Tuesday, 13 December 2016

NEJM Week of 24th November 2016 (#70)

Professor Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week of 24th November 2016 (#70)
University of Notre Dame Australia (Fremantle Campus)



Occasional Editorial Comment


None


Must Read Articles


None


Articles Recommended for Medical Students



CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL

Case 36-2016 — A 50-Year-Old Man with Acute Liver Injury


A 50-year-old man from India, with a remote history of alcohol use, was admitted to this hospital because of abnormal liver function test results, anemia, and acute kidney injury. A diagnosis was made.


ORIGINAL ARTICLE

BRIEF REPORT

Fully Implanted Brain–Computer Interface in a Locked-In Patient with ALS


Electrical signals from fully implanted surface electrodes over the cerebral motor cortex were decoded to allow a locked-in patient with ALS to control a computer cursor and type independently at a slow pace.


REVIEW ARTICLE

Von Willebrand’s Disease


Von Willebrand's disease is the most common inherited bleeding disorder and is generally transmitted as an autosomal dominant trait. It is mainly associated with mucosal bleeding and excessive bleeding after trauma or surgery. A variety of effective treatments are available.


IMAGES IN CLINICAL MEDICINE

Large Hiatal Hernia


An 81-year-old woman presented with vomiting. Chest radiography showed a large air–liquid shadow in the inferior retrocardiac position, suggesting a paraesophageal hernia. CT showed a large retrocardiac mass that was consistent with herniation of the stomach into the chest.



Important Articles Related to Mechanisms of Disease and Translational Research


CLINICAL IMPLICATIONS OF BASIC RESEARCH

BASIC IMPLICATIONS OF CLINICAL OBSERVATIONS

Nephron Protection in Diabetic Kidney Disease


This commentary discusses nephron protection in diabetic kidney disease and describes the way in which renin–angiotensin system inhibitors and the sodium–glucose cotransporter 2 inhibitor empagliflozin have renoprotective effects.



Other Articles which should interest medical students



ORIGINAL ARTICLE

Thresholds for Abdominal Aortic Aneurysm Repair in England and the United States


Hospital and registry data and national statistics showed a lower rate of abdominal aortic aneurysm repair and a larger mean aneurysm diameter at repair in England than in the United States; U.S. rates of aneurysm rupture and aneurysm-related death were lower.


IMAGES IN CLINICAL MEDICINE

Dizziness and Vertigo during MRI


A 33-year-old man participating in a research study underwent MRI in a 7-tesla MRI scanner. On entering the scanner, he had a spinning sensation for 2 minutes. Nystagmus, recorded with infrared goggles and shown in a video, continued for the entire 90-minute scanning period.



New Pharmacological Therapies


None


Other articles which may be of interest to certain students


ORIGINAL ARTICLE

TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes


Decitabine produced responses in patients with acute myeloid leukemia or myelodysplastic syndromes who had cytogenetic abnormalities associated with a poor prognosis, including 21 of 21 patients with tumors that contained TP53mutations.


EDITORIAL

Acute Myeloid Leukemia — Many Diseases, Many Treatments



Monday, 12 December 2016

NEJM Week of 17th November 2016 (#69)

Professor Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week of 17th November 2016 (#69)
University of Notre Dame Australia (Fremantle Campus)


Occasional Editorial Comment

The practice of medicine has moved into the molecular biological, pathophysiological, Nano technological, genetic, and immunological era.  Unless both medical students and their teachers are well informed of current advances in these areas, medical schools will graduate “bare foot” doctors without the scientific basis necessary to understand abnormal symptoms and signs, order the appropriate investigations, and develop the correct diagnosis(es) and management plan.  

When you read the CPC in today’s journal involving the management of a patient with metastatic oesophageal cancer, you will see where “personalized medicine” is heading and why it is imperative to have a scientifically broad-based knowledge in medicine to remain current. 

It is essential that students actively focus a significant amount of their time and to understanding these scientific areas during the first two years of medical school and to foster an intellectual curiosity to continue learning into the future. Clearly, most medical students engage as early as possible in medical school in areas they believe to be much more important in becoming a doctor, such as history taking and physical examination, frequently at the expense of their scientific training. Most medical schools have embarked on an integrated teaching curriculum (generally organ based) in which teaching revolves around a particular system e.g. cardiovascular. This teaching involves areas such as anatomy, physiology, biochemistry, cell biology, and immunology as well as specific diagnostic skills and history taking related to the particular organ system.  This system leads to learning history taking and physical examination from early in the first year, often at the expense of significant scientific learning.

