflow
Due to the shortage of medical seats in
India and the high costs involved, the
number of Indian students pursuing their
medical graduation in countries such as
China, Russia, Bangladesh, Philippines,
Ukraine and other countries has been
witnessing a steady increase over the
years. In the year of 2017–18, the MCI
issued eligibility certificates to more
than 14,000 such candidates compared
to over 8,700 in the previous year. The
National Eligibility cum Entrance Test
(NEET) is not mandatory for those who
wish to do their medical degree in
If the doctor is not
exposed to ethics
and the type of
patients he is dealing
with, then it will be
a loss to the doctor
and for the patient.
Dr Shivkumar Utture
President
Maharashtra
Medical Council
foreign countries. But the government
has decided to make NEET mandatory
from the next academic year.
Presently, in order to practice in the
country, foreign medical graduates have
to pass the Foreign Medical Graduate
Examination (FMGE) conducted by
the National Board of Examination
(NBE). The examination is conducted
twice in a year and medicos have to
score a minimum of 50 percent marks
in the examination. A maximum of
three attempts are allowed. However,
the number of medicos passing the
examination is very low. As per reports,
only 2,411 out of 9,274 medicos cleared
the examination in August 2018. It
was the highest number of candidates
clearing the examination. The pass
percentage was less than 10 in previous
years. Dr Jayakrishnan AV highlighted
the difference between the system
of training in India and those in other
countries as one of the reasons for the
low pass-percentage.
1 year
internship
(compulsory)
FEBRUARY 2019 / FUTURE MEDICINE / 13

column
the catalyst
Smoothen the process
of change
Different stakeholders have definitive roles to play to
in our ambitious healthcare goals
The year 2018 was a momentous year
for the Indian healthcare industry as I
had mentioned in my previous column.
It is in the midst of an unsettling flux, where
the prevailing order finds itself inadequate
to meet the emerging imperatives even as
the new order is struggling to find its form.
In this backdrop, 2019 will again be a very
momentous year, perhaps more so than
2018, and will likely witness the evolution of
a foundation for a future healthcare system,
models and practices. I am very optimistic
that these changes are for the good of
everyone in the long run, even though there
will be unavoidable challenges of transition.
Accordingly, my wishlist for 2019 includes
what I believe should become key imperatives
for different stakeholders to lubricate this
process of change in pursuit of the true north
for the sector.
Wellness Centre) and inpatient care insurance.
Importantly, I look forward
to the passing of the much needed and much
awaited National Medical Commission bill in
2019.
Private Healthcare: Transparency, efficiency
(both capital and operational) and empathy
should be the key elements of private health
care players’ imperatives for 2019 and ahead.
Theirs is the important agenda of building
credibility among stakeholders, both public
and policymakers. It will not help
them to play the victim as much of the
trust deficit emanates from the way the
players have conducted themselves, though
the degree may vary from one to another. This
has resulted in a lack of empathy
even for their legitimate issues. It is imperative
MURALIDHARAN NAIR
Central Government: The most important
expectation from the central government
is to focus on the real implementation of
what has already been conceptualised,
instead of rhetoric and optics for projecting
a transformation. The design of Ayushmann
Bharat (AB) has its heart in the right place,
but the implementation is currently focused
only on cosmetic aspects to derive political
mileage rather than to follow
the spirit of the design: A robust, primary
care-driven, holistic healthcare
management through a strong public
health system ably complemented by private
sector capabilities. Alas, I do not foresee
any change in the current approach till the
elections in May at least. And I sincerely
hope the scheme continues in its essence
— cosmetic changes notwithstanding —
irrespective of who comes to power after the
elections. One of the first things I will look
forward to will be a realistic budget outlay for
the scheme, separately for HWCs (Health and
for them to demonstrate transparency in
their commercial practices, and as a first step,
a robust costing system accompanied by a
true and patient-friendly billing structure is an
urgent need. Equally, given the headwinds on
pricing, the emergence of a value segment
(including extra urban markets) as a key
growth driver and stretched balance sheets,
optimising their infrastructure, the design of
procedures and resource utilisation (man,
material & machine), along with a robust
framework for capital prioritisation and
14 / FUTURE MEDICINE / FEBRUARY 2019

allocation will be a critical need, even while
staying fully committed to the agenda of
quality and patient safety.
Private Equity: I do foresee consolidation
and promoter stake sale in a big way where
PE players are going to play a bigger role in
times to come. While PE players have been
a critical catalyst in driving the efficiency
agenda, they have a time-bound agenda for
value creation and hence have a sharp focus
on short- to medium-term growth. This can,
at times, result in a higher performance in
the short-term but may not be conducive to
the long-term health of the business, or to
building best practices for the industry. This
problem gets compounded if PE bought
into an unrealistic business plan, which is
not uncommon. While PE players have
played and will play a critical role in shaping
the private healthcare industry, it is imperative
that they understand the underlying
nuances of business performance, growth
and sustainability in a dispassionate way
through competent, sincere diligence.
Importantly, they should set realistic
expectations for potential exit valuations
before doing a deal.
State Government: The government must
earn the moral right to regulate and dictate
to private players, if there has to be dignity,
balance and synergy in public and private
healthcare partnerships. While public
healthcare has a long way to go in many
states — which also unfortunately tend to
be also the most populous ones — it will be
very welcome to see them target at least a 5
percent increase of public consumption in the
public-private share of hospitalisation in the
states where the public share is less than 50
percent. At the same time, the government
should leverage the Health and Wellness
Centre model of AB to revamp their primary
care set up. Additionally, they should facilitate
greater focus on the quality of care, both by
incentivising quality-conscious players with
superior reimbursement rates and making
quality accreditation mandatory for all
hospitals with more than 30 beds.
People: The patient voice will be the allpowerful
change agent in future and it is
the need of the hour. Exercise your voice
and vote for a better healthcare. Do not
revere or revile the doctor, just respect him/
her like a professional. Trust between the
doctor and patient is crucial for efficient and
effective treatment and let not half baked
information from internet spoil the chemistry
of this relation even as you rightly evolve
from a relation of blind trust in doctors. Solicit
discussion, seek second opinion and be
aware of your treatment but trust him/ her
till there is a reason to doubt rather than the
other way, particularly based on half baked
information from internet. Understand that
knowledge is different from information in
STATES SHOULD FACILITATE
GREATER FOCUS ON THE
QUALITY OF CARE BY
INCENTIVISING QUALITY-
CONSCIOUS PLAYERS WITH
SUPERIOR REIMBURSEMENT
the same way as parenthood is different from
being a parent which even a teenager can
but it takes much experience for an adult
to understand parenthood. Last but not the
least, be accountable for your health.
Clinicians: Frankly, clinicians, as a community,
have to accept that the deepening mistrust
of the public is not without reason and hiding
behind high cost of medical education and
lengthy period of education etc as possible
reasons to explain their susceptibility to
succumb to commercial considerations over
Hippocratic oath, is just hollow and deplorable
I have said this before in a previous column,
repeating it again, know that “morality is
evolved self interest” and with the passing
of Consumer Protection Bill recently, the
element of rhetoric in the statement has been
replaced, substantially, with imminent legality.
In fact it is in their best interest, individually
and collectively, to be pro active and take
the lead in winning back the respect for their
integrity as well.
The author has long-standing association with
EY India but the views are strictly personal.
FEBRUARY 2019 / FUTURE MEDICINE / 15

cover story
STARTING TO
The spectre of the
devastating Alzheimer’s
disease looms large over
India’s fast-expanding
population of the aged
16 / FUTURE MEDICINE / FEBRUARY 2019

S HARACHAND
“Paramjit Rawat, aged 76, wheat complexion, 5’7”, wearing
half-sleeve white kurta and dhoti. Missing since 22/12/2018.
He was without footwear and walks with a stupor. Suffering
from memory disorder but can remember his house name
C4, Mayur Vihar, If found, please contact 991XXXXX76”
These sort of notices alongside the picture of the missing
person are not a rare sighting on the pages of India’s
national and regional newspapers these days.
The number of desolate people who are desperately
groping in the recesses of their memory even to find own
names are going up exponentially by the day as a cloud of
dementia descent upon the elderly in the world’s second
most populous country.
Though the exact figures are not available, an estimated
4.1 million people are suffering from some form of dementia,
according to the ‘Dementia India’ report published by the
Alzheimer’s and Related Disorders Society of India. The
numbers are expected to double in a decade and a half.
The life expectancy of the Indian population is increasing
with improving healthcare. So is the number of aged people.
Today, the majority of Indians live past their 70s. The elderly
population is growing rapidly, by 3 percent annually, according
to the India Ageing Report 2017.
Such long life was a rarity till some decades ago where
not many people lived through their 60s or even their 50s.
FEBRUARY 2019 / FUTURE MEDICINE / 17

A long life comes with its own intrinsic perils,
experts say.
“See, it’s a kind of trade-off. Here you buy
longevity at the expense of [living with] many
a disease,” points out Dr K Rajasekharan Nair,
Emeritus Professor of Neurology at Medical
College Hospital, Thiruvananthapuram, India.
The advances in modern medicine have made
a large number of diseases and conditions —
which could otherwise prove fatal — curable
or manageable. Survival has increased through
effective management of several chronic
conditions.
As the population of the elderly grows, the
number of cases with dementia will also go up,
because Alzheimer’s is, largely, a disease of the
elderly. Most often it begins in people over 65
years of age.
Symptoms subtle; progress slow
A neurodegenerative disease usually
progressing through a span of 8-10 years,
Alzheimer’s often starts with subtle symptoms
which are neglected by most people. Since
memory problems are a part of the ageing
process, most of us won’t pay heed to such
complaints until the disease starts manifesting
in its full and ugly form.
One of the characteristic features of
Alzheimer’s disease (AD) is the loss of
imminent or present memory, explains
Dr Rajasekharan Nair, who is also an expert
in cognitive neurology. “The person will
It’s a kind of tradeoff.
Here you buy
longevity at the
expense of [living
with] many a
disease.
Dr K Rajasekharan
Nair
Emeritus Professor
of Neurology
remember everything that happened 50 or
60 years back. His school days, his childhood
friends, his class teacher... but he would not be
able to recall what he had for lunch an hour
ago or the fact that his wife passed away a
year ago. They would not know the place they
were sitting then… All of a sudden, they begin
to feel that something is amiss.”
Generally, AD courses through different
stages of progression such as anomia (difficulty
in remembering the names of people and
objects); agnosia (inability to recognise things);
apraxia (loss of ability to carry out voluntary
movements) and aphasia (loss of language).
However, these classical symptoms may not
be typical to all patients. Alzheimer’s affects
people in different ways, each person may
experience symptoms — or progress through
the stages — differently. There are cases
where one or the other of these functions
retained. Areas involved with learning and
memory are usually affected first. Later, regions
involved in planning and carrying out tasks
start deteriorating. Ultimately, the areas of the
brain responsible for coordinating basic bodily
activities such as walking, and swallowing are
impaired.
Caring - A formidable challenge
With the progress of the disease, the person
loses interest in everything. Gradually, the
victim starts losing all the inhibitions. Inhibition
is one of the crucial functions of the brain.
WHEN ALZHEIMER’S
STRIKES
Age group of people with
Alzheimer’s dementia in US
44%
16%
4%
37%
85+ years
75-84+ years
65-74+ years

Nearly 100 billion neurons in the
brain exchange trillions of impulses
at a time. Controlling the surge of the
impulses is one of the prominent roles
of the frontal lobe. Inhibition, in a way,
helps us behave as well-mannered
people. It is an essential aspect of
social living. Once inhibition is lost,
we can become unruly. Behaviour
becomes unpredictable. When sitting
at home, they don’t know how to sit or
WHEN THE PATIENT LOSES
SELF-CARE, HE OR SHE
BECOMES A LIABILITY
FOR THE CAREGIVER
if they should be wearing clothes. This
happens due to the degeneration of
neurons. The person becomes unable
to perform everyday activities. When
the patient loses self-care, he or she
becomes a liability for the caregiver.
People in the final stages of the disease
are bed-bound and require aroundthe-clock
care. Naturally, more than the
patient, it is the caregiver who suffers
most in AD.
Estimated Lifetime Risk for
Alzheimer’s Dementia,
by Sex, at Age 45 and Age 65
25
20
15
10
5
0
Men
10.3%
Women
19.5%
11.6%
21.1%
45 Age 65
SOURCE: alz.org
APOE AND RISK OF ALZHEIMER’S
Besides older age and a family
history of Alzheimer’s, carrying
the ApoE-e4 gene is the greatest
risk factor for late-onset Alzheimer’s.
The ApoE gene provides
the blueprint for a protein that
transports cholesterol in the
bloodstream. Everyone inherits
one of the three forms of the ApoE
gene — e2, e3 or e4 — from each
parent. The e3 form is the most
common. The e4 form is the next
most common, and the e2 form is
the least common.
Having the e4 form increases
one’s risk of developing Alzheimer’s
compared with having the e3 form,
while having the e2 form may
decrease one’s risk compared with
having the e3 form. Those who
inherit one copy of the e4 form have
three times the risk of developing
Alzheimer’s compared with those with
two copies of the e3 form, while those
who inherit two copies of the e4 form
have an eight- to 12-fold risk.
Those with the e4 form are more
likely to develop Alzheimer’s at a
younger age than those with the e2
or e3 forms of the ApoE gene.
A meta-analysis including 20
published articles describing the
frequency of the e4 form among
people in the US who had been
diagnosed with Alzheimer’s found
that 56 percent had one copy of the
APOE-e4 gene, and 11 percent had
two copies of the APOE-e4 gene.
Another study conducted among
1,770 diagnosed individuals from 26
Alzheimer’s Disease Centers across
US, 65 percent had at least one copy
of the APOE-e4 gene.
Chromosome 21 and
gene mutations
Certain genetic mutations and the
extra copy of chromosome 21 that
characterises Down syndrome are
uncommon genetic changes that
affect the risk of Alzheimer’s.
An estimated 1 percent or less of
Alzheimer’s cases develop as a result
of mutations involving the gene for
the amyloid precursor protein (APP)
and the genes for the presenilin 1
and presenilin 2 proteins.
Those inheriting an Alzheimer’s
mutation to the APP or presenilin
1 genes are guaranteed to develop
the disease. Those inheriting an
Alzheimer’s mutation to the presenilin
2 gene have a 95 percent chance of
developing the disease. Individuals
with Alzheimer’s mutations in any of
these three genes tend to develop
symptoms before age 65, sometimes
as young as age 30, according to
2018 Alzheimer’s Disease Facts and
Figures by Alzheimer’s Association,
Chicago.
Recently, some more genes have
been identified to affect Alzheimer’s
risk, such as ABCA7, BIN1, CLU,
CR1, CASS4, CD2AP, CELF1, EPHA1,
FERMT2, HLA-DRB5, INPP5D, MEF2C,
MS4A, NME8, PTK2B, PICALM,
SORL1, SlC24A4 and ZCWPW1.
These genes are believed to have
a limited effect on the overall
prevalence of Alzheimer’s because
they are rare or increase risk only
slightly.
FEBRUARY 2019 / FUTURE MEDICINE / 19

Alzheimer’s drug discovery:
Leaving no stone unturned
large number of potential therapeutic
A candidates have been studied for
Alzheimer’s disease for the last two
decades with very few reaching the final
stage of commercialisation.
As per the National Institutes of
Health registry of the US, 244 drugs for
Alzheimer’s were tested in clinical trials
registered in the decade of 2002-2012.
However, only one — memantine — could
win approval from the US FDA.
Traditionally, the drug discovery
for Alzheimer’s has been riddled with
impeding factors like the slow pace of
clinical study recruitment, the inability
of animal models to reliably predict
whether an experimental treatment will
work in humans and the relatively long
time needed to observe whether an
investigational treatment affects disease
progression.
Today, the Alzheimer’s drug
discovery pipeline consists around 120
potential therapies at various stages
of development, according to the data
provided by Alzheimer’s Drug Discovery
Foundation, a non-profit organisation
based in New York, which supports drug
discovery for Alzheimer’s. The studies
explore various targets implicated in the
development and the progression of the
disease as biological processes go awry
with age. They include impaired clearance
of toxic misfolded proteins of amyloid and
tau, chronic systemic inflammation and
neuroinflammation, mitochondrial and
metabolic dysfunctions, vascular problems,
loss of synapses, epigenetic changes, ApoE
gene and neuroprotection mechanisms.
Misfolded protein targets
Nearly two-dozen drugs are in advanced
phase 3 clinical trials. The later-phase trials
are dominated by drugs targeting betaamyloid
and tau, the classic pathological
hallmarks of Alzheimer’s disease. While
52% are targeting amyloid or tau, other
strategies are gaining ground and are in
phase 1 or 2 trials.
One of the most notable candidate
molecules is Eisai’s BAN2401, which has
been found to reduce amyloid in the brain
of 81% of patients and slow cognitive
PICTURE COURTESY: Eisai Co
decline in 30%. BAN2401’s was the first
late-stage study data that successfully
demonstrated potential disease-modifying
effects on both clinical function and
amyloid beta accumulation in the brain,
and provides compelling evidence to
support the amyloid hypothesis as a
therapeutic target for Alzheimer’s disease,
Eisai said.
However, the additional clinical data
from a sub-trial in prodromal and mild
Alzheimer’s patients presented by the
company in the 11th Clinical Trials on
Alzheimer’s Disease Conference (CTAD)
in Barcelona in October 2018 showed
no significant difference in the rate of
cognitive decline for placebo patients,
based on the presence of ApoE- e4 allele,
a genetic risk factor for Alzheimer’s.
Beside BAN2401, which came out of
a strategic research alliance between Eisai
and BioArctic, the Japanese drugmaker
has three more product candidates for
Alzheimer’s in the clinical stage . These are
β-site amyloid precursor protein cleaving
enzyme (BASE) inhibitor elenbecestat and
anti-Aß antibody aducanumab — both in
Phase 3 — and anti-tau antibody E2814,
which is currently under preparation for
Phase 1, said a spokesperson from Eisai.
”We have three candidates targeting
Aß, as such BAN2401, aducanumab and
elenbecestat. The accumulation of Aß is
considered to accelerate the tau pathology
and might be the cause of neuronal cell
death, resulting from the accumulation of
Caring for a person with Alzheimer’s dementia poses
special challenges as people in the middle-to-later stages of
Alzheimer’s experience losses in judgment, orientation and
the ability to understand and communicate effectively. Family
caregivers must often help people with Alzheimer’s manage
these issues. Changes in the personality and behaviour of a
person with Alzheimer’s are the most challenging for family
caregivers.
Most importantly, individuals with Alzheimer’s require
increasing levels of supervision as the disease progresses.
This is where countries like India fall short due to inadequate
awareness of the disease. The tendency is always to ignore
memory problems in the elderly, simply attributing them as
part of the aging process. So, it is not uncommon that people
like Paramjit Rawat stray from home, often imperiling their
own life.
Imminent threat
Despite the high prevalence, only a small fraction of patients
have been formally diagnosed or treated in India, experts say.
The maximum number of new cases of dementia will
come from India and China, said Vijayalakshmi Ravindranath,
20 / FUTURE MEDICINE / FEBRUARY 2019

tau. The accumulation of aggressive factors
such as Aß and tau is the potential target
of Alzheimer’s disease treatment”, she said.
Two Phase 3 studies for elenbecestat
in patients with early Alzheimer’s disease
are ongoing. According to Eisai, the Phase
2 study conducted in the U.S. was the
first study of a BACE inhibitor to show a
statistically significant difference in amyloid
beta in the brain while also suggesting a
delay in the decline of clinical symptoms in
exploratory endpoints.
Regarding aducanumab, two Phase 3
studies are ongoing, and patient enrolment
was completed in July 2018.
The Swiss drug giant Roche
currently has two phase 3 programmes
for Alzheimer’s - crenezumab and
gantenerumab, both targeting betaamyloid.
They have another monoclonal
antibody in phase 2, targeting tau,
according to World Alzheimer Report 2018
by Alzheimer’s Disease International, UK.
Repurposed candidates
Some of the existing drugs are also being
tested for their potential in Alzheimer’s
treatment through what is called
repurposing. Repurposing involves the
testing of a drug that is effective in one
field to see if it’s effective in another.
The cholesterol-lowering drug
gemfibrozil can be effective in reducing the
levels of amyloid and brain inflammation
in preclinical studies conducted in mice,
showed the result of a study presented
at Alzheimer’s Association International
Conference (AAIC). Gemfibrozil, a micro-
RNA pathways modulator, works as an
agonist of the peroxisome proliferatoractivated
receptor a (PPARa). An early
pre-clinical study of the repurposed
gemfibrozil is underway to understand
its effect on amyloid plaque pathology,
neuroinflammation and memory in
THE DATA SHOWED THAT
NABILONE SIGNIFICANTLY
IMPROVED AGITATION
IN A TRIAL OF 39
MODERATE-TO-SEVERE
ALZHEIMER’S PATIENTS
subjects with intact cognition and mild
cognitive impairment.
The BEACON (Blocking Endothelial
Activation to Curb the Onset of
Neurodegeneration) trial is evaluating
the efficacy of dabigatran, a direct
thrombin inhibitor, to slow down the
harmful cascade in the early stages
of Alzheimer’s disease. Dabigatran is
currently approved to reduce the risk of
stroke and systemic embolism in patients
with non-valvular atrial fibrillation and for
the treatment and to reduce the risk of
reoccurrence of deep venous thrombosis
and pulmonary embolism. Research has
shown that factors such as high blood
pressure, diabetes and stroke can injure
blood vessels in the brain, resulting in
inflammation that could cause damage to
or the death of brain cells that occurs in
Alzheimer’s disease. The Phase I study will
look into the possible role of the brain’s
blood vessels in Alzheimer’s disease and
the effects of the drug dabigatran in a
repurposed use.
Nabilone, a synthetic cannabinoid
antiemetic used in chemotherapy, is
another potential repurposed candidate
being investigated. Researchers from
Sunnybrook Research Institute, University
of Toronto, recently presented the results
of a safety and efficacy study of nabilone
in patients with moderate to severe
AD. The data showed that nabilone
significantly improved agitation in a trial
of 39 moderate-to-severe Alzheimer’s
patients. Improvements were observed
with nabilone as early as two weeks.
Some patients experienced sedation
with nabilone, though 53 percent of
the patients tolerated the highest dose
(2 mg/day). As the pilot study showed
positive results, a larger Phase 3 study
is being planned. Agitation is a common
and persistent symptom in those
with Alzheimer’s disease and current
pharmacotherapies have modest efficacy
and poor safety. This study is funded by
the ADDF and the Alzheimer’s Society of
Canada.
Rotigotine, a dopamine agonist of
the non-ergoline class of medications
indicated for the treatment of Parkinson’s
disease (PD) and restless leg syndrome,
is under investigation as a potential
cognitive enhancer for Alzheimer’s.
Recently, preliminary findings from the
DOPAD trial, which tests the dopaminergic
Ph.D., director, Centre for Brain Research, while addressing
an Alzheimer’s Association symposium held recently in
Bengaluru. The number of the elderly in India would go
up from the current 143 million to 300 million by 2050,
she noted, emphasising the need to invest in research and
identify risk and protective factors that contribute to diseases
of the aging brain.
Globally, as many as 50 million people are afflicted with
dementia, and every three seconds someone in the world
develops dementia. Dementia is the seventh leading cause of
death worldwide, shows the 2018 World Alzheimer Report.
Unlike the western population, India has a high load of
vascular risk factors. That is another reason why the incidence
of dementia is high in the country. “In European countries or
in Japan, people take good control of the vascular risk factors
pretty early in their lives. Dementia numbers there are not
rising for the last couple of years. In India we don’t know how
to age gracefully,” comments Dr Ganesh Chauhan, Assistant
Professor at the Centre for Brain Research, Indian Institute of
Science, Bengaluru.
On the other hand, he adds, Indians do have certain
factors working in their favour, which are supposed to be
protecting them from neurodegenerative diseases, such as
the joint family system, bigger social networks, bilingualism
FEBRUARY 2019 / FUTURE MEDICINE / 21

