Professor Brian Andrews NEJM Recommendations for Medical Students and
Tutors
Week of the 5th November 2015 (#15)
University of Notre Dame Australia
(Fremantle campus)
Occasional Editorial
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Articles Recommended for Medical Students
This is a MUST read article
ORIGINAL ARTICLE
BRIEF
REPORT
Malignant Transformation of Hymenolepis
nana in a Human Host
In this case report, malignant transformation
and metastatic spread of Hymenolepis
nana, the dwarf
tapeworm, was identified in a patient with advanced HIV infection
Again I may appear
strange in my selection of articles that interest me the most, but this is one
of the most extraordinary case reports that I have ever read. Not only is the
case fascinating, but the detailed studies on the patient (excellent figures)
may well provide further insights into the question: What is relationship
between infection and malignancy?
A Colombian patient
with HIV and a CD4 count of 28/mm3 presented with prominent cervical
adenopathy together with multiple cannon ball lesions in the lungs and liver
and marked mediastinal and abdominal lymphadenopathy. The most likely clinical
diagnosis is a malignancy in a patient with HIV.
On extensive
immunohistopathological and genetic studies, the lesions fulfilled the
hallmarks of malignancy, particularly their invasive and metastatic properties
but their small size and some atypical features suggested malignant cells of
non-human origin. The cellular origin was from the tapeworm H. nana and deep sequencing indicated
the presence of mutations associated with malignant transformation.
This is the first
demonstration of a malignancy occurring in a multicellular parasite, including
tapeworms, and the first demonstration of this phenomenon occurring in a host,
particularly human. Rarely H. nana
has invaded immunosuppressed hosts but not undergo malignant transformation.
What are the driver mutations of malignancy in this situation? Does the
immunosuppression of HIV allow for driver mutations in the parasite? Does the
entire parasite migrate initially or only the parasitic DNA to a regional node?
What environmental factors in the host contribute to these changes? Can
malignant transformation be replicated in the nu-/nu-
(nude) mouse?
This is the nature of
research: you generate more questions than you answer, but after all that’s the
fun.
Perspective
New Math on Drug Cost-Effectiveness
With more expensive
drugs being introduced, some of them for highly prevalent conditions, and the
pace of generic conversion slowing, policymakers may want to consider
cost-effectiveness analyses for coverage decisions — but there would still be a
budgetary problem
Perspective
A Delicate Balance — Pharmaceutical Innovation
and Access
http://www.nejm.org/doi/full/10.1056/NEJMp1513227
Even with many new therapeutic options, the
proportion of health care spending devoted to retail prescription medications
remains about the same as it was in 1960. Relying on competitive markets to set
drug prices and encourage innovation seems to be working.
The above two Perspective
relate to the cost of new drugs-patient
accessibility-who pays-true R&D costs and demonstrate how the same
problem can be viewed by two observers and two antithetic analyses be drawn.
Clearly, I favour the opinion of the former, but find it difficult to accept
how an intelligent academic (endocrinologist and former Dean of Harvard Medical
School), who is now chief
medical officer and executive vice president of Pharmaceutical Research and Manufacturers
of America (PhRMA), can be swayed by industry.
Currently the major cost
of R&D for new drugs is shouldered by the American consumer/tax payer but,
as I indicated several weeks ago, if the TPP (and next the European-US trading
partnership) is approved, when any of the partnership countries approve usage
of new drugs, the tax payers of that county will then have to help the US tax
payer pay the costs for R&D. I can only assume this will be an enormous
increase in profit for big Pharma without any significant reduction in cost of
the drug within the trading partners.
ORIGINAL
ARTICLE
Pediatric Outcome after Maternal Cancer
Diagnosed during Pregnancy
Fetal exposure to
maternal cancer during pregnancy with or without treatment did not have an
adverse effect on cognitive, cardiac, or general development in early childhood
EDITORIAL
Cautious Optimism for Offspring of Women with
Cancer during Pregnancy
http://www.nejm.org/doi/full/10.1056/NEJMe1512188
Fortunately, cancer rarely complicates
pregnancy, with a cancer diagnosis in approximately 1 of 1000 pregnant women.
Thus, for busy obstetrical care providers who deliver 125 babies per year, the
odds that they will have a patient with cancer is one for every eight years in
obstetrical practice.
The message of this study is that for pregnant women with cancer (very
uncommon), who are treated optimally for cancer during the second and third
trimester of pregnancy, that by far the greatest risk for the child derives
from premature birth which is markedly increased in this population. The
risks of morbidity and mortality relate to the degree of prematurity (the same
as for matched premature controls). To date in this study, there have been no significant adverse effect
on cognitive, cardiac, or general development in early childhood (from 2-3
years).
The Editorial provides a much more detailed
analysis of the study and the Supplemental
index provides specific data on the study. I did learn that from data
generated in pregnant experimental animals that the platins more readily cross
the placental barrier, followed next by taxanes and with little penetration by
the anthracyclines. Further for the 125 mothers with cancer in this multicentre
European, mainly Caucasian, study that the commonest cancer was breast (62),
followed by haematological (20: 14 HL and 14 NHL), cervical (10) and ovarian
(9).
REVIEW ARTICLE
Functional Dyspepsia
Functional dyspepsia includes pain or burning
in the epigastrium, early satiety and fullness during or after a meal, without
an organic cause. It affects 5 to 11% of the population. Suitable workup and
treatment are summarized.
This
is an excellent review article co-authored by Nicholas Talley (of Talley and
O’Connor fame). It should be archived for future reference and read by all
medical students, particularly when they enter the clinical years. Dr. Tally
has spent a large part of his professional career involved in this area. Of
particular interest is a newer clinical sub classification, the symptom
complexes suggesting different approaches to pathophysiology and then treatment.
Recommended learning: Causes of dyspepsia; alarm
symptoms for upper GI disease
IMAGES
IN CLINICAL MEDICINE
Acral Lentiginous Melanoma
A classical picture of
an acral (heel) black non-healing ulcer.
Recommended learning: Review
the clinical presentations of melanoma, the differential diagnoses and broad
approaches to therapy.
CLINICAL
PROBLEM-SOLVING
A Breakthrough Diagnosis
A 19-year-old woman with multiple sclerosis
presented with altered mental status, respiratory distress, and abdominal
distention after a flight from Jordan to the United States.
This exercise in
clinic problem-solving (clinical reasoning) focusses on a patient who has developed
new onset ascites. A DD for the causes of ascites is reviewed, although the
ultimate cause is uncommon.
Recommended learning: Review
i) the pathophysiology, causes and treatment of ascites and use of the SAAG
(serum-ascites albumin gradient) and ii) review the diagnosis, causes and
treatment of spontaneous bacterial peritonitis (SBP).
Important Articles Related to Mechanisms of Disease and Translational Research
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