I believe the assessment process during the first two years should be heavily weighted towards the basic sciences in order for students to appreciate how important this area is in enjoying the practice of clinical medicine and understanding the scientific basis of specific questions and clinical signs when treating the patient.

In today’s recommendations, there are three articles (Editorial, Original article and Perspective) involving the biology of cyclins and cyclin-dependent kinases (cdk) and the use of a cdk inhibitor (palbociclib) in conjunction with letrazole in treating postmenopausal women with advanced ER-positive, HER-2 negative breast cancer. Students must understand the cell cycle – division cycle (mitosis) completely.  These are reviewed well in the Perspective and Wikipedia (mitosis). The first paragraph of the Perspective states:

 Orally available drugs that potently and specifically inhibit the activities of the cyclin D–dependent kinases CDK4 and CDK6 represent paradigm-shifting antineoplastic agents.  Unlike traditional cytotoxic drugs, which kill dividing cells by interfering with DNA replication (S phase) or mitosis (M phase) during the cell-division cycle, CDK4–CDK6 inhibitors arrest progression through the G1 phase, promoting transient cell-cycle withdrawal into a quiescent state (G0) or, possibly, permanent proliferative arrest.  Although cell-lineage identity and collateral signaling pathways may shape these different outcomes, either quiescence or senescence could avert tumor progression and help extend cancer-progression–free survival.

Another area of concern is the time in the medical school curriculum devoted to credentialing of procedures and having our graduated students “intern functional” on day one of their internship.  Do we require first year medical students to pass their first year exams after their first week of medical school? The reason for this requirement is the lack in the number of resident staff available to closely monitor and train new interns.  It is in essence a mechanism of passing on to medical schools the state cutback in public hospital funding. If medical schools do not remain vigilant, public teaching hospitals, and soon private hospitals, will be demanding increased remuneration from universities for their resident and consultant teaching time of medical students. This situation will result in fraying of the fabric between the teacher (senior residents and consultants) and the student. The apprenticeship model and goodwill now appear to be on the wane.



Must Read Articles



Perspective

FOCUS ON RESEARCH

A New Cell-Cycle Target in Cancer — Inhibiting Cyclin D–Dependent Kinases 4 and 6


Unlike traditional cytotoxic drugs, CDK4–CDK6 inhibitors arrest progression through the G1 phase, promoting transient cell-cycle withdrawal into a quiescent state or, possibly, permanent proliferative arrest (senescence), either of which could avert tumour progression.



REVIEW ARTICLE

Acute Pancreatitis


This review summarizes recent changes in the management of acute pancreatitis, encompassing fluid resuscitation, antibiotic use, nutritional support, and treatment of necrosis, and also addresses common misunderstandings and areas of controversy.



CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL

Case 35-2016 — a 62-Year-Old Man with Dysphagia


A 62-year-old man presented with metastatic oesophageal adenocarcinoma. Two months earlier, imaging revealed a distal oesophageal mass and enlarged lymph nodes; biopsy revealed adenocarcinoma that had metastasized to the lymph nodes. Management decisions were made.

This is an excellent discussion of the management of extensive metastatic oesophageal cancer, in particular the use of genetic analysis after failed primary and secondary chemotherapy protocols and radiotherapy.  Demonstration of two abnormal genes associated with the malignancy, especially MET amplification, led to the use of a MET tyrosine kinase inhibitor (crizotinib) and freedom from clinically apparent disease after four years! This is a classic example of “personalised medicine” and a glance into the future of clinical practice.



Articles Recommended for Medical Students



Perspective

Adding Value by Talking More


In many situations, having physicians and other clinical personnel talk more with patients and each other can be the least expensive and most effective approach for delivering better patient care, and new payment models provide incentives for such discussions.


