Professor
Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week
of 26th January 2017 (#79)
University
of Notre Dame Australia (Fremantle Campus)
Occasional Editorial Comment
Students have now returned and hopefully for reviewing
the articles from the week’s Journal.
You will receive an e-mail each week of the previous
week’s Journal review with a focus on areas students in my teaching groups felt
interested them the most. I will, however, also comment on articles not chosen
if I believe they are important to medical students and their teachers. You should open the blog from the e-mail as
the blog contains appropriate formatting which makes the reviews much easier to
read. A search of previous editions of the blog can be done from the top left
corner.
Full
articles can be reviewed using the UNDA library e-resources.
This is the first issue of the UNDA academic year and,
as the new MEDI6100 class will be receiving this weekly e-mail for the first
time, it is appropriate that I review the reasons this blob was developed. There are also many ancillary learning aids
associated with the Journal which I am will not attempt to duplicate.
The primary aim of the blog is to foster an interest in
every Notre Dame medical student and teacher the need to remain current in all
areas of the curriculum and to develop a yearning for continued long term
learning. My recommendations are not compulsory reading, however, I hope that
most students would read my weekly review and, at the least, explore the NEJM
titles to keep abreast of new developments which will determine the basis of
their future practice. Students will at a minimum become aware of areas and see
more relevance in their basic science teaching.
The NEJM is the most widely read journal
internationally with the highest impact factor of any journal.
My weekly review is in no way exhaustive. Articles are chosen for their specific
relevance to the evolving UNDA medical school curriculum, in order to update
the student particularly in:
1. basic
sciences (e.g. cell and molecular biology, immunology, genetics, pharmacology),
and
2. new
therapies.
The Journal contains the following sections:
1. Perspective:
Covers all curricular domains (health care systems, ethics and public health
are overrepresented). Many relate
specifically to medicine in the US. I
will not highlight these unless there is a specific application to Australian
medicine.
2. Original Articles:
Some articles will interest you, while others may not. If interested or in
doubt, always read the abstract and the introduction to the paper. The
introduction will provide an overview to the study and why it was performed.
This is a quick way to update your knowledge.
3. Review Articles:
State of the Art review articles are always interesting and encompass wide
areas. My suggestion is that these be
stored as hyperlinks in your long-term data base learning system, such as Evernote
which is free for moderate storage. You
can also include your long cases in Evernote for future use after medical
school.
4. Clinical Pathological Conference (CPC)
or Case Records of the Massachusetts General Hospital:
It is very interesting to follow the clinical reasoning of the discussant. As
an exercise, sit down with a colleague, consider the broad presenting symptom(s),
and develop a list of differential diagnoses before you read the case.
5. Images in Clinical Medicine:
Remember, if a consultant or tutor mentions a specific disorder and you want to
see it with the pathology, always check in this extensive data base. Apart from
Figures, videos are also included.
6. Editorials:
After reviewing the abstract of the original article, I always check the
editorials before I read the original article in detail. An editorial addressing a specific original
article will provide an independent in-depth overview of the results of the
study and comparisons with other studies.
7. Clinical Problem Solving:
These are usually challenging and will help to develop your skill in clinical
reasoning.
8. Clinical Implications of Basic
Research: Usually I find this a very interesting area in the
Journal. The author of the article has been solicited by a member of the
editorial board to write a short summary, with an instructive picture, of a
recent cutting edge basic science article (e.g. Science, Nature, PNAS) and to
hypothesise on the possible relevance to future human research.
Figures
and Tables: These are very well done, easy to
understand and can be saved in a Powerpoint format for presentations.
Errors:
Errors can occur and are usually mentioned in subsequent Corrections. As a word of general caution when reading any
article or book, if you cannot understand a statement or a Figure, always check
with a colleague as errors can occasionally occur and should not result in you
having a sleepless night.
Other
goodies: The NEJM has an extensive Video Collection of most
commonly performed clinical procedures which are extremely well illustrated and
explained. Enrol in Residents E-Bulletin where two key articles are reviewed
with Morning Report questions and Clinical Pearls. Moreover, there is a Weekly
Audio Summary as a Podcast of articles chosen as the most significant by the
editorial board.
You can also do searches of back issues for virtually
any topic in Medicine.
The entire weekly issue of the Journal is available
through the medical library as an e-journal and is readily searched.
Finally, I must state that the views expressed are mine
alone and you may not necessarily agree with them. At least this will provoke
discussion between students and encourage learning. Errors will invariably
occur and for these I apologize in advance. Please do not hesitate to contact with
questions or corrections when this happens.
