Chiefs’ Inquiry Corner – March 11th, 2019

March 11, 2019

Being an outstanding physician and lifelong learner requires stoking the flames of clinical curiosity.  In Chiefs’ Inquiry Corner (CIC) we attempt to succinctly answer actual clinical questions that have been raised on the wards and in the clinics of NYU’s teaching hospitals.  Our answers are not meant to be all encompassing or practice changing but rather to serve as springboards for further exploration.  For those of us with short attention spans, we hope CIC satisfies that craving for a morsel of knowledge in a digestible format.


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Anti-NMDA receptor encephalitis is a relatively recently-described syndrome, first reported in four young women with ovarian teratomas in 2005. The syndrome is characterized by autoantibodies to the N-methyl D-aspartate receptor. Patients often present with prodromal headaches, fever, and URI symptoms, followed by psychiatric symptoms such as anxiety, agitation, decreased levels of consciousness, bizarre behavior, disorganized thinking, and memory deficits. Symptoms often degenerate to reduction of verbal output, seizures, and autonomic instability. Approximately 80% of patients with NMDA-R encephalitis are women, often younger than 45 years of age, and 50-60% of these women will have an ovarian teratoma expressing neurologic tissue. Men are less often affected by NMDA-R encephalitis, and less often have an associated tumor. Approximately 75% of patients will have substantial regression of symptoms with initiation of treatment, which includes steroids, IVIG, plasmapharesis, and removal of the associated tumor. However, 25% of patients will have severe neurological impairment or die as a result of the disease. Factors that predict improved outcome include early treatment with appropriate immunotherapy, ovarian teratoma detection, and lower severity of symptoms.

References: Anti NMDA Receptor Encephalitis  
While all obese patients should be encouraged to make lifestyle changes in order to lose weight, these measures often fail to achieve sustained, clinically meaningful weight loss. Endocrine Society guidelines recommend adding pharmacotherapy to lifestyle changes in patients with a BMI ≥27 with one or more obesity-related comorbidities or a BMI >30 with or without such comorbidities, and a history of failure to achieve clinically meaningful and sustained weight loss (which is defined as >5% of total bodyweight). Five medications have been approved in the US for chronic weight management:  Phentermine, Orlistat, Lorcaserin, Naltrexone/Buproprion, and Liraglutide.  These drugs have all been shown to achieve at least 5% mean weight loss in placebo-controlled clinical trials.  Choosing between these medications should take into account a patient’s comorbidities, and the expected side effect profile.  If 3-5% weight loss is not achieved in 3-4 months, a new weight loss plan should be considered.  It is also important to avoid medications for other chronic conditions that promote weight gain, as many obese patients have comorbid metabolic conditions that can be treated with medications that lead to weight gain.

References: Pharmacotherapy for Weight Loss  
A transjugular intrahepatic portosystemic shunt (TIPS) is a percutaneous procedure meant to decompress the portal system that is used commonly patients with portal hypertension secondary to cirrhosis. Placement of a TIPS results in increased flow through the systemic venous system, and thus increased venous return to the right heart. In patients with a pre-existing cardiomyopathy or known pulmonary hypertension, this additional volume challenge can lead to pulmonary edema and worsen pulmonary pressures. Consistent with this, known heart failure, severe tricuspid regurgitation, and severe pulmonary hypertension are all absolute contraindications to TIPS. However, in patients without such cardiac history, screening prior to TIPS is controversial. The prevalence of pulmonary hypertension in the population of advanced cirrhotics is fairly high (estimated as high as 16%), leading some to pursue routine cardiac testing including echocardiogram prior to TIPS in patients regardless of cardiac history. However, the American Association for the Study of Liver Disease (AASLD) guidelines do not support routine echocardiograms, right heart catheterization, or fluid challenge as a means of pre-procedure screening

References: AASLD TIPS Guidelines  
N-acetylcysteine (NAC) is a reducing agent with a primary role in the treatment of acetaminophen-induced hepatotoxicity. Whether NAC is beneficial in patients with alcoholic hepatitis is less well understood. A 2011 placebo controlled trial of patients with severe alcoholic hepatitis randomized 180 participants to a standard 28-day course of prednisolone plus a 5-day protocol of NAC, or prednisolone plus 5 day protocol of placebo. Patients treated with both prednisolone plus NAC did not demonstrate significantly lower mortality rates at 6 months post treatment compared to patients treated with prednisolone and placebo (27% vs 38%, p=0.07), the study’s primary endpoint. However, co-treated patients did exhibit significantly lower mortality rates at 1 month post treatment (8% vs 24%, p<0.006). Such data suggest a possible role for NAC in the treatment of severe alcoholic hepatitis, though it remains to be seen whether this benefit is indeed durable.

References: NAC for severe alcoholic hepatitis  
Hypercalcemia is a common complication of malignancy, occurring in up to 30% of patients during the course of illness, most commonly during the metastatic phase of disease. There are several well-described pathophysiologic mechanisms to explain cancer-related hypercalcemia; the most common etiologies being 1) direct osteolysis as a result of bony invasion of metastatic disease, and 2) a paraneoplastic process driven by parathyroid hormone-related peptide (PTHrP), a correlate of parathyroid hormone commonly secreted by solid tumors. While the prognosis in patients with hypercalcemia secondary to malignancy is presumed to be poor, the impact of treating hypercalcemia in this population has remained unclear. A recent retrospective Australian cohort study reviewed records of 63 patients with hypercalcemia of malignancy admitted to a palliative unit that were treated with intravenous bisphosphonates. Patients were excluded if they had received cancer-directed therapy within 4 weeks of their presentation. Thirty-six patients were found to have a reduction in serum calcium concentration with IV bisphosphonate therapy. Patients without a prior history of hypercalcemia were more likely to achieve normocalcemia than those who had previously been found to have elevations in their serum calcium. Intravenous bisphosphonate therapy was associated with improvement in patient symptoms, irrespective of serum calcium concentration, and moreover, reduction in serum calcium concentration was associated with a significant improvement in mortality (p = 0.0016). While this study has a number of limitations, including its small sample size and retrospective design, it suggests a role for the use of IV bisphosphonate therapy for symptom improvement, as well as a potential impact on survival – albeit small – in this terminal population.   

References: Treatment of malignancy-associated hypercalcemia