Professor Brian Andrews NEJM Recommendations
for Medical Students and Tutors
Week of 18th August 2016 (#56)
University of Notre Dame Australia (Fremantle
Campus)
Occasional Editorial Comment
None
Must Read or Save Articles
CLINICAL PRACTICE
Genital
Herpes
Herpes
simplex virus type 1 and type 2 cause genital herpes. Antiviral therapy is used
for symptomatic outbreaks, and as daily suppressive therapy, it reduces
recurrences of symptoms, asymptomatic viral shedding, and the risk of HSV-2
transmission.
This is an excellent review on HSV genital infections
with the usual clinical pictures (Figure 1). It probably reveals little new
information to the student in their clinical years after completing their
preclinical and O&G training. The
article is current, with good evidence-based strategies in the diagnosis and
management of genital HSV infections including the use of antiviral agents for
treating active infection and for reducing risk of vertical transmission. This article
should be stored for future reference.
Recommended
learning:
1. Review
the biology of HSV-1 and HSV-2, clinical presentations, diagnosis and,
management.
2. Review
the antiviral agents used to treat HSV infection and to reduce transmission.
Articles Recommended for Medical Students
Perspective
Worldwide
Thyroid-Cancer Epidemic? The Increasing Impact of Overdiagnosis
Dramatic
increases have been seen over recent decades in the reported incidence of
thyroid cancer, but owing to new modes of screening, hundreds of thousands of
cases may be overdiagnoses — diagnosis of tumors that would not, if left alone,
result in symptoms or death.
This article discusses the “epidemic” increase in the
incidence of small papillary carcinoma of the thyroid in eight high income,
selected countries over the past two decades (Figure 1). The increase in the
frequency of diagnosis is attributable to new diagnostic techniques which are associated
with increased medical surveillance and access to health care.
Several points can be drawn from the article:
1. In
spite of this marked increase in the diagnosis of thyroid cancer, the thyroid
cancer mortality rates have not significantly changed.
2. When
1235 Japanese patients with papillary micro-carcinomas were followed with
watchful waiting for 75 months, only 3.5% had clinical progression of the
malignancy and none died.
3. Data
on thyroid cancer collected post-Fukushima using increased surveillance
technology will need to be interpreted with caution as any increase in the
number of patients with thyroid cancer cannot be automatically attributed to a
radiation effect.
4. It
may well be that papillary micro-carcinoma of the thyroid is similar biologically
to prostate cancer, in that the only way to predict future disease progression
in the individual patient will be by genomic analysis, proteomics, and the
behaviour of cultured tumour cells in specific culture environments
(personalised medicine).
5. As
the sensitivity of diagnostic techniques increases, there will be an increase
in the diagnosis of micro-malignancies.
The management of asymptomatic micro-malignancy must clearly be
considered in advance without resorting to unnecessary major surgery, thus mandating
a detailed understanding of the early biology of the individual tumour.
ORIGINAL ARTICLE
Acetaminophen versus Ibuprofen in Young
Children with Mild Persistent Asthma
There
has been concern that acetaminophen may exacerbate asthma. These investigators
found no difference in asthma control among young children treated for minor
illnesses with acetaminophen as compared with ibuprofen.
EDITORIAL
Acetaminophen
and Asthma — A Small Sigh of Relief?
This is a 48-week randomized, double-blinded,
parallel-group trial that compared as needed use of acetaminophen with
ibuprofen for fever or pain in 300 children (226 completed the trial) aged
between 12 to 59 months. All had mild
persistent asthma and were maintained on standard asthma-controller medication
(low dose inhaled glucocorticoids, montelukast or cromolyn). The hypothesis
tested was whether acetaminophen use resulted in more exacerbations of asthma compared
with ibuprofen use.
The study found that there was no difference between
acetaminophen or ibuprofen use in the primary outcomes which included the
number of asthma exacerbations leading to systemic corticosteroid usage or more
difficult to control asthma attacks. One question raised in the Editorial was
whether acetaminophen use in otherwise healthy children or in pregnancy can
lead to the development of asthma in children.
