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Aug 26, 2016

A new dotted line

The story

Part of the reason you went into medicine was to justify your bad handwriting. But these days 'signature' refers more and more to gene expression patterns, not the beautiful mess you scratch all over home health aide forms.

For kids

Cultures from febrile children can take days to identify bacterial pathogens. Enter RNA expression signatures: a two transcript RNA biosignature developed from microarray samples collected from infected children was able to differentiate bacterial infection from viral infection with a sensitivity of 100% and specificity of 96% in a validation set of about 150 patients. Further prospective studies are needed, but the technology is promising as a real-time clinical assay to determine if sick children need antibiotics. 
JAMA

For adults

This week's MINDACT trial examined whether the presence of a low-risk 70-gene signature could spare chemotherapy in early-stage breast cancer patients with high-risk clinical disease. When chemotherapy was held in the subset of patients with a low-risk gene signature, they had a 5-year rate of metastasis-free survival that was 1.5% lower than the rate of similar patients who received chemo. The test could allow half of women with high-risk early stage breast cancer to decline chemotherapy, but the slightly higher risk of recurrence may leave some doctors and patients feeling uncomfortable.  
NEJM

The takeaway

It's a bright future for personalized medicine, and it's going to be filled with some sticky risk vs. benefit conversations. Patient attitudes and preferences will play a large role in therapy.

Say it on rounds

When your white coat is cut for someone twice your size

Residency is not fashion forward, but linking obesity to cancer is very much in vogue. A report from the International Agency for Research on Cancer links excess body weight to these 13-types of cancer. The agency looked primarily at observational studies, and found esophageal and endometrial carcinomas to have the strongest relationships with BMI. Experts say obesity has surpassed smoking as the number one modifiable risk factor in cancer.
NEJM

When you finally fix your phone screen, only to drop it again

Some things are beyond repair. Here's hoping otherwise in ischemic stroke, where a phase I 'first in man' study found that stem cell injections to ischemic regions of the brain were safe and well tolerated. Some patients saw improvements in disability scores and quality of life, and some saw MRI evidence of improved myelination. Up next: phase 2.
Lancet
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When your patients will do anything to stop taking their meds

The right imaging might boost their case. Statins are great at preventing heart attacks, but the number needed to treat is high in low-risk populations. Investigators used advanced imaging techniques to measure coronary artery calcium (CAC) and carotid plaque burden (cPB) to reclassify ASCVD risk status. They found that low CAC scores could save about 1 in 4 elderly patients from taking statins unnecessarily. 
JACC

Brush up

Pancreatic adenocarcinoma

The most lethal common cancer (mortality rate of > 90%) presents late and responds poorly to therapy. Alarm symptoms include abdominal pain, weight loss, fatigue and anorexia. Painless jaundice is present in tumors of the pancreatic head (over 60% of cases), and half of patients develop diabetes. Surgical resection is the best hope for cure. The Whipple procedure, or pancreaticoduodenectomy, is for pancreatic head and neck tumors, while distal pancreatectomy is performed for body or tail tumors.

What's the evidence

For combination chemotherapy in unresectable pancreatic adenocarcinoma? A 2011 RCT of 342 patients found that FOLFIRINOX therapy significantly improved median survival and quality of life compared to prior standard-of-care gemcitabine monotherapy. A 2013 RCT of 861 patients found that the addition of nab-paclitaxel to gemcitabine also increased overall survival compared to gemcitabine alone. FOLFIRINOX is the standard of care for 'fit' patients, while nab-pacltaxel/gemcitabine is thought to be more tolerable.

What your finance friends are talking about

Mylan Pharmaceuticals CEO Heather Bresch is feeling really frustrated these days. Prices for the company's Epi-Pen rose 400% in the last decade, while the boss's salary is up 600% in the same time period. The change amounts to about $16 million per year. 

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