Sunday 26 February 2017

NEJM Week of 2nd February 2017 (#80)

Professor Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week of 2nd February 2017 (#80)
University of Notre Dame Australia (Fremantle Campus)



Occasional Editorial Comment


None


Must Read Articles



CLINICAL PRACTICE

Long-Acting Reversible Contraception


This article reviews methods of long-acting reversible contraception, including IUDs and hormonal implants. These methods are about 20 times as effective as pills, patches, and rings and are safe for almost all women, including those in a postpartum or postabortion period.

Most fourth-year students felt this was a good review of contraceptive devices, but that they did not learn anything new. This is an excellent article for third year medical students beginning their O&G rotation..



Articles Recommended for Medical Students


Perspective

Learning to Drive — Early Exposure to End-of-Life Conversations in Medical Training


Sent to visit a chronically ill patient at home, a medical student finds that his inexperience can be a strength. Instead of worrying about the right words and how to say them, he learns how to listen — exactly what the patient needs as she faces end-of-life decisions.

This type of scenario should be considered for inclusion in the first and second year curriculum. It emphasises the importance of listening carefully and actively to patients in their home setting even when they talk about topics that don’t appear to be directly related to their medical condition. My prediction is that for many students a bond will be established between the student and the patient and more visits will ensue.  For this curricular addition to succeed, assessment should be kept to a minimum


IMAGES IN CLINICAL MEDICINE

Actinic Granuloma


A 50-year-old woman presented with asymptomatic, annular plaques on her forehead and the dorsum of her hands. Over time, the lesions gradually increased in number and slowly extended centrifugally.


IMAGES IN CLINICAL MEDICINE

Calcific Pancreatitis Associated with Alcohol Use


A 50-year-old man with alcohol dependence presented with acute symptoms of hematemesis. Imaging revealed extensive calcification of the pancreas.


CLINICAL PROBLEM-SOLVING

Making the Connection


A 41-year-old man with a BMI of 49.1 undergoes Roux-en-Y gastric bypass. Eight years later, he presents to his primary care physician with pain in the epigastric region and the left upper quadrant of the abdomen that is exacerbated by eating.

Last week this patient was discussed in a case presentation format.

It is now time to include indications and complications of bariatric surgery in the medicine and surgical end of year assessment. UNDA students doing their electives in surgery in private hospitals are being exposed to significant numbers of bariatric surgical procedures. General practitioners will be increasingly managing these patients and their complications long-term.

Recommended learning: Indications, types, and complications of bariatric surgery.



Important Articles Related to Mechanisms of Disease and Translational Research



CLINICAL IMPLICATIONS OF BASIC RESEARCH

The Antigenicity of the Tumor Cell — Context Matters


When is a neoantigen not a neoantigen? A recent study suggests that T cells in a patient with cancer are more likely to “miss” mutant peptides generated by somatic mutations than are the T cells in a healthy person.

This presents a fascinating concept whereby mutant melanoma neoantigens, which are unable to be recognized by host cytotoxic T cells, are isolated and transferred to donor dendritic cells.  Dendritic cells are then used to activate normal donor T cells. T cell receptor genes are then isolated and inserted into T cells from a healthy second donor and then demonstrated to kill the original melanoma cells. The possibility exists that isolated specific T cell receptor DNA from melanoma cells could be inserted into T cells from a patient with melanoma, the cell population then expanded ex vivo and infused back into the original patient.



Other Articles which should interest medical students



ORIGINAL ARTICLE

Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer


With a median follow-up of 13 years, a randomized comparison of radiotherapy with or without antiandrogen therapy in patients with a rising PSA level after prostatectomy showed that 2 years of antiandrogen therapy resulted in a significantly higher overall survival rate.


EDITORIAL

Improved Therapy for PSA Recurrence after Prostatectomy


This study focuses on a specific group of 760 patients with prostate cancer who had stage T2 or T3 disease and were treated by radical prostatectomy and lymphadenectomy and who subsequently developed detectable levels of PSA. Within a period of 12 weeks of detecting the PSA, patients were randomized into two groups.  One received radiotherapy alone and the other received radiotherapy plus 24 months of antiandrogen therapy (oral bicalutamide). The median follow-up period for surviving patients was 13 years. The results indicated that for the group receiving radiation plus antiandrogen therapy, there was a significantly longer-term survival rate, fewer deaths from prostate cancer, and lower frequency of metastatic prostate cancer.

