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Aug 11, 2017

Hide and seek

The story

Your blood is mostly notable for high caffeine levels and the remnants of every respiratory virus in the hospital. But somewhere in there lies floating DNA fragments. Can they be used to find cancer?

A promising tool

Just like you can imagine a future where you spend more time seeing patients than writing progress notes, scientists see a future where cancer can be screened in the peripheral blood well before tumors advance to late stages. The current promise lies in cell free DNA (cfDNA): circulating DNA fragments that have escaped cells and travel in the bloodstream. Our tech is getting better at finding tumor DNA in the midst of normal cfDNA, but scientists still don't always know what they're looking for or which signs of early cancer are dangerous. 

A conspicuous virus

Though admittedly better known for causing mono during your college finals, the Epstein Barr virus is a perfect candidate for cfDNA screening. Not only is it closely linked to nasopharyngeal cancer in East Asia, it replicates so quickly in cancer cells that it's a lot easier to see in the bloodstream than typical tumor material. Each cancer cell carries about 50 copies of the viral genome, and the amplification target – the equivalent of the virus's fingerprint in the eyes of gene-sequencing machines – is repeated up to 10 times in each genome.

A proof-of-concept

With EBV a seemingly perfect fit to test the power of cfDNA as a screening procedure, researchers evaluated 20,000 people in Hong Kong for detectable EBV DNA. Patients who screened positive underwent confirmatory testing with another round of cfDNA analysis followed by imaging and nasal endoscopy. The total screening procedure found cancers at earlier stages than historical controls and boasted a sensitivity and specificity greater than 97%. This animated video has more.
NEJM 

The takeaway

This study is a landmark validation for cfDNA screening. And while the EBV virus makes nasopharyngeal cancer an easier target than other tumors, expect to see a lot more cfDNA in oncology clinic soon.

Say it on rounds

When your patient's CIWA score jumps to 15

You can treat those kinds of shakes, but Parkinson's disease is a different story. Current drugs do little to slow or stop disease progression. A 60-patient single-center RCT found that weekly exenatide injection led to significant improvements in motor function scores after 48 weeks compared to placebo. You may recognize exenatide as a GLP-1 agonist used in diabetes, though researchers think the medication's efficacy in Parkinson's is related to anti-oxidant properties rather than glycemic control. Look for further testing of this promising concept.
Lancet

When you can't commit to plans because you never know when you'll leave work

You want something in your life to feel predictable. A prospective study of over 13,000 patients with stable coronary disease found that the biomarkers NT-proBNP and high-sensitivity troponin predicted cardiovascular death better than any of the study's other clinical variables or biomarkers over a median of 4-year follow-up. When combined with age, LDL cholesterol, and clinical variables including smoking, diabetes, and peripheral arterial disease, the complete model, named 'ABC-CHD', was able to predict CV death in 80% of patients in both a derivation and validation cohort.
JACC

When your Instagram post gets fewer likes than expected

Don’t be sad! Or at least try not to be sad in a way that’s obvious to a computer. Researchers applied machine learning tools to 44,000 Instagram posts from 170 people, about half of whom had a history of clinical depression. The resulting computer algorithm was able to predict depression better than the average general practitioner. Depressed participants posted more often and their posts drew more comments, while non-depressed participants drew more likes. And if you prefer to hear the info in filter terms, people suffering from depression used Inkwell, while happier folks used Valencia. 
EPJ Data Sci

Brush up

Acute respiratory distress syndrome (ARDS)

Despite a continuous presence in your ICU, ARDS remains clinically under-recognized. Look for bilateral opacities on X-ray that occur within 7 days of a clinical insult. Much of the damage is thought to be driven by immune cell attack on alveoli that causes fluid to accumulate in the lungs. This impairs oxygenation and places patients at risk for barotrauma during mechanical ventilation. Despite advances in ICU care and lung-protective ventilation, mortality in severe ARDS remains high at up to 46% of patients. 

What's the evidence

For lung-protective ventilation in ARDS? The landmark ARDSNet trial of 2000 found that a low tidal volume strategy (6cc / kg of ideal body weight with plateau pressures < 30 cm H2O) led to better ARDS outcomes. But recent data suggests that the driving pressure, the difference between plateau and positive end-expiratory pressure (PEEP), may be equally or more important. A 2017 prospective cohort study of 2,400 patients found that lower peak, plateau, and driving pressures were more closely associated with improved survival than tidal volume.

What your tech friends are talking about

After a media firestorm surrounding an anti-diversity memo from a now-fired Google computer engineer, take a look at Adam Grant's evaluation of the biology and social science behind gender differences in the math and sciences.

Spread the word

A big shout out to our new writing crew for a smooth transition to start the academic year

  

We're off for summer break next week and will return on August 25th

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