Nov 10, 2017

Just breathe

The story

Despite what you see in the resident lounge, synergistic therapy isn't always Diet Coke and Red Bull. Take a look at new combo therapies for cystic fibrosis.

The problem

More than 80,000 people worldwide have cystic fibrosis (CF), where decreased mucus clearance leaves patients prone to infection and progressive organ damage. At blame is the CFTR protein, which either doesn't do it's job (escorting chlorine ions out of the cell) or doesn't find its way to the cell membrane. Two new classes of CF modulator therapies target both of these problems, and while they've shown promising early results when used in combination, use has been limited by toxic side effects.

The parts

CF combo therapies mix a potentiator, which increases chlorine outflow from CFTR, with a corrector that helps send CFTR to the cell surface. Ivacaftor, the potentiator, has modest effects when used as monotherapy. The corrector lumacaftor helps, but causes respiratory side effects and prohibitive drug-drug interactions.

The study

Enter tezacaftor, a new corrector with a more tolerable safety profile. Tezacaftor-ivacaftor improved lung function with fewer toxic effects than previous combination therapies in an RCT of 500 patients homozygous for the most common CF mutation (Phe508del). After 24 weeks, patients on tezacaftor-ivacaftor saw improvements in FEV1 compared to placebo, and the annual rate of pulmonary exacerbation was 35% lower in the treatment group. 

The takeaway

Tezacaftor-ivacaftor can slow functional decline and keep CF patients out of the hospital. We're hopeful more is on the way for this notoriously difficult-to-treat disease.

Say it on rounds

When daylight savings has you off your game

It's not just in your head. A cohort study that examined morning vs. afternoon aortic valve surgery in 600 patients found that major cardiac events were half as common in the afternoon group. The authors linked their findings to changes in circadian gene expression that make the heart less vulnerable to ischemia-reperfusion injury in the afternoon. A smaller, randomized group of 90 patients had lower markers of cardiac injury during afternoon surgery.

When you wonder how everyone finds out about Dilaudid and Benadryl

You spend plenty of time convincing your patients to try non-opiate pain meds. Here's some data to back you up: an RCT of 400 ED patients with acute arm or leg pain found no difference in self-reported pain scores 2 hours after treatment with Tylenol and ibuprofen compared to Tylenol and oxycodone, hydrocodone, or codeine. In the midst of a nationwide opioid epidemic very much related to excess prescriptions, limiting opioid exposure in the ED can only help.

When the patient asks 'is this your first time doing this?'

Some questions are hard to answer. Consider alcohol and cancer risk: the American Society of Clinical Oncology released a sweeping statement about alcohol use in cancers, but how much is too much? Compared with nondrinkers, heavy drinkers (> 8 drinks per week in women, > 15 in men) were at higher risk for cancers of the head and neck, breast, liver, colon and esophagus. For most of these cancers, risk increases with amount consumed in a roughly linear fashion. And for light drinkers? The authors estimate that one drink per day is associated with a 5 - 10% increase in breast cancer risk.
J Clin Oncol

Brush up

Mesenteric ischemia

Though rare, mesenteric ischemia can be fatal. Look for the classic 'pain out of proportion to exam' in patients with comorbid vascular diseases. A tender abdomen and elevated lactate can signal full-thickness bowel injury and impending circulatory collapse. Use CT angiogram to confirm the diagnosis. Your first call should be to arrange for surgical repair. While you're waiting for the OR, start IV fluids and give systemic anticoagulation and antibiotics.

What's the evidence

For endovascular vs. open intervention in acute mesenteric ischemia? Endovascular repair provides faster access for clot removal, but open repair allows surgeons to resect necrotic bowel. A 2011 trial of 70 patients found that in-hospital mortality was lower among patients who received endovascular intervention vs. open surgery, though many consider the trial size too small to draw firm conclusions.

What your dermatology friends are talking about

If you're looking for inspiration, read about how researchers used gene therapy to regenerate an entire body's worth of skin in a critically-ill 7-year-old. But if you just want to see human skin growing in a glass dish, well, there's this

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