slug
therapy, were presented. The trial in
94 mild Alzheimer’s patients tested
whether rotigotine improved cognitive
function, including executive function, and
activities of daily living after six months of
treatment.
Focus on synapses
The focus of a few of the clinical studies
are synapses, the junctions between nerve
cells, which are important for memory and
cognition. Current treatments increase
levels of the neurotransmitter acetylcholine
with modest impact on Alzheimer’s
symptoms.
Researchers from Vanderbilt University
Medical Center reported preliminary
results from a Phase 1 study of novel
drug compound VU319 that modulates
muscarinic (M1) synaptic receptors. So far,
a total number of five doses of VU319
have been tested in patients and they
have been well-tolerated. After analysing
the data from a multiple-ascending
dose study to assess the safety and
tolerability of seven consecutive-day
dosing, the researchers are aiming a
Phase 2a VU319 study in people with
mild cognitive impairment in the latter
half of 2019. It will be a proof-of-concept,
double-blind, placebo-controlled study to
assess the ability of VU319 to modulate
brain networks. Previous drugs targeting
M1 produced improvement in cognitive
performance and behavioural disturbances
in Alzheimer’s patients, but failed in Phase
3 trials due to intolerable (cholinergic) side
effects, as per ADDF data.
Other candidates targeting synaptic
activity and neurotransmitters include
Takeda’s TAK-071 (Phase 1) as a
combination treatment with donepezil,
a palliative treatment for Alzheimer’s,
Agenebio Inc’ s AGB101 (Phase2/3),
Heptares’ HTL0009936 (Phase 1),
THE USFDA APPROVED
THE FIRST HUMAN
CLINICAL TRIALS WITH
APOE2 GENE THERAPY
H Lundbeck/Otsuka’s Lu AE58054
(idalopirdine) 5-HT6 receptor antagonist
and Boehringer Ingelheim’s BI 409306
phosphodiesterase 9A inhibitor (Phase 2).
ApoE approach & cell therapy
Several gene therapy and stem cell
approaches for dementia are in the
experimental stage. Among the genes,
ApoE4 is the most targeted genetic risk
factor for Alzheimer’s disease. People
with two copies of the ApoE -e4 variant
of the gene are up to 12 times more
likely to develop Alzheimer’s and to get
it at younger ages. Dr Ronald Crystal of
Weill Cornell Medicine uses ApoE- e2, the
protective variant of the gene delivered
to the brain, to counteract the negative
effects of ApoE -e4. Dr Crystal recently
received FDA approval to proceed to
the first human clinical trials with ApoE2
gene therapy. In a different approach, Dr
Anastasia Khvorova et al. of the University
of Massachusetts Medical School are
developing RNAi constructs, which are
called anti-sense oligonucleotides, to
reduce APOE gene expression, according
to the ADDF, which funds the studies.
Ageless Regenerative Institute is
studying adipose-derived stromal cells as a
cell therapy approach to protect neurons.
The investigations have reached Phase 2
stage.
AstroStem by Nature Cell Co. Ltd is
another stem cell therapy being explored
in Phase 1/2.
Some of the leading pharmaceutical
companies, including Novartis, Eli Lilly,
Janssen, Biogen, AbbVie, AC Immune,
AB Science, AstraZeneca, Genentech,
Sanofi, MSD as well as universities and
Alzheimer’s organisations are also working
on the Alzheimer’s drug pipeline, which is
broadening by the day.
etc. Socialisation is a very protective factor.
The hunt for a cure
Even as Alzheimer’s grows to epidemic proportions,
researchers are scrambling for a remedy for the disease,
which is considered one of the most challenging medical
mysteries of our time.
No pharmacologic treatment is available today to slow or
stop the damage and destruction of neurons. Rivastigmine,
galantamine, donepezil, memantine, memantine combined
with donepezil, and tacrine are the six therapies approved by
the US FDA to temporarily improve symptoms in Alzheimer’s.
Over 120 drugs are now in clinical trials as part of the
search for novel treatments for Alzheimer’s disease. Many of
these trials are in phase 2, with results expected to be out in
the next few years. Presently, a good proportion —about 20%
— of all the clinical studies revolve around beta-amyloid and
tau, the culprit proteins implicated in the development and
progression of the neurodegenerative disease.
It is, however, not clear if amyloid and tau represent valid
drug targets. “We don’t understand the exact mechanism.
But most researchers are not ready to abandon these classic
22 / FUTURE MEDICINE / FEBRUARY 2019

COST OF ALZHEIMER’S
Cost of
Alzheimer’s and
other dementias
in 2018 in US
$277 billion
By 2050, these costs could rise as high as
$1.1 TRILLION
2018 2050
5.7 million
Americans are living
with Alzheimer’s
Between 2000 and 2015, deaths from
Alzheimer’s disease increased
123%
14 million
people will have Alzheimer’s
1 in 3
seniors die
with Alzheimer’s
or another
dementia
GENOME-WIDE STUDY ON
DEMENTIA IN INDIA SOON
A
large, genome-wide study on Alzheimer’s
and other forms of dementia is expected to
start soon in India.
Named the Srinivasapura Aging Neuro
Senescence and Cognition (SANSCOG), the
study will be conducted by the Centre for Brain
Research (CBR), Bengaluru.
“The study aims to look at genetic
susceptibility and also the role of environmental
factors that contribute to complex diseases like
Alzheimer’s,” said Dr Bratati Kahali, Scientist
at the Centre for Brain Research (CBR), Indian
Institute of Science, Bengaluru.
A team of qualified doctors, psychologists
and social workers will examine 10,000 people
above 45 years from Srinivaspura taluk in the
Kolar district of Karnataka annually for a period
of 10 years to comprehend the factors that
cause dementia.
The people, belonging to the middle age
group, were chosen to study their susceptibility
to develop or not to develop a neurogenerative
disease later on. How a person leads his life
in his 30s and 40s can determine what he or
she is going to be in his 60s and 70s. Added
to that is one’s genetic susceptibility. These can
be assessed only through population-based
studies, she added.
The study will employ latest tools like next
generation sequencing and high-throughput
screening technologies to cover the entire
genome rather than one gene.
“It is going to be a large study, not only
in terms of numbers, but also in terms of the
technology used,” claimed Dr Ganesh Chauhan,
Assistant Professor at CBR.
Currently, there is no data available from
therapeutic studies in India. Whatever is
available is from certain pockets with a small
sample size. Preliminary work on the study has
started. The project will go full-scale by the end
of March 2019, he added.
Every
65
seconds
someone in the
United States
develops the disease
SOURCE: alz.org
FEBRUARY 2019 / FUTURE MEDICINE / 23

pathologies,” quips Dr Howard Fillit,
MD, Chief Science Officer of Alzheimer’s
Drug Discovery Foundation (ADDF),
New York, a non-profit organisation
which supports scientists around the
globe who are investigating novel drugs
to prevent, treat and cure Alzheimer’s
disease.
Therapeutic attempts to remove
or lower the production of betaamyloid
have been largely unsuccessful
in altering the disease course of
Alzheimer’s disease. Since Alzheimer’s
has a complex and interrelated set of
causes, we will need more than one
drug to treat the disease, like with
cancer.
Probe on lifestyle
As far as late-onset Alzheimer’s is
concerned, the greatest risk factors are
older age, having a family history of
SINCE ALZHEIMER’S HAS A
COMPLEX AND INTERRELATED
SET OF CAUSES, WE WILL
NEED MORE THAN ONE DRUG
TO TREAT THE DISEASE
Alzheimer’s and carrying the ApoE-e4
gene.
Prevention studies are also looking
to identify the link between lifestyle and
dementia. Several major clinical trials
are underway around the world to test
the effect of adopting healthier lifestyle
habits to prevent cognitive decline,
Alzheimer’s and other dementias. In
the U.S., the Alzheimer’s Association is
leading the U.S. Study to Protect Brain
Health Through Lifestyle Intervention
to Reduce Risk (US POINTER). The US
POINTER is a two-year clinical trial to
evaluate whether lifestyle interventions
can protect cognitive function in older
adults at increased risk for cognitive
decline.
Earlier, a landmark study called
the Finnish Geriatric Intervention
“We are at a pivotal
time in Alzheimer’s
research”
Dr Howard Fillit, MD is Founding
Executive Director and Chief
Science Officer of Alzheimer’s
Drug Discovery Foundation (ADDF),
New York. ADDF is a nonprofit
organisation which supports
scientists around the globe who are
investigating novel drugs to prevent,
treat and cure Alzheimer’s disease. A
geriatrician and neuroscientist,
Dr Fillit says he is committed to
conquer Alzheimer’s through drug
discovery. Edited excerpts from an
interview with FM:
A look at the current drug
discovery pipeline shows that most
drugs in late-phase trials target
either beta-amyloid or tau. And
beta amyloid’s exact mechanism in
Alzheimer’s is yet to be conclusively
established. How do you comment
on it?
Historically, drug development
in Alzheimer’s has focused on the
damaged proteins, amyloid and tau,
the hallmarks of Alzheimer’s disease.
Although we don’t understand the
exact mechanism, most researchers
are not ready to abandon beta
amyloid (or tau) as targets. It is
currently not known if these classic
pathologies (amyloid and tau)
represent valid drug targets and if
these targets alone are enough to
treat Alzheimer’s disease. Although
therapeutic attempts to remove
or decrease the production of
beta-amyloid have been largely
unsuccessful in altering the disease
course of Alzheimer’s disease,
researchers learned important
information from those clinical trials
even if they didn’t immediately result
in treatments for Alzheimer’s patients.
And recent clinical trials suggest that
[attempts to overcome] problems with
the clearance of beta-amyloid may yet
prove fruitful.
While many late-stage clinical
trials are targeting amyloid, it’s likely
we’ll need more than one drug to
treat Alzheimer’s, like with cancer,
because it has multiple causes. At the
ADDF, our scientific strategy is based
on the biology of aging - the leading
risk factor for Alzheimer’s disease.
Alzheimer’s has a complex and
interrelated set of causes, so drugs
targeting more than one of those
causes will be needed to effectively
treat it. Targeting the common
biological processes of aging may be
an effective approach to developing
therapies to prevent or delay agerelated
diseases, such as Alzheimer’s.
What are the most promising
candidates for Alzheimer’s that ADDF
is currently supporting?
Since 1998, the ADDF has awarded
over $120 million to fund over 580
drug development programmes in
19 countries. We support a diverse
pipeline of drug targets beyond beta
amyloid. Alzheimer’s drugs aimed
at neuroinflammation, genetics
and epigenetics, neuroprotection
and metabolic and mitochondrial
dysfunction are now in clinical trials
or nearly there. We need to pursue
all these targets and look for new
ones. We need more rigorous trials.
Alzheimer’s is a complex disease; [and
will] likely involve combination therapy
– an approach that’s standard of care
in diseases like diabetes, heart disease,
cancer, HIV/AIDS.
An epigenetic drug being
developed for Alzheimer’s—ORY-2001
by Oryzon Genomics—is preparing for
phase 2 trials. It works by inhibiting
a protein that “turns down” the
expression of several genes that are
beneficial to the brain. By helping
these genes express more, ORY-2001
may slow cognitive impairment and
restore memory deficits in patients
with Alzheimer’s and other disorders.
Another promising candidate is
C-31 (also called LM11A-31), which
was developed by Dr Frank Longo,
a professor at the Stanford School
of Medicine and the founder of the
24 / FUTURE MEDICINE / FEBRUARY 2019

iotechnology firm PharmatrophiX.
Dr Longo is working on a remarkable drug
candidate that could restore lost cognitive
function and lead to the first regenerative
therapy for Alzheimer’s.
A third example is the work of
Dr Michela Gallagher, professor of
Psychology and Neuroscience and the
head of the Neurogenetics and Behavior
Center at Johns Hopkins University. She
is also the founder of AgeneBio, Inc., a
pharmaceutical development company that
has initiated a Phase 3 trial recently to slow
the progression of Alzheimer’s dementia.
The ADDF is a funder of Dr Gallagher’s
therapeutic development of AGB-101,
the first and only treatment to target
hippocampal hyperactivity, a condition
characteristic of the amnestic mild
cognitive impairment stage of Alzheimer’s
disease.
Diagnostic Accelerator, in partnership
with Bill Gates, is reportedly exploring the
possibility of a blood test for Alzheimer’s.
What is the present status of the study?
Critical to our success in finding effective
ways to prevent and treat Alzheimer’s is
the development of reliable, affordable and
accessible biomarkers – just as cholesterol
is an early biomarker for heart disease.
This will allow us to better understand
how the disease progresses, more easily
identify people for clinical trials and more
accurately monitor their response to
treatments. That is why the Alzheimer’s
Drug Discovery Foundation partnered with
Bill Gates, the Dolby family and the Charles
and Helen Schwab Foundation to create
the Diagnostics Accelerator.
This initiative will help to accelerate
the development of novel biomarkers
from blood and other peripheral fluid and
tissue. It is my hope that in the next few
years a blood test will be available for the
diagnosis of Alzheimer’s disease.
Dr Howard Fillit
NEW THERAPEUTICS FOR
AD WILL COME FROM
THE UNDERSTANDING
OF THE EFFECTS OF AGING
ON THE BRAIN
Using the biomarker specific model
of precision medicine, we will be able to
predict more accurately which treatment
and prevention strategies will work in
different at-risk populations of people who
have Alzheimer’s disease or other forms of
dementia.
Despite the increasing burden of
the disease, there are not many real
breakthroughs in Alzheimer’s drug
research. Is it because of the poor
understanding of the disease or due to
other hurdles?
Today we know more about Alzheimer’s
and the human brain than at any other
time in history.
Alzheimer’s research did not result
in real progress until the mid-1980s.
One of the reasons is that Alzheimer’s
disease and related dementias were
thought to be a normal part of aging.
So, until it was realized that Alzheimer’s
disease was not a normal part of
aging, there was little interest in finding
treatments for it.
It typically takes at least 30 years
for drugs to be developed out of basic
scientific research. The first drug to treat
Alzheimer’s was not approved by the U.S.
Food and drug administration until 1993,
decades after drugs for cancer and heart
disease were approved.
Another major challenge has been
the lack of affordable and noninvasive
biomarkers as tools to better diagnose,
monitor disease progression and make
clinical trials more efficient and rigorous.
Where do you see Alzheimer’s drug
discovery in the next five years down the
lane?
Even though we don’t yet have a cure
for Alzheimer’s disease, I’ve never been as
optimistic as I am now about the potential
for new drugs to prevent and treat this
devastating disease. We are at a pivotal
time in Alzheimer’s research with better
diagnostics, a solid scientific understanding
and more than 120 drugs in clinical trials
looking at novel treatments for Alzheimer’s
disease. Many of these trials are in phase 2
and expected to read out within the next
few years.
New therapeutics for Alzheimer’s
disease will come from this understanding
of the effects of aging on the brain. Our
success in fighting Alzheimer’s disease will
likely come from combination therapies -
because Alzheimer’s disease has multiple
underlying causes, it will likely require a
combination of drugs to effectively treat
it. Precision medicine using combination
therapy is likely needed for better
treatment outcomes in Alzheimer’s disease,
just as it is for cancer.
Now more than ever, we need to push
forward the opportunity for new drug
discoveries.
See the detailed version of the interview on
www.futuremedicineindia.com
FEBRUARY 2019 / FUTURE MEDICINE / 25

Study to Prevent Cognitive Impairment
and Disability (FINGER) showed heart
health management, a healthy diet and
increased exercise, plus intellectual and
social stimulation can slow cognitive decline
in at-risk older adults. FINGER studies are
being carried out in China, in Singapore and
in Australia.
Tackling stigma
The costs of long-term care for individuals
with Alzheimer’s are substantial, as
dementia is one of the costliest conditions
to society. The total per-person health
care and long-term care payments from
all sources for Medicare beneficiaries with
Alzheimer’s or other dementias were
over three times as great as payments for
other Medicare beneficiaries in the same
age group in the US, according to 2018
Alzheimer’s Disease Facts and Figures by
Alzheimer’s Association, Chicago.
Such cost estimations are yet to be
carried out through studies in India, where
AD has not become a public health concern
yet like in many other parts of the world.
Stigma is yet another issue. A substantial
amount of stigma is still attached to
dementia in India. “Not only dementia,
almost every disease affecting the brain is
considered ‘paagal’ (lunacy) in many parts
of India. Woh toh paagal hai (the person
is mad) … this is the way people describe
individuals with neurological disorders,”
comments Dr Chauhan.
Chauhan and others in CBR are part
of a soon-to-be-launched large-scale
genome-wide study on Alzheimer’s and
other dementias in the country. Currently,
whatever data on Alzheimer’s is available
is limited to certain pockets, or based on
the information provided by hospitals.
Initial results of the study could be out
within the next couple of years. The data
will put things in perspective. Hopefully, a
clear understanding about the prevalence
and other aspects of the disease could
not only help create appropriate policies,
but also bring down the stigma. As World
Alzheimer’s Report 2018 by Alzheimer’s
Disease International, UK points out: “More
diagnosis means more awareness. More
awareness means less stigma. Less stigma
means more hope.”
Not only dementia,
almost every
disease affecting
the brain is
considered ‘paagal’
(lunacy) in many
parts of India.
Dr Ganesh Chauhan
Assistant Professor
Centre for Brain
Research
Bengaluru
TAU TANGLES AND AMYLOID
Two proteins in the brain are heavily
involved in the development of Alzheimer’s,
agree most scientists. Beta-amyloid (Aβ)
reaches abnormal levels in the brain of
people with Alzheimer’s and forms plaques
that collect between neurons and disrupt cell
function. The amyloid cascade hypothesis
considers that the deposition of the amyloid-β
peptide in the brain parenchyma is a central
event in Alzheimer’s disease pathology.
Tau proteins forms neurofibrillary tangles
inside neurons which block the neuron’s
transport system.
However, it is not clearly known exactly
26 / FUTURE MEDICINE / FEBRUARY 2019

BLOOD TEST FOR
ALZHEIMER’S MARKER?
Washington University scientists, in
collaboration with C2N Diagnostics,
showed that the protein tau increases in
blood after peripheral administration of an
anti-tau antibody.
The study in mice found that the level
of tau increase in blood correlated with the
tau pathology in the brain.
C2N Diagnostics, LLC based St Louis,
Missouri has developed technology
platforms like the Stable Isotope Spike
Absolute Quantitation (SISAQ) and Stable
Isotope Labeling Kinetic (SILK) that
enable the measurement of the absolute
concentration of peptides and specific
proteins in both CSF and plasma.
“We focus on a variety of assays
– using the primary platform of mass
spectrometry – to quantitate proteins
and other biomolecules implicated
in neurodegeneration,” said Joel B.
Braunstein, MD, CEO, C2N Diagnostics.
These assays are currently available
for use in preclinical research and clinical
research drug development settings. Some
of these assays may be used in the future
to serve as a clinical diagnostic aid in the
detection and monitoring of pathways
implicated in Alzheimer’s disease and
other forms of neurodegeneration, he
added.
CASCADE
how these proteins relate to each
other.
Impairments in cholesterol and
glucose metabolism, inflammation,
oxidative stress and dysfunctional
‘garbage collection system of the
brain’ are all supposed to help
push the amyloid accumulation,
which then probably causes
damage to the synapses leading
to tau aggregation.
New findings show both
Aβ and tau oligomers bind to
amyloid-β protein precursor
(AβPP). And the presence of this
protein is required for both Aβ
and tau to enter neurons and
induce abnormal synaptic function
and memory. It is also proposed
that extracellular oligomers of
Aβ and tau act in parallel and
upstream of AβPP in Alzheimer’s
pathogenesis.
However, therapeutic
approaches aimed at decreasing
Aβ levels and tau-based clinical
trials are yet to produce positive
findings.
FEBRUARY 2019 / FUTURE MEDICINE / 27

esearch
FLUID DIAGNOSIS
FOR DEMENTIA
Integration
of molecular
biomarkers could
chart the course of
precision medicine
in Alzheimer’s
disease
DR RAJANI KANTH VANGALA
A
typical diagnosis of dementia
is based on a history of illness,
cognitive deficits and their
patterns. Along with the abovementioned
tests, there is now a shift
towards diagnosing specific forms
of Alzheimer’s disease (AD) using
molecular biomarkers. There has been
enormous progress in identifying fluid
biomarkers for AD in the past 20
years. Pathologically, AD is defined
by 1. a neuronal loss of brain regions,
specifically in medial temporal lobe
structures and temporoparietal cortices,
2. neurofibrillary tangles composed of
truncated and hyperphosphorylated
tau protein, 3. the extracellular neuritic
plaques with deposits of β-amyloid
peptides. There are several subtypes of
dementia
which
are diagnosed using different
biomarkers to evolve better
therapy and precision medicine.
In β-amyloid pathology, the
42-amino-acid isoform of β-amyloid
(Aβ42) forms the major component
of senile plaques leading to cerebral
amyloid angiopathy in AD. Enzymelinked
immunosorbent assay
(ELISA) based Aβ42 concentration
measurement in CSF has been
verified in many studies (Olsson et al.,
2016), where reduced levels reflect
sequestration to senile plaques as
was also shown in positron emission
tomography (PET) imaging. These
reduced levels of Aβ42 can indicate
pre-clinical stages of AD or dementia
with Lewy bodies (DLB), commonly
associated with cerebral Aβ aggregation.
28 / FUTURE MEDICINE / FEBRUARY 2019