Must Read Articles
None
Articles Recommended for Medical Students
Perspective
Allocating
Organs to Cognitively Impaired Patients
Should
patients’ cognitive function be weighed in the allocation of organs? This
debate raises important questions, from the ethics of making judgments
regarding others’ quality of life to the science of cognitive impairment’s
effect on post-transplantation survival.
This is a topical article in which the ethical
arguments representing both sides are clearly presented and are accompanied by
supporting evidence. It would be interesting to consider this for CD discussion.
INTERACTIVE MEDICAL CASE
Making
the Connection
This
interactive feature presents a 41-year-old man who presented with
hyperlipidemia and a history of morbid obesity since childhood. Test your
diagnostic and therapeutic skills at NEJM.org.
As bariatric surgery in the private sector is
increasingly performed, students during their surgical rotations will be
frequently exposed to these procedures in the patients they follow. As such, a
generalized knowledge of the procedures (usually sleeve gastrectomy and
Roux-en-Y) and a detailed knowledge of the early and late post-operative
complications should be acquired. This is a case-based learning process (will
now replace the Short Answer Format in UNDA written clinical examinations) and
in the next issue of the Journal it will be presented in article format.
IMAGES IN CLINICAL MEDICINE
Radiation-Induced
Angiosarcoma after Breast-Cancer Treatment
A
72-year-old woman presented with skin changes on her left breast; 5 years
earlier, she had undergone lumpectomy and radiation therapy for breast cancer.
Examination revealed an area of skin that had an ecchymotic appearance, with no
underlying mass or nodular tissue.
Recommended
learning: Review the role of radiotherapy in the management of
breast cancer.
IMAGES IN CLINICAL MEDICINE
Taenia
solium
A
48-year-old man presented with abdominal discomfort and lethargy. Examination
revealed pallor, and laboratory studies showed mild anemia. Colonoscopy
revealed a proglottid from a tapeworm, shown in a video, in the rectosigmoid
colon.
Recommended
learning: Review the biology, clinical presentations, and
treatment of hookworms and tapeworms.
ORIGINAL ARTICLE
A
Recombinant Vesicular Stomatitis Virus Ebola Vaccine
This
final report updates preliminary data on an attenuated, replication-competent,
recombinant vesicular stomatitis virus–based vaccine candidate designed to
prevent Ebola virus disease. The results supported the safety and immunogenicity
of up to two doses of the vaccine.
This recombinant VSV Ebola vaccine as currently studied
should be particularly useful for medical personnel and the population in the
centre of an Ebola epidemic but not for sustained population protection against
the Ebola virus due to the short term antibody response to the vaccine.
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL
Case
3-2017 — A 62-Year-Old Man with Cardiac Sarcoidosis and New Diplopia and
Weakness
A
62-year-old man with sarcoidosis was admitted to this hospital because of
diplopia and weakness. Examination of the CSF revealed elevated opening
pressure and leukocytosis. The patient’s condition deteriorated rapidly. He
died 10 days later. A diagnosis was made.
In a Google search the discussant asked a specific
question: “What causes the most rapidly
fatal meningoencephalitis?” The first answer was the first hit on the page.
This emphasises the importance of using correct search terms when asking
questions.
This reminds me of a case I managed of acute onset
polyarthritis occurring in a 28-year-old male with common variable
immunodeficiency. Several weeks before this patient presented, the first
description of an association between Ureaplasma
urealyticum polyarthritis in patients with hypogammaglobulinemia was made
by Max Cooper in the NEJM. When I performed my initial literature search I
inadvertently searched for only agammaglobulinemia and was not rewarded with a
positive association. Fortunately, the synovial fluid culture was positive
within 48 hours.
Important Articles Related to Mechanisms of Disease and
Translational Research
None
Other Articles which should interest medical students
REVIEW ARTICLE
Systemic
Therapy for Metastatic Renal-Cell Carcinoma
Kidney
cancers have been extensively studied, and insights from an increased
understanding of tumor biology have led to increases in survival rates.
Therapies aimed at tumor signaling pathways and immunotherapies have improved
the outlook for patients with renal cancer.
Most students who read this article did so to update
their knowledge on renal-cell carcinoma. However, once they began they became
fixated on the cell biology and new pharmacological agents presented in Figure
1. Interested students reviewed the role of the VHL (von Hippel-Lindau) gene in
the control of HIF (hypoxia-inducing factor) function. Normally the VHL gene is
responsible for the ultimate degradation of tissue HIF. If a loss-of-function
mutation occurs in the VHL gene, which happened in 52% of patients with renal
cell carcinoma, HIF is no longer degraded.