The nuances of the study are discussed in the editorial, together with descriptions of current studies addressing areas which arise from the study.



New and Novel Therapies



ORIGINAL ARTICLE

Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease


With a median follow-up of 13 years, a randomized comparison of radiotherapy with or without antiandrogen therapy in patients with a rising PSA level after prostatectomy showed that 2 years of antiandrogen therapy resulted in a significantly higher overall survival rate.



EDITORIAL

Go with the Flow


While sickle cell crises are not a common occurrence in WA, patients are occasionally admitted to teaching hospitals. The basis for the study is that sickled erythrocytes aggregate and bind to endothelial receptors by P-selectin leading to microvascular occlusion and a sickle cell crisis.  The monoclonal antibody described (crizanlizumab) binds to P-selectin on erythrocytes lessening adhesion interactions and, in this study, resulted in a 45.3% lower frequency of sickle cell crises and a longer time period to first or second crises. The long-term potential complications of this therapy have not yet been defined.

I believe that this monoclonal antibody may well find another therapeutic niche in the treatment of chronic inflammatory diseases in limiting movement of inflammatory cells from the circulation into the tissues. However, remember the use of the monoclonal antibody against a4-integrins (natalizumab), a very effective therapy in progressive multiple sclerosis which limited the traffic of T cells into the CNS, however resulted in an increased frequency of the fatal disease, progressive multifocal leukoencephalopathy.

The editorial provides a brief review of the pathophysiology of sickle cell disease, reviews the protective role of foetal haemoglobin and describes the mechanism of action of hydroxyurea in this disease.

Recommended learning:

1.     Review the pathophysiology, clinical presentations and management of haemolytic anaemias.
2.     Review the normal physiology and pathophysiology involved in haemoglobin synthesis. 



Articles Some Medical Students Found Interesting



ORIGINAL ARTICLE

A Fully Magnetically Levitated Circulatory Pump for Advanced Heart Failure


In a randomized trial, 294 patients with advanced heart failure were assigned to receive either a new centrifugal-flow pump or an axial-flow pump. At 6 months, the centrifugal-flow pump was associated with better outcomes


ORIGINAL ARTICLE

Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure


In this trial, patients with advanced heart failure were assigned to an intrapericardial centrifugal-flow LVAD or an axial-flow LVAD. The intrapericardial device was noninferior to the axial-flow device with respect to survival free from disabling stroke or device malfunction.


EDITORIAL

Mechanical Circulatory Support Devices — In Progress


Some students were interested in the two articles and the editorial involving the current use of left ventricular assist devices in patients with advanced heart failure. These devices are being used in tertiary hospitals in Perth.  While the data presented showed little difference in outcomes between the two types of devices described, what amazed me was the degree of miniaturization that has occurred over the past thirty years, as demonstrated by the current use of centrifugal flow-pumps contained within the pericardial sac (Figures 1 in each article).



Monday 20 February 2017

NEJM Week of 26th January 2017 (#79)

Professor Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week of 26th January 2017 (#79)
University of Notre Dame Australia (Fremantle Campus)


Occasional Editorial Comment


Students have now returned and hopefully for reviewing the articles from the week’s Journal.
You will receive an e-mail each week of the previous week’s Journal review with a focus on areas students in my teaching groups felt interested them the most. I will, however, also comment on articles not chosen if I believe they are important to medical students and their teachers.  You should open the blog from the e-mail as the blog contains appropriate formatting which makes the reviews much easier to read. A search of previous editions of the blog can be done from the top left corner.

Full articles can be reviewed using the UNDA library e-resources.