Unfortunately (for ethical reasons), there was no
placebo control and thus the study was unable to determine if both
acetaminophen and ibuprofen use was associated with asthma exacerbations.
Recommended
learning:
1. Review
the Australian guidelines for acetaminophen use in paediatric patients.
1. Review
the pathology, clinical presentations, and management of asthma in paediatric
patients.
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL
Case
25-2016 — A 33-Year-Old Man with Rectal Pain and Bleeding
A
33-year-old man presented with painful bowel movements and rectal bleeding.
Physical examination and sigmoidoscopy revealed sentinel skin tags, multiple
fissures, and mucosal inflammation of the distal rectum. A diagnosis was made.
All should read this very informative CPC of a patient
presenting with intermittent rectal pain and bleeding. The differential
diagnosis encompasses both common perianal pathology and proctitis. It should
be noted that the patient was not properly examined by the original physician,
who unfortunately, attributed the pathology to “bleeding haemorrhoids,” leading
to a further three month’s delay in making the correct diagnosis.
Recommended
learning:
1. Review
causes of rectal bleeding in the various age groups.
2. Review
the diagnosis, pathology, and management of common perianal conditions.
3. Review
the causes and management of proctitis.
IMAGES IN CLINICAL MEDICINE
Takayasu’s
Arteritis
A
previously healthy 36-year-old Japanese woman presented with blood pressure
that was difficult to control after an emergency cesarean section. CT revealed
a disrupted abdominal aorta, severe stenosis of the renal arteries, and
development of numerous collateral arteries.
This is an interesting Japanese patient with Takayasu’s
arteritis who presented with severe hypertension during pregnancy. She was
subsequently found to have renal artery stenosis as the cause of her
hypertension which responded to nifedipine and immunosuppression with
prednisolone and infliximab.
I have an interesting anecdote to relate regarding the
use of “pulseless disease” for Takayasu’s arteritis. Years ago I was in Cairo
for a visit sponsored by the Egyptian Rheumatology Society. I had just finished
delivering a talk on Vasculitis in which I used the term “pulseless disease”
when I was challenged by an extremely forthright rheumatologist from the
audience on the use of that term. I was subsequently
informed that she was Assad’s personal physician. She indicated that “the reason you Americans
refer to this as “pulseless disease” is because you fail to make an early
diagnosis.” I was not about to create a potential international incident over
terminology, besides which she made a credible point.
Recommended
learning: Review my two lectures on Vasculitis given in the
clinical years.
IMAGES IN CLINICAL MEDICINE
Gastric
Anisakiasis
A
previously healthy 36-year-old woman presented with a 2-day history of severe
chest pain and epigastric pain associated with nausea and vomiting. The patient
reported that she had consumed uncooked salmon approximately 2 hours before the
chest pain developed.
As somebody who would never eat uncooked fish, I refer
this case for reflection to all “sushi eaters.” While I understand a trained
sushi chef can recognise the larvae in the fish being prepared (in this case
salmon), I prefer that my GIT not to be invaded by the “sushi worm” due to
culinary oversight. The review of anisakiasis in UpToDate is succinct and
informative. This roundworm is the fish equivalent of human ascariasis. The
video accompanying the case is educational and endoscopic removal of the
gastric worms is therapeutic.
Recommended
learning: Review the biology of roundworms that infect humans.
Important Articles Related to Mechanisms of Disease and
Translational Research
CLINICAL IMPLICATIONS OF BASIC RESEARCH
Melanoma
and the Microenvironment — Age Matters
When
it comes to melanoma, age matters — specifically, the molecular changes in the
vicinity of the melanoma cell in the skin of older persons.