In order to make diagnostics more
accessible, blood is preferable, and
plasma Aβ42 measurement using Single
Molecule Array (Simoa) technique could
quantify to sub-picogram per mL levels
(limit of quantification of 0.04pg/mL).
A large-scale Swedish BioFINDER study
found weak, but significant, correlations
between both plasma AB42 and
AB42/40 ratio to corresponding CSF
measurements.
The abnormal phosphorylation
and truncation of tau proteins, which
constitute major neurofibrillary tangles
in AD, are also detectable in blood
samples. It has been shown that
increased levels of plasma tau levels
may correlate with AD. Longitudinal
studies have shown that increased
plasma tau levels have significant
correlation with future cognitive decline
as well as in hypometabolism measured
by FDG PET. However, many clinical
studies reported that there is a large
overlap of tau levels between cases of
tauopathies and controls, suggesting
that more studies may be needed to
take it into clinical practice. Alternatively,
T-tau or P-tau measurement in neuronenriched
exosomes may help as a better
biomarker.
Neurogranin and cognitive decline
One of the key features of AD is
axonal degeneration, which is linked
with the onset of cognitive decline
and Aβ pathology. It has been
demonstrated that higher levels of
CSF T-tau lead to increased intensity
of neurodegeneration. Some more
markers like fatty acid-binding protein
(FABP) family and visinin-like protein
1 (VLP-1; VSNL1) do show a weak but
significant association to AD. T-tau
and neurofilament-light (NF-L) assays
are also being used for performing
ultrasensitive blood tests, but these are
in early stages of development. A recent
study on a cohort of Alzheimer’s Disease
Neuroimaging Initiative (ADNI) study
showed a marked increase in plasma
NF-L levels, with receiver operating
curve (ROC) area under the curve (AUC)
of 0.87, which is comparable to CSF
AD biomarkers.
One of the earliest clinical
characteristic of AD is memory
impairment due to subtle alterations in
synaptic efficiency in the hippocampus
prior to frank neuronal degeneration.
One of the most important proteins,
called neurogranin (Ng; NRGN), is a
dendritic protein highly abundant in
neurons. It is involved in long term
potentiation of synapses, particularly in
hippocampus and basal forebrain. CSF
Ng concentrations were observed to
be increased in AD (Hellwig et al, 2015;
Kvartsberg et al., 2015a,b; Thorsell et
THERE IS A STRONG
CORRELATION BETWEEN
HIGHER LEVELS OF
NEUROGRANIN AND
COGNITIVE DECLINE. SOME
OF THE NOVEL EMERGING
BIOMARKERS INCLUDE
SNAP25 AND RAS-RELATED
PROTEIN RAB3A
al., 2010; Kester et al., 2015), but not in
other neurodegenerative diseases. New
studies have also reported that there
is a strong correlation between higher
levels of Ng and cognitive decline and
brain atrophy (Tarawneh et al., 2016).
Some of the novel emerging biomarkers
include synaptosomal-associated protein
25 (SNAP25) and Ras-related protein
RAB3A.
Emerging biomarkers
Glial cells in the brain are important for
normal nutrient supply and form part
of the blood-brain barrier. These cells
play important roles in repair following
CNS injury and resident macrophages
microglia form the primary active
defense players. Loss of synaptic
plasticity and neuronal function in
AD can be linked to activation of
both cell types, but more so the glial
cells. Interesting findings related to
variants of myeloid cells 2 (TREM2;
TREML2) gene specifically expressed
in microglia cells has raised interest
in the possibility of identifying better
biomarkers for glial activation (Lue
et al., 2015; Guerrerio et al., 2013;
Jonsson et al., 2013). Increased levels
of secreted ectodomain of TREM2 in
CSF were in concordance with that of
T-tau and P-tau levels in AD patients.
Similarly, several other biomarkers of
astrocytes, microglia and macrophagederived
proteins, like CD14, YKL-40
and C-C chemokine receptor 2 with
its ligand C-C chemokine ligand
2 (CCL2) levels were present in
increased levels in AD patients CSF.
The validation of these biomarkers
in blood has not yet resulted in any
conclusive outcomes. Approximately
50% of frontotemporal dementia (FTD)
cases are reported to show increased
levels of hyperphosphorylated TDP-
43 proteinopathy. It has also been
observed to be associated with the
impairment of cognitive capabilities of
aging patients.
Obviously, CSF has proven to be the
best source of biomarkers for detecting
tangle and plaque pathology for
clinical utility, but there are emerging
biomarkers that are reshaping the
diagnosis and therapeutic approaches
in AD. The new discoveries and
findings do suggest that, for now, a
combination of CSF, blood and PET
may be the best option. However,
blood biomarkers are on brink of
being a viable option for the screening
and early clinical management of
patients with AD. The last 20 years
of research on fluid biomarkers has
given extraordinary results and ADCSF
biomarker toolbox looks set to better
define precision medicine.
FEBRUARY 2019 / FUTURE MEDICINE / 29

drug approvals
Chinese nod
for IBS drug
linaclotide
Ironwood Pharmaceuticals,
Inc has received marketing
authorisation from the
National Medical Products
Administration (NMPA) for
linaclotide (Linzess) in China
for the treatment of adult
patients with irritable bowel
syndrome with constipation
(IBS-C).
Linaclotide is a guanylate
cyclase-C (GC-C) receptor
agonist. The drug binds to the
GC-C receptor locally, within
the intestinal epithelium.
Activation of the GC-C results
in increased intestinal fluid
secretion accelerated transit
and a decrease in the activity
of pain-sensing nerves in the
intestine.
The NMPA approval is
based on a phase III global,
multicentre, clinical trial, jointly
conducted by AstraZeneca
China and Ironwood, in five
countries, which evaluated the
efficacy and safety of Linzess
in patients with IBS-C.
Nivolumab plus ipilimumab combo
to treat renal cancer in EU
The European Commission has approved
the combination of nivolumab (Opdivo)
3 mg/kg plus low dose ipilimumab (Yervoy)
1 mg/kg for the first-line treatment of
patients with intermediate- and poor-risk
advanced renal cell carcinoma (RCC).
This decision represents the first
approval of an Immuno-Oncology (I-O)
combination therapy for patients with this
type of cancer in the EU, Bristol-Myers
Squibb Company announced.
The approval is based on results from
the Phase 3 CheckMate -214 clinical trial,
which was stopped early following a
planned interim analysis that showed that
the combination of nivolumab plus lowdose
ipilimumab demonstrated a significant
increase in overall survival, with a 37%
decreased risk of death in intermediateand
poor-risk patients compared to a
current standard of care, sunitinib.
Nivolumab plus low-dose ipilimumab
Launch of linaclotide
in China is expected in the
second half of 2019.
Orphan drug
status for
apraglutide
Therachon AG said the US
FDA granted Orphan Drug
Designation for apraglutide
for the treatment of short
bowel syndrome (SBS).
Apraglutide is a glucagonlike
peptide-2 receptor
agonist.
SBS results from extensive
intestinal resection due to
chronic inflammatory bowel
disease (IBD), acute events
such as mesenteric infarction
or congenital abnormalities.
SBS is a severe, chronic
condition associated with
also demonstrated a higher objective
response rate of 41.6% versus 26.5% for
sunitinib and a complete response rate
of 9.4% for the nivolumab plus low-dose
ipilimumab cohort versus 1.2% for the
sunitinib arm.
CheckMate -214 is a Phase 3,
randomized, open-label study evaluating
the combination of nivolumab 3 mg/kg
plus ipilimumab 1 mg/kg versus sunitinib
in patients with previously untreated
advanced RCC. In the intermediate- and
poor-risk study population, 425 patients
received nivolumab 3 mg/kg plus
ipilimumab 1 mg/kg every three weeks
for four doses, followed by nivolumab
3 mg/kg every two weeks, and 422 patients
received sunitinib 50 mg once daily for four
weeks, followed by two weeks off every
cycle.
Patients were included regardless of
their PD-L1 status.
reduced or complete loss of
intestinal function, known as
‘intestinal failure’. Intestinal
failure caused by SBS can
be life-threatening and is
characterized by malabsorption
and malnutrition. Affected
individuals are dependent
30 / FUTURE MEDICINE / FEBRUARY 2019

on daily parenteral support,
typically requiring between 10 –
15 hours of parenteral feeding
per day. Parenteral support
is associated with infections,
blood clots and poor quality
of life.
In the US, Orphan Drug
Designation provides orphan
status to investigational
therapies aimed to treat
rare diseases and disorders
affecting fewer than 200,000
people.
Therachon is a
clinical-stage global
biotechnology company
pursuing programmes in
rare conditions with wellcharacterized
biological
root causes, including both
short bowel syndrome and
achondroplasia.
Devimistat gets
orphan drug
desig in EU
The European Medicines
Agency (EMA) has granted
orphan drug designation
to devimistat (CPI-613), for
the treatment of metastatic
pancreatic cancer.
Devimistat, developed
on Rafael Pharma’s Altered
Metabolism Directed (AMD)
platform, targets the altered
regulation of metabolic
processes specific to cancer
cells. It is highly specific,
simultaneously attacking
multiple targets, minimally
toxic and has broad spectrum
activity across a wide variety
of cancers, the company said.
Devimistat is currently
being evaluated in 7 trials
as a single agent, as well
as in combination with
standard drug therapies for
hematological malignancies
and solid tumours.
In pancreatic cancer,
devimistat in combination
with modified folfirinox
exhibited an objective
response rate of 61%, median
overall survival of 19.9 months
and median progression-free
survival of 9.9 months.
Devimistat also exhibited
a good safety profile both
as a single agent and in
combination with other
standard-of-care drugs.
Devimistat has previously
been granted orphan drug
designation for pancreatic
cancer, AML, MDS, peripheral
T-cell lymphoma and Burkitt
lymphoma by the US FDA.
Tdap vac
for repeat
vaccination
The US FDA has approved
the expanded use of
Tetanus Toxoid, Reduced
Diphtheria Toxoid and
Acellular Pertussis (Tdap)
Vaccine Adsorbed (Adacel) to
include repeat vaccination to
help protect against tetanus,
diphtheria and pertussis. It is
now the first and only Tdap
vaccine in the US approved
for a repeat dose in people
10 through 64 years of age 8
years or more after the first
vaccination, Sanofi Pasteur
said.
The FDA licensure was
based on clinical data from
a study of the safety and
effectiveness of repeat
vaccination in adults. In the
study of more than 1,300
adults (aged 18 through
64 years), participants
received either the vaccine
or a tetanus-diphtheria (Td)
vaccine 8-12 years after a
previous dose of the vaccine.
US FDA panel recommends romosozumab for osteoporosis
The US FDA Bone,
Reproductive and Urologic
Drugs Advisory Committee
(BRUDAC) recommended the
approval of romosozumab
(Evenity) for the treatment of
postmenopausal women with
osteoporosis at high risk for
fracture.
Eighteen of 19 members
voted in favour of the
approval yes for approval,
Amgen and UCB announced.
Romosozumab is an
investigational bone-forming
monoclonal antibody that
inhibits the activity of
sclerostin. This enables
romosozumab to rapidly
increase bone formation
and reduce bone resorption
simultaneously.
The romosozumab
development programme
includes 19 clinical studies
that enrolled approximately
14,000 patients. Notable
phase 3 studies include
FRAME, a placebocontrolled
study with 7,180
postmenopausal women
with osteoporosis at risk for
fracture; ARCH, an active
comparator-controlled study
with 4,093 postmenopausal
women with osteoporosis and
with prior history of fracture;
and STRUCTURE, an active
comparator-controlled study
with 436 postmenopausal
women with osteoporosis.
The BRUDAC evaluated
the FRAME and ARCH studies
in its review of the clinical
benefit and risk profile of
romosozumab.
32 / FUTURE MEDICINE / FEBRUARY 2019

Five new approvals for pembrolizumab in Japan
Pembrolizumab (Keytruda)
has been granted approval
in Japan for the first-line
treatment of advanced nonsmall
lung cancer (NSCLC)
as both monotherapy
and in combination with
chemotherapy.
Pembrolizumab is the first
anti-PD-1 approved in Japan
with new MSI-H indication,
regardless of tumour type,
Merck said.
Pembrolizumab has
simultaneously received
five new approvals from
the Japan Pharmaceuticals
and Medical Devices Agency
(PMDA) for three expanded
uses in advanced NSCLC, one
in melanoma, as well as a
new indication in advanced
microsatellite instability-high
(MSI-H) tumours.
PDMA has granted new
approvals following priority
review for pembrolizumab
in combination with
pemetrexed and platinumbased
chemotherapy
(cisplatin or carboplatin)
for the first-line treatment
of unresectable, advanced/
recurrent nonsquamous
NSCLC regardless of PD-L1
expression; Pembrolizumab in
combination with carboplatin
and paclitaxel or nabpaclitaxel
for the first-line
treatment of unresectable,
advanced/recurrent squamous
NSCLC regardless of PD-L1
expression; Pembrolizumab
monotherapy in the firstline
treatment of PD-L1-
positive unresectable,
advanced/recurrent
NSCLC; Pembrolizumab
monotherapy as adjuvant
therapy for melanoma
and pembrolizumab
monotherapy for the
treatment of advanced/
recurrent MSI-H solid tumours
that have progressed after
chemotherapy.
A companion diagnostic to
detect MSI-H, the MSI test kit
FALCO by FALCO Biosystems
Ltd., has also been approved.
In addition to the adjuvant
therapy approval, dosage and
administration for all patients
with melanoma have been
changed from an intravenous
infusion of 2 mg/kg over
30 minutes at a three-week
interval to intravenous infusion
of the fixed dose of 200 mg
over 30 minutes at a threeweek
interval.
Previously, pembrolizumab
was approved in Japan for
the treatment of curatively
unresectable melanoma;
PD-L1-positive unresectable,
advanced or recurrent
NSCLC; relapsed or refractory
classical Hodgkin lymphoma;
and curatively unresectable
urothelial carcinoma that
progressed after chemotherapy.
Pembrolizumab is
marketed by MSD in Japan
and is co-promoted with Taiho
Pharmaceutical Co., Ltd.
The results of the study
published in the Journal
of the Pediatric Infectious
Diseases Society showed a
second dose of the
Tdap vaccine in adults
administered 8-12 years
after a previous dose found
no significant differences
in adverse events between
vaccine groups.
FDA fast-tracks
stem cell
therapy for SCD
Fast track designation has
been granted for CTX001
for the treatment of sickle cell
disease (SCD) by USFDA.
CTX001 is an
investigational, autologous,
gene-edited hematopoietic
stem cell therapy for patients
suffering from severe
hemoglobinopathies.
HbF is a form of the
oxygen-carrying haemoglobin
that is naturally present at
birth and is then replaced
by the adult form of
haemoglobin. The elevation
of HbF by CTX001 has
the potential to alleviate
transfusion-requirements for
ß-thalassemia patients and
painful and debilitating sickle
crises for sickle cell patients.
In October 2018, CRISPR
and Vertex announced the
FDA acceptance of the
Investigational New Drug
application (IND) for CTX001
for the treatment of SCD, and
enrolment in a phase 1/2 trial
in SCD is currently underway
in the US. The companies are
also evaluating CTX001 for the
treatment of ß-thalassemia,
and enrolment in a Phase
1/2 trial in ß-thalassemia is
currently open at multiple
clinical trial sites in Europe.
Japanese nod to
PNP drug Tarlige
Tarlige tablets has been
granted marketing
34 / FUTURE MEDICINE / FEBRUARY 2019

approval in Japan for the
treatment of peripheral
neuropathic pain (PNP).
This drug, an a2d ligand
created by Daiichi Sankyo,
was submitted for marketing
approval in February 2018
on the basis of the results
of a phase 3 clinical trial
in patients with diabetic
peripheral neuropathic
pain (DPNP) and a phase 3
clinical trial in patients with
postherpetic neuralgia (PHN).
Both trials were conducted in
Asia and including Japan.
a2d (Alpha 2 delta) ligand
binds to the a2d subunits of
voltage-dependent calcium
channels
DPNP leads to numbness
to the extremities and is one
of the most common longterm
3 major complications of
diabetes.
Crizanlizumab
is breakthrough
therapy for VOCs
The US FDA has granted
breakthrough therapy
designation crizanlizumab
(SEG101) for the prevention of
vaso-occlusive crises (VOCs)
in patients of all genotypes
with sickle cell disease (SCD),
Novartis said.
The designation was
granted based on positive
results of phase II SUSTAIN
trial, which compared
the P-selectin inhibitor
crizanlizumab with placebo
in patients with sickle cell
disease.
SUSTAIN showed that
crizanlizumab reduced the
median annual rate of VOCs
leading to health care visits by
45.3% compared to placebo
in patients with or without
hydroxyurea therapy. The
study also demonstrated that
crizanlizumab significantly
increased the percentage
of patients who did not
experience any VOCs vs
placebo during treatment.
Also known as sickle
cell pain crises, VOCs are
unpredictable and extremely
painful events that can lead
to serious acute and chronic
complications.
Tabramycin PARI
for CF in EU
The European Medicines
Agency has approved
tobramycin (Tobramycin
PARI) a new hybrid medicine
for the treatment of chronic
Pseudomonas aeruginosa
infection in cystic fibrosis (CF).
Tobramycin is an
aminoglycoside antibiotic
which primarily affects
bacterial protein synthesis
resulting in rapid
concentration-dependent
bacterial cell death.
Tobramycin PARI is a
hybrid medicine of TOBI
nebuliser solution which
has been authorised in
the EU since 10 December
1999. However, the new
product contains a different
strength of tobramycin and is
administered using a different
nebuliser device, allowing it
to be inhaled over a shorter
period.
According to EMA,
Tobramycin PARI is indicated
for the management of
chronic pulmonary infection
due to Pseudomonas
aeruginosa in patients aged
6 years and older with cystic
fibrosis (CF).
Ibrutinib in
combo with
obinutuzumab
for CLL/SLL
AbbVie announced that
the US FDA approved the
use of ibrutinib (Imbruvica)
in combination with
obinutuzumab (Gazyva) for
adult patients with previously
untreated chronic lymphocytic
leukemia/small lymphocytic
lymphoma (CLL/SLL).
The new approval expands
the use of ibrutinib which can
already be administered as a
single agent or in combination
with bendamustine and
rituximab (BR) for adult CLL/
SLL patients.
Ibrutinib is a once-daily
Bruton’s tyrosine kinase (BTK)
inhibitor that is administered
orally.
The FDA approval is based
on results from the phase
3 iLLUMINATE (PCYC-1130)
study, which showed the
combination of ibrutinib plus
obinutuzumab significantly
improved progression-free
survival (PFS) compared
to chlorambucil plus
obinutuzumab in previously
untreated CLL/SLL patients
who were 65 years or older,
or less than 65 years old with
coexisting conditions.
Patients treated in the
ibrutinib arm experienced
a 77 percent reduction in
risk of progression or death
compared to the chlorambucil
plus obinutuzumab arm.
The chemotherapy-free,
anti-CD20 combination
regimen also showed an
85 percent reduction in risk
of progression or death
compared to chlorambucil
plus obinutuzumab when
evaluating PFS in patients
with high-risk disease (17p
deletion/TP53 mutation, 11q
deletion, or unmutated IGHV).
The FDA also updated
the ibrutinib label to include
additional long-term efficacy
follow-up supporting its use as
a single agent in CLL/SLL from
the Phase 3 RESONATE (PCYC-
1112) and RESONATE-2 (PCYC-
1115, PCYC-1116) international
studies.
The recommended
dose of Imbruvica for CLL/SLL
is 420 mg orally once daily
until disease progression or
unacceptable toxicity as
a single agent or in combination
with obinutuzumab, or BR.
When administering ibrutinib
in combination with rituximab
or obinutuzumab, consider
administering ibrutinib
prior to rituximab or
obinutuzumab when given on
the same day.
FEBRUARY 2019 / FUTURE MEDICINE / 35

straight talk
“EVERYTHING CAN BE
MADE A STORY”
PROF K RAJASEKHARAN NAIR
was the former Director, Professor
& Head, Department of Neurology,
Medical College, Trivandrum. One of the
pioneering leaders in neurosciences
in India, he served as president of
Neurology Society of India (NSI), Indian
Academy of Neurology (IAN) and
Indian Epilepsy Association (IEA). An
eminent neurologist and a well-known
writer, Dr Nair is the recipient of many
awards and honours from different
universities and scientific bodies from
India, UK and USA, including Lifetime
Achievement Award in Neurology by
IAN, Chennai (2017), and Kerala Sahitya
Academy Award for the Best Scholarly/
Scientific Literature (2014). He has
published over 138 papers in different
peer-reviewed neurology and general
medicine journals. He is also the author
of nearly two dozen books, both in
English as well as Malayalam. Currently
Emeritus Professor of Neurology,
Medical College, Trivandrum,
he teaches movement disorders and
cognitive neurology.
Dr Nair discusses the profession,
practice and teaching of neurology and
his pursuits as a writer in
a free-wheeling conversation with
S HARACHAND of Future Medicine.
Excerpts:
You have been practicing as a clinician and a teacher in
neurology for over five decades now. How do you see the
specialty evolved over the years?
When I started the first neurology department at
Medical College, Trivandrum in 1973 soon after completing
my training in Glasgow, I had an extremely tough time
convincing the authorities about the need for such a
specialty. I was the lone neurology teacher in this part
of the world. I used to do everything myself. I needed to
conduct exams. I needed to give training.. all by myself...
In a short time, I formed an association of teachers in
neurology, involving my students, to promote academic
activities. TAN organised around forty CMEs over the years.
As usual, securing funding for the programme was the
biggest challenge at that point of time. We also came out
with ten books for teaching neurology. In these years, I could
also become the president of prestigious organisations
like Neurology Society of India (NSI), Indian Academy of
Neurology (IAN) and Indian Epilepsy Association (IEA). It
was not easy for a southerner like me to get into the top
echelons of these medical bodies.
The practice of neurology has changed dramatically
over the years. I studied neurology in a conventional way.
But I used to teach neurology in a manner which seemed
unconventional at that time. Today, I am studying neurology
as the cutting-edge of medicine. The exponential growth
of the subject is so beautiful, so good. Seeing the way it
has emerged..is absolutely pleasant. The difference is so
remarkably huge that no one can deny it. However, the new
doctors, who go by a technology-oriented methodology,
have a problem. Quite often, they tend to forget the fact
that the person sitting at the other side of the table is a
human being, with his own fear. The man is least interested
in the MRI finding of a tiny growth in the pineal body. He’s
bothered only about his headache. He is worried about what
will happen to his wife and his child if anything goes wrong.
The man sitting at this side of the table does not recognise
the you in you. The you in you or the I in I is different from
what the machine shows. No machine, till date, what should
I say, can truly reflect all emotions of human being or any
living thing...
Medical profession has become much more demanding
and complex in today’s world. What is your view?
I believe that a clinician has a much bigger role in today’s
36 / FUTURE MEDICINE / FEBRUARY 2019

world. He can be instrumental in changing
society. Like treating the sick, the clinician
can treat the society as a whole. But there
are times the medical professionals do not
receive what they legitimately deserve.
Today, we talk a lot about the Kerala
model of health care. It is often touted
as a runaway success story and a great
model which others can look to emulate.
When you look at the success of Kerala’s
well-touted healthcare model, you will
find that it is no one else, but the doctors
who are the real architects and who
made the model a resounding success. It
was the doctors who dared to go to the
Very few people know that it was
Dr Rustom Jal Vakil, a cardiologist
from Mumbai, who pioneered the
use of reserpine for hypertension.
It was the first-ever medicine to be
used against hypertension.
Prof K Rajasekharan Nair
PHOTO: SHIJITH SREEDHAR
far-off hinterlands, the remotest villages;
they were the ones who crossed rivers,
traversed forests and climbed hills to reach
out to communities living in the far-off
locales to make it happen and came back
afflicted with endemic diseases like malaria
and filariasis...
But the credit for the success went to
the so-called planners of the programme.
Again, very few people know that it
was Dr Rustom Jal Vakil, a cardiologist
from Mumbai, who pioneered the use
of reserpine for hypertension. It was the
first-ever medicine to be used against
hypertension. Extracted from the roots of
Rouwolfia serpentina (Sarapagandha),
use of reserpine was popular in India as
a routine anti-hypertensive agent. At that
time, the West did not have any drug
treatment to lower blood pressure. They
regarded the condition as benign.
Vakil, in 1949, published the 1st clinical
report on R. serpentina therapy in the
British Heart Journal. The article really
fired the imagination of the international
FEBRUARY 2019 / FUTURE MEDICINE / 37

esearch community. In his paper, Vakil
summarized 10 years of his experience
with Rauwolfia. After an extensive trial of
various hypotensive remedies in thousands
of cases of hypertension, Vakil found
Rauwolfia to be the most consistently
successful agent. In addition, Vakil sent
a questionnaire to 50 physicians from
all over India, and 46 of those voted for
Rauwolfia as the best hypotensive agent in
their experience.
A well-known neurologist and
academician, you are also renowned for
your writings. Your first published fiction
was a novel. How do you eminently
combine these two diverse streams?
My first published novel ‘Oru Puzhayude
Katha’ (The Story of a River) was not pure
fiction. It is also a scientific novel. The
novel discusses the story of the decay of
a river called Chaliyar river, which was the
bloodstream serving a large number of
villagers in a northern part of Kerala. An
industrial unit in the locale was polluting the river and its
environment with its effluents. It was affecting the lives of
so many poor people living on the banks of the river. For
me, the issue was so compelling. I wanted to write about
it but I was not finding time because of my extremely busy
schedule. In those days, as the head of the department
of neurology at Medical College Hospital, Trivandrum my
routine started in the early morning hours and ended late in
the night.
Fortunately, I chanced to get the time to write the book
while in Libya where I was assigned with the responsibility
of setting up a department of neurology at Garyounis
University, Benghazi... The Libyan authorities took nearly
three weeks to arrange the necessary facilities for me. I
managed to complete the novel within this time gap. Oru
Puzhayude Katha, which was published in 1979, was the first
environmental novel in the Malayalam language. I am not
sure how many people are aware of this fact.
Are you working on any new books presently?
Yes. My latest book is currently in print. It is written in
Malayalam and is expected to be published in the next two
months’ time. The title of the book is ‘Munpe Nadannavar’
(Those Who Walked Ahead). For a change, it is a homage
to my contemporaries, but is also the story of disregard and
neglect. You know, the person who brought neuroscience
to India is a Keralite. His name is Dr Jacob Chandy. He was
living for fifteen years in Kottayam totally unheard of. And
he died there, unknown, forlorn. Nobody, not even anyone
from the medical community, bothered to take care of him,
the great man. The only mistake he did was that he decided
to come back and settle in his homeland. I discussed his
case among our circle. Many of them didn’t even know him.
Since I am the only person who is alive today in the clan and
the only one who can write, I thought it is my duty to pay
homage to that great man.
And the second book that I am working currently on is
about how we understand our perception or experience and
how they can turn, what should I say, faulty? The book has
these ‘faulty’ perceptions and sensations people experience
as its theme. For instance, if you drop a pen before some
of my patients, they will get absolutely frightened. They will
think that it is a snake or something, and will try to wriggle
out of the situation and run away... I thought of the idea of
putting together the cases of these ‘faulty’ sensations. To
achieve this, one needs deep knowledge in the subject. And
secondly, the person should know how to write. Among the
doctors’ fraternity, I don’t see anybody else who can write.
So, again I thought I should do it.
What would you prefer to be known as — a neurologist
or as a writer?
A neurologist. Till the end of my life.
I started teaching neurology even before I joined for
38 / FUTURE MEDICINE / FEBRUARY 2019