This is the first issue of the UNDA academic year and, as the new MEDI6100 class will be receiving this weekly e-mail for the first time, it is appropriate that I review the reasons this blob was developed.  There are also many ancillary learning aids associated with the Journal which I am will not attempt to duplicate.
The primary aim of the blog is to foster an interest in every Notre Dame medical student and teacher the need to remain current in all areas of the curriculum and to develop a yearning for continued long term learning. My recommendations are not compulsory reading, however, I hope that most students would read my weekly review and, at the least, explore the NEJM titles to keep abreast of new developments which will determine the basis of their future practice. Students will at a minimum become aware of areas and see more relevance in their basic science teaching.
The NEJM is the most widely read journal internationally with the highest impact factor of any journal.
My weekly review is in no way exhaustive.  Articles are chosen for their specific relevance to the evolving UNDA medical school curriculum, in order to update the student particularly in:
1.     basic sciences (e.g. cell and molecular biology, immunology, genetics, pharmacology), and
2.     new therapies.

The Journal contains the following sections:

1.     Perspective: Covers all curricular domains (health care systems, ethics and public health are overrepresented).  Many relate specifically to medicine in the US.  I will not highlight these unless there is a specific application to Australian medicine.

2.     Original Articles: Some articles will interest you, while others may not. If interested or in doubt, always read the abstract and the introduction to the paper. The introduction will provide an overview to the study and why it was performed. This is a quick way to update your knowledge.

3.     Review Articles: State of the Art review articles are always interesting and encompass wide areas.  My suggestion is that these be stored as hyperlinks in your long-term data base learning system, such as Evernote which is free for moderate storage.  You can also include your long cases in Evernote for future use after medical school.

4.     Clinical Pathological Conference (CPC) or Case Records of the Massachusetts General Hospital: It is very interesting to follow the clinical reasoning of the discussant. As an exercise, sit down with a colleague, consider the broad presenting symptom(s), and develop a list of differential diagnoses before you read the case.

5.     Images in Clinical Medicine: Remember, if a consultant or tutor mentions a specific disorder and you want to see it with the pathology, always check in this extensive data base. Apart from Figures, videos are also included.

6.     Editorials: After reviewing the abstract of the original article, I always check the editorials before I read the original article in detail.  An editorial addressing a specific original article will provide an independent in-depth overview of the results of the study and comparisons with other studies.

7.     Clinical Problem Solving: These are usually challenging and will help to develop your skill in clinical reasoning.

8.     Clinical Implications of Basic Research: Usually I find this a very interesting area in the Journal. The author of the article has been solicited by a member of the editorial board to write a short summary, with an instructive picture, of a recent cutting edge basic science article (e.g. Science, Nature, PNAS) and to hypothesise on the possible relevance to future human research.

Figures and Tables: These are very well done, easy to understand and can be saved in a Powerpoint format for presentations.

Errors: Errors can occur and are usually mentioned in subsequent Corrections.  As a word of general caution when reading any article or book, if you cannot understand a statement or a Figure, always check with a colleague as errors can occasionally occur and should not result in you having a sleepless night.

Other goodies: The NEJM has an extensive Video Collection of most commonly performed clinical procedures which are extremely well illustrated and explained. Enrol in Residents E-Bulletin where two key articles are reviewed with Morning Report questions and Clinical Pearls. Moreover, there is a Weekly Audio Summary as a Podcast of articles chosen as the most significant by the editorial board.
You can also do searches of back issues for virtually any topic in Medicine.

The entire weekly issue of the Journal is available through the medical library as an e-journal and is readily searched.

Finally, I must state that the views expressed are mine alone and you may not necessarily agree with them. At least this will provoke discussion between students and encourage learning. Errors will invariably occur and for these I apologize in advance. Please do not hesitate to contact with questions or corrections when this happens.


Must Read Articles


None


Articles Recommended for Medical Students


Perspective

Allocating Organs to Cognitively Impaired Patients


Should patients’ cognitive function be weighed in the allocation of organs? This debate raises important questions, from the ethics of making judgments regarding others’ quality of life to the science of cognitive impairment’s effect on post-transplantation survival.

This is a topical article in which the ethical arguments representing both sides are clearly presented and are accompanied by supporting evidence. It would be interesting to consider this for CD discussion.