IMAGES IN CLINICAL MEDICINE

Tabes Dorsalis and Argyll Robertson Pupils


A 47-year-old man with HIV infection had shooting pains in his legs, progressive difficulty in walking, tinnitus, and incontinence. Examination showed Argyll Robertson pupils, which are nonreactive to bright light but constrict when focused on a near object. A video is available at NEJM.org.

Great Argyll Robertson pupils, but is the examiner’s attire professionally appropriate?


IMAGES IN CLINICAL MEDICINE

Heterotopic Pregnancy


A 34-year-old woman with a history of appendectomy presented to the ED with acute abdominal pain. An intrauterine pregnancy had been diagnosed by her gynaecologist. Transvaginal ultrasonography revealed a 4-cm right adnexal mass and free fluid in the peritoneal cavity.



Important Articles Related to Mechanisms of Disease and Translational Research


None


Other Articles which should interest medical students


ORIGINAL ARTICLE

Effect of Short-Term vs. Long-Term Blood Storage on Mortality after Transfusion


In a pragmatic trial, more than 30,000 patients requiring blood transfusion were randomly assigned to receive blood after short-term storage or long-term storage. In-hospital mortality did not differ significantly between the two groups.


New Pharmacological Therapies


EDITORIAL

CDK4 and CDK6 Inhibition in Breast Cancer — A New Standard

       

ORIGINAL ARTICLE

Palbociclib and Letrozole in Advanced Breast Cancer


Among women with previously untreated hormone-receptor–positive advanced breast cancer, the addition of the cyclin-dependent kinase inhibitor palbociclib to letrozole therapy resulted in longer progression-free survival than that with letrozole alone.

This article is a game-changer.


Other articles which may be of interest to certain students


None


Wednesday, 7 December 2016

NEJM Week of November 17, 2016 (#68)

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


Tuesday, 6 December 2016

NEJM Review Week of November 3, 2016

Professor Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week of 3rd November 2016 (#67)
University of Notre Dame Australia (Fremantle Campus)


Occasional Editorial Comment


I have just returned from the American College of Rheumatology meetings in Washington DC and am behind in my weekly NEJM reviews. Over the next two months while students are on vacation, I will attempt to be brief in my comments and highlight articles which I believe to be the most important and ones which the students may read for intellectual pleasure over this period.  I would also like to believe that each week all students and teachers review the titles of all article on line and read at least the abstracts of interest.


Must Read Articles


Perspective

BECOMING A PHYSICIAN

Tolerating Uncertainty — The Next Medical Revolution?


When we become obsessed with finding the right answer, at the risk of oversimplifying the richly iterative and evolutionary nature of clinical reasoning, the result is the very antithesis of humanistic, individualized patient-centered care.

This is a Perspective article that MUST be read by all students and teachers. It is one of the most significant articles I have read this year as it focuses on the practice medicine in the grey-zone and accepts the concept of uncertainty in the diagnosis and treatment of the patient. It helps offers a way in which medicine can be practiced in parallel with the black-white interface concept of medicine projected by the computer screen and clearly stresses the need of the personal doctor-patient relationship. It reinforces “I really don’t know what the diagnosis is,” especially when it comes from the consultant and, should we as teachers, pause when a student makes this statement.  On occasions, maybe the student is correct.


CLINICAL PROBLEM-SOLVING

Just a Cut


A 51-year-old surgeon lacerated his left ring finger near the volar distal interphalangeal joint with a fillet knife while cleaning fish after a late summer day of fishing in coastal New England seawaters. Twelve hours later, he awoke with throbbing pain in his fingertip.

This is an excellent article describing what can go wrong if you cut your finger with a knife while filleting fish and you happen to be a surgeon taking adalimumab (a TNFa inhibitor) for rheumatoid arthritis. The article involves the anatomy of the hand, infection involving tendon sheaths and the urgency and aggressiveness in treating this type of infection.



Articles Recommended for Medical Students



REVIEW ARTICLE

Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway


The PD-1 pathway plays an essential role in maintaining immunologic self-tolerance. However, cancers can subvert the role of this pathway and blind the immune system to their presence. The molecular details of the pathway are discussed.


ORIGINAL ARTICLE

BRIEF REPORT

Fulminant Myocarditis with Combination Immune Checkpoint Blockade


Fatal autoimmune myocarditis with rhabdomyolysis and refractory arrhythmias developed in two patients treated with a combination of anti–CTLA-4 and anti–PD-1 blockers. On histologic examination, a myocardial infiltrate similar to that seen in acute cardiac allograft rejection was observed.