PHOTO: SHIJITH SREEDHAR
my DM. In hindsight, when I look back
sometimes, I feel some of my decisions
were not proper. For one, I used to teach
post post-graduate students. A few batches
passed through my hands. In between,
I happened to teach two batches of
undergraduate students. That was purely
out of compulsion by someone whom I
cannot say no to. Then I stopped it as I was
not able to find enough time. But when I
look back at those jam-packed classrooms
which seemed to swell each day, I feel that I
should have done more. I realize there is an
advantage of teaching MBBS students. There
is a large number of students with fresh
minds. They also imbibe and absorb things
much faster...
And the second thing is about not
participating in public functions. As a rule, I
never attended any public meetings. Now, I
see there are so many people around who
would like to listen to speeches. There are
very many who would love to read books.
When I published a book that comes around
1000 pages and cost nearly 900 rupees, it
got sold out like anything in a short time.
I have been
writing since
my childhood.
Everything can
be made a story.
Probably, that is
what a raconteur
does...
Now the second edition is being printed...
But I am exceedingly happy with what I am
doing.
So, your practice, teaching and writing
will all go hand in hand...
I have been writing since my childhood.
Everything can be made a story.
Probably, that is what a raconteur does...
I am teaching my favourite subjects
— movement disorders and cognitive
neurology. And I am practising neurology
even today, even though [it is] for select
patients who come seeking me. Touch
wood, I can say I am very old. It is because
of nothing but God’s grace. A lot many in
my generation have passed away. Many
others are sick. Most of them stopped
working. I have my own problems too, but
still, I keep going. I keep myself awake till
late in the night... studying neurology...
All I wanted to say is that there
exists a power beyond the limits of our
comprehension. To deny it is fashion. Deny
it or not, without the power, we are but a
big zero.
FEBRUARY 2019 / FUTURE MEDICINE / 39

case reports
CYST OR CYSTICERCUS?
Brain infections caused by
tapeworm larvae are
not uncommon in India
Rajesh (name changed), a 10-year-old boy from
Kolhapur, was a studious kid. However, lately, he
had started reading his books while lying down.
His father, who was the principal of a local school, was
unhappy seeing these reading habits and would keep
nagging his son to sit in an appropriate upright position
while reading. Rajesh, however, would get headaches
while reading in a sitting position and for the past
month or two, he was able to read for longer
periods without a headache only if reading while
lying down on his back. The arguments continued
between father and son for several months until
Rajesh’s condition worsened, and his headaches
become more severe and accompanied with vomiting
and visual blurring. Rajesh’s father then realized there
may be more to his reading habits and had to seek
medical advice from a paediatrician. The paediatrician
recommended an ophthalmic checkup and a CT scan of the
brain. Funduscopic examination revealed papilledema and
the CT scan showed a cyst in the third ventricle. Rajesh was
then referred to Dr Uday Andar, a paediatric neurosurgeon at
Bombay Hospital, Mumbai, for further management.
Dr Andar recommended an MRI brain scan which showed a
pedunculated cyst within the third ventricular cavity. Surgery
40 / FUTURE MEDICINE / FEBRUARY 2019

was immediately scheduled, and the cyst was excised micro
endoscopically without any complications.
Interestingly, the cyst turned out to be cysticercus.
Cysticercus is a tapeworm belonging to the genus Taenia.
They look like a small sac-like vesicle similar to a bladder.
These tapeworms commonly reside in the muscles of pigs
and cattle and their eggs are typically ingested with raw or
undercooked contaminated pork or beef or through raw
contaminated vegetables in salads. The eggs hatch inside
the human host and can move anywhere in the body via
the bloodstream, including the brain. Brain infections can be
especially dangerous as they may lead to neurocysticercosis,
which is one of the major causes of acquired epilepsy.
Depending on the location of the cyst in the brain, it
may even result in death in case of high pressure due to
hydrocephalus. Cysticercus is likely to be present at multiple
locations, and upon further investigation, Rajesh was found
to have cysticercus in the leg calf muscles as well. This is
typically visualized as lumps under the skin.
Because of the pedunculated nature of the cyst in the
third ventricle of the brain, whenever Rajesh would sit and
bend forward to read, the foramen of Monro would get
blocked and cerebrospinal fluid would collect
in the ventricles increasing the intracranial
pressure and causing headaches. Whenever
Rajesh was in a supine position, the cyst
would move backwards and the block would
be released, allowing the cerebrospinal fluid
to flow freely and relieve the headache. For
Rajesh, this condition worsened as the cyst
enlarged, and finally, when the cyst was large
enough to block the ventricles, it resulted
in hydrocephalus and consequently visual
blurring. Had it been left untreated much
longer, it could have resulted in death due to
the increase in intracranial pressure.
Cysticercus is not uncommon in India,
especially in a city like Mumbai, where
vegetables are grown along the railway
tracks and exposed to all sorts of human and
animal excreta. Dr Andar advocates that both
vegetables and meats be thoroughly cleaned
and cooked well before being consumed.
WHENEVER THE BOY WOULD
SIT AND BEND FORWARD TO
READ, THE FORAMEN OF MONRO
WOULD GET BLOCKED
Often, early diagnosis is missed in
children, either because the child does
not complain, or the parents ignore minor
complaints until the condition worsens.
Dr Andar advises that ‘children complaining
of headaches for more than 7-10 days be
carefully investigated. Though there is no
literature to support this, clinical experience
teaches one to be more prudent than sorry
and investigate such children early on.’
With the current technological advances
in the field of non-invasive investigations
such as CT scans and MRIs, it is definitely
advisable to investigate early and thereby
prevent catastrophes and the risk of high
morbidity. In Rajesh’s case, it turned out to
be a cysticercus. However, it could have been
a tumour. Early diagnosis and treatment is
essential in such cases.
DR SHIVANEE SHAH
42 / FUTURE MEDICINE / FEBRUARY 2019

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FEBRUARY 2019 / FUTURE MEDICINE / 43

case reports
A HARROWING SWALLOW
Aspirated foreign bodies should be considered as a differential in any
young child with unexplained cough
Small children, especially those younger than 3 years,
are prone to putting small objects in the mouth. With
their limited chewing capabilities and high respiratory
rates, these objects are inadvertently swallowed in. Further
their tendency to laugh and run around while eating also
increases the chances of the object being aspirated into the
trachea. Most often these are food items. However, it is not
uncommon for children to explore non-food items, resulting in
the aspiration of foreign bodies. Some of the most commonly
found non-food items include small toys and jewelry.
Aspirated objects have the propensity to get lodged in the
right bronchus as it is wider and has more direct extensions
from the trachea.
Clinical presentation may be extremely variable depending
on the location of the aspirated object. Most often, the child
experiences sudden coughing bouts or choking. In worst
cases, if the object is large and causes a total or near-total
occlusion of the airway, it can result in death or hypoxic brain
damage. However, the more difficult and tricky cases are the
ones in which the aspiration goes unnoticed and the child
may present with persistent or recurrent coughing bouts,
pneumonia or lung abscess.
Diagnosis can be made through one of several imaging
methods. The first test is typically a chest X-ray, using
anteroposterior and lateral films. Food objects are radiolucent
and may, therefore, be difficult to visualize via radiography.
However, in case of suspicion of foreign
body aspiration, radiologists often look for
an area of focal over-inflation or an area
of atelectasis, depending on the extent of
the airway blocking. In case of a normal
chest X-ray, other imaging techniques such
as computed tomography and magnetic
imaging may be explored to determine the
position of the foreign body. Non-invasive
methods such as computed tomography
with virtual bronchoscopy can be performed
IN CASE OF SUSPICION OF
FOREIGN BODY ASPIRATION,
RADIOLOGISTS OFTEN LOOK
FOR AN AREA OF FOCAL
OVER-INFLATION
in cases of sharp objects that have a high risk
of damaging the lung.
Once the location is identified, it is
imperative to remove the foreign object
to avoid further complications. Rigid
bronchoscopy under general anaesthesia is
the procedure of choice for removing objects.
Bronchoscopic removal may fail in case of
peripheral location or technical difficulties.
In such cases when the foreign body
cannot be grasped by endoscopic forceps,
bronchoscopy should be abandoned, and
an open surgical procedure or thoracotomy
should be considered.
Here is a case of a 5-year-old female
child who had swallowed an LED bulb with
two small, sharp metal prongs. She was
immediately taken to a local hospital where
a chest X-ray revealed the position of the
bulb in the left thoracic cavity. No foreign
body was found in an upper gastrointestinal
44 / FUTURE MEDICINE / FEBRUARY 2019

endoscopy. A bronchoscopy under general anaesthesia was
attempted to remove the bulb. However, this procedure
had to be abandoned due to
bleeding. Post bronchoscopy,
the child went into asystole
and required cardiopulmonary
resuscitation. She was kept
on mechanical ventilation and
inotropic support overnight in
a cardiac intensive care unit for
12 hours until she stabilized.
She was then transferred
to a specialized center for
further management and
referred to Dr Rajeev Redkar,
THE LED BULB APPEARED
TO BE EMBEDDED IN
THE LUNG PARENCHYMA
AND THE PATIENT
WAS PREPARED FOR A
THORACOTOMY
consulting paediatric surgeon. A chest computed tomography
with virtual bronchoscopy was done to visualize the foreign
body and the location was confirmed to be in the left lower
bronchus. The LED bulb appeared to be embedded in the
lung parenchyma with the prongs only partially in the airway
and the patient was prepared for a thoracotomy. Due to
its close proximity to the heart and major vessels, General
Dr V Ravishankar, a cardiothoracic surgeon, was consulted.
Dr Minhaj Sheikh, a consultant paediatric intensivist, was
also part of the medical team. Left lower bronchus was
identified and opened minimally. The foreign body was
carefully removed and the incision closed
with interrupted non-absorbable sutures.
The procedure was completed without any
bleeding and complete expansion of the
left lower lobe was confirmed post foreignbody
removal. An intercostal drain was
kept in place for 2 days post surgery. The
patient was kept on orals for 24 hours and
discharged within 4 days.
It was a harrowing experience for the
child and her family.
This is the primary reason for the alert
on toys with small parts: “Not suitable for
children under 3”. However, 3 is not a magic
age and older children also put objects in
the mouth with devastating consequences.
Aspirated foreign bodies should be
considered as a differential in any young child
with an unexplained cough, and Dr Redkar
cautions that the medical team should
also consider the potential risks involved
during and after bronchoscopy in case of
tracheobronchial foreign body aspirations.
DR SHIVANEE SHAH
FEBRUARY 2019 / FUTURE MEDICINE / 45

case reports
WOLFRAM AND A DEVICE
How continuous glucose monitoring tech came to the rescue of
a complicated genetic condition
A
25-year-old male patient presented with repeated
episodes of loss of consciousness and seizures. These
episodes were associated with hypoglycemic events,
especially at night. The patient and his family were extremely
worried and consulted with Dr Arun Menon, Endocrinologist,
Amrita Institute of Medical Sciences, Kochi. The patient had
type 1 diabetes since childhood, progressive deafness, and
was visually impaired. He had been previously diagnosed with
Wolfram syndrome type 1.
Wolfram syndrome is characterized by juvenile onset
diabetes mellitus and optic atrophy. It is primarily an
autosomal recessive inherited disorder that affects 1 out
of 100,000 to 1 out of 770,000 individuals worldwide.
Because of the associated neurodegenerative presentation,
it is also referred to by the acronym, DIDMOAD (diabetes
insipidus, diabetes mellitus, optic atrophy and deafness).
Often, a variety of other symptoms may
also be associated, such as ataxia, seizures,
depression, gastrointestinal problems, sleep
conditions, autonomic neuropathy etc..
Depending on the genetic mutation,
Wolfram syndrome can be type 1, caused
due to mutations in the WFS1 gene, or type
2, caused due to mutations in the WFS2
or CISD2 gene. WFS1 gene encodes for the
protein wolframin, which plays a role in
protein folding by regulating calcium levels
in the endoplasmic reticulum of cells. In
the pancreas, it is specifically important for
folding of the proinsulin protein. In the inner
ear, it is required for maintaining calcium
levels essential for hearing. Mutations in
46 / FUTURE MEDICINE / FEBRUARY 2019

adapted exceptionally well and managed to
regularize his life style as well as his glucose
levels with the help of the pump. This HbA1c
levels improved from 13% to 8.2% between
June 2017 to February 2018.
To ensure appropriate glucose monitoring
in addition to insulin delivery, the patient was
started on a continuous glucose monitoring
system. This is a cell phone app based realtime
glucose monitoring system that provides
continuous interstitial glucose profiles
directly on the cell phone. This system sends
regular alerts on the cell phones based
app, effectively preventing hyperglycemic or
hypoglycemic episodes and allowing for even
better glucose level control. Other benefits of
using such a continuous monitoring system
include a reduction in checking interstitial
glucose to twice a day only, and that too only
wolframin result in improper functioning of the endoplasmic
reticulum, and consequently, cell death. Prominently, insulinproducing
beta cells are affected, which results in diabetes
mellitus; and a gradual loss of the cells and the optical nerve
eventually results in blindness. Cell death in other organs may
cause a variety of other signs and symptoms associated with
Wolfram syndrome.
Currently, there is no cure for this syndrome and longterm
prognosis is completely dependent on the affected
organs. Several therapeutic options, including drugs that can
balance calcium levels in the ER or improve protein folding
and trafficking in the ER, and stem cell therapy to regenerate
the destroyed cells are being explored. However, as of now,
treatment is only supportive and based on the symptoms in
each individual. Most individuals with Wolfram syndrome have
an average lifespan of only 30-40 years.
The patient and his parents were extremely worried
because of the nocturnal hypos which significantly affected
their quality of life. The patient was already being treated with
multiple daily injections of insulin. However, this treatment
was not effective and resulted in unpredictable episodes of
hyperglycemia and hypoglycemic without any recognizable
warning signs. The patient was consequently afraid of taking
the insulin as the effect was unpredictable and even small
doses could result in dangerous hypos. To provide a more
continuous treatment strategy, Dr Menon started him on an
insulin pump. The continuous subcutaneous insulin infusion
(CSII) allows for constant, continuous infusion of insulin under
the skin. The insulin pump was effective in immediately
stabilising the glucose levels. However, a major concern was
whether the patient would be able to manage the pump with
his visual and hearing impairment. Surprisingly, the patient
THE PATIENT WAS AFRAID OF
TAKING THE INSULIN AS THE
EFFECT WAS UNPREDICTABLE
AND EVEN SMALL DOSES COULD
RESULT IN DANGEROUS HYPOS
for calibration purposes. As of September
2018, the patients HbA1c levels were at 7.3%.
While these are still higher than normal,
they are much improved compared to a year
ago, and the patient is able to manage his
glucose levels much more effectively and is
witnessing far fewer hypoglycemic episodes.
While diabetes and related conditions
are dramatically increasing worldwide,
technology is also advancing by leaps and
bounds. Several monitoring and drug delivery
devices are available now, even as others are
in the pipeline, to make it simpler to control
diabetes and continue retaining good quality
of life. Dr Menon is optimistic for the future:
“With the technological advances, it is now
possible to get real-time glucose profiles for
a better understanding of how glucose levels
fluctuate in each individual, and treatment
should be tailored accordingly.”
DR SHIVANEE SHAH
FEBRUARY 2019 / FUTURE MEDICINE / 47

esearch snippets
Light-emitting
implant to control
overactive bladder
Aaron D. Mickle et al have developed
a miniaturized, implantable device
that could potentially help people with
bladder problems in providing chronic
stability by stimulating specific cell types.
The soft bio-optoelectronic implant can
detect overactivity in the bladder and
use light from tiny bio integrated LEDs
to tamp down the urge to urinate. The
researchers had conducted the study
on a rat model where the soft stretchy
belt-like device was implanted around
the bladder. Light-sensitive protein,
opsins, were injected into the bladder.
The opsins were carried by a virus that
binds to nerve cells in the bladder,
making them sensitive to light signals.
The activity of the bladder could be
controlled using an external hand-held
Bluetooth device. During abnormally
frequent emptying of bladder, the
external device can send a signal that
activates the micro-LEDs on the device,
which activates the sensory neurons
in the bladder, thus restoring normal
bladder activity. Unlike conventional
continuous stimulation protocols,
this integrated closed loop operation
essentially delivers therapy only when a
problem is detected, avoiding discomfort
and pain. Though the stable expression
of opsin using the viral approach is still
a concerning issue, researchers hope
to soon develop it to help people who
suffer from severe bladder problems.
Source: Nature volume 565, pages361–365 (2019)
Published: 02 January 2019 https://www.nature.
com/articles/s41586-018-0823-6
Sexism among brain
tumours
Yang et al. showed a significant
role for sex difference among
patients of aggressive brain tumour
glioblastoma, marking the need to
optimise the therapeutic regimen for
each patient. The research identified
a remarkable distinction in molecular
subtyping among glioblastoma of
male and female patients, indicating
the need to stratify the tumours for
effectiveness of treatment in a sexspecific
manner. The researchers
performed a quantitative imagingbased
measure of response among
the patients using MRI scans
and survival data from a cancer
research database. The cohort of
63 patients involved 40 males and
23 females who received standard
chemotherapy. While initial tumour
Candida infections
in brain may impair
memory
Yifan Wu et al reported that the
common yeast Candida albicans
could cross the blood-brain barrier to
trigger inflammatory response leading
to the formation of granulomatous
growth velocities were the same, only
female patients showed a steady and
significant decline in tumour growth.
On the application of sophisticated
statistical algorithms, the difference
in molecular subtypes among males
and females were identified, revealing
that their survival was driven by very
different molecular pathways. The
study thus suggests that greater
precision in glioblastoma molecular
subtyping can be achieved through
sex-specific analyses. The researchers
suggest that a personalised approach
in treatment would greatly improve
outcome for the patients in the future.
Source: Science Translational Medicine 02
Jan 2019: Vol. 11, Issue 473, eaao5253
DOI:10.1126/scitranslmed.aao5253 http://stm.
sciencemag.org/content/11/473/eaao5253
structures and mild memory impairment.
The study reveals a resemblance
between the granuloma-type structures
with plaques found in Alzheimer’s
disease. The researchers injected a
dose of 25,000 C. albican cells into a
mouse model. The yeasts showed to
cross the blood-brain barrier triggering
the microglia. They also produced a
number of molecules that mediated
inflammatory response. This led to
48 / FUTURE MEDICINE / FEBRUARY 2019

capture of yeasts within a granule-type
structure in the brain called fungusinduced
glial granuloma (FIGG). Resultant
accumulation of amyloid precursor
protein within the periphery of the
granuloma revealed the possibility for
fungal involvement in the development
of neurodegenerative diseases. The
mice cleared the infection in 10 days
leaving active microglia and FIGG for
about 21 days. They also displayed mild
memory impairment that resolved with
fungal clearance. The research supports
a need for future studies on long-term
neurological consequences of sustained
C. albican infection.
Source: Nature Communications, Volume 10,
Article number: 58 (2019) Published: 04 January
2019 https://www.nature.com/articles/s41467-
018-07991-4
Inhalable mRNA offers
new therapeutic
delivery to lungs
Asha Kumari Patel et al developed
an effective method for nebulized
delivery of in vitro mRNA providing
a clinically relevant delivery system
to lung epithelium. The delivery was
facilitated by hyperbranched poly
beta-amino esters (hPBAEs) vectors.
Unlike previously used carriers, hPBAEs
are positively charged biodegradable
polymers. hPBAE protects the mRNA
from degradation during inhalation
and ensures their proper entry into
the lungs. The researchers produced
protein encoding inhalable mRNA in a
suspension from within nanoparticle
spheres. The mice used in the study
were allowed to inhale the droplet
suspension as mist via nebulizer. It
induces the production of luciferase
protein 24 hours after inhalation of
hPBAE. Repeated inhalations helped
maintain a steady concentration of the
bioluminescent protein within the lungs.
The study reveals the therapeutic utility
of the innovation which could help treat
a range of lung diseases.
Source: Advanced Materials 2019, 180511604
January 2019 https://doi.org/10.1002/
adma.201805116
—Compiled by Divya Choyikutty
Closed-loop neuromodulation
device to stimulate brain
Andy Zhou et al demonstrated a wireless artefactfree
neuromodulation device -WAND that could help
treat various neurological disorders. Using a closed-loop
neuromodulation system WAND can record as well as
stimulate over 128 channels in the brain with the ability
to fully cancel the stimulation. The device is currently
experimented in a rhesus macaque in delaying specific arm
movements. WAND can record abnormal electrical activity
in diseases such as epilepsy and regulate the stimulation
to counteract the electrical signals of the brain. This could
help patients overcome tremors and other movement
disorders. Researchers suggest that the ability to actually
stimulate and record in the same brain region could
help provide effective therapy in a variety of neurological
conditions in the future. WAND can be used as a generalpurpose
research tool for preclinical investigations of
stimulation-based therapeutic interventions and variety of
other applications with minor modifications.
Source:Nature Biomedical Engineering Volume 3, pages15–26 (2019) 31
December 2018 https://www.nature.com/articles/s41551-018-0323-x
50 / FUTURE MEDICINE / FEBRUARY 2019

column
the cellview
Need for alternative
technologies
Why reducing sequencing costs may not be a complete
answer to increasing genome-wide studies
DR RAJANI KANTH
VANGALA
The author is medical
scientist and former
director of SGRF,
Bangalore
There has been a significant
advancement in genomic sequencing
technologies with the inception of
NextGen Sequencing. However, in India
and South Asia, there is a lack of largescale
studies with long-term follow up to
understand if there are any South Asian
or India-specific genetic markers. The
biomarker discovery is largely dependent
on biospecimen collection and storage.
Even though sequencing costs are
coming down, the biospecimen collection,
processing, transport and storage systems
have remained very complex and costly.
The present-day collection systems are not
aimed at a single collection plus storage;
therefore, processing the collected samples
is a necessary step. In many studies which
involve collecting samples from different
centres, it will involve transportation of the
samples on dry ice. Furthermore, after the
samples are received, they need immediate
transfer into liquid nitrogen tanks or into
deep freezers. Long term maintenance of
these storage systems is a costly affair.
Therefore, a long-term accessible
biorepository is a major bottleneck for
such important studies as all biomarkers
will need careful evaluation and validation
before translating them into clinical practice.
I have been in the field of biomedical and
biomarker translational research for more
than two decades. In my experience, apart
from other factors, a proper biorepository
with low-cost maintenance is of high
importance, with special emphasis on low
cost. In my previous organization, a largescale
clinical biomarker study was started.
With a lot of effort from several clinical
and scientific groups, more than 12,000
biospecimens were collected over a decade.
However, these samples were extremely
difficult to maintain due to the spiraling costs
of maintenance of freezers, manpower and
power. Therefore, it became very evident
that if we were to conduct any meaningful
genomic studies, we need alternative
technologies which can truly help research
and reduce the costs.
The molecular diagnostics market is
expanding at a good pace, but if we are to
make the genome more amenable for regular
diagnostics, it is very important to reduce
costs and develop technologies for the
Indian community. At the same time, these
technologies should always be compared
to existing methods and must be validated
for several downstream applications. Apart
from different applications, the suitability to
different tissue types is also very important
as specific tissues need preservation. An ideal
technology will be that which can be used
to collect the biospecimens, and without any
major processing, can be used for long-term
storage at room temperature or ambient
temperature. This technology can truly bring
a revolution in the progress in genomic
studies in India and enable sequencing
research and diagnostics to be carried out
more robustly. Our new institute, Institute for
Applied Research and Innovation (InARI), has
been working on such a technology called
“Insta-Preserve RT”, which we are now ready
to bring into the market.
52 / FUTURE MEDICINE / FEBRUARY 2019

disease
INDIA’S CANCER
BURDEN
Cancers contributed 5% of the total
disabilities and 8.3% of all deaths in
India in 2016, shows a state-wise study
The number of cancer-related
deaths in India more than doubled
between the years 1990 and 2016,
according to a paper titled “The Burden
of Cancers and Their Variations Across
the States of India: The Global Burden
of Disease Study 1990–2016” published
in the October 2018 edition of Lancet
Oncology.
The paper gives a comprehensive
summary of the patterns and time
trends of the total cancer burden as
well as specific cancer types
in each state of India
estimated as a
The crude cancer
incidence rate in
India increased by
28.2%
part of the Global Burden of Diseases,
Injuries, and Risk Factors Study (GBD)
2016. The article was authored by a
group called ‘India State-Level Disease
Burden Initiative Cancer Collaborators’.
Setting
Though there have been previous
attempts to review the estimates of
cancer incidence and mortality in India
and its different regions, the present
article presents a comprehensive report
of the patterns and time trends.
54 / FUTURE MEDICINE / FEBRUARY 2019