INTERACTIVE MEDICAL CASE

Making the Connection


This interactive feature presents a 41-year-old man who presented with hyperlipidemia and a history of morbid obesity since childhood. Test your diagnostic and therapeutic skills at NEJM.org.

As bariatric surgery in the private sector is increasingly performed, students during their surgical rotations will be frequently exposed to these procedures in the patients they follow. As such, a generalized knowledge of the procedures (usually sleeve gastrectomy and Roux-en-Y) and a detailed knowledge of the early and late post-operative complications should be acquired. This is a case-based learning process (will now replace the Short Answer Format in UNDA written clinical examinations) and in the next issue of the Journal it will be presented in article format.


IMAGES IN CLINICAL MEDICINE

Radiation-Induced Angiosarcoma after Breast-Cancer Treatment


A 72-year-old woman presented with skin changes on her left breast; 5 years earlier, she had undergone lumpectomy and radiation therapy for breast cancer. Examination revealed an area of skin that had an ecchymotic appearance, with no underlying mass or nodular tissue.

Recommended learning: Review the role of radiotherapy in the management of breast cancer.


IMAGES IN CLINICAL MEDICINE

Taenia solium


A 48-year-old man presented with abdominal discomfort and lethargy. Examination revealed pallor, and laboratory studies showed mild anemia. Colonoscopy revealed a proglottid from a tapeworm, shown in a video, in the rectosigmoid colon.

Recommended learning: Review the biology, clinical presentations, and treatment of hookworms and tapeworms.


ORIGINAL ARTICLE

A Recombinant Vesicular Stomatitis Virus Ebola Vaccine


This final report updates preliminary data on an attenuated, replication-competent, recombinant vesicular stomatitis virus–based vaccine candidate designed to prevent Ebola virus disease. The results supported the safety and immunogenicity of up to two doses of the vaccine.

This recombinant VSV Ebola vaccine as currently studied should be particularly useful for medical personnel and the population in the centre of an Ebola epidemic but not for sustained population protection against the Ebola virus due to the short term antibody response to the vaccine.


CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL

Case 3-2017 — A 62-Year-Old Man with Cardiac Sarcoidosis and New Diplopia and Weakness


A 62-year-old man with sarcoidosis was admitted to this hospital because of diplopia and weakness. Examination of the CSF revealed elevated opening pressure and leukocytosis. The patient’s condition deteriorated rapidly. He died 10 days later. A diagnosis was made.

In a Google search the discussant asked a specific question:  “What causes the most rapidly fatal meningoencephalitis?” The first answer was the first hit on the page. This emphasises the importance of using correct search terms when asking questions.

This reminds me of a case I managed of acute onset polyarthritis occurring in a 28-year-old male with common variable immunodeficiency. Several weeks before this patient presented, the first description of an association between Ureaplasma urealyticum polyarthritis in patients with hypogammaglobulinemia was made by Max Cooper in the NEJM. When I performed my initial literature search I inadvertently searched for only agammaglobulinemia and was not rewarded with a positive association. Fortunately, the synovial fluid culture was positive within 48 hours.


Important Articles Related to Mechanisms of Disease and Translational Research


None


Other Articles which should interest medical students


REVIEW ARTICLE

Systemic Therapy for Metastatic Renal-Cell Carcinoma


Kidney cancers have been extensively studied, and insights from an increased understanding of tumor biology have led to increases in survival rates. Therapies aimed at tumor signaling pathways and immunotherapies have improved the outlook for patients with renal cancer.

Most students who read this article did so to update their knowledge on renal-cell carcinoma. However, once they began they became fixated on the cell biology and new pharmacological agents presented in Figure 1. Interested students reviewed the role of the VHL (von Hippel-Lindau) gene in the control of HIF (hypoxia-inducing factor) function. Normally the VHL gene is responsible for the ultimate degradation of tissue HIF. If a loss-of-function mutation occurs in the VHL gene, which happened in 52% of patients with renal cell carcinoma, HIF is no longer degraded.  Excessive HIF then results in activation of HIF target genes which include VEGF (responsible for new vessel formation in the tumour) as well as the growth factors FGF and PDGF and survival factors (PDL1 and-L2).

