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Mar 8, 2019

Second go

The story

It took a near-death experience to spark the first cure of HIV 12 years ago. Now a second patient has achieved remission with a less toxic regimen.

One up

You can’t get into your car when you forget your keys, and HIV can’t enter T cells if it can't bind to its favored coreceptors. A tiny slice of the population has innate resistance to HIV infection due to the delta 32 mutation in CCR5. In 2007, the 'Berlin' patient Timothy Ray Brown received a stem cell transplant for acute myeloid leukemia from a homozygous delta 32 donor. After grueling therapies and life-threatening complications – total body irradiation, sepsis, a second transplant for AML relapse – he emerged cured of HIV. Attempts to achieve remission in similar patients have failed.

Two down

The 'London' patient is an adult man with HIV who had Hodgkin Lymphoma refractory to first-line chemotherapy and salvage regimens. He received a stem cell transplant from a homozygous delta 32 donor with a reduced intensity conditioning regimen (less toxic than regimens used for AML) per standard-of-care. His clinical course included mild graft versus host disease and viral reactivation of EBV and CMV, but on the whole was relatively uncomplicated. Fourteen months later, he remains in remission from HIV, and a panel of tests designed to check for latent viral activity remain negative.
Nature

The takeaway

A second cure shows that ultra-toxic measures aren't essential to success. The results have patients and scientists hopeful that gene editing could play a key role in future therapies.

Say it on rounds

When the call room's darker than your apartment

It's still hard to get restful sleep. New results from iCOMPARE, the program director (PD)-led evaluation of flexible (27-hour call eligible) vs. standard (max of 16 hours / shift) intern duty hours in 63 internal medicine programs, found that average nightly sleep in flexible programs was non-inferior to standard programs over a 14-day period (6.85 hrs v.s 7 hrs). Red flags: intern alertness in the flexible programs arm failed to meet non-inferiority criteria, and flexible program interns were less alert and more fatigued on 27-hour shifts. Like prior iCOMPARE results, we wonder what would've happened if interns designed the trial rather than PDs.
NEJM

When the EMR crashes in the middle of your note

Don't give up on technology. Directly observed treatment (DOT) is crucial for preventing drug resistance and poor outcomes in tuberculosis (TB) patients at high risk for poor adherence, but the required daily clinic visits are a pain. A RCT of 226 high-risk TB patients found that video-observed therapy (VOT) via a study-provided smartphone produced higher rates of 2-month compliance (70% vs. 31%) than DOT. VOT was also less expensive.
Lancet

When everyone's coughing but you feel fine

Why only a minority of people who are genetically susceptible to celiac disease develop gluten intolerance remains unclear. A Norwegian case-control study of 220 at-risk children found that those with early exposure to enterovirus were 50% more likely to develop celiac disease than the non-exposed. High viral burdens and long duration of infection were associated with increased risk. Infection with adenovirus, another common intestinal virus, was not associated with celiac disease.
BMJ

Brush up

Adult epilepsy

See it to believe it with adult epilepsy: a reliable eyewitness account combined with an appropriate clinical history is essential to diagnosis. The disorder has a bimodal age distribution in which infants less than 1 and adults > 50 are at greatest risk. Over 50% of affected adults have a significant comorbidity, from psychiatric disorders to manifestations of the metabolic syndrome. Antiseizure meds are used with the aim of stopping seizures at the earliest possible opportunity without causing side effects.

What's the evidence

For long-term remission of epilepsy? A 2016 analysis of 650 patients with unprovoked epileptic seizures in high-income countries found that 80% of patients who completed 25-year follow-up were in remission. In low-income countries, many patients will enter remission without antiseizure medications. Unfortunately, premature mortality for both patients with epilepsy and a single unprovoked seizure was higher than for the general population.  

What your culinary friends are talking about

When is sea bass actually sea bass? Less than half the time. Analysis of fish DNA found that 20% of fish are mislabeled, including a whopping 74% of fish at sushi venues.

Spread the word

Send your interns something to look forward to

  

We're off next week and will return on March 22nd.

Best of luck to all of the med students participating in the Match! Interns everywhere can't wait to meet you. 

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