Professor
Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week
of 28th April 2016 (#40)
University
of Notre Dame Australia (Fremantle Campus)
Occasional Editorial Comment
None
Must Read Articles
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL
Case
13-2016 — A 49-Year-Old Woman with Sudden Hemiplegia and Aphasia during a
Transatlantic Flight
A
49-year-old woman was brought to the ED 2 hours after the onset of hemiplegia
and aphasia during a transatlantic flight. Examination revealed evidence of
acute ischemic stroke. Additional diagnostic studies were performed.
This is a very interesting, must read article which
describes the optimal management of an acute middle cerebral artery occlusion.
It also describes the use of the initial stroke assessment tool FAS, part of
the FAST assessment which was first described in Cincinnati and to which T for
time was added by the Australian Stroke Association. Also discussed is the use
of the ABCD2 in stroke assessment that was presented in my review
last week.
The patient’s pathology relates to an embolic stroke
from a thrombosis either from the right renal vein due to carcinoma of the
right kidney and/or from the left common iliac vein associated with the
May-Turner syndrome. This syndrome consists of >50% severe stenosis of the
left common iliac vein compressed by an overlying right common iliac artery and
accounts for a prevalence of 6.3% of patients with cryptogenic stroke and a
patent foramen ovale. The May-Turner syndrome can be demonstrated in 25% of
asymptomatic patients.
Recommended
learning: Management of acute stroke; review methods to detect
peripheral DVTs including their sensitivity and specificity; consider the
biology by which cancer can activate the clotting process, including a review
of tissue factor and the current state of patent foramen ovale and indications
for closure.
Must Save Articles
None
Articles Recommended for Medical Students
Perspective
Have
Tobacco 21 Laws Come of Age?
Recent
research has shown that laws raising the minimum age for purchase of tobacco
products to 21 are effective, enjoy very high levels of public support, and
have minimal economic impact in the short term. The time seems right for
federal adoption of this approach.
This excellent perspective reviews the state of the “tobacco
21 laws” in the US and the reasons they should be widely adopted throughout Australia,
as California did last week. Surveys indicate that current smokers and previous
smokers strongly support these laws and cross-sectional data reveal a 47%
reduction in the smoking rate among high school students and an overall
reduction in smoking prevalence of 12% when these laws are instituted. The age
group most impacted are teens between 15 to 17 years who reduce smoking by
20.8-30%. In the US, these laws would result in only a 2-3% reduction in annual
tobacco sales. When the reduced taxes generated are compared to the annual
health care savings, the financial benefits are abundantly clear.
The time has come for these laws to be enacted in
Australia and for the AMA and other bodies to actively promote this political
and public health cause.
Recommended
learning: Review methods the GP can use to help patients stop
smoking.
Perspective
Colorectal
Cancer on the Decline — Why Screening Can’t Explain It All
U.S.
colorectal-cancer incidence has dropped by more than 45% since its peak in the
mid-1980s, and related mortality has fallen by more than half. But though
screening is often credited for these trends, it cannot explain such large
decreases.
This perspective discusses other potential reasons,
apart from screening, that may contribute to the progressive decline in the
incidence of colorectal cancer.
REVIEW ARTICLE
Workplace
Violence against Health Care Workers in the United States
Violence
against health care professionals in the workplace is underreported and
understudied. Additional data are needed to understand steps that might be
taken to reduce the risk.
This important article, not regarded as significant by
the medical students, outlines the types of workplace violence (WPV) against
health-care workers, the most common sites of occurrence, and the types of
perpetrators of the violence. In the US (and I also assume Australia), the
highest number of all work-place assaults occurs against health-care workers,
particularly against nurses.
It discusses barriers against reporting (only 30% of
nurses and 26% of doctors report WPV) as victims regard this as “part of the
job.” Potential solutions are discussed.
This article should be read by all medical students,
doctors and nurses and is particularly important in the current ICE epidemic in
WA.
IMAGES IN CLINICAL MEDICINE
Aortocoronary
Saphenous-Vein–Graft Aneurysms
A
78-year-old woman who had undergone coronary aortic bypass surgery 30 years
earlier presented to the ED with shortness of breath and fatigue. Chest
radiography revealed a mediastinal, hilar mass lesion on the left side.
This is an interesting chest X-ray and CT angiogram. In
a younger patient, Behcet’s syndrome with aneurysm formation should be
considered.
