Professor Brian Andrews NEJM Recommendations
for Medical Students and Tutors
Week of the 21st January 2016 (#26)
University of Notre Dame Australia
(Fremantle Campus)
Occasional Editorial Comment
None
MUST READ SECTION
CLINICAL
PRACTICE
Postmenopausal Osteoporosis
http://www.nejm.org/doi/full/10.1056/NEJMcp1513724
Management of postmenopausal osteoporosis
includes non-pharmacologic treatment (e.g., weight bearing exercise and
fall-prevention strategies) and pharmacologic treatment. Bisphosphonates are
considered first-line treatment in most women; benefits and rare potential
risks are discussed.
This is an excellent review of the current management
of postmenopausal osteoporosis with extensive current bibliography and an
evidenced based discussion which is easy to read. Students should keep this
link for the future.
Recommended
learning:
1. Causes, diagnosis and treatment of osteoporosis
2. Falls in the elderly
Articles Recommended for Medical Students
ORIGINAL
ARTICLE
CDX2 as a Prognostic Biomarker in Stage II and
Stage III Colon Cancer
CDX2 is expressed in most colon cancers, but
approximately 4% do not express this transcription factor. Lack of CDX2
expression marks a subset of cancers with a more aggressive natural history.
Adjuvant chemotherapy primarily benefits patients with stage II CDX2-negative
tumors.
EDITORIAL
Prognostic Subgroups among Patients with Stage
II Colon Cancer
This is an interesting
paper which highlights one of the ways that genetic markers, or in this case
the transcription factor CDX2, can be utilized to direct specific therapy in
patients with colon cancer.
In patients with colon
cancer (not rectal), the therapy for stage I disease (surgery alone) and stage
III disease (surgery + adjuvant chemotherapy) are generally well established.
The question arises with the management of Stage II disease: which patients would benefit by the addition of chemotherapy and
which patients do not need chemotherapy and its attendant adverse effects?
This article attempts
to provide an answer to this question by measuring the presence or absence of
nuclear CDX2 by both immunohistochemical and microarray analyses in colon
cancer specimen of patients with stage II disease. Most colon cancers express
nuclear CDX2 but a minority (5-7%) fail to express this marker. It is the latter
group who have a higher recurrence rate after surgery alone and their five year
survival with chemotherapy can be increased from 56% to 91%, highlighting the
use of a marker to predict a poorer outcome and to improve survival by the
addition of adjuvant chemotherapy.
IMAGES
IN CLINICAL MEDICINE
Taenia saginata Infestation
http://www.nejm.org/doi/full/10.1056/NEJMicm1504801
A 38-year-old man presented with worsening
abdominal pain, vomiting, anorexia, generalized weakness, and weight loss that
had begun 3 days earlier. He had a history of eating raw beef. Examination of
stool showed an embryonated egg containing an oncosphere.
CASE
RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL
Case 2-2016 — An 84-Year-Old Woman with Chest
Pain, Dyspnea, and a Rash
http://www.nejm.org/doi/full/10.1056/NEJMcpc1502149
An 84-year-old woman was admitted to the
hospital because of chest pain, respiratory distress, and a purpuric rash.
Initial chest imaging showed bilateral patchy and confluent opacities, a
finding consistent with pulmonary edema. A diagnostic procedure was performed.
This
is a discussion of an interesting systemic disease presenting with purpura and
extensive ecchymoses: the latter are not only palpable but associated with the
characteristic and diagnostic yellowish infiltrate and capillary instability.
On bedside teaching last year, we saw a patient with this disorder and a
monoclonal antibody against coagulation factor VIII. Review the
echocardiographic findings in this disorder.
Important Articles Related to
Mechanisms of Disease and Translational Research
CLINICAL
IMPLICATIONS OF BASIC RESEARCH
Kindling the Kidney
Investigators have generated kidney-like
organoids — complete with nephrons, collecting ducts, stroma, and vasculature —
from induced pluripotent stem cells.
This is a fascinating
2015 study by Taguchi et al in Cell Stem Cell where pluripotent stem
cells are derived from individual skin epidermal cells and, by the addition of a
specific growth factor cocktail, transforming these cells into three
dimensional nephron organoids. I predict that in the next twenty years,
transplant recipients will provide autologous stem cells from their own skin
and these will then be used to generate their own renal transplant. But still,
there is yet a long way to go. The reviewer indicates that even now, these
preparations could be used to screen for the nephrotoxic effects of new and
current drugs and also obtaining organoids from patients with genetic kidney
disease to determine pathogenetic mechanisms and test new therapies.
Recommended learning:
1.
Review the types of stem cell used in transplantation
2. Review the structure and
function of the nephron
Other areas which should be of interest to medical students
ORIGINAL
ARTICLE
Mutations in TUBB8 and Human Oocyte Meiotic Arrest
Mutations in a tubulin gene caused infertility
due to oocyte arrest in about a third of families tested. The investigators
found that the mutant tubulins wreak havoc on microtubule assembly in the
oocyte.
EDITORIAL
Exacting Requirements for Development of the
Egg
The hallmark of successful human reproduction
is the fusion between a haploid spermatozoon and a metaphase II oocyte. The
generation of such an oocyte involves a series of steps whereby
germinal-vesicle oocytes (in which the nuclei are intact) at prophase I are
stimulated to resume meiosis and mature to metaphase II, a sequence of events
that prepares the oocyte for fertilization.
The Editorial provides an excellent Figure demonstrating the meiotic
maturation of human oocytes. Further, the mutations described in TUBB8
producing meiosis I oocyte arrest would be recognised by the absence of the
first polar body in patients undergoing IVF. We await the description of
further genetic mutations. The science is amazing.
Perspective
HISTORY
OF MEDICINE
Regulating Homeopathic Products — A Century of
Dilute Interest
http://www.nejm.org/doi/full/10.1056/NEJMp1513393
In 2015, U.S. government agencies began
considering greater regulation of both homeopathic drugs and the advertising of
such products. These actions came after more than a century of missed
opportunities to regulate homeopathic medicines
This
is an excellent history of homeopathy in the US for those interested in the
history of medicine, particularly the evolving role in regulation, or lack
thereof.
ORIGINAL
ARTICLE
Shared Genetic Predisposition in Peripartum and
Dilated Cardiomyopathies
Peripartum cardiomyopathy shares clinical
features with idiopathic dilated cardiomyopathy, a disorder associated with
mutations in more than 40 genes. This study shows that mutations in some of
these genes, notably TTN, also have a strong association with
this condition.
ORIGINAL
ARTICLE