Excessive HIF then results in activation of HIF target genes which
include VEGF (responsible for new vessel formation in the tumour) as well as
the growth factors FGF and PDGF and survival factors (PDL1 and-L2).
While the names of most of these newer pharmacological
agents used to treat cancer (in this case renal cancer), need not be remembered,
this Figure should allow the student to see the relevance of the pathways they
are taught in cell biology and pathways they usually forget readily.
Again, mention is made of one of the important check
point inhibitors, nivolumab, which binds to PD-L (programmed cell death ligand)
on the surface of tumour cells, protecting the cytotoxic T cell from undergoing
apoptosis and allowing it to kill the tumour cell.
The review then describes the drugs and their
combinations used in trials to treat metastatic renal cell cancer. As a note to
those few with any interest in the management of metastatic renal cell cancer,
an algorithmic approach is provided.
Recommended
learning: Review the epidemiology, pathology, clinical
presentations and basic therapeutic approach to a patient with renal cell
cancer.
Perspective
Repealing
the ACA without a Replacement — The Risks to American Health Care
President
Barack Obama explains why Republicans’ plan to repeal the Affordable Care Act
with no plan to replace and improve it is so reckless: doing so would
jeopardize financial security and access to care for tens of millions of
Americans.
While this article is not directly applicable to the
practice of medicine in Australia (and I hope never will be), it is written by
a very intelligent, thoughtful, informed President Obama at the end of his
presidency.
SPECIAL ARTICLE
Tobacco-Product
Use by Adults and Youths in the United States in 2013 and 2014
According
to a 2013–2014 survey of nearly 46,000 U.S. adults and youths, 28% of adults
were current users of tobacco and 9% of youths had used tobacco in the previous
30 days. Approximately 40% of users used multiple products, with cigarettes
plus e-cigarettes the most common combination.
While I found the statistics on tobacco-product use in
the US very interesting, I had to review snus pouches, bidis and kreteks as
vehicles to obtain the effects of tobacco-products.
Of interest in Table 2 (the prevalence of tobacco use
according to product type and age), the use of E-cigarettes is only slightly
less than cigarette use in youths (12 -17 years).
New and Novel Therapies
EDITORIAL
Bezlotoxumab
— A New Agent for Clostridium difficile Infection
ORIGINAL ARTICLE
Bezlotoxumab
for Prevention of Recurrent Clostridium difficile Infection
Bezlotoxumab
is human monoclonal antibody against Clostridium difficile toxin B.
In two controlled trials, a single intravenous dose of bezlotoxumab, given in
addition to antibiotic treatment, provided protection against recurrent
infection for up to 12 weeks.
This article and the accompanying editorial discuss the
efficacy of a single infusion of a monoclonal antibody (bezlotoxumab) against C. difficile toxin B in patients with
primary or recurrent C. difficile
infection who are being treated with standard-of-care antibiotics
(metronidazole or vancomycin both approx. 47% or fidaxomicin 3.5% - Table 1).
2655 patients at 322 sites in 30 countries were studied. The infusion usually
commenced three or more days after the start of antibiotics (varied) when the
disease severity had improved and when the concentration of stool toxin B was
markedly reduced. Addition of a monoclonal antibody against the A toxin added
no clinical advantage to that of bezlotoxumab alone. The selection of antibiotics was at the
discretion of the treating physician. No other therapies were allowed in this
study (such as faecal microbiota transplantation). The primary end point was
recurrence (a new episode after initial clinical cure) within 12 weeks of the
infusion.
The study showed approximately 50% reduction in the
recurrence within 12 weeks in the group treated with bezlotoxumab over the placebo.
The rates of sustained cure rates (no recurrence within 12 weeks) was 64% for
bezlotoxumab versus 54% in the placebo group. However, the initial cure rates
were 80% in both the bezlotoxumab and placebo groups.
The cost of C.
difficile in the US in 2011 was estimated to be 40 billion dollars. However,
a cost-benefit analysis for the routine use of bezlotoxumab in C. difficile infection was not
provided. Clearly before this therapy
could be widely employed, specific subgroups who would benefit need to be
identified.
Recommended
learning: Review pseudomembranous colitis, C. difficile biology and natural history of infection, diagnosis
and recommended treatment in Australia.
Specific Articles Medical Students Found Interesting
ORIGINAL ARTICLE
Therapeutic
Hypothermia after In-Hospital Cardiac Arrest in Children
In
this multicenter trial, therapeutic hypothermia, as compared with therapeutic
normothermia, did not confer a significant survival benefit in comatose
children who survived in-hospital cardiac arrest.