Figure 1 summarises the article which discusses a
recent study by Kaur et al (reference 2). The hypothesis is that the aging
microenvironment in the skin influences the behaviour of melanoma cells. The
aging environment is associated with smoothing of the D-E junction with thinning
of the epidermis and degeneration of dermal collagen. Older dermal fibroblasts
produce proteins, such as sFRP2-(frizzled-related protein 2), that lead to
increased intracellular concentrations of reactive oxygen species (ROS) which
contribute to DNA damage in cells. Conversely, fibroblasts from the
microenvironment of younger epidermis produce scavengers (SOD3, PRDX6) of ROS.
The researchers found that when melanoma cells were injected into the dermis of
young mice, the melanoma cells grew faster producing large local tumours with
low metastatic potential. When melanoma cells were injected into the dermis of older
mice, the melanoma cells were slower growing but had high metastatic potential.
In patients with melanoma who are older than 55 years, levels of sFRP2 are
higher than in patients with melanoma who are younger than 40 years. The
implications for the role of sFRP2 and the possible association with melanoma
oncogene activating mutations, especially BRAF V600E, in older patients with
melanoma will need to be further explored.
Other Articles which should interest medical students
ORIGINAL ARTICLE
A
Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis
In
this 12-month, placebo-controlled trial involving patients with primary biliary
cholangitis who had an inadequate response to ursodiol, treatment with
obeticholic acid, a farnesoid X receptor agonist, decreased alkaline
phosphatase and total bilirubin levels.
EDITORIAL
Primary
Biliary Cholangitis — A New Name and a New Treatment
This is an important article on the use of obeticholic
acid (a semisynthetic bile acid) in primary biliary cholangitis (originally
called primary biliary cirrhosis) where ursodiol was ineffective in controlling
the inflammatory process in the liver. Treatment with obeticholic acid, with or
without ursodiol, for 12 months was associated with a significant reduction in
the elevated serum alkaline phosphatase and a small reduction in serum
bilirubin which remained below the upper normal range. An increase in pruritus
was an unexpected and unexplained adverse effect.
Obeticholic acid binds to and is an agonist of the
farnesoid X receptor (FXR) (bile acid receptor). When bile acids, such as obeticholic acid,
bind to and activate the FXR, the FXR is translocated to the nucleus resulting
in downregulation of the enzyme cholesterol 7 hydroxylase which is responsible
for converting cholesterol to bile acids. Thus, when bile acid levels are high,
less cholesterol is converted to bile acids. When bile acid levels are low
(e.g. when bile binding resins, such as cholestyramine, are taken to bind bile
acids in the GIT and reduce their enterohepatic recirculation), cholesterol 7
hydroxylase is activated thus converting cholesterol to bile acids and reducing
the serum cholesterol level.
The FXR receptor is involved not only in bile acid
synthesis but also exhibits an antifibrotic effect and modulation of the immune
and inflammatory responses.
Recommended
learning:
1. Review
cholesterol metabolism and the biology of bile acids.
2.
Review the definition and causes of chronic
active hepatitis, including primary biliary cholangitis.
Interesting articles which have not been reviewed
Perspective
Counting
Better — The Limits and Future of Quality-Based Compensation
A
Seattle medical group found that although performance improved on the quality
metrics it emphasized, those metrics didn't reflect the essence of patient care
and the focus felt stifling to clinicians. So the group began charting a
different path toward higher-value care.
Perspective
The
Cost of Residency Training in Teaching Health Centers
When
the full net cost of residency training in an ambulatory setting is considered,
including direct and indirect costs and revenue attributable to residents'
services, it becomes clear that the current payment rate for Teaching Health
Centers is far from adequate.
SPECIAL ARTICLE
Genetic
Misdiagnoses and the Potential for Health Disparities
This
study shows that for variants initially classified as pathogenic that were
later reclassified as benign, the misclassification would have been prevented
had racially diverse populations been considered in the original studies of the
variants.
HEALTH POLICY REPORT
Mental
Health and Substance-Use Reforms — Milestones Reached, Challenges Ahead
Legislation
regarding mental health parity and other health policy reforms have improved
access to treatment for mental health and substance-use disorders, but ongoing
problems include a shortage of mental health specialists and lack of systemwide
integration.