Methodology of the study
Data from multiple sources, including 42
population-based cancer registries and
the national sample registration system
of India was used. The study presents
data on:
1 The incidence of 28 types of cancer
in every state of India from 1990 to
2016
2. Death rates and trends of all
types of cancers
3. Disability-adjusted life years
(DALYs) for each type of
cancer
4. The contribution of
major risk factors
to the cancer
DALYs in
India
Rajasthan
58.8
72.6
Haryana
71.0
103.3
Himachal
Pradesh
69.8
91.6
Punjab
58.0
85.5
Jammu &
Kashmir
69.1
79.2
Delhi
64.6
102.9
Uttarakhand
69.3
91.0
Uttar Pradesh
72.0
79.0
Bihar
44.9
53.9
RISING NUMBERS
Crude annual incidence
rate of all cancers together
in the states of India,
1990 and 2016
1990 2016
Jharkand
58.0
64.3
Arunachal
Pradesh
75.9
78.5
Meghalaya
69.0
81.4
Sikkim
67.8
74.4
Tripura
52.9
69.0
Assam
68.7
90.2
Nagaland
63.1
70.3
DALY (Disability Adjusted
Life Years)
Madhya
Pradesh
69.4
83.1
Gujarat
55.5
75.8
It is a metric for reporting the
disease burden due to mortality
and morbidity caused by a disease.
It is the measure recommended by
the National Health Policy of India for
tracking disease burden. Disability for
each cancer was estimated by splitting
the prevalence into four sequelae:
diagnosis and primary treatment,
controlled phase, metastatic phase and
the terminal phase. Each prevalence
sequelae were then multiplied with
specific disability weights to see the
‘years lived with disability’ (YLDs). The
years of life lost (YLLs) was calculated
from the age-specific mortality estimates
and the reference life expectancy for
that age group. DALYs were computed
Maharashtra
62.0
80.2
Goa
52.5
97.0
Karnataka
76.2
101.6
Kerala
74.1
135.3
Andhra
Pradesh
58.1
76.6
Tamil Nadu
58.9
82.9
Telengana
54.9
72.6
W Bengal
63.9
85.4
Chhattisgarh
58.8
82.0
Odisha
68.6
83.6
Incidence
rate per
100,000
Mizoram
89.1
121.7
Manipur
48.1
64.3
> 105
90-104.9
75-89.0
60-74.9
45-59.9
SOURCE: thelancet.com
FEBRUARY 2019 / FUTURE MEDICINE / 55

as the sum of YLLs and YLDs, for each
type of cancer for the location, year, age
and sex.
The data is reported for 31
geographical units in India, including 29
states, Delhi and union territories other
than Delhi.
Summary of the Results: The
article states that all cancers together
contributed 5.0% of the total DALYs
and 8.3% of the total deaths in India in
2016, an increase of 90.9% and 112.8%
respectively from 1990. The highest crude
cancer DALY rates in 2016 were in the
states of Mizoram, Kerala, Assam, Haryana
and Meghalaya. The estimated number of
incident cancer cases in India increased
from 548,000 in 1990 to 1,069,000 in
2016. The crude cancer incidence rate in
India increased by 28.2% from 63.4 per
THE CRUDE CANCER
INCIDENCE RATE WAS THE
HIGHEST IN KERALA AND
MIZORAM
100,000 in 1990 to 81.2 per 100,000 in
2016. The crude cancer incidence rate
was the highest in Kerala and Mizoram,
followed by Haryana, Delhi, Karnataka,
Goa, Himachal Pradesh, Uttarakhand and
Assam.
The number of deaths due to cancer
in India increased from 382000 in 1990
to 813000 in 2016. The crude cancer
death rate in India in 2016 was 61.8 per
100,000, as compared with 44.2 in 1990.
The cancer types responsible for
more than 5% of the total cancer DALYs
among both sexes combined in 2016
were stomach cancer (9.0%), breast
cancer (8.2%), lung cancer (7.5%), lip
and oral cavity cancer (7.2%), pharynx
cancer other than nasopharynx (6.8%),
colon and rectum cancer (5.8%), leukemia
(5.2%), and cervical cancer (5.2%).
Stomach cancer was responsible for the
highest DALYs among all cancers in India
in both 1990 and 2016. Among females,
CHANGE IN DALYS FOR DIFFERENT TYPES OF CANCERS IN INDIA,
1990–2016
Type of cancer 2016 1990 Change
Stomach cancer
Breast cancer
Lung cancer
Lip and oral cavity cancer
Pharynx cancer other than nasopharynx
Colon and rectum cancer
Leukaemia
Cervical cancer
Oesophageal cancer
Brain and nervous system cancer
Liver cancer
Non-Hodgkin’s lymphoma
Gallbladder and biliary tract cancer
Larynx cancer
Pancreatic cancer
Ovarian cancer
Prostate cancer
Bladder cancer
Nasopharynx cancer
Thyroid cancer
Myeloma
Hodgkin’s lymphoma
Uterine cancer
Kidney cancer
Mesothelioma
Malignant skin melanoma
Testicular cancer
Non-melanoma skin cancer
SOURCE: thelancet.com
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
1
4
7
5
6
8
3
2
9
11
15
12
14
10
16
17
20
22
18
19
23
13
21
25
26
27
24
28
36.2%
114.9%
136%
102.9%
106.1%
109.6%
35%
21.6%
59.3%
85.2%
206.1%
133.9%
169.4%
40.5%
122.6%
157.2%
140.3%
104%
29.1%
36.8%
158.5%
-30.3%
37.5%
124%
126.6%
110.7%
-29.8%
90.2%
56 / FUTURE MEDICINE / FEBRUARY 2019

CHANGE IN INCIDENCE RATE
Type of cancer 2016 1990 Change
Breast cancer
1 4 188.3% 89.2%
Lip and oral cavity cancer
2 3 95.9% 28.5%
Cervical cancer
3 1 19.7% -21.4%
Stomach cancer
4 2 23.7% -18.8%
Lung cancer
5 6 116% 41.8%
Pharynx cancer other than nasopharynx 6 5 104.8% 34.4%
Colon and rectum cancer
7 7 128.6% 50%
Oesophageal cancer
8 8 43.9% -5.5%
Leukaemia
9 9 33% -12.7%
Prostate cancer
10 17 221.2% 110.8%
Larynx cancer
11 10 45.6% -4.5%
Liver cancer
12 15 178.6% 82.9%
Gallbladder and biliary tract cancer 13 14 138.7% 56.7%
Ovarian cancer
14 18 165.5% 74.2%
Non-Hodgkin’s lymphoma
15 16 138.5% 56.5%
Brain and nervous system cancer 16 11 76% 15.5%
Pancreatic cancer
17 13 99.1% 30.6%
Non-melanoma skin cancer
18 12 89.8% 24.6%
Thyroid cancer
19 21 171.7% 78.4%
Bladder cancer
20 22 153.7% 66.5%
Uterine cancer
21 23 121.6% 45.5%
Kidney cancer
22 24 160.8% 71.2%
Nasopharynx cancer
23 20 25% -17.9%
Mutiple Myeloma
24 25 148.9% 63.4%
Hodgkin’s lymphoma
25 19 -26.1% -51.5%
Malignant skin melanoma
26 28 175.9% 81.1%
Testicular cancer
27 26 20.4% -21%
Mesothelioma
28 27 101.5% 32.2%
breast, cervical, and stomach cancer were
responsible for the highest DALYs in 2016.
The highest cancer DALYs among males in
India in 2016 were lung cancer, followed
by lip and oral cavity cancer, other pharynx
cancer and stomach cancer.
Among these cancers, the agestandardised
incidence rate of breast
cancer increased significantly by 40.7%
from 1990 to 2016, whereas it decreased
for stomach (39.7%), lip and oral cavity
cancer (6.4%), cervical cancer (39.7%),
oesophageal cancer (31.2%) and leukaemia
(16.1%). The study found substantial
inter-state heterogeneity in the agestandardised
incidence rate of different
types of cancers in 2016, with 3.3 times
to 11.6 times variation for the four most
frequent cancers (lip and oral, breast, lung,
and stomach).
Tobacco use, alcohol use and dietary
risks were estimated by GBD to contribute
to the highest cancer DALYs in 2016: They
were responsible for 10.9%, 6.6% and 6.0%
of the total cancer DALYs, respectively.
Tobacco use was the leading factor.
Summary
The authors interpret the study finding
by concluding that the data should be
used to strengthen the infrastructure and
human resources for cancer prevention and
control at both the national and state levels.
Efforts should focus on the ten cancers
contributing the highest DALYs in India,
including cancers of the stomach, lung,
pharynx other than nasopharynx, colon and
rectum, leukaemia, oesophageal, and brain
and nervous system, in addition to those
of the breast, lip and oral cavity and
cervical cancer, which are currently the
focus of screening and early detection
programmes.
Source: https://www.thelancet.com/journals/
lanonc/article/PIIS1470-2045(18)30447-9/
fulltext
Reviewed by Dr Krishnakumar
Thankappan, Professor, Dept
of Head & Neck Surgery and
Oncology, Amrita Institute of
Medical Sciences, Kochi
drkrishnakumart@gmail.com
FEBRUARY 2019 / FUTURE MEDICINE / 57

onco surgery
NOVEL
58 / FUTURE MEDICINE / FEBRUARY 2019

SURGICAL OPTIONS
IN BREAST CANCER
Oncoplastic techniques like nipple sparing surgery and procedures to reduce
lymphedema are being explored currently in breast cancer surgery
DIANE M RADFORD
Nipple-sparing mastectomy
(NSM) in the United States was
first described by Drs.
Joseph Crowe and Randall Yetman of
the Cleveland Clinic (CCF) in
2004. Incision placement for the
procedure can be inframammary,
periareolar, lateral, upper outer
quadrant, lateral with a periareolar
extension, medial, and transareolar.
When the tumour is superficial in
location, preserving the skin anterior
to the tumor can compromise the
oncologic goal of clear margins. The
technique of Tumour Ultrasoundguided
Incision (TUGI) for NSM
developed by Dr Stephen Grobmyer
and colleagues at CCF overcomes this
problem.
The technique employs
intraoperative ultrasound to locate
the tumour and delineate the skin
overlying it. The incision is then based
on the tumour location, removing the
skin anterior to the tumour en bloc
with the NSM. This approach balances
oncologic safety and technical
outcomes.
Lymphedema is the nemesis of
axillary nodal surgery for breast cancer,
impacting patient quality of life and
resulting in significant functional,
Round
periareolar
Elliptical
periareolar
LYMPHEDEMA IS THE NEMESIS
OF AXILLARY NODAL
SURGERY FOR BREAST
CANCER, IMPACTING PATIENT
QUALITY OF LIFE AND
RESULTING IN SIGNIFICANT
MORBIDITY
psychological, and social morbidity.
Although the increased use of sentinel
node biopsy, either when nodes are
clinically negative, or following neoadjuvant
therapy (NAC), has resulted
in lower lymphedema rates, the rates
following full axillary dissection can be
up to 77%.
Techniques to reduce lymphedema
Inferior
extension
Lateral
extension
include axillary reverse mapping
(ARM), meticulous dissection of arm
lymphatics with loupe magnification,
microsurgical lymphaticovenous
bypass, and a triple mapping
technique following NAC which
incorporates Indocyanine Green (ICG)
fluorescence for sentinel node bypass.
Slides illustrating these techniques
were shown.
Dr Diane M Radford
MD, FACS, FRCSEd is
with Cleveland Clinic
Foundation, Ohio, USA.
She discussed the
advances in oncoplastic
surgery techniques
for breast cancer, and
surgical methods to
reduce lymphedema
in her presentation at
MVRCanCon, Kozhikode,
India, recently.
FEBRUARY 2019 / FUTURE MEDICINE / 59

hospital news
FICCI lauds move to accord
‘industry status’ to hospitals
The Federation of Indian Chambers
of Commerce and Industry (FICCI),
the largest business organisation
in the country, has welcomed the
government’s announcement of
according ‘industry status’ and support
for land acquisition, clearances and
funding to private hospitals to boost
expansion of healthcare infrastructure in
tier 2 and 3 cities.
“In India, a skewed distribution
of hospital beds, with their heavy
concentration in the metros, has long
been a challenge in reaching the last
mile with quality healthcare provision.
This opportune step by the government
strongly reinforces private healthcare
providers’ commitment towards
improving access to quality care,” said
Sangita Reddy, Senior VP, FICCI, and
Joint MD, Apollo Hospitals Enterprise Ltd,
in a media release.
In the last decade, 70% of the
new bed capacity additions were in
the private sector, which also caters to
70% of the in-patient and 60% of the
outpatient healthcare demand in the
country.
“The key to engage more private
healthcare organisations will be a viable
model for their sustainability,” said Brig
Dr Arvind Lal, Chair, FICCI Health Services
Sangita Reddy
Committee and CMD, Dr Lal Path Labs
Ltd. The new hospitals, which would
be mandated to be empaneled under
Pradhan Mantri Jan Arogya Yojana
(PMJAY), or Ayushman Bharat, should
be allowed to charge other patients
who can afford to pay as per market
rates, as the current PMJAY package
rates may not be sustainable to set up
and run operations in such locations, he
said.
Apart from aiding the expansion
of bed capacity, the new hospitals will
open avenues for employment in tier
2 and 3 cities in the healthcare sector,
FICCI said in the statement.
Paras opens
multi-specialty
hospital at Panchkula
Paras Healthcare has inaugurated a new,
232-bed multi-super-specialty hospital
in Panchkula, Haryana.
Paras Hospitals Panchkula will
provide comprehensive cancer care
facilities ranging from chemotherapy,
surgical oncology, radiation therapy and
nuclear medicine. Equipped with a PET
CT scan centre, radiation oncology
will include the latest third generation
technology of LINAC along with VMAT,
IGRT and IMRT.
The hospital will have 44 specialties,
including cardiology, cardiac surgery,
orthopaedics and joint replacement,
nephrology and kidney transplant, cancer
care, gastroenterology and GI surgery,
urology, neurology and neurosurgery.
Located near Nada Sahib Gurudwara,
this is Paras Healthcare’s second hospital
in the city after Paras Bliss which has been
providing specialized mother and child
care, reports said.
Manipal Hospitals launches lifesaving
care training for public
Aimed at creating awareness
and training people with lifesaving
techniques, Manipal Hospitals
Bengaluru organized ‘You can save life
anywhere’ campaign coinciding with
World Ambulance Day.
The campaign kicked off with
Manipal Ambulance Response
Services (MARS) ambulance rally to
spread the message of ‘Give Way
Save a Life’ to the public. The training
programmes for the public included
cardiopulmonary resuscitation (CPR)
and automated external defibrillator
(AED).
People can further avail these
training programmes across all the
hospitals of Manipal by booking via
the hospital’s website. The training will
be available every second Saturday of
the month. Initially, the hospital aims
to train people in batches starting
with admin staff of metro and malls
in Bengaluru, police, students and the
general public.
GPS-enabled MARS vehicles
are equipped with critical lifesaving
systems. Manipal’s fleet of ambulance
also has Central Monitoring System,
which relays images of patient
condition direct to Emergency
Response Centre.
60 / FUTURE MEDICINE / FEBRUARY 2019

policy
LOOPHOLES
IN THE LAW
Though a good initiative,
the Surrogacy Bill that was
passed in the lower house
of the Indian parliament is
lacking in many respects,
say experts
In a significant development, Lok
Sabha recently passed the muchawaited
Surrogacy (Regulation)
Bill 2016, which bans commercial
surrogacy in the country. The
Surrogacy Bill was introduced in
Lok Sabha in 2016 with an aim
to regulate surrogacy in India and
protect women from exploitation. The
bill is now in the Rajya Sabha for its
ratification. The government move
to ban commercial surrogacy in the
country came after reports of misuse
of women and campaigns against
commercial surrogacy by various
organizations.
India emerged as a favourite
surrogacy hub for couples across
the world over the years. There
were several incidents of unethical
practices, exploitation of surrogate
mothers, abandonment of children
born out of surrogacy and import
of human embryos and gametes.
The Law Commission of India had
also recommended the prohibition
of commercial surrogacy through
legislation as lack of legislation
had resulted in a huge increase in
commercial surrogacy and widespread
unethical practices in the area of
surrogacy. The bill, which proposed
62 / FUTURE MEDICINE / FEBRUARY 2019

AUGUST 2018/ FUTURE MEDICINE / 85

anning of commercial surrogacy,
however, allowed altruistic surrogacy.
Who is a ‘close relative’?
Dr Ranjana Kumari, Director, Centre
for Social Research, said, “A few
years ago we conducted researches
in places such as Jamnagar, Surat,
Bombay, Delhi and Hyderabad, where
commercial surrogacy is prevalent.
As part of the study, we consulted
stakeholders, including surrogate
mothers, and it was found that
women are indiscriminately exploited.
In the report we submitted to the
Union government, we suggested
the regulation of surrogacy and not a
total ban on surrogacy. However, the
present legislation banned commercial
surrogacy.”
The Surrogacy Bill proposes that
the intending couple must be Indian
citizens and married for at least five
years, and either or both members of
the couple should be infertile. As per
the bill, the intending couple should
THE BILL IS NOT CLEAR IN
THE CASE OF EMBRYOS AND
GAMETES IN CRYOSTORAGES
IN THE COUNTRY. THE
CURRENT SITUATION DOES
NOT ALLOW THEIR EXPORT
not have any surviving child biologically
or through adoption or surrogacy
earlier. The bill also states that the
surrogate mother should be a close
relative, who is married and having a
child of her own. However, it did not
define close relative. As per the bill, the
child born out of surrogacy procedure
shall be deemed to be a biological
child of the intending couple and the
child shall be entitled to all the rights
and privileges available to a natural
child.
Under the bill, central and state
governments will appoint appropriate
authorities to grant eligibility
certificates to the intending couple
and the surrogate mother. The bill
proposes imprisonment for a period of
10 years and a fine of up to Rs 10 lakh
if surrogacy is undertaken for a fee,
advertised or the surrogate mother is
exploited.
Silent on cryostorage
Commenting on the bill, Dr Alex C.
Varghese, Former President, Academy
of Clinical Embryologists, said: “The
surrogacy bill is a good initiative. There
should be some kind of checks as
there can be lots of practices which are
not ethical. Commercial surrogacy also
puts a question mark on womanhood.
In India, there are more chances of
unethical practices, and based on that,
this kind of law is very valid.” He added
that there may be some loopholes in
the bill and more discussions may be
required to check those loopholes.
The bill proposed that the intending
couple and the surrogate mother need
eligibility certificate, but it does not
specify a time limit for granting the
certificates. Though the bill states that
the surrogate mother should be a close
relative, it also does not define close
relative. As per the bill, the approval
of the appropriate authority and the
consent of the surrogate mother are
required for an abortion. However, it
does not give any role for the intending
couple in the decision for abortion.
The bill has also proposed banning
the storage of embryos and gametes
for surrogacy purpose in contrast to
the existing ICMR guidelines, which
allow storage of embryos for a period
of five years. “The bill is not clear in
the case of embryos and gametes
in cryostorages in the country. The
current situation does not allow their
export. As they are a form of life, they
cannot be destroyed,” said Dr Alex C.
Varghese.
As per the bill, no person shall
establish surrogacy clinics for
undertaking surrogacy unless they are
duly registered under the Act.
64 / FUTURE MEDICINE / FEBRUARY 2019

