Professor Brian Andrews NEJM Recommendations for Medical Students and
Tutors
Week of the 12th November 2015 (#16)
University of Notre Dame Australia
(Fremantle campus)
Occasional Editorial
Comments
There are several very important articles in this week’s journal which I
have indicated by #.
Articles Recommended by and for Medical Students
ORIGINAL
ARTICLE
#Effect of PCI on Long-Term Survival in
Patients with Stable Ischemic Heart Disease
Patients
in the COURAGE trial who gave permission for long-term survival tracking were
followed for up to 15 years. There was no difference between the PCI and
medical-therapy groups in all-cause mortality
We
have been waiting for this follow-up article on the COURAGE study for the past
10 years. The original study results were published in the NEJM in 2007
comparing two groups of randomly selected patients with chronic stable angina
(definition under Patients in METHODS, and many were “sick cookies”), one group
treated with PCI + optimal medical management (OMM) and the other with optimal
medical management alone (defined in TREATMENT and FOLLOW-UP). Overall, after
the first five years the survival outcomes were essentially the same in each
group. There were clearly some caveats, e.g. one third of patients in the OMM
crossed over to revascularization in the original follow-up period with a
median time of 11 months but with much less crossover in the later parts of the study (2.7%/year).
The
authors provide a detailed discussion of the limitations of the study, but when
this study was extended up to 15 years, there was no further difference in
survival between the groups with stable ischaemic heart disease. A very complicated, expensive but well
conducted and very important study. A keeper.
Is
there a difference in management of this group in Australia in the Public or
the Private system?
Recommended learning: Non-interventional
(medical) management options of patients with stable chronic ischaemic heart
disease
REVIEW
ARTICLE
#Elder Abuse
Because older victims of abuse tend to be
isolated, their interactions with physicians are important opportunities to
recognize abuse and intervene. This review explores the manifestations of elder
abuse and the role of multidisciplinary teams in its assessment and management
This
is an excellent review article that should be read by all.
My
eyes were certainly reopened by reading this article in realizing the full
extent of elder abuse and the frequency in several large US studies (7.6 –
10%). It may well be significantly higher, particularly when the most common
cause of abuse, financial abuse, is considered. This article reviews
definitions and prevalence, risk factors, sequelae, clinical evaluation and
interventions. All of these are clear and easily read (excellent, explicit,
practical, detailed Tables). While some medico-legal aspects of management may
differ between the US and Australia, the basic principles still apply. Of note
in nursing homes, the commonest cause of elder abuse is that perpetrated by
nursing home residents in the form of physical, verbal and sexual aggression.
Recommended learning: Elder abuse in Australia.
Does it differ from the US? How is it manifested and what is the frequency in
underdeveloped countries?
CASE
RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL
A 72-Year-Old Woman with Proteinuria and a
Kidney Mass
A 72-year-old woman presented with flank
pain, proteinuria, and a new kidney mass. Magnetic resonance imaging of the
kidney revealed a complex, solid mass (3 cm x 2.9 cm x 2.9 cm) in the lower
pole of the right kidney. Diagnostic tests were performed
This is interesting
bedtime critical reasoning and learning exercise. This is a patient with a
renal mass, microscopic haematuria, CKD stage 2 and who develops proteinuria
within the nephrotic syndrome range, though she does not develop the nephrotic
syndrome. There is an excellent discussion and consideration of major causes of
proteinuria.
Recommended learning: Nephritic versus nephrotic presentations of
renal disease. Causes and the immuno-histopathology of nephrotic syndrome. DD
of a renal mass, physical findings associated with a large kidney, review
carcinoma of the kidney and its presentations.
Important Articles Related to Mechanisms of Disease and
Translational Research
Perspective
FOCUS
ON RESEARCH
#The Path to Cancer — Three Strikes and You're
Out
Focusing on driver-gene mutations and the
pathways they control has rendered complex cancer-genome landscapes
intelligible. In solid tumours of adults, alterations in as few as three driver
genes appear to suffice for a cell to evolve into an advanced cancer.
