Jul 12, 2019

Tone down

The story

There's no zap button to stop rounds from spiraling out of control, but in the right circumstances T cells can be coaxed to chill. Here's how teplizumab is reinventing prevention in Type 1 Diabetes (T1D). 

The background

Modern medicine is all about immune modulation, and T1D is a natural target. Evidence for autoimmunity – in this case T cells attacking beta cells of the pancreas – can be present for years before insulin levels drop. The presence of autoantibodies defines stage 1 disease, while dysglycemia, or an impaired response to glucose loads, marks stage 2. Both stages are asymptomatic and offer a chance to stave off disease progression. 

The study

Anti-CD3 antibody teplizumab exhausts active CD8+ T cells without compromising critical immune function. A phase 2 study of 76 participants with stage 2 T1D found that one-time treatment with teplizumab doubled the median time-to-diagnosis of overt diabetes (48 months with teplizumab vs. 24 months with placebo) without major adverse events. At the conclusion of the study, which had median follow-up of over 2 years, 57% of patients in the treatment group were free of diabetes vs. 28% of patients who received placebo. Treatment was given over 2 weeks in the outpatient setting.

The takeaway

With the morbidity and complexity of care tied to T1D, a one-time treatment to delay or prevent symptomatic disease would be game-changing. Further studies, including who benefits most and how to screen for at-risk patients, are up next.

Say it on rounds

When you confuse Juul pens with USB drives

Yep, you're getting older. With long-term outcomes for e-cigarette users largely unknown, a cross-sectional analysis of Population Assessment of Tobacco and Health data found that every-day and some-day vaping was associated with approximately 2x the risk of myocardial infarction (MI) compared to never smokers in logistic regression analysis. Daily use of e-cigs together with combustible cigs was associated with almost 7x excess risk. Prior MI was not associated with e-cigarette use, abating concerns around reverse causality that arose in similar datasets.
J Am Heart Assoc

When you drop your pager on the reg

Psychosomatic? Cervical spine injury often impairs hand grasp and closure, functions that affected patients rate as more important to independence than walking. A proof-of-concept study of 16 patients with upper limb paralysis following traumatic C5-C7 injury explored use of nerve transfer from 'expendable' nerves – excess nerves from functional muscles – to restore grasp, pinch, elbow extension, and hand opening (see video). Participants saw significant improvements in a mix of primary outcomes measuring strength and independence.

When you think the splash on your scrubs is just water

It helps to be sure. While widened mediastinum on chest x-ray (CXR) is part of the med school ABCs, plain films are not sufficient to rule out aortic aneurysm. In a secondary analysis in which radiologists blindly evaluated CXRs from a previously completed study, CXR alone was about 54% sensitive for acute aortic syndromes (AAS). Sensitivity and specificity improved when CXR was combined with a clinical probability assessment tool, but not enough to rule out AAS. The same authors have previously shown that D-dimer can help stratify patients for advanced imaging.
Acad Emerg Med

Brush up

Nonnarcotic pain management

Addiction crises aside, patients develop tolerance to opioids and the meds tend to have minimal long-term impact on chronic pain. You'll navigate nonnarcotic pain management every day in clinic and on the wards. Remember that depression, anxiety, emotional distress, and lack of social support are tied to poor pain outcomes, and the data for psychological interventions like cognitive behavioral therapy (CBT), mindfulness, and stress management are getting stronger. For meds, here's a table of your non-opioid analgesic agent toolkit, along with indications and potential risks.

What's the evidence

For mindfulness-based interventions and CBT in chronic low back pain? A 2016 RCT of 340 patients found that both mindfulness-based stress reduction (MBSR), which includes training in meditation and yoga, and CBT improved disability scores and self-reported back pain compared to usual care at 6-month follow-up even though most patients attended less than half of the weekly classes in their program. No difference was seen between MBSR and CBT.

What your OB friends are talking about

The Cleveland Clinic reported North America's first live birth from a deceased donor uterus transplant. Worldwide, about a dozen women have used transplants to give birth after the procedure debuted in Brazil in December.

Podcast fun

A big thanks to The Curbsiders for having The Scope's @ArmandGottlieb on Hotcakes to talk shop on recent lit. Check it out here.

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