exotica
THE MIND-BODY
CONNECTION IN CANCER
Currently, there is not enough scientific evidence to support the theory that
one’s attitude alone can directly impact cancer progression
DR SUMIT GHOSHAL
Most doctors know that every
patient responds differently to
treatment. Often two patients
with the same clinical condition,
receiving the same treatment, will show
a very different clinical course. While
one recovers faster or better than
expected, the other appears refractory
to treatment. This phenomenon,
which involves the interplay of several
factors such as the patient’s mental
strength, the incentive and motivation
to recover and the determination to
fight the disease, is often as crucial as
the treatment and intervention by the
doctors.
While healthcare professionals such
as doctors and nurses have known
this for generations, the reasons are
becoming clear only in recent years. In
the context of cancer, it has to be viewed
as the coming together of three separate
trains of thought: One, that human
feelings and emotions are expressed in
terms of neuro-chemical substances;
two, that these neuro-chemicals exert
an impact on the immune system (both
cell-mediated and humoral); and three,
that cancer cells can be combated and
even controlled by strengthening the
immune system. A combination of these
three ideas has given birth to a new
discipline of medical research, known as
Psycho-Neuro-Immunology or PNI.
In recent years, more and more
cancer specialists have started to believe
that the human immune system can be
an invaluable ally in the battle against
malignancy. “One reason that cancer
cells thrive is that they are able to hide
from your immune system. Certain
immunotherapies can mark cancer
cells, so that it is easier for the body’s
immune system to find and destroy
them,” says a recent article published by
the National Cancer Institute, a member
of the National Institutes of Health (NIH)
network. Immune therapies can be
THE EXISTING RESEARCH
FOCUS ON THE IMPACT OF
EMOTIONS AND BEHAVIOR
ON THE CLINICAL COURSE OF
CANCER AFTER IT HAS BEEN
DIAGNOSED
of many types: cytokines, monoclonal
antibodies, treatment vaccines and
even BCG (originally discovered as a
preventive against tuberculosis).
Impact of emotions
On the other hand, we also know
that emotions are chemical reactions
mediated by hormones and other
biochemical such as serotonin,
dopamine, oxytocin, endorphins, etc.
Numerous scientific articles published
globally in the past few years have
expounded the concept that these
same chemicals also affect the immune
system – both cell mediated and
humoral. In an article in Frontiers in
Behavioural Neuroscience published last
year (doi: 10.3389/fnbeh/.2018.00056),
Aki Takahashi et al, have written that
“individuals with high aggression display
heightened inflammatory cytokine
activity and dysregulated immune
responses such as slower wound
healing. Similar findings have been
observed in patients with depression,
and comorbidity of depression and
aggression was correlated with stronger
human dysregulation.”
So, when we put these two concepts
together, what do we get? The perfectly
conceivable idea that anger, depression
and other negative emotions are
capable of slowing down the immune
response to cancer and retard the
effectiveness of traditional cancer
therapies! While this appears quite
logical and obvious, we still have to see
if it is supported by experimental and
scientific evidence.
Much of the existing research, both
in India and abroad, focuses on the
impact of emotions and behavior
on the clinical course of cancer
after it has been diagnosed.
Thus Dr Raghavendra Mohan
Rao and his colleagues in
the Centre for Academic
Research, HCG Foundation,
Bangalore, writing in Indian
Journal of Palliative Care (Indian J
Palliat Care 2017; 23-225-30) point out:
“Treatment-related distress can manifest
as anxiety or depressive disorders in
some cancer patients, leading to a
heightened feeling of hopelessness, a
66 / FUTURE MEDICINE / FEBRUARY 2019

lack of will to survive, a loss of control
over one’s life, low self-esteem and other
indicators. Studies have also shown that
such a state of mind can lead to sleep
disturbances, aberrant cortisol rhythms,
poor anti-tumor immune response, a
decrease in overall and disease-free
survival with early relapse/recurrence,
and heightened distress.”
Likewise, in a 2013 review article
published in Brain, Behaviour and
Immunity, Paige Green MacDonald et
al. write that stressful experiences in
life and a state of depression have
been linked with poorer survival rates
and greater frequency of death in a
wide range of cancers, including those
originating in the breast, lung, head and
neck, hepatobiliary system and blood.
The article (http://dx.doi.
org/10/1016/j.bbi.2013.01.003 ) also
points out that symptoms of depression
have an adverse impact on the survival
of patients with metastatic kidney
cancer. On the other hand, amelioration
of depressive symptoms was clearly
linked with better clinical outcomes in
advanced cases of breast cancer. In
addition, the potential for damage on
account of unsatisfactory or unfulfilling
social relationships was as serious as the
risk conferred by excessive alcohol and
tobacco use!
“People under stress have a lower
level of T-cell mediated immunity,”
says Dr Navin Salins, a palliative care
AMELIORATION OF
DEPRESSIVE SYMPTOMS
WAS CLEARLY LINKED WITH
BETTER CLINICAL OUTCOMES
IN ADVANCED CASES OF
BREAST CANCER
physician with Kasturba Medical College,
Manipal. He also mentions other studies
conducted in HCG, Bangalore that have
revealed that “mind-body intervention”
such as yoga have a definite role in
controlling the nausea, vomiting and
other symptoms of anti-cancer therapy.
Insufficient evidence
But can this set of ideas be taken
one step further, and be used for the
prevention of cancer? Perhaps not in the
near future, because a number of Indian
scientists have pointed out that the
evidence on this aspect is insufficient at
the present time.
“I have done one retrospective study
about five years ago where I found
some correlation ‘Fear of Cancer’ and
‘Cancer Recurrence’, keeping in mind
this concept that anxiety and stress can
compromise our immune system and
help cancer to recur,” says Dr Suchitra
Mehta, Director and Head, Psycho-
Oncology, HCG NCHRI Cancer Centre,
Nagpur.
Speaking on similar lines, Bincy
Mathew, a psycho-oncologist with
Manipal Hospitals, New Delhi and
founder of non-profit organization
www.psycho-oncology.in, says: “One’s
attitude and its influence on cancer is
still a big debate in cancer circles. In
my experience, I have not found
strong enough scientific
evidence that one’s attitude
alone can directly impact
cancer progression or
the immune system. But
many studies have proven
that one’s emotions may
contribute to stronger,
better immunity during
cancer treatment.”
The jury is therefore out
on exactly how much impact
psychological factors can have on
individual cancer patients and how
these findings can be put to use.
However, these developments hold out
the hope that before too long, mental
and psychological training would
play a significant part in cancer therapy
as a whole.
FEBRUARY 2019 / FUTURE MEDICINE / 67

devices&gadgets
Hemoblast Bellows to control
bleeding in laparo surgery
Biom’up’s Hemoblast
Bellows Laparoscopic
Applicator has received
marketing approval from
US FDA for all minimallyinvasive
procedures.
The new approval
expands the indications
of the Hemoblast Bellows
device and enables
surgeons to use the
haemostatic powder
for both traditional and
laparoscopic surgeries with
the same patient.
The 35cm long
polycarbonate applicator
fits easily into the existing
applicator and delivers
Hemoblast powder to
minimally invasive bleeding
sites in under one minute.
Hemoblast Bellows
is the only surgical
haemostatic agent
approved by the FDA based
on the validated Spot
Grade Surface Bleeding
Severity Scale (SBSS), which
demonstrates its ability to
control a range of bleeding
from minimal (oozing), mild
(pooling) and moderate
(flowing) bleeding.
Hemoblast Bellows is
proven to control bleeding
with flow rates up to 117
mL per minute, Biom’up
said.
Hemoblast Bellows can
be used to control bleeding
in a broad range of
procedures, such as cardiac,
general and orthopaedic
surgeries.
patients treated with the
device under a continued
access protocol.
Bioventus
launches
biphasic
bone graft
Amplatzer device
to treat heart
defect in infants
The US FDA approved
Amplatzer Piccolo
Occluder, a device to treat
the congenital patent
ductus arteriosus (PDA)
announced Abbott
Pharmaceuticals.
The device is intended for
use in infants >3 days old at
the time of procedure who
may be nonresponsive to
medical management
and who may not be
able to undergo corrective
surgery.
The pea-sized device is a
self-expanding wire mesh
that is inserted through an
incision in the leg and guided
through vessels to the heart,
where it is placed to seal the
opening.
The approval was
supported by the ADO II AS
study which included 50
patients with a PDA, with
additional safety and
efficacy data obtained from
Bioventus has launched
Osteomatrix+, a biphasic
bone graft for use in bone
remodelling in a variety
of orthopaedic and spine
applications.
Osteomatrix+ is a
moldable bone graft
substitute consisting of
bovine collagen and biphasic
hydroxyapatite/ß-tricalcium
phosphate granules
designed to produce a
reliable, porous scaffold and
sustained osteoconductivity
throughout the bone
remodeling process.
Osteomatrix+ has more
unique handling properties,
including improved
moldability, flexibility
and versatility, than its
predecessor, according to the
company.
Bioventus’ portfolio
includes offerings for
osteoarthritis, surgical and
non-surgical bone healing.
68 / FUTURE MEDICINE / FEBRUARY 2019

New ablation
catheter to
treat AFib
TactiCath Contact Force
Ablation Catheter, a new
ablation catheter designed
to help physicians treat atrial
fibrillation (AFib), has been
granted approval by US FDA.
The sensor-enabled
TactiCath SE delivers more
precise images of the heart
overlaid with real-time
electrical activity information.
The catheter also utilises
the advanced ergonomic
design for better reach and
manoeuvrability during
cardiac ablation procedures.
Physicians have begun
exploring the use of new
tools such as “contact force”
technology during ablation
procedures to help them
avoid applying too much
pressure to heart tissue or
insufficient pressure, Abbot
said.
Perflow wins
4 patents for
neurovascular
technology
Perflow Medical has been
issued four international
patents that for the novel
Stream Dynamic Neuro-
Thrombectomy Net and
Cascade Non-Occlusive
Remodeling Net.
Perflow’s global portfolio
of eight issued patents
includes two new patents
from the European Patent
Office (EPO), one from the
Medtronic launches mobile
app to support pacemakers
Medtronic plc has
launched MyCareLink
Heart mobile app to
support the portfolio of
pacemakers that can
communicate directly with
patients’ smartphones and
tablets.
Compatible with
Medtronic BlueSync
technology-enabled
pacemakers, the
MyCareLink Heart mobile
app is designed to securely
and wirelessly send device
data to the Medtronic
CareLink network via smart
technology, eliminating
the need for a dedicated
bedside monitor or
other remote monitoring
hardware.
BlueSync technologyenabled
pacemakers
include the Azure
pacemaker and Percepta,
Serena and Solara
quadripolar cardiac
resynchronization therapy
pacemakers (CRT-Ps).
Data collected by these
devices is encrypted
and sent to the CareLink
network through the
MyCareLink Heart mobile
app, providing physicians
with timely alerts on
clinically-relevant patient
events. The app also makes
select pacemaker data
easily accessible to patients
including transmission
success history, pacemaker
battery information,
answers to common
questions about living with
a pacemaker, and updates
on physical activity.
MyCareLink Heart
Mobile App provides
patients with information
about transmissions
that have been sent to
their doctors, as well
as confirmation when
transmissions are received
by physicians. It also allows
patients to record weight,
blood pressure and heart
rate in the app, and to
track these measurements
over time to help better
understand health status.
This information is only
stored on their mobile
device; it is not sent to the
clinic.
Further. the
app allows patients
to catalogue symptomatic
events which can be
reviewed with their
physicians during in-person
clinic visits.
China National Intellectual
Property Administration
(CNIPA), and one from the
Japanese Patent Office (JPO).
Perflow’s Cerebral Net
technology platform is
designed to expand treatment
options with real-time control
and overall improved device
performance. The company
currently has two commercial
products with CE Mark
available for use in Europe,
with a third product in latestage
development. The
Stream Net, the company’s
first product, has been used
across Europe and provides
full control and dynamic
wall apposition during the
treatment of acute ischemic
stroke. The Cascade Net,
which was launched last
year, is a device that allows
blood flow without the risk
of coil entanglement during
embolization of intracranial
aneurysms.
Both devices allow the
physician to manipulate
the net diameter, length,
and radial force to optimize
contact with the vessel wall
and improve control through
tortuous anatomy during
neurovascular procedures.
Fujifilm launches
Apollo X
mammalian
expression system
Fujifilm Diosynth
Biotechnologies has
FEBRUARY 2019 / FUTURE MEDICINE / 69

introduced Apollo mammalian
expression system, Apollo X.
The Apollo X advanced
mammalian expression system
is capable of delivering titres
in excess of 10 g/L.
CHO-DG44-derived host
cell line selected through a
directed evolution approach
to control and manage
cellular heterogeneity, is
one of the key components
of the system. The selected
cell line has been fully
sequenced and analysed,
a novel expression vector
with a proprietary leader
sequence developed for
efficient secretion and high
productivities without the
need for amplification.
Its cell culture medium
is specifically screened for
achieving high titres by
monitoring initial cell
growth, controlling peak
cell density and maintaining
high cell viability, streamlined
units of operations
for efficient process
implementation.
Apollo X cell line
development timelines
have been reduced by 30%,
from gene to clonal cell line
compared to the original
Apollo expression system.
Digital laparoscopic system gets
510(k) clearance
TransEnterix, Inc
announced the
company received FDA
510(k) clearance for its
Senhance Ultrasonic
System.
The Senhance System
is a new abdominal
robotic surgery platform
to receive FDA clearance
since 2000 and is the
first digital laparoscopic
surgical platform to offer
the security of haptic
force feedback that allows
surgeons to feel the forces
the instruments generate
when handling delicate
tissue.
It uses reusable
instruments that help
keep per-procedure costs
similar to that of traditional
laparoscopic surgeries, as
well as 3 mm instruments
for microlaparoscopic
procedures that enable
virtually scarless incisions
for patients.
Advanced energy
devices, including
ultrasonic devices,
represent some of the
most versatile and critical
tools for surgeons in
minimally invasive surgery.
These instruments
deliver controlled energy
to effectively ligate
and divide tissue and
minimize thermal injury to
surrounding structures.
In the US, the
Senhance System is
cleared for laparoscopic
colorectal, gynaecological,
inguinal hernia and
cholecystectomy surgery.
Wearable BP
monitor
HeartGuide
launched in US
H
eartGuide,
a wearable
oscillometric blood
pressure monitor in the
design of a wristwatch
recently received 510K
FDA clearance as a medical
device.
HeartGuide is launching
with a new mobile app,
HeartAdvisor – a digital health
service from Omron with
insights and coaching to
help users.
HeartGuide can
hold up to 100
readings in memory
and all readings can
be transferred to a
new corresponding
mobile app,
HeartAdvisor, for
review, comparison
and treatment
optimisation.
HeartAdvisor is now
available through Apple
iTunes and Google
Play stores and will be
upgraded with additional
features throughout 2019.
Omron is initially launching
HeartGuide in the US with
plans to roll out the product
in Europe and Asia later this
year.
Neuro aspiration
device for MRI
procedures
approved in US
The US FDA approved
ClearPoint Pursuit, a neuro
aspiration device for MRI
Interventions.
The new neuro aspiration
70 / FUTURE MEDICINE / FEBRUARY 2019

Benchtop blood analyser
Erytra Eflexis get USFDA ok
Grifols received US FDA
approval of Erytra Eflexis,
a fully automated, benchtop
analyzer. The system performs
pretransfusion compatibility
testing using DG gel
technology.
The blood typing analyser
facilitates multiple lab
configurations and requires
minimal laboratory technician
interaction.
Erytra Eflexis incorporates
two lab configurations
in a single instrument so
laboratories can select
the solution best suited to
various workflow needs and
capacities. This smart,
flexible and intuitive
system optimises workflow
efficiency and improves
daily workloads, providing
laboratories with a high
level of flexibility and
adaptability, the company
said.
Interchangeable sample
and reagent linear racks allow
easy, continuous loading
of cards, reagents and
samples. The device features
real random access with a
capacity of up to 200 cards,
72 samples and 46 liquid
reagents.
device is indicated for the
controlled aspiration of
blood, clotted blood, cystic
components of tumours,
abscesses, colloid cysts, and
cerebral spinal fluid using a
manual syringe during the
surgery of the ventricular
system or cerebrum.
It leverages the ClearPoint
navigation system from MRI
interventions and is designed
to be used under MRI
guidance.
The Pursuit device was
designed in collaboration with
the Mayo Clinic. It is being
placed under a limited market
release at a select number of
U.S. hospitals.
The company expects to
launch Pursuit commercially in
the first half of 2019.
Non-invasive
test for
concussion
wins FDA nod
Marketing permission has
been granted by US FDA
for EyeBOX, a non-invasive,
baseline-free aid in diagnosis
of concussion.
EyeBOX is easy to use test
that collects and analyses
over 100,000 data
points to generate an
objective assessment
that is unique to
each patient. It can
be used as aids in
the diagnosis of
concussion in patients
5 to 67 years of
age, Oculogica said.
EyeBOX uses
eye-tracking to
provide objective
information to aid in the
assessment of patients with
suspected concussion via an
easy to take, 4-minute test.
A binocular camera then
tracks each eye and gathers
data that ultimately leads to
a score that rates the severity
of brain injury; a score =10
is Oculogica’s threshold for a
concussion.
The FDA approval was
supported by results from the
DETECT clinical study which
included 282 patients with
suspected traumatic brain
injury.
Results showed that
compared with a clinical
reference standard for a
concussion, EyeBox had high
sensitivity to the presence of
concussion; a negative result
was consistent with a lack of
concussion.
The company plans to
market the device for use in
paediatrics ages 5 and older
and adults up to 67 years of
age, starting with a pilot launch
for select, qualified sites.
72 / FUTURE MEDICINE / FEBRUARY 2019

Bioelectronic
device for
sinus pain
The US FDA has approved
ClearUP Sinus Pain Relief
for the treatment of sinus
pain due to allergic rhinitis in
adults.
The device is a
bioelectronic treatment and
a new way to treat allergyrelated
sinus pain from
environmental allergies like
mould, dust, pollen, dander
as well as food allergies. The
advanced neuromodulation
technology uses gentle
microcurrent.
The handheld device
measures the user’s skin
properties to target the
optimal treatment points.
As the user glides the
device along the outer nasal
passage, gentle microcurrent
waveforms stimulate the
nerves under the skin to
relieve sinus pain. Each
5-minute treatment can be
personalised at 3 intensity
levels and can be used up to
4 times a day.
As the device glides along
the cheek, nose, and brow
bone, it locates areas of the
skin with low impedance,
where current can pass most
easily. At these treatment
points, the device emits lowcurrent
electrical stimulation,
called Microcurrent, to
stimulate underlying nerve
fibres.
Electrical stimulation
of nerves has been used
to reduce the sensory
perception of pain. Research
has also shown that electrical
stimulation can activate
sympathetic nerve fibres and
promote constriction of blood
vessels, which can result in the
shrinking swollen tissue.
Smartwatch for
monitoring seizure in kids
Embrace smartwatch
for tracking seizures
in children as young as
age 6 has been granted
marketing approval by
USFDA.
The watch uses an
electrodermal activity
sensor to measure
sympathetic nervous system
activity. The latest approval
has made it the first non-
EEG based physiology
signal seizure monitor to be
cleared for use in paediatric
patients. The Embrace
was previously approved
in January 2018 for adults
aged =21 years.
The smartwatch
identifies certain motion
and physiological signals
associated with generalized
tonic-clonic seizures and
promptly alerts caregivers.
The Alert App immediately
sends a call and SMS to
your caregivers when
Embrace detects patterns
that may be associated
with a convulsive seizure.
Embrace bagged the
marketing rights after the
positive results of a clinical
test which was conducted
among 141 epilepsy
patients, out of which 80
patients were aged 6 to 21
years and 61 patients were
aged >21 years. The data
demonstrated an accuracy
rate of 98% for detecting
generalized tonic-clonic
seizures. The overall false
alarm rate (FAR) for adults
was 0.67 and 1.35 for
paediatrics, Empatica Inc
said.
FEBRUARY 2019 / FUTURE MEDICINE / 73

MERIL’S
MYVAL
Indigenous transcatheter aortic valve replacement
technology makes India proud
Vapi never figured in India’s
science hotspots until now.
But this small industrial town
in Gujarat—predominantly a chemical
manufacturing hub on the Maharashtra
border, has started attracting young
scientific talent in the biomedical
engineering field, thanks to the
unrelenting medical technology research
and development efforts of a company
that made India proud of late.
The country’s first indigenous
Transcatheter Aortic Heart Valve
MILESTONES
2006 2009
Thought
of Meril
2008
State-of-the-art
manufacturing facility
at Vapi, Gujarat, India.
Launched flagship
product, BioMime,
Nexgen, Crypton &
Haiku
74 / FUTURE MEDICINE / FEBRUARY 2019

Replacement (TAVR) device, an
important milestone that made the
Indian med-tech industry proud, was
successfully developed in this tiny town.
Meril Life Sciences, the Vapibased
med-tech company received
approval for launching its indigenous
TAVR technology— Myval THV—from
the Central Drugs Standard Control
Organisation (CDSCO) in October. With
this, Meril has become the first Indian
company in the world to make this
technology commercially available,
MERIL LIFE SCIENCES
RECEIVED APPROVAL FOR ITS
TAVR TECHNOLOGY— MYVAL
THV—FROM THE CDSCO IN
OCTOBER 2018
promising to give long-established
multinational brands tough competition.
TAVR, an established treatment
modality for patients who are at a
high risk or unwilling to undergo open
heart valve replacement surgery, is a
minimally invasive procedure in which
the doctor inserts a replacement valve
into the patient’s native diseased valve
via a catheter inserted through the
femoral artery. This is an alternative
way to replace diseased valves without
undergoing the traditional open heart
procedure, which some patients may not
tolerate. The market for transcatheter
aortic valve implantation (TAVI), which
is growing rapidly with the increasing
cases of aortic valve stenosis, has so
far been catered to by multinational
med-tech giants such as the US-based
Edwards Lifesciences and Medtronic,
Ireland.
Long and passionate effort
Meril has been working on this project
for the last six years. Though its 150
strong R&D team at the Vapi campus
has had several other firsts to their
credit, including a completely indigenous
ultra-thin strut bio-degradable polymerbased
Sirolimus DES—BioMime in
2010, a thin-strut Sirolimus eluting
bioresorbable vascular scaffold — MeRes
100 in 2016, Myval is one of their most
prestigious projects.
“Since its inception, Meril has
played a leading role in developing
and introducing innovative medical
technologies. The TAVR technology
has been developed after 6 years of
extensive research and is backed by
robust bench testing, pre-clinical and
clinical data. We are committed to take
this technology to over 100 countries
and benefit thousands of patients
2010
2011
Established direct presence through
subsidies in Germany and Brazil and
grew international presence to over
60 countries.
Established International presence over
30 countires and got validation from
European Commission through CE mark
BioMime became
preferred brand
in south asian
countries.
Launched a
completely indigenous
PTCA balloon catheter,
MOZEC.
Demonstrated Meril’s
Innovation by introducing
BioMime Aura
2012
2013
Presented at EuroPCR, first
animal studies of MeRes
Bioresorbable Vascualar Scaffold
and Myval Transcatheter Aortic
Valve (TAVI) System
Expanded presence in more
than 100 countries through strong
partnerships across regions
FEBRUARY 2019 / FUTURE MEDICINE / 75

The innovation that
we could bring in
Myval’s design is
clinically significant
as compared
to all existing
technologies.
Sanjeev Bhatt
Vice President
Corporate Strategy
Meril Life Sciences
across the globe,” says Dr P K Minocha,
director, Research & Development, Meril
Life Sciences.
The launch of the indigenously
developed transcatheter heart valve
is an assertion of the company’s
fundamental belief that it will focus on
novel, clinically relevant and best-in-class
devices to alleviate human suffering
and improve quality of life, according to
Meril’s senior management.
Clinically differentiated
“Meril has always been dedicated
towards design and development
of novel, clinically relevant and bestin-class
devices to alleviate human
suffering and improve quality of life.
For us, it is a proud moment to be the
first Indian company to commercially
make this therapy available in the
country,” says Sanjeev Bhatt, vice
president, Corporate Strategy, Meril Life
Sciences.
The regulatory approval for Myval
came after successful completion of
extensive clinical studies in India.
“All the patients are doing well post
Myval procedure and during follow-up,”
says a confident Bhatt.
The product demonstrates that it
is possible to develop such a complex
medical device completely in India by
Indian scientists.
“We have not outsourced the
technology and it’s fully developed
here in this campus and within our
own means. And more importantly,
the innovation that we could bring
in its design is clinically significant as
compared to all existing technologies,”
Bhatt said in an interview with Future
Medicine.
Because of its unique design,
the product sits at the annulus in
a precise manner, Bhatt said. It
therefore prevents leakage, known as
paravalvular leakage (PVL), associated
with the implantation of a prosthetic
heart valve, whether using a traditional
76 / FUTURE MEDICINE / FEBRUARY 2019

