Professor
Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week
of March 9, 2017 (#85)
University
of Notre Dame Australia (Fremantle Campus)
Occasional Editorial Comment
This will be the last episode of my NEJM blog. I thank
you for your readership and hope that I have stimulated some medical students
to regularly review a medical journal of their choice, at least weekly, and to
learn to critically review the articles.
Must Read Articles
SOUNDING BOARD
Realizing
the Potential of Cancer Prevention — The Role of Implementation Science
Accumulating
evidence shows that there are simple methods of reducing the incidence of
cancer and cancer-related mortality in people at average and high risk. Further
study is needed to better understand how these lifesaving, cost-effective
measures can be put to greater use.
This is a short, must read article from the US that
discusses the scientific basis for cancer prevention and how the scientific,
evidence-based knowledge already acquired can be optimized and standardized to
prevent cancer. This is not to say that new research must not be acquired in
cancer biology, therapy and prevention, but that the current knowledge should
also be used optimally.
The first paragraph provides an excellent overview and
should be read by all. Table1 reviews the risk modifiers in cancer prevention
and a CDC analysis of the data from each US state. It is interesting, although
predictable, that California has the highest per-capita consumption of fruit
and vegetables of any state, but of more significance is that Massachusetts,
the only US state with universal health care, has the highest percentage of its
population screened for colon, breast and cervical cancer. This is a statistic
that will fall on the deaf ears of the Trump administration.
REVIEW ARTICLE
Psoriatic
Arthritis
Psoriatic
arthritis occurs in up to 30% of people with psoriasis and can have serious
debilitating effects on the peripheral joints, spine, tendon insertions, and
fingers. Management has improved, but complete disease control is not yet
achievable.
While most students will not read this review article
in its entirety, the Figures and Tables should at a minimum be reviewed. The
sections on Coexisting Conditions, Causes
and Pathophysiological Features and Therapy make for interesting
reading. This should be read by MEDI6400
students prior to their musculoskeletal rotation.
Recommended
learning: HLA-B27
associated spondyloarthropathies.
Articles Recommended for Medical Students
Perspective
Anesthesia
and Developing Brains — Implications of the FDA Warning
The
FDA has issued a warning regarding use of general anesthetic and sedation drugs
in children under 3 years of age and in pregnant women in their third trimester
— a warning that will change practice and raise questions that currently have
no clear answer.
The genesis of this concern is predicated upon in vitro and animal studies on species
ranging from roundworms to nonhuman primates where all of the anaesthetic
agents tested resulted in acute neuroanatomical consequences and associated
long-lasting functional effects.
Without human
data, on December 14, 2016, the FDA
issued a “Drug Safety Communication” (www.fda.gov/Drugs/DrugSafety/ucm532356.htm) warning that general anesthesia and
sedation drugs used in children less than 3 years of age or in pregnant women
in their third trimester who were undergoing anesthesia for more than 3 hours
or repeated use of anesthetics “may affect the development of children’s
brains.” This warning will result in a labelling change for 11 common general
anesthetics and sedative agents that bind to GABA or NMDA receptors, including
all anesthetic gases such as sevoflurane, and the intravenous agents propofol,
ketamine, barbiturates, and benzodiazepines.
While the duration of most anaesthetics is less than
three hours, this warning will still send a chill through most parents whose
child needs an anaesthetic but hopefully will not lead to postponing necessary
surgery. Studies are currently underway to address this possible concern in
humans and hopefully the results will be obtained soon.
Perspective
At
Risk for Serious Mental Illness — Screening Children of Patients with Mood
Disorders or Schizophrenia
The
lack of attention paid to the millions of children born to a parent with
schizophrenia, bipolar disorder, or recurrent major depression is out of phase
with the massive need in primary care and the available scientific evidence.
This Perspective highlights the need for the general
practitioner, in particular, to consider the potential risks to the child or
adolescent of developing a mental illness if one of their parents is affected
by schizophrenia, bipolar disorder, or recurrent major depression. The recent population prevalence was estimated
at 4% in a large European cohort. The
risk to the child or adolescent of a parent with mental illness developing a
mental illness is estimated at 15 -20 times more than where none of the parents
have mental illness.
The article discusses four major system based problems
and provides possible solutions. I consider this is a very important article to
read.
ORIGINAL ARTICLE
Long-Term
Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia
After
nearly 11 years of follow-up, long-term administration of imatinib was shown to
be associated with prolonged control of chronic myeloid leukemia and no
cumulative or late toxic effects have emerged.