IMAGES IN CLINICAL MEDICINE
Oral
Amalgam Tattoo Mimicking Melanoma
A
49-year-old woman without a personal or family history of melanoma presented with
an asymptomatic pigmented lesion on her tongue that was suggestive of oral
melanoma. The patient reported that she had undergone a dental procedure 3
months before the appearance of the lesion.
It sure looked like an intraoral melanoma.
Important Articles Related to Mechanisms of Disease and
Translational Research
CLINICAL IMPLICATIONS OF BASIC RESEARCH
The
CRISPR Way to Think about Duchenne’s
Duchenne's
muscular dystrophy is caused by a loss-of-function mutation in DMD. Studies of
the CRISPR–Cas9 method of excising the mutated region show efficacy in a mouse
model of the disease.
The reviewed studies represent further research into
Duchenne’s muscular dystrophy (DMD) using murine models of DMD and attempts to
remove the loss of function mutation in the Dmd gene using an adenovirus-associated
virus (AAV). The vector contained DNA
from both the CRISPR-Cas9 endonuclease protein to remove the mutated dystrophin
segment and two DNA segments to identify cleavage sites in the dystrophin DNA.
While this approach is variably successful in the animal models, much work
still needs to be done before it could be applied to humans.
A more likely successful scenario in humans might be to
either:
1. isolate
and amplify autologous muscle satellite cells (local stem cells which
differentiate into myocytes), or
2. isolate
unrelated autologous stem cells, e.g. from skin, and convert them to muscle satellite
cells
Individual satellite cells could be transfected ex vivo with full length dystrophin DNA
after the entire dystrophin DNA containing the mutated DNA has been removed
using CRISPR-Cas9 gene editing. This would insure production of full length
dystrophin (not able to be produced in the murine models) and would provide
time for improvement and increased selectivity in the rapidly evolving gene
editing technology.
Other Articles which should interest medical students
ORIGINAL ARTICLE
Transcatheter
or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients
In
a randomized trial involving more than 2000 patients, transcatheter aortic-valve
replacement was noninferior to surgical replacement in the primary end point of
death from any cause or disabling stroke at 2 years.
EDITORIAL
Will
TAVR Become the Predominant Method for Treating Severe Aortic Stenosis?
All medical students chose the article and the
editorial for review. This is a major advance in therapy for high-risk patients
with severe aortic stenosis unable to undergo surgical valve replacement. As indicated
in the editorial, these patients were not intermediate-risk patients, but
rather had less-severe severe aortic stenosis. Further studies will determine
if transcatheter (via the femoral artery) aortic valve replacement (TAVR) is
overall more effective (duration of effectiveness, short and long-term
complications, total cost and a larger valve surface area without paravalvular
leakage) than surgical valve replacement in patients with moderately severe
aortic stenosis requiring replacement who have high or intermediate-risk. As
the authors indicated, the results of this study are already outdated with
improvements both in techniques and in the use of more advanced TAVR devices.
ORIGINAL ARTICLE
A
Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA
In
this phase 1 study involving 76 healthy volunteers in England, a single dose of
a monovalent chimpanzee adenovirus vaccine elicited immune responses to Ebola
virus. The immune response was superior after a booster dose of a modified
vaccinia Ankara strain.
ORIGINAL ARTICLE
Phase
1 Trials of rVSV Ebola Vaccine in Africa and Europe
In
this set of four phase 1 studies, a recombinant vesicular stomatitis virus
(rVSV)–based Ebola vaccine induced Ebola virus–specific immune responses and
was associated with side effects that included fever and transient arthritis,
rash, and VSV viremia.
The rVSV-ZEBOV (uses VSV as the vector and incorporates
a Zaire Ebola virus glycoprotein) vaccine produces a neutralizing antibody
titre at 6 months. There is no current evidence that a single dose of this
vaccine produces CD8+ cell mediated immunity. However, this vaccine results in
dose-dependent side effects, particularly short-lived arthritis in the second
week after vaccination in 22% of patients.
The second study utilizes a chimpanzee adenovirus 3
vaccine containing the similar ZEBOV Zaire Ebola virus surface glycoprotein
(ChAd3) followed by a booster dose of a modified vaccinia Ankara (MVA) strain
which contained, in addition to ZEBOV, antigens from two other Ebola strains as
well as the Marburg virus. This resulted
in specific Ebola viral antibody titres X12 that produced by the ChAd3 vaccine
alone (B cell response) as well as a cytotoxic CD8+ T cell response lasting for
up to 6 months.
As Ebola vaccines and their protocols continued to
improve, it should not be too long before an effective vaccine is available for
general human use and which will hopefully be broadly effective against further
Ebola viral strains.