IMAGES IN CLINICAL MEDICINE

Emphysematous Cystitis


A 72-year-old woman with poorly controlled hyperlipidemia and diabetes presented to the ED with lower abdominal pain. Examination revealed lower abdominal tenderness, and blood tests revealed leukocytosis and elevated C-reactive protein and glucose.


IMAGES IN CLINICAL MEDICINE

Ocular Flutter in the Serotonin Syndrome


A 46-year-old woman was brought to the ED because of agitation. On arrival, she had a fever, tachycardia, and ocular flutter, as well as rigidity in the legs and myoclonus in the arms. Videos are available at NEJM.org.


Important Articles Related to Mechanisms of Disease and Translational Research


None


Other Articles which should interest medical students


None


New Pharmacological Therapies


ORIGINAL ARTICLE

Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer


In patients with advanced HR-positive, HER2-negative breast cancer, the addition of the cyclin-dependent kinase inhibitor ribociclib to letrozole was associated with a significantly higher rate of progression-free survival than placebo.

This is ground-breaking therapy whereby a cyclin-dependent kinase inhibitor (ribociclid) together with letrazole has been shown to be more effective than letrazole alone in post-menopausal women with either recurrent or metastatic HR positive, HER2 negative breast cancer.



Other articles which may be of interest to certain students


None

Friday, 4 November 2016

NEJM Week of 27th October, 2016 (# 66)

Professor Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week of 27th October 2016 (#66)
University of Notre Dame Australia (Fremantle Campus)



Occasional Editorial Comment



Over the past three editions of the Journal, readers have been fortunate to be exposed to a series of articles written on "Serious Mental Illness" by NEMJ national correspondent. Dr Lisa Rosenbaum.  I have found these articles to exhibit an uncommon sense of humanity in their discussion of doctor/patient relations.  The descriptions of the personal level of interactions with patients from all walks of life by the staff, particularly psychiatrists, at the MGH is an example of patient care that members of the medical profession should seek to emulate.
 
I regard these articles as an essential component of the unwritten curriculum for all medical students and teachers at the University of Notre Dame Australia.



Must Read Articles



MEDICINE AND SOCIETY

Unlearning Our Helplessness — Coexisting Serious Mental and Medical Illness


Patients with coexisting serious mental and medical illnesses often don't recognize that they need treatment, and those who do may be unlikely to complete it. Caring for such patients successfully requires dedication, flexibility, collaboration, persistence, and love.

I will not attempt to summarize the article but rather draw attention to the concept of “learned helplessness” and how it may be recognised and managed in the physician. This is a quote from the final three sentences of the article: It entails recognizing that a disease doesn’t define a person, without pretending that it doesn’t exist or warrant treatment. It requires understanding that autonomy may be achieved not in an instant but over time (in a patient with serious mental illness).  And it means knowing when a refusal of care is a symptom and when it’s a dying wish.  

  

Articles Recommended for Medical Students



ORIGINAL ARTICLE

A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation


In this trial, long-term supplemental oxygen treatment did not result in longer survival over no use of supplemental oxygen among patients with stable COPD and moderate resting desaturation (SpO2, 89 to 93%) or moderate exercise-induced desaturation.


EDITORIAL

Clinical Usefulness of Long-Term Oxygen Therapy in Adults


Long-term oxygen therapy has been previously demonstrated to improve prognosis in patients with COPD and chronic severe hypoxaemia (PaO2 less than or equal to 55 mm Hg and a SaO2 <88%, breathing ambient room air) or moderate hypoxaemia with signs of right heart failure or polycythaemia.

This article addresses the question of long-term oxygen therapy in patients with stable COPD and resting pulse oximeter readings (SaO2) from 89-93% (compared with a group receiving no supplemental oxygen). In order to increase the number of patients in the study, the researchers added a group of patients with stable COPD who exhibited moderate exercise-induced desaturation. The study group that desaturated only with exercise received supplemental oxygen only during exercise and sleep.
 