EDITORIAL
Imatinib
Changed Everything
Early published work in 1990 demonstrated that the
insertion of the bcr/abl gene of the Philadelphia chromosome into murine
haematopoietic stem cells resulted in chronic myelogenous leukaemia (CML) in
the mice.
Subsequent to
the development of a selective inhibitor of the abl tyrosine kinase, Brian
Drucker, one of the authors of the present study, in 1996 used this drug to
inhibit the growth of bcr/abl positive cultured haematopoietic cells. In 2001, he extended this work and published
the positive results of the safety and efficacy of this drug (imatinib) in the
treatment of human CML.
In the current study, he and colleagues present the 10
year follow-up data on the use of imatinib in the treatment of CML. While there
are many nuances in the study and subgroup analyses, overall this drug has
proved to be extremely effective in treating CML. Its use produced few significant adverse
effects and patients frequently died of unrelated comorbidities.
Prior to the introduction of imatinib into clinical
medicine, medical schools had no difficulty in finding CML patients with large
spleens for OSCI examinations. Sustained splenic enlargement in CML is now a rare
occurrence.
Imatinib basically changed the face of therapeutics in
the field of oncology with the development and use of a “designer drug” for the
first time. The Editorial provides a very informative historical review of this
area as well as a glimpse into the future.
IMAGES IN CLINICAL MEDICINE
Grouped
Pustules on an Erythematous Base
A
27-year-old woman presented with painful lesions on her left arm. A diagnosis
was made with the use of a Tzanck smear.
This is a classic skin picture of HSV infection and a
positive Tzanck test, useful in diagnosing HSV or VZV infection if
immunofluorescence and PCR are not available.
IMAGES IN CLINICAL MEDICINE
Glucagonoma-Associated
Rash
A
65-year-old man with type 2 diabetes presented with weight loss and other
symptoms that occurred after a rash had developed on his arms, genitals,
buttocks, and legs. Imaging showed a pancreatic lesion.
Important Articles Related to Mechanisms of Disease and
Translational Research
None
Other Articles which should interest medical students
ORIGINAL ARTICLE
Chimpanzee
Adenovirus Vector Ebola Vaccine
This
update of a preliminary report from November 2014 presents safety,
immunogenicity, and long-term durability data from a trial of an Ebola vaccine
in humans that is based on a chimpanzee adenovirus type 3 construct with the
Ebola Zaire and Sudan glycoprotein inserts.
EDITORIAL
One
Step Closer to an Ebola Virus Vaccine
This article and accompanying editorial describe a
replication-defective recombinant chimpanzee adenovirus type 3–vectored
ebolavirus vaccine (cAd3-EBO) which is used to induce immunity against the
Ebola virus. The vaccine immunogen encodes the glycoprotein from Zaire and
Sudan species. This phase 1,
dose-escalation, open-label trial of the vaccine was administered to 20 healthy
adults, 10 receiving a lower (2x1010 particle-unit dose) and 10 a
higher dose (2x1011 particle-unit dose). T cell responses were assessed over an eight
week period with optimal CD4 and CD8 responses obtained from the higher dose. Durability of the antibody response was best
preserved at 48 weeks with the higher dose. Efficacy and phase 2 studies are currently
underway.
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL
Case
7-2017 — A 73-Year-Old Man with Confusion and Recurrent Epistaxis
A 73-year-old man with a history of heart failure, pulmonary hypertension, and a hepatic venovenous malformation presented with confusion. CT of the abdomen revealed pneumatosis of the ascending colon to the level of the hepatic flexure. Diagnostic tests were performed.
This is a classic clinical diagnosis of a case of hereditary
haemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) which was
confirmed by genetic analysis. The most interesting aspect of this case was the
clinical presentation with hepatic encephalopathy produced by a large
portal-systemic shunt within an hepatic AV malformation. I was also unaware of
an ENT procedure (Young’s procedure) used to obliterate the nostrils to avoid serious
blood loss from recurrent epistaxis.
The genes associated with HHT are involved with the TGFb – BMP signalling pathway. The specific gene mutation associated with
this patient involved the ACVRL1 (ALK1, HHT2) gene associated with later age
onset, recurrent nose bleeds, AV malformations in the liver, and spine and
pulmonary hypertension without shunting.
New and Novel Therapies
None
Articles Some Medical Students Found Interesting
None