(surgical) or transcatheter (TAVI)
approach.
Secondly, this design is also
associated with zero new pacemaker
implantation rates post procedure,
which is an important benefit for
the patient already treated for valve
replacement. This is because its
precise placement mechanism doesn’t
excite the conduction system. Since
the tolerance at this zone is minimum,
only a precise deployment of the
device can avoid exciting the system.
In the current genre of devices, usually
there are upto double digit rates of
needing new permanent pacemakers.
A study published in the Journal
of American College Cardiology
(JACC) in 2016 found that patients
who undergo minimally invasive
heart valve replacement, typically
a TAVR, sometimes develop heart
rhythm problems that necessitate the
placement of a permanent pacemaker.
However, when a new pacemaker is
needed soon after TAVR procedure,
patients often have worse outcomes
than those who do not need a
pacemaker. The study, based for the
JACC report, also showed that such
risks are both short- and long-term and
include lengthier stays at hospital and
intensive care units as well as a greater
risk of death.
Proud moment
“For us, it is a proud moment to be the
first Indian company to commercially
make this therapy available in the
country. Through the commercialisation
of this technology, Meril will soon bring
a next-generation treatment modality to
THE ULTIMATE MERIT OF THIS
INDIGENOUS TECHNOLOGY
DEPENDS ON THE RESPONSE
THAT IT RECEIVES FROM THE
CARDIAC SURGEONS IN THE
COUNTRY
thousands of patients globally, making
India proud of this achievement,” claims
Bhatt.
According to him, Meril realises that
if it has to do very complex science in
areas where no alternatives exist at the
moment, it has to be in keeping with
its primary philosophy of identifying
an unmet need and then providing its
whole infrastructure, knowhow, talent
and even the training for doctors by
becoming a perfect facilitator of that
new concept and technology.
Although the critics say that the
Indian devise was built on the existing
technology platform that is already
available in the market, Meril argues that
every novel design has been developed
by improvising existing platforms, which
is a fact everywhere in the world and
India is not an exception.
But the ultimate merit of this
indigenous technology depends on
the response that it receives from the
cardiac surgeons in the country.
“We have found Myval to be safe
and easy to use in the initial series of
procedures. But a longer follow up data
will be needed to study the long term
durability and cardiovascular outcomes,
though the cost has been proved
advantageous,” said Dr Hisham Ahmed,
a senior cardiac surgeon at Amrutha
Institute of Medical Sciences, Kochi,
whose team has implanted Myval in four
patients so far.
Aortic valve stenosis is one of the
most prevalent heart diseases globally
and the number of cases at any
conservative estimate would cross 3 to
3.5 per cent of the elderly population.
Currently available estimates show
that more than 1 million cases of aortic
stenosis are diagnosed per year in
India alone, mainly due to age related
degradation of the aortic valve—an
important cause not only in India but
in other parts of the world as well.
Although less invasive procedure to
replace the valve is the much sought
after treatment today, the number of
such procedures is comparatively less
in India due to cost and access issues.
Indigenous technology and more
awareness can bring in more volumes
and counter pricing and affordability
issues.
This is part of a series that features India’s
First & Most Unique institutions, facilities,
technologies, products etc in the medical
and healthcare space.
FEBRUARY 2019 / FUTURE MEDICINE / 77

guidelines
MANAGEMENT OF
UTERINE CANCER
Consensus document for the management of endometrial carcinoma by
Indian Council of Medical Research 2018
Carcinoma endometrium is the
most common gynecological
malignancy in the developed
countries with age standardized
incidence rate of 2.3 per 100,000. In
developing countries, cervical cancer
still remains the leading cause of
gynecological cancers, but there is a
recent increase in the incidence of
endometrial cancer. In India, the total
number of estimated new cases of
endometrial cancer in 2018is 13,328
with an estimated 5010 deaths. The
age standardized incidence rate (ASIR)
of endometrial cancer in India is
2.1/100,000 women. The rise is mainly
attributed to the changing trends in
the lifestyle and reproductive profile of
women especially in urban areas. The
majority of cases present in 6th and
7th decade of life with the mean age of
diagnosis being 60 years.
HISTOPATHOLOGIC VARIANTS
Endometrial adenocarcinoma is the
most common histology of uterine
cancer. There are two distinct subtypes,
which have different incidence,
clinical picture, molecular pattern and
biological behavior.
Type 1 Endometrial Carcinoma:
Type 1 endometrial cancers comprise
approximately 80% of uterine
cancers. These tumours are estrogen
responsive and are seen in pre- or perimenopausal
age group. They are of
endometrioid histology and are usually
well differentiated. Type 1 endometrial
carcinomas are usually associated with
prolonged and unopposed estrogen
exposure as seen in women with
obesity, anovulatory cycles, infertility,
78 / FUTURE MEDICINE / FEBRUARY 2019

and estrogen-secreting tumours. These
tumours usually have a favorable
prognosis with >90% 5-year survival
rate. They are characterized by K-ras
overexpression, PTEN, PIK3CA, KRAS
mutations, and microsatellite instability.
Type 2 Endometrial Carcinoma:
Type 2 endometrial cancers comprise
the remaining 10-20% of cases. They
are estrogen independent and usually
arise from an atrophic endometrial
background. They occur in women
who are older, postmenopausal,
multiparous, non-obese, smokers, and
tamoxifen users. They include grade 3
endometrioid adenocarcinoma, serous,
clear cell, mucinous and squamous
variety. They are aggressive tumours
and often show deep myometrial
invasion and extrauterine spread. Type
2 tumours are associated with worse
prognosis with a recurrence rate of
50% and overall survival (OS) of 35%.
They are associated with genetic
alteration in E-cadherin, p53 and HER2/
neu expression.
DIAGNOSTIC WORKUP
Detailed history: The usual presenting
complaints are abnormal uterine
bleeding and postmenopausal bleeding.
Risk of carcinoma endometrium in a
woman with postmenopausal bleeding
is approximately 10%.
Clinical presentation with
advanced disease includes urinary
or rectal bleeding, constipation,
pain, lower extremity lymphedema,
abdominal distention due to ascites,
hepatomegaly, jaundice, cough and/or
hemoptysis.
History of use of hormones,
diabetes, hypertension, and tamoxifen
use should be elicited.
Previous menstrual and obstetric
history: History of early menarche
or late menopause, history of
prolonged and heavy periods and
history of menstrual abnormalities in
perimenopausal transition.
Family history of uterus and
colorectal cancer, especially if
endometrial cancer is diagnosed
TYPE 2 TUMOURS ARE
ASSOCIATED WITH GENETIC
ALTERATION IN E-CADHERIN,
P53 AND HER2/NEU
EXPRESSION
at age

outcome (disease specific survival or
recurrence).
FURTHER EVALUATION
After confirming the diagnosis, further
laboratory investigations and detailed
imaging is done to assess the surgical
risk, extent of disease, and to plan the
appropriate surgical treatment.
Advanced imaging
MRI abdomen and pelvis with
contrast: MRI is the most accurate
modality for assessing the size and
extent of tumour, myometrial invasion,
extension to cervix and adnexal
pathology. Contrast enhanced MRI
to exclude myometrial invasion and
cervical extension is mandatory,
when planning for fertility preserving
options.
CT abdomen with pelvis (contrast):
Poor soft tissue differentiation of CT
scan limits its use to assess the local
extent of disease. The sensitivity and
specificity of CT in assessing the extent
of myometrial invasion range from
40% to 83% and from 42% to 75%,
respectively. CT scan is mainly utilized
for assessing extra pelvic disease and
lymph node involvement.
Positron emission tomography/
computed tomography (PET/CT): This
has little benefit in assessing primary
tumour extension. PET/CT has sensitivity
of 50% to 100% and specificity of 87%
to 100% in detecting regional lymph
node metastasis. Routine use of PET CT
is not indicated for preoperative staging
purpose. PET/CT is highly sensitive and
specific for detecting positive pelvic
and/or paraaortic lymphadenopathy as
well as distant metastases in selected
high-risk patients and also those with
recurrent disease.
PET/MR imaging systems have
recently been developed to take
advantage of MRI’s high soft tissue
resolution and improve the anatomic
assessment.
Other preoperative work up
Complete blood count, renal and liver
functional tests, serum electrolytes,
urinalysis, blood glucose and viral
markers.
Cancer Antigen 125 (CA 125): The
preoperative serum levels of CA 125
could be elevated in patients with
extrauterine spread of the disease
and can be utilized for monitoring
the clinical response after therapy in
selected patients.
Chest X-ray to rule out lung metastasis
should be done. If the chest X-ray
is suspicious of metastasis, CT chest
without contrast is advised.
– Patients diagnosed with
endometrial malignancy prior to 50
THE SENSITIVITY AND
SPECIFICITY OF CT IN
ASSESSING THE EXTENT
OF MYOMETRIAL INVASION
RANGE FROM 40% TO 83%
AND FROM 42% TO 75%,
RESPECTIVELY
years and those with significant family
history of endometrial and colorectal
cancers should undergo genetic
evaluation.
Histological Classification of
Endometrial Carcinoma (2014
WHO)
Endometrioid adenocarcinoma
Endometrioid adenocarcinoma variants
• With squamous differentiation
• Secretory variant
• Ciliated cell variant
Mucinous adenocarcinoma
Serous endometrioid intraepithelial
carcinoma
Serous adenocarcinoma
Clear cell carcinoma
Mixed cell carcinoma
Undifferentiated carcinoma
• Monomorphic type
• De-differentiated type
Neuroendocrine tumours
• Well differentiated neuro endocrine
tumour (carcinoid tumour)
• Poorly differentiated small cell
neuroendocrine tumour
• Poorly differentiated large cell
neuroendocrine tumour
Staging of Carcinoma
Endometrium
Endometrial cancer should be surgically
staged with histological assessment of
grading and extent of disease. AJCC-
(American Joint Cancer Committee)
Tumour-Node-Metastasis (TNM) and
FIGO 2009 staging for carcinoma
endometrium is depicted in Table A.
Cases should also be stratified
based on degree of differentiation
• G1- 5% or less of a non-squamous
or non-morular solid growth pattern.
• G2- 6%-50% of a non-squamous or
non-morular solid growth pattern.
• G3- more than 50% of a nonsquamous
or non-morular solid
growth pattern.
PROGNOSTIC FACTORS
The following prognostic variables have
been identified (3,19)
FIGO stage
Age
Histological type
Histological grade
Nuclear grade
Myometrial invasion
Cervical stromal invasion
Lymphovascular space invasion
Tumour size >2 cm
Positive peritoneal cytology
Hormone receptor status
DNA ploidy and other biological
markers
Type of primary therapy - Surgery or
Radiation
TREATMENT
Surgical treatment remains the
mainstay of therapy for both early as
well as advanced disease. Complete
surgical staging involving examination
of the bowel, peritoneal, liver and
splenic surface should be done.
Biopsy(s) from suspicious areas should
be taken.
80 / FUTURE MEDICINE / FEBRUARY 2019

TABLE A
STAGING OF ENDOMETRIAL CARCINOMA AND CARCINOSARCOMA
TNM
STAGING
Tx
T0
Tis
FIGO
STAGING
Primary Tumour (T)
SURGICO- PATHOLOGICAL FACTORS
Primary tumour cannot be assessed
No evidence of primary tumour
Carcinoma in situ (Preinvasive carcinoma)
T1 I Tumour confined to corpus uteri
T1b IA Tumour limited to endometrium or invades less
than one half of myometrium
T1b IB Tumour invades one half or more than one half of
myometrium
T2 II Tumour invades stromal connective tissue of the
cervix but not extend beyond the uterus
T3a IIIA Tumour involves serosa and/ or adnexa (direct
extension or metastasis)
T3b IIIB Vaginal involvement (direct extension or metastasis)
or parametrial involvement
IIIC
IV
Metastasis to pelvic and/ or paraaortic nodes
Tumour invades bladder and/ or bowel mucosa
and/or distant metastases
T4 IVA Tumour invades bladder mucosa and/ or bowel
Nx
N0
Lymph nodes (N):
Regional lymph nodes cannot be assessed
No evidence of regional lymph nodes
N1 IIIC1 Regional lymph node metastasis to pelvic lymph
nodes (Positive pelvic nodes)
N2 IIIC2 Regional lymph node metastasis to para- aortic
nodes, with or without positive pelvic lymph nodes
Metastasis (M):
M0 No distant metastasis
M1 IV B Metastasis to inguinal lymph nodes, intraperitoneal
disease, liver, lung or bone.
Though peritoneal cytology does
not change staging, it is recommended
to collect peritoneal fluid for cytology
by both FIGO and TNM.
Omental biopsy or omentectomy
is indicated in patients with
non-endometrioid histology,
G3 endometrioid tumour and
carcinosarcomas.
The standard surgical management
for uterine cancer is extra fascial total
hysterectomy with bilateral salpingooophorectomy
with or without lymph
node assessment. For younger
women who are desirous of future
child bearing, fertility preserving
management can be advised after
thorough evaluation and detailed
counselling.
The route of surgery can be open
or minimally invasive (laparoscopic
or robotic). Several studies have
proved the feasibility, safety, efficacy
of minimally invasive approach
with comparable survival rates.
However, during laparoscopic surgery
morcellation or tumour fragmentation
is not permissible in patients with
endometrial carcinoma.
Lymphadenectomy
Supporting Evidence review:
The extent of lymphadenectomy
has been a matter of debate and
has been extensively investigated in
several studies. The baseline rate of
nodal disease in endometrial cancer
is approximately 9%. The extent of
lymphadenectomy is important to
decide the need to administer adjuvant
therapy but may also impart some
therapeutic benefit. The overall surgical
complication rate of lymphadenectomy
varies from 6% to 20% depending
mainly on the surgical expertise. In
order to determine which patients
are at low risk of nodal metastasis, so
that lymphadenectomy can be safely
omitted, several risk stratification
systems have been developed.
1. In 2000, a model was suggested
by Mayo Clinic that could help in
identifying cases with low risk of
nodal spread and high disease-free
FEBRUARY 2019 / FUTURE MEDICINE / 81

survival (DFS) based on frozen section
evaluation of uterus. They found that
women with Grade 1 to 2 endometrioid
tumours, inner 50% myometrial
invasion and tumour size

location of pelvic SLN being medial
to the external iliac, ventral to the
hypogastric, or in the superior part of
the obturator region. Occasionally the
lymphatic trunks do not cross over
the obliterated umbilical and move
upwards following the mesoureter and
seen in the common iliac presacral
region also. Considering the low
volume nodal metastasis ultra-staging
is recommended to detect the
disease. A side-specific nodal
dissection should be performed in
cases of failed mapping and any
suspicious or grossly enlarged nodes
should be removed regardless of
mapping.
SLN mapping should be undertaken
for the surgical staging of uterineconfined
disease with no obvious
factors, stage 1 can be further subdivided
into three risk categories. This
stratification is useful to plan adjuvant
therapy.
Adjuvant treatment according to
FIGO Stage and Grade of tumour
Radiotherapy plays an important role
in the management of endometrial
cancer.
STAGE I A
G1–G2: Observation
The risk of pelvic node positivity is
as low as 50%, LVSI, lymph
node metastasis and tumour diameter
>2 cm. Based on the presence of these
RISK STRATIFICATION OF
ENDOMETRIAL CARCINOMA
Low risk
Intermediate
risk
High risk
IB G3: external beam radiation therapy
(EBRT) and vaginal brachytherapy
STAGE II
Stage 1A (G1,2),
endometrioid disease
Stage 1A (G 3),
endometrioid type,
stage 1B (G1,2),
endometrioid type
Stage 1B (G3),
endometrioid type
All stages, nonendometrioid
type
Surgical treatment
Radical hysterectomy with bilateral
salpingo-oophorectomy and bilateral
pelvic ± para-aortic lymphadenectomy
When surgery is not feasible due to
medical contraindications (in ~5%–10%
of patients), or because of irresectable
disease, external beam radiation
therapy with or without intracavitary
brachytherapy can be considered.
Surgical treatment
Maximal surgical cytoreduction is
indicated in patients with a good
performance status and resectable
tumour.
STAGE III B
Vaginal involvement is usually treated
with a combination of external radiation
and intracavitary / interstitial radiation,
tailored according to the disease extent.
Adjuvant treatment
Chemotherapy
If positive nodes are detected
concurrent chemoradiotherapy
consisting of EBRT with platinum and
taxane based chemotherapy can be
considered. If paraaortic nodes are
involved, extended field radiation
should be considered.
STAGE IV
Systemic therapy + pelvic radiotherapy
If positive nodes are detected,
radiotherapy can be considered.
Recurrent endometrial cancer
Recurrent endometrial cancer is
treatable but not curable unless it is
confined to the vaginal cuff or pelvis.
Widely metastatic recurrence carries
poor prognosis. The treatment for
84 / FUTURE MEDICINE / FEBRUARY 2019

ecurrent endometrial cancer depends
on the anatomic location of the
recurrence.
TREATMENT FOR LOCAL
RECURRENCE
Distant metastasis should be ruled out
by imaging with PET-CT/ contrast CT.
Treatment should be individualized
based on the following factors (3,32):
• Whether recurred in previously
irradiated area
• Whether complete resection is
possible
• Disease free interval
• Grade of disease
These patients experience a 5-year
local control rate of 42%–65% and a
5-year overall survival rate of 31%–53%.
(43)
While this treatment approach has
a good response rate, it is not without
side effects. Indeed, the rate of grade
4 complications has been reported to
be as high as 9%, and many patients
who receive radiation to the pelvis
experience vaginal stenosis, cystitis,
THE RATE OF GRADE 4
COMPLICATIONS HAS BEEN
REPORTED TO BE AS HIGH
AS 9%, AND MANY PATIENTS
WHO RECEIVE RADIATION
TO THE PELVIS EXPERIENCE
VAGINAL STENOSIS, CYSTITIS,
PROCTITIS, AND CHRONIC
DIARRHOEA
proctitis, and chronic diarrhoea, which
significantly impacts their life.
Surgery
In cases where complete surgical
resection appears possible, surgical
exploration and resection with negative
free margins and intraoperative
radiotherapy if available.
Radiotherapy
Isolated vaginal recurrence - Surgical
excision and Pelvic radiation +
brachytherapy.
Inoperable pelvic recurrence - consider
palliative pelvic radiation.
Chemotherapy
If previously irradiated and inoperable,
palliative chemotherapy is to be
considered. Platinum and taxane based
chemotherapy regimens are used.
Treatment for nodal recurrence:
If not irradiated previously – External
beam radiotherapy + Chemotherapy
TREATMENT FOR METASTATIC
DISEASE
Palliative chemotherapy
Palliative chemotherapy is
recommended if previously not
exposed to chemotherapy or there
has been a long disease-free interval
after previous chemotherapy. Single
cytotoxic agents have been reported
to achieve a response rate up to 40%
in chemotherapy-naïve patients with
metastatic endometrial cancer.)
FEBRUARY 2019 / FUTURE MEDICINE / 85

Platinum based compounds,
anthracyclines and taxane are the
commonly used agents. Paclitaxelbased
combination regimens are
preferred for first-line chemotherapy of
advanced and recurrent endometrial
cancer.
Endometrial cancer recurring
after first-line chemotherapy is largely
a chemo resistant disease. Various
agents have been tested in a number
of small phase II trials in patients
previously exposed to chemotherapy.
Only paclitaxel has consistently shown a
response rate >20%.
In the case of systemic metastases,
chemotherapy has a poor track record
in improving survival, with most trials
reporting response rates of less than
20%, progression-free survival of 3–6
months, and overall survival of less than
12 months when using chemotherapy
in the recurrent setting.
Hormonal therapy:
• For endometrioid histology only.
• Progestational agents: Tamoxifen
and aromatase inhibitors are also
used.
• Predictors of response: welldifferentiated
tumours, a long
disease-free interval and the
location and extent of extra pelvic
(particularly pulmonary) metastases.
• The overall response to progestins
is ~25%.
Palliative radiation can be
considered for bone metastasis and for
control of vaginal bleeding.
PRICIPLES OF RADIOTHERAPY IN
THE MANAGEMENT OF UTERINE
CANCER
Pelvic Radiotherapy
Should include gross disease
(if present), parametria, vagina
(depending on extent of involvement),
paravaginal tissues, iliac nodes (internal,
external, lower common iliac), presacral
nodes (if cervix is infiltrated).
Extended field radiotherapy should
include the pelvic and entire common
iliac and paraaortic lymph node region
ideally up to the level of renal vessels.
External beam radiotherapy dose
for microscopic disease 45-50 Gy
preferably with CT based planning and
conformal therapy.
Brachytherapy
Brachytherapy should be administered
4-6 weeks from the time of surgery /
when the vaginal cuff has healed well
but not beyond 12 weeks.
Treatment volume should include
the vault and upper two thirds of the
vagina.
SEVERAL HORMONAL AGENTS
HAVE BEEN INVESTIGATED
INCLUDING MEGESTROL
ACETATE ALTERNATING WITH
TAMOXIFEN, PROGESTATIONAL
AGENTS ALONE, AROMATASE
INHIBITORS, TAMOXIFEN
ALONE OR FULVESTRANT
WITH VARIABLE RESPONSE
For High Dose Rate brachytherapy
7Gy x 3 fractions, calculated at 0.5 cm
depth from vaginal surface or 6Gy x 5
fractions, calculated at vaginal mucosal
surface.
For High Dose Rate brachytherapy
after external beam therapy a dose of
6Gy x 2 or 3 fractions prescribed to
vaginal mucosal surface.
Palliative Radiation
Palliative radiation should depend upon
patient’s performance status and needs
to be tailored as per need / extent of
disease.
Medically inoperable Stage I / II
Intracavitary application with or without
pelvic RT
Intracavitary application 70-75Gy
point A, when pelvic RT is combined
45-50 Gy and intracavitary 30-35 Gy.
Whole body irradiation was
compared with systemic therapy and
was found to have more side effects
than systemic therapy hence not
preferred.
Role of systemic therapy
Adjuvant systemic therapy plays an
important role in extrauterine disease.
Paclitaxel with carboplatin has been
used in systemic therapy. In patients
with high grade deeply invading
tumours of the uterine endometrium,
systemic therapy is used to prevent
distant metastasis.PFS is shown to
improve with adjuvant sequential
chemotherapy/RT.
Hormonal Therapy
In patients with endometrioid histology
hormonal therapy has been tried.
Patients with recurrent or metastatic
endometrioid tumours who have
low grade tumour with an indolent
course should be offered hormonal
treatment. Several hormonal agents
have been investigated including
megestrol acetate alternating with
tamoxifen, progestational agents
alone, aromatase inhibitors, tamoxifen
alone or fulvestrant with variable
response. Response depends upon ER/
PR receptor positivity, long diseasefree
interval, location and extent of
metastasis. Tamoxifen, acting through
ER, would increase expression of
PR and is thus likely to enhance the
sensitivity to medroxyprogesterone
acetate (MPA) ormegestrol acetate
(MA). In a systematic review, 11%–56%
of grade 1 and 2 tumours were shown
to respond to progestins, with the
response rate generally higher for PRpositive
tumours. Importantly, toxicity
was remarkably low, with the rate of
grade 3 and 4 events being less than
5%.
Overall, progestins remain a valid
option not only for patients with
recurrent receptor-positive tumours
after chemotherapy, but also for
patients with well differentiated (low-
86 / FUTURE MEDICINE / FEBRUARY 2019