The results of the study on 738 patients from 42 centres over a period ranging from 1-6 years showed that the group receiving supplemental oxygen did not differ from those who did not receive supplemental oxygen with respect to time to death or time to hospitalization.  Further, oxygen supplementation did not result in improved secondary outcomes (incidence of COPD exacerbations, adherence to oxygen regimen, 6 minute walk distance, severe exercise-induced severe desaturation or quality of life and well-being).


ORIGINAL ARTICLE

Child–Parent Familial Hypercholesterolemia Screening in Primary Care


This study assessed child–parent screening for familial hypercholesterolemia in primary care practices. For every 1000 children screened, 8 persons who had positive screening results for familial hypercholesterolemia were identified.


EDITORIAL

What Should Be the Screening Strategy for Familial Hypercholesterolemia?


10, 095 children between the ages of 1 to 2 years were screened when they attended their PCP for routine immunizations. Blood was removed by heel prick and screened for familial hypercholesterolaemia. The children were considered positive if they had either an elevated cholesterol level (above the 99.2th percentile) on two occasions three months apart, or if they had an elevated cholesterol level together with a familial hypercholesterolaemia mutation. If they were positive, their parents were also screened.

 The mutation prevalence was 1 in 273 children (not all had an increased cholesterol level at the time). For every 1000 children screened, 4 children and 4 parents were positive and considered at high cardiovascular risk in the future. 

The Editorial provides an overview of the study and an in-depth analysis of screening methodology including advantages and disadvantages. Universal screening, selective universal screening and cascade screening are explained in the context of this disorder. Whether o screen or not to screen all comes down to a cost/risk-benefit analysis which is what we do in the everyday practice of clinical medicine. 


REVIEW ARTICLE

Hepatic Encephalopathy


The brain dysfunction associated with liver failure can have diverse manifestations. The main pathogenesis is metabolic derangement of cell function and brain edema. Prompt recognition and treatment may reverse, at least partially, some of the abnormalities.

This is an excellent clinical review on hepatic encephalopathy. Figures and Tables provide a summary of the article. The section on current treatment is particularly worth reading.


IMAGES IN CLINICAL MEDICINE

Emphysematous Pyelonephritis


A 51-year-old man presented with fever and general malaise of 2 weeks' duration. He had poorly controlled diabetes mellitus at the time of presentation. Imaging studies revealed gas collection in the parenchyma and perinephric space of the left kidney.

This case of emphysematous pyelonephritis due to E. coli, in a patient with diabetes mellitus and a neurogenic bladder, was treated with IV antibiotics and did not require nephrectomy. This is second in the series of emphysematous infections involving the urinary tract either due to E. coli or K. pneumoniae.


IMAGES IN CLINICAL MEDICINE

Clonus Associated with Tropical Spastic Paraparesis


A 53-year-old woman with tropical spastic paraparesis reported several months of worsening weakness of the legs and feet. On examination, she had severe spasticity and weakness of both legs and feet, bilateral Babinski sign, and bilateral patellar clonus, shown in a video.

The video should be reviewed to see bilateral patellar clonus. This patient suffered from tropical spastic paraparesis (human T-lymphotropic virus–associated myelopathy) which results in progressive spastic paraplegia.


CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL

Case 33-2016 — A 30-Year-Old Woman with Severe Lower Abdominal Pain and Chills


A 30-year-old woman presented to this hospital with abdominal pain, nausea, and chills. Evaluation showed tachycardia, bilateral lower-quadrant abdominal tenderness, leukocytosis, and an elevated CA-125 level. Imaging studies showed adnexal cysts. A diagnosis was made.

This 30-year-old patient had fever, lower quadrant abdominal pain and was found to have bilateral pelvic masses on CT. Excellent differential diagnoses were presented together with a discussion of the causes of an elevated CEA level.



Important Articles Related to Mechanisms of Disease and Translational Research



CLINICAL IMPLICATIONS OF BASIC RESEARCH

The Hypoxia Response Pathways — Hats Off!


This year's Lasker Award for basic medical science recognizes the work of investigators who uncovered a pathway that has a central role in effecting the myriad cellular responses to hypoxia.

In MED100 pathology, the role of HIF (hypoxia-inducible factor) in the pathogenesis of the acute inflammatory process was discussed. This article summarises the research on HIF which was the basis for the 2017 Lasker award.

