Professor
Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week
of 23rd February 2017 (#83)
University
of Notre Dame Australia (Fremantle Campus)
Occasional Editorial Comment
None
Must Read Articles
ORIGINAL ARTICLE
Assessing
the Risks Associated with MRI in Patients with a Pacemaker or Defibrillator
A
total of 1500 nonthoracic MRI examinations were performed on patients with a
non–MRI-conditional pacemaker or ICD, after programming of the devices in
accordance with a standardized protocol. No patient whose device was
appropriately programmed had device or lead failure.
Over the past twenty years, pacemakers and implantable
cardioverter-defibrillators (ICDs) have been designed to reduce the risks associated
with MRI when used per defined protocol.
It is estimated that there are approximately eight
million devices world-wide that are non-MRI-conditional or potentially not “MRI
safe.” It is also estimated that approximately half of the patients with these
devices will require an MRI in their lifetime.
1500 patients with non-MRI conditional devices were
studied and received standard MRIs (77% for either the brain, cervical spine or
lumbar spine). No MRIs were obtained of the thoracic cavity. MRI machines with a magnetic field strength
of 1.5 tesla were used. Devices were
programmed as per protocol before and after the MRI (MRIs were not performed on
patients whose ICDs were pacing-dependent). During the study, there was no
significant magnetic field-induced cardiac lead heating, although one patient
experienced ICD failure, with the device needing to be replaced as protocol had
not been followed with appropriate pre-MRI programming of the device. Otherwise
no significant adverse events occurred.
CLINICAL PRACTICE
Screening
for Chlamydia trachomatis Infections in Women
Chlamydial
infection may result in pelvic inflammatory disease, infertility, and ectopic
pregnancy. Chlamydia screening is recommended in sexually active women younger
than 25 years of age and other women at increased risk and can be performed on
vaginal swabs or urine samples.
This is an excellent case-based review on chlamydial
infections in women. The epidemiology, pathology and clinical presentations are
defined followed by a discussion of screening strategies (see box insert for
Key Clinical Points on screening). Treatment strategies and areas of
uncertainty are outlined. This should be read by all medical students.
Recommended
learning: Genital infections due to Chlamydia trachomatis.
IMAGES IN CLINICAL MEDICINE
Empyema
Necessitatis
A
40-year-old man presented with fever, weight loss, dyspnea, and cough. Physical
examination revealed a tender, bulging anterior thoracic mass.
This is an unusual complication of an empyema which,
due to tuberculosis, tracks through the parietal pleura into the chest wall.
There is an interesting clinical picture and CT scans.
Recommended
learning: Review the pulmonary pathology of tuberculosis.
Articles Recommended for Medical Students
Perspective
Recreational
Cannabis — Minimizing the Health Risks from Legalization
Twenty
percent of the U.S. population now lives in states that have passed ballot
initiatives to allow cannabis to be sold for recreational use. The net effect
of cannabis legalization on public health is uncertain, and much will depend on
how the laws are implemented.
This interesting Perspective
summarises what is known and unknown regarding recreational cannabis use with
respect to health effects, legalization, and public health policies. After
reading this, I realized how much evidence based information needs to be gathered.
Important Articles Related to Mechanisms of Disease and
Translational Research
None
Other Articles which should interest medical students
ORIGINAL ARTICLE
Tight
Glycemic Control in Critically Ill Children
Tight
glycemic control has not improved outcomes in studies involving critically ill
adults or children after cardiac surgery. A controlled study involving
hyperglycemic critically ill children who had not undergone cardiac surgery
showed no benefit of tight glycemic control.
After this study involving tight glycaemic control in
critically ill children (lower-target group at 4.4 – 6.1 mmol/L and
higher-target group at 8.3 – 10.0 mmol/L), it now appears that in most studies
to date on critically ill adults and children that clinical outcomes are not
improved with tight glycaemic control.
As this study demonstrates, patients in the lower-target group (tight
control) had more health care-associated infections and more episodes of severe
hypoglycaemia.
IMAGES IN CLINICAL MEDICINE
Gastric
Gyri — Pediatric Ménétrier’s Disease
A
5-year-old boy presented with nausea, vomiting, and intermittent abdominal
pain. Images showed giant cerebriform enlargement of rugal folds in the fundus
and the body, which were suggestive of Ménétrier’s disease.
When considering the gastrointestinal causes of
hypoalbuminemia, one of the rarer causes, Menetrier’s disease, may need to be
considered.
Recommended
learning: Review the mechanisms, clinical entities associated
with and approach to the management of hypoalbuminemia.
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL
Case
6-2017 — A 57-Year-Old Woman with Fatigue, Sweats, Weight Loss, Headache, and
Skin Lesions
A
57-year-old woman presented with fatigue, night sweats, weight loss, headache,
abdominal pain, and skin lesions. Laboratory testing revealed
hypergammaglobulinemia and hypocomplementemia. Diagnostic tests were performed.
This CPC provides an
excellent differential diagnosis of a patient presenting with fatigue, night
sweats, weight loss, headache, abdominal pain, and skin lesions. This patient is also found to have lacrimal
gland enlargement, hypergammaglobulinemia, hypocomplementemia and increased
plasma cells on a biopsy. I would not have even considered giant cell arteritis
in my DD. The diagnosis is an IgG4-related disease, the group of which also
includes disorders such as autoimmune pancreatitis and idiopathic
retroperitoneal fibrosis.
IgG4 related disorders
have been previously discussed in issues # 64,
http://www.nejm.org/doi/full/10.1056/NEJMcpc1610097
and #14 http://www.nejm.org/doi/full/10.1056/NEJMra1104650.