STUDIES SHOWING IMPACT OF HORMONAL THERAPY IN
TREATMENT OF ENDOMETRIAL CARCINOMA
Trial Treatment given PFS OS Response rate
GOG
81(48)
GOG
12(49)
GOG
119(50)
GOG
168(51)
Ma et al
(52)
Group 1 : MPA 1000mg
daily (n=154)
Group 2: MPA 200 mg
daily (n=145)
2.5months 7
months
15%
MA 800 mg daily 3.2 11 25%
MPA 100 mg BD on
alternating weeks
+Tamoxifen 20 mg daily
continuous
33 3 13%
Anastrozole 1 mg/day 1 6 9%
Letrozole 2.5mg daily 4 9 9.4%
grade) endometrioid adenocarcinomas
that are positive for hormone receptors
but are not suitable for chemotherapy.
Menopausal hormone therapy
(MHT) in survivors
Endometrial cancer is considered
hormonally dependent hence the
use of HRT in patients who have
undergone oophorectomy was
previously considered harmful. The use
of estrogen replacement therapy in
patients with profound hypoestrogenic
symptoms may be considered after
counseling the patient especially in
women who had early stage low grade
endometrioid disease. In advanced
stage and high-risk cases use of
FEBRUARY 2019 / FUTURE MEDICINE / 87

selective estrogen receptor modulators
(SERMs) and non-hormonal therapy
should be considered as first line.
Fertility preserving therapy
Patients who want to preserve
childbearing function may be
considered for fertility preserving
options after thorough evaluation and
after explaining the deviation from
standard therapy. A pre-operative
counseling with reproductive medicine
and genetics specialists is desirable.
Young women with stage IA grade
1 disease without myometrial or
cervical involvement can be considered
for medical management with
progestational agents. They should
be carefully evaluated for other risk
factors like breast cancer, deep vein
thrombosis, myocardial infarction,
stroke, pulmonary embolism, and
smoking. The drugs used are
medroxyprogesterone acetate (400–
600 mg/day), megestrol acetate
(160–320 mg/day), and levonorgestrel
releasing intrauterine systems, with
or without GnRH analogues, have
been tried with variable success
rates. Patients need to be on followup
3-monthly with endometrial
biopsy with or without hysteroscopy.
Treatment should be discontinued if
disease persists for more than 6-12
months, or if there is progression
of disease (proven by histology) in
patients with stable disease after 6
months of treatment. Imaging should
be repeated after 6 months to rule out
myometrial involvement or extrauterine
or ovarian involvement. Definitive
treatment should be considered
when childbearing is complete, if
there is progression of disease or if
no reversal of disease after 12 months
of treatment. Patients on high dose
progesterone should also be monitored
for the side effects of progesterone.
RESPONSE TO MEDICAL
THERAPY FOR FERTILITY
PRESERVING MANAGEMENT OF
CARCINOMA ENDOMETRIUM
Author,
Year
Qin et al,
2016 (54)
Simpson
et al,
2014(55)
Gallos et al,
2012(56)
Intervention
MPA/MA 83%
MPA/MA 55%
MPA/MA
Others 76%
Ramirez
et al,
2004(57)
FOLLOW UP
Endometrial
resection
MPA/MA 75%
Response
rate
Every 3 months up to a period of two
years, then 6 monthlies up to 5 years
thereafter annually.
At every visit the patient is asked
in detail for symptoms of potential
recurrence and complete systemic
examination and pelvic examination
is performed. The use of imaging
andserumCA-125 is advised according
to symptoms. Vault cytology has
limited significance and is reserved for
patients with no prior radiation therapy.
Mammography can be done as per
standard guidelines for breast cancer
screening. For patients at risk of colon
cancer (Lynch syndrome), colonoscopy
must be requested everyone to two
years, to start at 20-25 years or 10
years before the youngest case in the
immediate family (American Cancer
Society recommendation for colorectal
cancer early detection).
Survival: Prognosis for carcinoma
endometrium is generally favourable.
Disease stage remain the most
significant prognostic factor (59) as
seen in Table B.
SCREENING
Currently routine screening for
endometrial cancer for asymptomatic
population with average risk or with
above-mentioned risk factors including
tamoxifen intake has not proven
beneficial and is not recommended.
The American Cancer Society (ACS)
recommends that women at the onset
of menopause be informed about risks
and symptoms of endometrial cancer,
i.e., unexpected bleeding or spotting,
and should be encouraged to report
immediately if these symptoms occur.
Women who are taking tamoxifen
therapy for prevention of recurrence
or development of contralateral
breast cancer are at increased risk of
developing uterine cancer. However,
routine screening with ultrasound
or endometrial biopsy is not
recommended. These women should
be advised to report if there is any
abnormal vaginal discharge or bleeding
per vagina.
Women with family history of Lynch
syndrome are at high risk of developing
carcinoma endometrium and should be
advised to undertake regular screening.
In these women screening should start
at the age of 35 years, or 5-10 years
prior to the diagnosis of any Lynch
associated cancer in the youngest
family member and consist of annual
endometrial sampling.
—Prepared as an outcome of ICMR
Subcommittee on Uterine Cancer
TABLE B
STAGE WISE SURVIVAL RATES FOR CARCINOMA ENDOMETRIUM
STAGE I A I B II IIIA III B III C IV A IV B
SURVIVAL 88% 75% 69% 58% 50% 47% 17% 15%
88 / FUTURE MEDICINE / FEBRUARY 2019

events
Maiden neuroscience session unfolds
secrets of consciousness
Kerala Literature Festival 2019 opens an era of science debates starting from this year
DIVYA CHOYIKUTTY
The first-ever session on
neuroscience at Kerala Literature
Festival (KLF) unfolded the hidden
capabilities of the human brain at the
fourth edition of the annual literary
event.
The session highlighted the scope
and relevance of a deep understanding
of neuroscience, and its possibilities in
modern healthcare.
Thus began an era of science
debates at Asia’s second-largest
literature festival that saw an illustrious
gathering of eminent authors, artists,
philosophers and activists discussing
and sharing insights with a vibrant
audience.
The session ‘Locating consciousness
in the brain’ marked its importance
at the event as the speakers
Dr K Rajasekharan Nair, an eminent
neurologist and science author,
Dr Vishwanathan Chathoth, a well-known
rationalist, and Dr Ethiran Kathiravan, a
genetic scientist and author, explored
the deep and complex neuronal network
in the brain. The session was moderated
by CH Unnikrishnan, founder & editor,
Future Medicine, India’s premium
medical science news magazine.
“Who we are is determined by the
activity that happens within our brain,
based on what we see, touch or hear,”
said Dr K Rajasekharan Nair. That is
how our external stimuli makes us.
The activities within the hundreds of
billions of neurons that make up the
complex neuronal network in our brain
“IF A DOCTOR KNOWS THE
STORY OF A PATIENT, HE
SURELY CAN BE A GREAT
DOCTOR AND A WRITER.”
— DR B EKBAL
determines all our actions, he says.
“We become materialistic when we
realise that consciousness is a process.
It does not have individuality,” said Dr
Vishwanathan, explaining that it is never
an entity. He explains consciousness as
a process that happens within the brain,
and that it can never be independent
of it.
He also described the hyper-normal
activity of the brain in autism, which
unlocks a special ability to perceive
things more intensely, inhibited in the
normal brain.
Exploring the scientific location of
consciousness, Dr Kathiravan explained
that it happens where the complex
neuronal network works together at
the same time. “Neuronal network is
very complex. When it works together
at the same time, there [it] creates our
consciousness.” he said.
Another key scientific session
— ‘Medicine and Literature’ — was
addressed by Dr M V Pillai, an eminent
physician specialised in Internal Medicine,
Hematology and Medical Oncology,
Dr Khadija Mumtaz, a well-known
Malayalam author and a physician,
and Dr B. Ekbal, a public health activist
and a neurosurgeon. It closely analysed
the relationship between literature
and medicine and criticised the
malpractices happening around the field
of medicine.
Connecting literature and medicine,
Dr Ekbal said, “If a doctor knows the
story of a patient, he surely can be a
great doctor and a writer.”
The four day event, which had 500
speakers and 180 sessions on topics
spanning from literature, media, politics,
religion, films to socio-economic issues,
was attended by 2.7 lakh audience.
90 / FUTURE MEDICINE / FEBRUARY 2019

ADVERTORIAL
‘ECP a clinically proven
natural bypass’
Dr Bimal Chhajer, MBBS, MD, who
pioneered non-invasive cardiology in
India, is a well known personality in the
field of medical science. Born in 1961,
Dr Chhajer passed out his MBBS from
Kolkata and MD from Lucknow. He
served at the All India Institute of Medical
Science (AIIMS), New Delhi between
1989 and 1995 as a senior resident and
assistant professor. After resigning from
AIIMS in 1995, Dr Chhajer founded a
lifestyle-based treatment of coronary
heart disease along with conservative
drug-based modern medical care. The
lifestyle-based treatment included
very low fat vegetarian diet and stress
management along with Yoga, walking
and patient education on healthy life.
This treatment was named Science and
Art of Living (SAAOL) with its first centre
opened in New Delhi in September, 1995.
SAAOL is currently the largest chain of
non-invasive cardiology clinics in the
world with 72 centres in about 62 cities
including India and abroad. As part of
the SAAOL initiative, Dr Chhajer has also
pioneered a special cooking method
known as Zero Oil Cooking for the heart
patients by which Indian spices were
cooked with water instead of oil and
developed more than 1000 recipes.
Dr Chhajer has authored more than 70
books on heart and health and many
of the books have been translated and
published in 9 different Indian languages.
Dr Chhajer’s heart health workshops
are very popular and are arranged all
across the world where he educates heart
patients about how to reverse heart disease
and avoid Bypass Surgery/Angioplasty.
Honoured with several awards, including
Rajiv Gandhi Rashtriya Ekta Award, Dr
Chhajer’s video talks on YouTube have got
some 10 million views.
SAAOL introduced the US FDA approved
External Counter Pulsation (ECP) therapy
in its clinics in 2006. Dr Chhajer, who has
in his credit more than 1,50,000 successful
treatments of coronary heart disease
patients with his non-invasive care,
talks about the advantages of ECP as a
scientifically proven natural bypass in an
interview. Excerpts:
Could you explain what is ECP and its
advantages?
External Counter Pulsation therapy
is a wonderful treatment that can help
preventing and healing of all forms
of disease that stem from circulatory
disorders of the vascular system,
such as angina, coronary disease,
coronary atherosclerosis, congestive
heart failure, ischemic brain disease,
ischemic optic disease, poor peripheral
circulation. It is especially helpful for
patients with heart disease who are not fit
for procedures or who cannot be cured by
procedure.
ECP system consists of three sets of
92 / FUTURE MEDICINE / FEBRUARY 2019

inflatable pressure cuffs wrapped around
the calves and the lower and upper
thighs, including the buttocks. In
synchronization with each cardiac cycle,
obtained with an integrated 3-lead
ECG, the cuffs are sequentially inflated
from the calves to the buttocks during
diastole to produce an arterial retrograde
flow towards the aortic root to increase
coronary blood flow. ECP simultaneously
increases venous return to raise the
cardiac output. The cuffs are deflated
simultaneously before the onset of systole
to provide an empty vascular space,
reducing systemic vascular resistance
in the lower extremities to receive blood
ejecting from the heart, significantly
reducing the workload and oxygen
demand of the heart.
The patients can feel the change after
7-10 days of therapy an indication of well
being which improves the circulation due
to revival of dormant collateral arteries
with improved blood flow in affected
regions ,also resulting in endothelial
function.
Innumerable research papers outcomes
state that the patients with heart failure
with varying degrees of seriousness (NYHA
Classes I II III IV, with class I being less
serious and class IV being most serious)
improve in their classification and could
be classified in less severe class due to
improved exercise tolerance and overall
well being.
How does the counter pulsation
technique function in the body?
ECP therapy, which was approved by
US FDA and in practice for more than 30
years, triggers the body to create tiny blood
vessels (known as collaterals) that act like
a natural bypass, carrying blood around
larger blocked vessels. Chest pain is then
reduced because the heart is again able to
receive oxygen rich blood.
It acts by decreasing the after load
that the heart has to pump against, and
increase the preload that fills the heart,
increasing the cardiac output. In this way,
ECP is similar to the intra aortic balloon
pump (IABP). Since it increases pressure
in the aorta while the heart is relaxing
(during diastole) ECP also increases blood
flow into the coronary arteries, which also
occurs during that phase.
Another theory is that cuff inflation/
deflation increases the force of the blood
flow to the heart, causing the cells lining
the blood vessels to produce chemicals
that widen the blood vessels, allowing
blood to flow through more freely.
Are there enough clinical studies to
establish the safety and efficacy?
Yes, there are research papers and
clinical trials to support the same.
Published in peer reviewed medical
journals, these studies have demonstrated
ECP Therapy as a non-invasive, safe, low
cost and highly effective treatment for
patients with coronary artery disease.
There are 8 randomised controlled trials
(RCT) documenting the clinical outcomes
and mechanisms of action of enhanced
ECP Therapy. The most well known
RCTs were the multicentre study of
ECP (MUST) in the treatment of patients
with angina pectoris and Prospective
Evaluation of ECP Congestive Heart
Failure (PEECH) study. There is also
subgroup study analyzing data from the
PEECH trial for heart failure patients age
65 or older.
Another multicentre study of External
Counterpulsation (MUST-EECP) in
2006 to evaluate the safety and efficacy
of ECP on exercise-induced Myocardial
Ischemia and Anginal Episodes, which
was published in the Journal of American
College of Cardiology (Rohit R. Arora,
MD, Tony M. Chou, MD,† Diwakar Jain,
MD,‡ Bruce Fleishman, MD,§ Lawrence
Crawford, MD,\ Thomas McKiernan, MD,
Richard W. Nesto, MD# New York, New
York; San Francisco, California;
New Haven, Connecticut; Columbus,
Ohio; Pittsburgh, Pennsylvania; Maywood,
Illinois; Boston, Massachusetts et. all.),
have also shown that enhanced external
counter pulsation reduces angina and
extends time to exercise-induced ischemia
in patients with symptomatic CAD.
Treatment was relatively well tolerated
and free of limiting side effects in most
patients.
How critical is the role of ECP in “nooption”
patients?
A recent study (Anil Kumar Gothwal,
Sanjay Mittal, Sound Shore Medical Centre
of Westchester, New York Medical College,
New Rochelle, USA , and Escorts Heart
Institute and Research Centre,
New Delhi) concluded that refractory
angina is growing in prevalence and
has become an increasingly challenging
problem in clinical practice. While
various forms of treatment have been
tried, results from clinical studies
suggest that ECP therapy has the most
favourable risk/cost-benefit profile.
This therapy is the only FDA-approved
non-pharmacological approach to
refractory angina that has been supported
by sham-controlled data. It is also
recommended by the American Heart
Association as a potential therapy for
refractory angina as a class IIb indication,
though its usefulness/efficacy is relatively
less well established. Given the rapid
development of ECP over the past few
years, it is hoped that the use of this
modality will soon receive greater priority
than at present. In the future, more
patients are expected to benefit from this
innovative treatment for angina and other
cardiovascular conditions.
This is a sponsored article. FM editorial holds no responsibility for the information therein.
FEBRUARY 2019 / FUTURE MEDICINE / 93

ADVERTORIAL
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procedures
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The Philips Azurion 7 C20 with FlexArm
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The full flexible and compact set-up of
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Image beam rotation
Part of the X-ray tube which continually
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This is a sponsored article. FM editorial holds no responsibility for the information therein.
94 / FUTURE MEDICINE / FEBRUARY 2019

calendar
Upcoming conferences
FEBRUARY
1-2 SURGERY
Basic Surgical Skills Course
Dervan
1-3 OTORHINOLARYNGOLOGY
PHONOCON 2019: 15th Annual
Conference of the Association of
Phonosurgeons
Kolkata
5-9 GYNECOLOGY
All India Congress of Obstetrics
and Gynaecology (AICOG) 2020
Lucknow
6-10 PAEDIATRICS
Illness to Wellness Pedicone
Mumbai
7-9 NEUROLOGY
Neonatal Neurology: stateof-the-art
in inborn errors of
metabolism, seizures, and
pathophysiology of brain
damage Course
Bangalore
7-9 GASTRO-ENTEROLOGY
Annual Congress of Indian
Association of Gastrointestinal
Endosurgeons (IAGES)
Bhubaneswar
8-9 CLINICAL ANATOMISTS
Society of Clinical Anatomists
Chennai
8-10 PEDIATRICS
Conference of Indian Association
of Pediatric Anaesthesiologists
(IAPA)
New Delhi
8-10 PLASTIC SURGERY
Annual Meeting of Indian
Society of Cleft Lip Palate
and Craniofacial Anomalies
(Indocleftcon)
Varanasi
ONCOLOGY
Conference of Society of
Oncologic Imaging India
New Delhi
9-10 PEDIATRICS
IAPEN Clinical Nutrition Congress
(ICNC-2019)
Mumbai
13-14 RADIOLOGY
International Conference on
Public Health, Radiology, Nuclear
Medicine & Imaging
Chennai
14-15 NEUROSURGERY
International Conference on
Conjoined Twins (ICCT)
New Delhi
14-17 ONCOLOGY
MEDINSPIRE - An International
Multidisciplinary Medical Summit
Mumbai
15-16 CLINICAL RESEARCH
ISCR Conference
New Delhi
15-17 PHYSIOTHERAPY
Society of Indian Physiotherapist
Annual Conference (Society of
Indian Physiotherapist Annual
Conference)
New Delhi
15-17 NEUROLOGY
Annual Conference of the Indian
Society of Neuroanaesthesiology
and Critical Care (ISNACC)
Gurgaon
HEPATOLOGY
Advanced Institute of Liver
& Biliary Science (AILBS)
International Conference 2019
New Delhi
21-23 ORTHOPAEDICS
Ranawat Orthopaedic
Conference
New Delhi
21-24 CARDIOLOGY
ASCVTS & IACTSCON
Chennai
22-24 CARDIOLOGY
World Congress on Cardiac
Imaging Clinical Cardiology
(WCCICC)
Mumbai
ANAESTHESIOLOGY
Conference of the Indian
Association of Cardiovascular
Thoracic Anaesthesiologists
(IACTACON)
Kolkata
NEUROLOGY AND
PSYCHIATRY
MDSICON
New Delhi
28-3 CARDIOLOGY
India Live Conference
Mumbai
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
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
International Conference on
Medical & Health Science
(ICMHS)
Panjim
The announced dates of the conferences may change
96 / FUTURE MEDICINE / FEBRUARY 2019

ook review
THE IMPORTANCE OF
BEING INFORMED
NAVIGATING LIFE
WITH MIGRAINE AND
OTHER HEADACHES
William B Young, MD,
FAAN, FANA, FAHS and
Stephen D Silberstein,
MD, FAHS, FAAN, FACP
pp241
Oxford University Press
Managing a neurologic disorder is
new territory. To effectively manage
a neurologic condition, the person
should be armed with new information and
new skill sets. Informed involvement of the
patient in the treatment programme can
lead to better care and better outcomes.
But one cannot escape the question of how
such information could help in curing the
condition.
Presenting their book, Navigating Life
with Migraine and Other Headaches, authors
William B. Young and Stephen D. Silberstein
seek to address this question, underscoring
the importance of being informed about your
condition.
Headache is one of the most common
complaints patients consult neurologists for.
It is the seventh most common symptom
for which they visit primary care providers.
Headache is such a common symptom
that it often goes overlooked, undertreated,
overtreated or untreated. Many people think
that “nothing can be really done”. While
many others, including some doctors, seem
to cherish certain notions: For example,
without aura, tingling, numbness and blurred
vision, a headache cannot truly be called
migraine. But it remains a fact that most of
the people suffering from migraine do not
experience aura or any of these symptoms.
You can avail the best new treatments
if you land up with the right expert. The
key requisite is that you should be armed
with the right kind of information about the
condition.
Spread across three sections, the book
explains migraine and other headaches
in simple terms. All the known forms of
migraine, migraine equivalents, their triggers,
symptoms, patterns as well as the hormonal
aspects of the condition are discussed at
length. Then it goes on with various drugs
as well as other alternative and behavioural
treatments for migraine. The authors point
out that migraine can occur at any age. Even
very young children are suspected of having
migraine, but it is difficult to diagnose it until
they learn to speak.
Sinus headaches and headaches related
to disorders of the neck, post-trauma,
trigeminal neuralgia etc are classified under
Secondary Headaches and Neuralgia section.
THE MORE PRECISELY YOU PIN
DOWN AND COMMUNICATE
YOUR PROBLEM, THE MORE
LIKELY YOU WALK OUT OF
YOUR DOCTOR’S OFFICE WITH
A PLAN RIGHT FOR YOU
While listing some of the headaches that
require urgent medical attention, the book
also mentions some of the unusual type of
headaches such as ice pick headaches and
sexual activity headache.
The book provides up-to-date and useful
answers to the questions that concern most
to the patients and caregivers, illustrated
with real-life experiences of patients and
families.
Physician’s decision is not “a one
shoe fits all” enterprise. The more precisely
you pin down and communicate your
problem, the more likely you walk out of your
doctor’s office with a plan right for you, says
the book.
FEBRUARY 2019 / FUTURE MEDICINE / 97

OUR DEVOTION THAT MAKES
THE DIFFERENCE
DR INDIRA HINDUJA
Senior Gynaecologist and ART Specialist
We in India often have the tendency to get
excited about a big breakthrough or a curious
discovery that has happened in the West,
expressing deep regret that our country lags far behind.
But what we do not realise is the fact that this country is
equally, if not more, capable of doing such things if we
put our real potential to work. We may have constraints
like inadequate resources and infrastructure, but these are
resolvable issues if one has the will to pursue his or her
passion with full devotion.
I don’t think that Indian brains are any less as far
as research in science and technology is concerned,
especially in the area of biomedical research. In this field,
India has got many natural advantages too, including the
diverse nature of the human race, wider genetic variations
and a broader lifestyle and disease profile, among others.
I want to tell new generation doctors and aspiring
biomedical researchers that we are not inferior to anyone
and we have the brightest brains in this country itself.
What we lack often is the commitment and the courage
to take on the challenges.
Be passionate about what you want to do in life and
have full faith in your capabilities to take that dream
forward. More importantly, try not to find faults with
others for your failures. Instead, learn from your mistakes
and take your failures as bigger steps towards success.
One should realise that blaming others for one’s own
failure is just an excuse and will never help in achieving
progress. On the contrary, failures may prove to be the
biggest opportunities for you later, if you overcome them
and proceed further.
In my journey of IVF research, I have many a time felt
terrible when I missed opportunities or faced difficulties
in pursuing my work due to sudden departures of
teammates or even accusations and non-cooperation
from organisations and senior colleagues. But now, I feel
that many such difficult situations have actually helped
me develop the courage to become more committed and
deeply involved in my work, which has ultimately helped
me achieve what I wanted.
If you are fully devoted to something that you are
passionate about, there will open a hundred other doors
even if the one in front of you is closed. Once you decide
to take the plunge and show your dedication, trust me,
everything else, including money and infrastructure, will
follow. From my own experience, I can confidently say that
nothing can stop you from your achievements if you are
determined to take the mission on. There will be people
to push you up as well as pull you down. But both these
should not affect your determination and hard work.
— As told to CH Unnikrishnan
98 / FUTURE MEDICINE / FEBRUARY 2019

RNI Number KERENG/2012/44529