The following is the final paragraph of the article:
All three of these 2016 Lasker awardees have been involved in efforts to exploit such oxygen-sensing pathways for therapeutic gain. For example, Semenza did early groundwork showing the salutary effects of HIF in preclinical ischemia models, Kaelin and Ratcliffe established that the PHDs (prolyl hydroxylase domain enzymes) could be inhibited with drug-like molecules, and all three have probed the role of HIF in cancer. First-generation PHD inhibitors, which stabilize HIF, are being developed for renal failure, tissue ischemia, and tissue regeneration. Conversely, HIF inhibitors are being developed for cancer (especially clear-cell renal carcinoma) and specific diseases such as pulmonary arterial hypertension (see Fig. 1 for the biology of HIF under normal and low oxygen conditions and in the von Hippel-Lindau syndrome).



Other Articles which should interest medical students


Perspective

Days Spent at Home — A Patient-Centered Goal and Outcome


If “high-value, patient-centered care” is to be more than rhetoric, health care organizations need to measure outcomes that matter to patients, such as days spent at home in the last 6 months of life. There is substantial variation in this patient-centered outcome.

The following is a quote from this article:
Health policy often stumbles when there is uncertainty about what we are trying to maximize in health care. It is clear that one goal is to minimize costs, but there should be counterbalancing measures to be maximized. Mortality is not a sufficient measure to define excellence in care; in fact, no single performance metric will suffice. Outcome measures that reflect what truly matters to patients can define performance in ways that increase the engagement of patients, clinicians, and provider organizations in the redesign of care.

In US studies, patients in their last six months of life (180 days) spent between 120 -146 days at home depending on the region of the country (Fig. 1). In a large UK study, the Camden Commissioning Group (CCG), unusual data was produced (Fig. 2). The more patients accessed home hospice and home-health care, the fewer the days the patients spent at home.  This result was attributable to the findings that: when providers did more of one thing, they did not do less of another. There is a difference between doing more and doing better. The Camden CCG experience indicates, however, that when health care providers and community groups collaborate with the goal of increasing days spent at home, progress can be made.

Results of surveys indicate that:
1.     86% of patients want to be at home in their final days under ideal circumstances, but some prefer to be in a medical care facility for many reasons e.g. not having a supportive family, not wanting to be a burden, and preferring hospitals, for such reasons as perceived better pain relief and care.
2.     Patients do want to be placed on a respirator to gain an extra week of life.
3.     Patients are not opposed to drugs that relieve symptoms but ultimately may shorten their lives.


SPECIAL ARTICLE

Public-Access Defibrillation and Out-of-Hospital Cardiac Arrest in Japan


In Japan, the use of public-access defibrillation for patients with out-of-hospital cardiac arrest increased substantially from 2005 to 2013. The rate of 1-month survival with favorable neurologic outcome was significantly higher with than without public-access defibrillation.

Between 2005 and 2013, there were 43,762 documented bystander witnessed cardiac arrests in Japan. 4499 (10.3%) were treated with public-access defibrillators.  Usage of defibrillators increased from 1.1% in 2005 to 16.5% in 2013 due to increasing public access. The primary outcome assessed was survival at one month with favourable neurological outcomes. This was 38.5% for patients treated with public-access defibrillators compared with 18.2% for those not treated with early defibrillation (adjusted odds ratio of 1.80). The number of neurologically functional survivors increased from 6 in 2005 to 201 in 2015 (P< 0.001).



New Pharmacological Therapies


ORIGINAL ARTICLE

Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis


In a randomized trial, over 500 patients with sepsis received levosimendan or placebo in addition to usual care. Levosimendan did not result in a lower likelihood of organ dysfunction or lower mortality.

Levosimendan, a calcium-sensitizing drug with inotropic and vasodilatory properties, was added to usual standard of care for adults with sepsis. The aim was to determine if addition of the drug reduced the frequency of severe organ dysfunction and mortality rate. The results indicated that levosimendan did not reduce the risk of severe organ dysfunction or the mortality rate but did lead to a higher risk of supraventricular tachycardia and a lower likelihood of successful weaning from the respirator. A brief summary of the physiological effects of sepsis is contained within the Introduction.



Other articles which may be of interest to certain students


None.