New and Novel Therapies
ORIGINAL ARTICLE
Inhibiting
Plasma Kallikrein for Hereditary Angioedema Prophylaxis
In
patients with hereditary angioedema with C1 inhibitor deficiency, swelling
episodes are related to the release of bradykinin from high-molecular-weight
kininogen from kallikrein action. Lanadelumab, which inhibits kallikrein
action, reduced the rate of attacks of angioedema.
EDITORIAL
Kallikrein
Inhibition for Hereditary Angioedema
Hereditary angioedema (HA), due to a functional deficiency
in C1 (esterase) inhibitor (types I and II), is a rare disorder and is usually
autosomal dominant in inheritance. Deficient
function of C1INH results in ongoing activation of the classical complement system
with reduced C4 levels, activation of the coagulation system and activation of
the kallikrein-kinin system (Fletcher factor deficiency is a rare congenital
absence of prekallikrein which does not produce any significant clinical
manifestations). Kallikrein generation from prekallikrein leads to excessive
proteolysis of high MW kininogen and formation of bradykinin which results in
vasodilation, vascular leakage, oedema and pain. 80% of patients with HA exhibit reduced
production of C1INH, while 20% have functional inhibition of C1INH usually due
to autoantibodies (SLE and B cell lymphomas).
The clinical manifestations of HA result from
intermittent subcutaneous oedema of the hands, feet, face and abdominal wall
and from submucosal oedema of the mouth, airways, GIT and genitourinary
system. There is no urticaria or
pruritus associated with this condition. Patients usually present with
recurrent painful swelling of lips, tongue, and airways compromising breathing
and abdominal pain.
This study employs the prophylactic use of a monoclonal
antibody (lanadelumab) against kallikrein, resulting in reduced cleavage of
high MW kininogen and reduced plasma levels of bradykinin, which leads to fewer
episodes of clinical angioedema.
The prophylactic use of
this monoclonal antibody was effective and produced no significant adverse events
in this brief six week, phase 1b study.
This is really an “appetiser study” responsible in part for some of the
literature pollution that occurs. If this study had not been performed at the
MGH in Boston, it would not have been published in the Journal. As the authors indicate in their discussion, the full
phase 3 six-month (24 week) study is under way and had undoubtedly been
completed at the time of submission and subsequent publication of this study.
Maybe the results of another agent for treating HA are soon to be published in
the Journal.
Articles Some Medical Students Found Interesting
Perspective
HISTORY OF MEDICINE
The
Death of Animals in Medical School
Although
live animals had been used in medical education for millennia, with recent
changes at Johns Hopkins and the University of Tennessee, every core U.S.
medical school curriculum has now ceased this practice. It is worth considering
the causes and implications of this milestone.
This is an interesting historical review of the use of
live animals in medical education in the US.
ORIGINAL ARTICLE
Genetic
Drivers of Kidney Defects in the DiGeorge Syndrome
A
third of patients with the DiGeorge syndrome have congenital kidney and urinary
tract anomalies. This study provides evidence that haploinsufficiency
of CRKL is associated with such anomalies in the DiGeorge syndrome
and in sporadic congenital kidney and urinary tract anomalies.
I found this to be a fascinating study, though none of
the medical students in my groups felt the same, until we discussed the article
in some detail.
This is a truly an extensive and elegant study involving
2080 patients with congenital kidney and urinary tract abnormalities and 22,094
controls. The authors performed a genome wide search for structural variants in
22q11.2 in the above two cohorts.
This article illustrates the following:
1. 30%
of patients with DiGeorge syndrome have congenital renal and urinary tract
abnormalities. They also exhibit the
more well-characterized thymic aplasia with profound T cell immunodeficiency, hypoparathyroidism
leading to hypocalcaemia, congenital cardiac malformations frequently requiring
early surgery and facial and neck abnormalities.
2. Most
non-renal manifestations of the DiGeorge syndrome are associated with small deletions
in chromosome 22, resulting in loss of function in TBX1 (the tbx1 gene
translates the T-box 1 protein).
3. The
T-box 1 protein appears to be necessary for the normal development of large
arteries that carry blood out of the heart, muscles and bones of
the face and neck, and glands such as the thymus and parathyroid
(Wikipedia).
4. The
hypothesis was generated that if renal abnormalities in DiGeorge syndrome were
not attributable to deletions involving the tbx1 gene on 22q11.2, could another
deletion in a nearby area of 22q11.2 on chromosome 22 be responsible?
5. The
authors identified a heterozygous 370 kB deletion in 22q11.2 containing a
series of nine genes that when absent were associated with the renal defects in
the DiGeorge syndrome. Further characterization of these genes identified the three
important responsible genes, snap29,
aifm3 and crkl. However, absence of the crkl gene alone
resulted in renal agenesis or hypodysplasia.
6.
CRKL encodes
an adapter protein that regulates intracellular signalling transduction from
multiple growth factors, including the fibroblast growth factors, which
are key regulators of kidney and urinary tract development (article).
7. In
zebra fish embryos, the authors produced a crkl
loss of function mutation which resulted in renal defects. In a mouse model,
inactivation of crkl resulted in similar
renal abnormalities to those in humans.
8. In
1.1% of the 2080 humans with congenital renal abnormalities and in 0.01% of the
population controls, heterozygous deletions of 22q11.2 were identified.
9. The
authors have identified a gene crkl
that is responsible for the congenital renal abnormalities of the DiGeorge
syndrome and a small number of patients with sporadic congenital renal and
urinary tract abnormalities.