ORIGINAL
ARTICLE
#The Genetic Evolution of Melanoma from Precursor
Lesions
Genetic analysis of melanomas from 37
patients sampled in 150 different areas showed that BRAF mutations were present from the first
stages of tumor development, and progressively more malignant lesions showed
acquisition of abnormalities in a predictable sequence
The article is
fascinating and the description of the path to caner in the Perspective section
very illuminating.
The Perspective
discusses progressive driver-gene mutations in four malignancies (melanoma,
colon, pancreas, cervical) on the way to metastatic disease. These are well illustrated in the Figure and
all should at least look at the Figure.
This Perspective
parallels a wonderful study on the
development of melanoma from precursor lesions and documents not only the
changes in pathology as a non-malignant lesion progresses to malignancy but
also the parallel genetic changes that occur in the tissue lesion.
This is clearly an extremely important
article for those who study the genetics of cancer, dermatologists, surgeons,
any student of the skin and interested medical students.
Recommended learning: This will give students who have completed
the section on Neoplasia in MED200 a
chance to review the chapter on Neoplasia (Robbins and Cotran, pp 259-330) and
the adenoma-carcinoma progression in colon cancer (p823).
CLINICAL
IMPLICATIONS OF BASIC RESEARCH
Targeting Stem Cells in Chronic Myeloid Leukemia
with a PPAR-γ Agonist
Combining a tyrosine kinase inhibitor
(imatinib) and a thiazolidinedione (pioglitazone) is proposed for the treatment
of chronic myeloid leukemia
When CML is treated with tyrosine kinase inhibitors (e.g.
imatinib), the majority of patients will achieve and maintain clinical
remission while they remain on long term therapy which is very expensive. Fewer
than 10% of patients achieve true molecular remission, with the majority still
maintaining a small number of quiescent, non-dividing CML stem cells in their
blood and marrow. The inhibitor removes actively dividing cells, but not
quiescent cells.
Using
an agonist of the PPAR-g receptor (the
intranuclear glitazone receptor) (e.g. a thiazolidinedione, such as
pioglitazone used in the treatment of diabetes mellitus), there is depletion of
the residual quiescent CML stem cells.
What will be the therapeutic implications of this important observation?
Recommended learning:
Review the PPAR-g receptor, JAK-STAT
pathways in cell biology and determine how the thiazolidinediones work in
diabetes mellitus.
Other areas which should be of interest to medical students
Perspective
Docs and Nukes — Still a Live Issue
Physicians have played a key role in warning
governments and the public about the danger of nuclear war and the need to
abolish nuclear weapons. That role is still needed: existing nuclear warheads
pose an existential threat to humanity
Since the end of the
Cold War, almost 25 years ago, there appears to have been a progressive loss in
interest by physicians worldwide in the risks of a potential nuclear conflict.
To me, the risk now appears greater than during the Cold War with the
preservation of massive nuclear arsenals by the currently confrontational major
powers and the risks of less stable powers and splinter groups with the
potential to develop “dirty bombs.” Students should read this Perspective to
review the past in the hope that these problems should not develop in the
future.
Of more immediate
concern, however, is nuclear power as it relates to Climate Change. With the
reduction in the burning of fossil fuel to generate energy, which will
eventually occur, pressure will be brought upon the Australian government to
allow the development of nuclear generating reactors around the coast of
Australia to generate “clean energy.” Nuclear mishaps have and will continue to
occur e.g. Japan, the Ukraine and Three Mile Island, further polluting our
planet. Then, of course, the question will arise “where will Australia dump its
(? and other money bearing countries) nuclear waste?” It will certainly not be
in the PMs backyard, probably some “vacant large area” in the middle of
Australia. All Australians must remain vigilant as I predict that this scenario
is inevitable and will unfold as the Climate Change crisis progressively
worsens.
