Professor
Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week
of 10th November 2016 (#68)
University
of Notre Dame Australia (Fremantle Campus)
Occasional Editorial Comment
Both last week’s and today’s issue contain articles on
check-point inhibitor therapy as immunotherapy for metastatic malignancy.
Currently the most commonly treated tumours are metastatic melanoma, non-small
cell lung cancer and squamous cell cancer. I predict that soon there will be a
large number of tumours treated with these therapies, once inhibitory check
points (PD-1 and CTLA4 and their inhibitors) can be readily identified by
immunohistochemistry and/or genetic analysis on immune cells surrounding the
tumour. The extensive review in last week’s issue (Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway http://www.nejm.org/doi/full/10.1056/NEJMra1514296 )
characterises
the molecular and biochemical pathways involved including inhibition of PD-1
and CTLA4.
Students must be aware of the basic cell biology of
these pathways as these are becoming increasingly important in oncology. This
is clearly the first field in which “personalised medicine” is being practiced
due to advances in genetics and immunology. Rheumatology will be the next.
I recommend that
every student and teacher read a December 3, 2016 article in the New York Times
titled “Immune System, Unleashed by Cancer Therapies, Can Attack Organs” (http://www.nytimes.com/2016/12/03/health/immunotherapy-cancer.html)
as this is the type of cell biology you must understand in order to remain
intellectually current and capable of discussing these areas with patients and
practicing medicine in the future. There is also a simple diagram in the NYT article of
how these therapies work. Don’t forget that patients are reading
these articles and it is a good idea to know a little more than your patient. The
article particularly focuses not only on the costs of these monoclonal
antibodies (small molecule intracellular inhibitors that inhibit synthesis of
CTLA4, PD-1, PD-L1 and PD-L2 will soon be available) as well as the adverse
effects of unleashing the normal inhibitory immune system with loss of
peripheral tolerance e.g. onset of autoimmune diseases such as type 1 diabetes
mellitus.
See my earlier comments in #59 (search blog for check
point). The Editorial in this issue
(Divide and Conquer Lung Cancer http://www.nejm.org/doi/full/10.1056/NEJMe1611003 )
provides detailed information also on the chemotherapy used for mutations in
proto-oncogenes, kinases and the EGF-R.
In medicine there is always a potential risk in
everything you do to and for your patient, including advice or drug therapy.
Must Read Articles
Perspective
Meaning
and the Nature of Physicians’ Work
Perhaps
the greatest opportunity for improving physicians' professional satisfaction in
the short term lies in restoring our connections with one another. We will have
to rebuild a sense of teamwork, community, and the ties that bind us together
as human beings.
This article MUST be read by all students and teachers.
Articles Recommended for Medical Students
CLINICAL
PRACTICE
Heart
Failure with Preserved Ejection Fraction
Management
of heart failure with preserved ejection fraction includes diuretics, treatment
of coexisting conditions, aerobic exercise, self-care, and disease management
programs, but medications that are effective for reduced ejection fraction have
not been beneficial.
IMAGES IN CLINICAL MEDICINE
Diagnosing
Myasthenia Gravis with an Ice Pack
A
68-year-old man presented with unilateral ptosis. Neurologic examination
revealed ptosis of the left eye after a sustained upward gaze. Myasthenia
gravis was suspected, and an ice-pack test was performed with an instant cold
pack over the left eye
IMAGES IN CLINICAL MEDICINE
Hemothorax
after Thoracentesis
A
65-year-old woman with atherosclerotic cardiovascular disease and renal failure
was hospitalized for acute respiratory failure and bilateral pleural effusions.
To rule out empyema, thoracentesis was performed. Hemothorax developed shortly
after the procedure.
Important Articles Related to Mechanisms of Disease and
Translational Research
CLINICAL IMPLICATIONS OF BASIC RESEARCH
Mitochondrial
Matchmaking
Mitochondrial
replacement therapy involves engineering an ovum or a single-cell embryo such
that the mutant mitochondria are replaced with “healthy” mitochondria. A recent
study of mice shows some unexpected health outcomes as the mice age.
See previous Perspective article on mitochondrial
transfer and associated comments in #35 (http://www.nejm.org/doi/full/10.1056/NEJMp1600893).
Recommended
learning: The role of the mitochondrion in cell biology and
clinical disease.
Other Articles which should interest medical students
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL
Case
34-2016 — A 17-Year-Old Boy with Myopia and Craniofacial and Skeletal
Abnormalities
A
17-year-old boy was seen in the medical genetics clinic because of myopia,
craniofacial and other skeletal abnormalities, and pectus excavatum.
Ophthalmologic examination revealed ectopia lentis, and imaging studies showed
osteoporosis. Diagnostic testing was performed.
Perspective
Vitamin
D Deficiency — Is There Really a Pandemic?
The
claim that large proportions of North American and other populations are
deficient in vitamin D is based on misinterpretation and misapplication of the
Institute of Medicine reference values for nutrients — misunderstandings that
can adversely affect patient care.
ORIGINAL ARTICLE
Pembrolizumab
versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer
In
a randomized trial involving patients with previously untreated advanced
non–small-cell lung cancer, pembrolizumab was associated with a higher response
rate, longer progression-free and overall survival, and fewer adverse events
than was platinum-based chemotherapy.
ORIGINAL ARTICLE
Prolonged
Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy
Patients
with surgically resected stage III melanoma are at high risk for recurrence.
The 5-year survival rate with ipulimumab was 11 percentage points higher than
that with placebo (65% vs. 54%), but there were substantial immune-related
toxic effects
ORIGINAL ARTICLE
Nivolumab
for Recurrent Squamous-Cell Carcinoma of the Head and Neck
Patients
with platinum-refractory head and neck cancer had significantly longer survival
with nivolumab treatment than with standard, single-agent therapy. Response
rates were also higher and quality of life maintained longer with nivolumab.
New Pharmacological Therapies
None
Other articles which may be of interest to certain students
None