While the names of most of these newer pharmacological agents used to treat cancer (in this case renal cancer), need not be remembered, this Figure should allow the student to see the relevance of the pathways they are taught in cell biology and pathways they usually forget readily.

Again, mention is made of one of the important check point inhibitors, nivolumab, which binds to PD-L (programmed cell death ligand) on the surface of tumour cells, protecting the cytotoxic T cell from undergoing apoptosis and allowing it to kill the tumour cell.

The review then describes the drugs and their combinations used in trials to treat metastatic renal cell cancer. As a note to those few with any interest in the management of metastatic renal cell cancer, an algorithmic approach is provided.

Recommended learning: Review the epidemiology, pathology, clinical presentations and basic therapeutic approach to a patient with renal cell cancer.


Perspective

Repealing the ACA without a Replacement — The Risks to American Health Care


President Barack Obama explains why Republicans’ plan to repeal the Affordable Care Act with no plan to replace and improve it is so reckless: doing so would jeopardize financial security and access to care for tens of millions of Americans.

While this article is not directly applicable to the practice of medicine in Australia (and I hope never will be), it is written by a very intelligent, thoughtful, informed President Obama at the end of his presidency.

SPECIAL ARTICLE

Tobacco-Product Use by Adults and Youths in the United States in 2013 and 2014


According to a 2013–2014 survey of nearly 46,000 U.S. adults and youths, 28% of adults were current users of tobacco and 9% of youths had used tobacco in the previous 30 days. Approximately 40% of users used multiple products, with cigarettes plus e-cigarettes the most common combination.

While I found the statistics on tobacco-product use in the US very interesting, I had to review snus pouches, bidis and kreteks as vehicles to obtain the effects of tobacco-products.
Of interest in Table 2 (the prevalence of tobacco use according to product type and age), the use of E-cigarettes is only slightly less than cigarette use in youths (12 -17 years).  



New and Novel Therapies

EDITORIAL

Bezlotoxumab — A New Agent for Clostridium difficile Infection



ORIGINAL ARTICLE

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection


Bezlotoxumab is human monoclonal antibody against Clostridium difficile toxin B. In two controlled trials, a single intravenous dose of bezlotoxumab, given in addition to antibiotic treatment, provided protection against recurrent infection for up to 12 weeks.

This article and the accompanying editorial discuss the efficacy of a single infusion of a monoclonal antibody (bezlotoxumab) against C. difficile toxin B in patients with primary or recurrent C. difficile infection who are being treated with standard-of-care antibiotics (metronidazole or vancomycin both approx. 47% or fidaxomicin 3.5% - Table 1). 2655 patients at 322 sites in 30 countries were studied. The infusion usually commenced three or more days after the start of antibiotics (varied) when the disease severity had improved and when the concentration of stool toxin B was markedly reduced. Addition of a monoclonal antibody against the A toxin added no clinical advantage to that of bezlotoxumab alone.  The selection of antibiotics was at the discretion of the treating physician. No other therapies were allowed in this study (such as faecal microbiota transplantation). The primary end point was recurrence (a new episode after initial clinical cure) within 12 weeks of the infusion.
The study showed approximately 50% reduction in the recurrence within 12 weeks in the group treated with bezlotoxumab over the placebo. The rates of sustained cure rates (no recurrence within 12 weeks) was 64% for bezlotoxumab versus 54% in the placebo group. However, the initial cure rates were 80% in both the bezlotoxumab and placebo groups.

The cost of C. difficile in the US in 2011 was estimated to be 40 billion dollars. However, a cost-benefit analysis for the routine use of bezlotoxumab in C. difficile infection was not provided.  Clearly before this therapy could be widely employed, specific subgroups who would benefit need to be identified.

Recommended learning: Review pseudomembranous colitis, C. difficile biology and natural history of infection, diagnosis and recommended treatment in Australia.



Specific Articles Medical Students Found Interesting


ORIGINAL ARTICLE

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children


In this multicenter trial, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant survival benefit in comatose children who survived in-hospital cardiac arrest.