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Oct 14, 2016

Toward progress

The story

If residency moved as quickly as the pace of cancer breakthroughs, you'd already be done. And then someone else would have a borderline-intimate relationship with the barista at the hospital's 24-hour coffee shop. We've got you covered with the biggest breakthroughs from this week's European Society of Medical Oncology meeting, starting from head to toe.

Speak up

We found out in April that anti-PD1 immunotherapy behemoth nivolumab ("nivo", generic name Opdivo) improves overall survival (OS) in recurrent head and neck cancer. The final results from the 360 patient Checkmate-141 trial, published this week, show that nivo also allows patients to maintain throat functional status during therapy. So while many head and neck cancer patients suffer from an impaired ability to eat, speak or swallow due to disease progression or harsh chemotherapy, quality of life was stable on nivo.
NEJM

Breathe deep

Anti-PD1 drugs have revolutionized the care of relapsed and treatment refractory advanced non-small cell lung cancer (NSCLC). In the first-line setting, pembrolizumab (Keytruda), the Coke to nivo's Pepsi, improved OS and was better tolerated than chemotherapy in patients with NSCLC whose tumors expressed high levels of the protein PD1. Pembrolizumab should quickly become the standard of care first-line treatment for these patients, which represent about 25% of advanced NSCLC diagnoses. 
NEJM

Stay abreast

Ribociclib and similar drug palbociclib block CDK4, a cell regulatory protein that is frequently overexpressed in breast cancer. A 670 patient trial of women with advanced hormone receptor-positive breast cancer found that the addition of ribociclib to the endocrine therapy letrozole improved progression-free survival (PFS) by 20% vs. letrozole alone at 18 months. The study was the largest to date of CDK inhibitors in breast cancer, and helps confirm the treatment benefit of this class of meds. 
NEJM

Over-reach

Like your pager, ovarian cancer is notoriously hard to break, even with your best shot. Enter nariparib, a small molecule PARP inhibitor that poisons cancer cells by impairing their ability to repair DNA. Patients with platinum-sensitive recurrent ovarian cancer who received nariparib saw PFS more than double relative to placebo in what some investigators have called the biggest medical breakthrough in the history of ovarian cancer. Up to 70% of ovarian cancer patients could be eligible for treatment.
NEJM

Say it on rounds

When you used to have hobbies, and now you have moonlighting

Be wary of too much of a good thing. Take supplemental oxygen in the ICU: a large single-center study found that patients had lower ICU-mortality with a conservative oxygen strategy (PaO2 target of 70 to 100 mm Hg) vs. a conventional oxygen strategy (PaO2 target of up to 150 mm Hg). The conservative group also had a lower incidence of shock, liver failure, and bloodstream infections. Researchers think that too much oxygen forms free radicals that can damage organs like the lungs, but multicenter trials are needed to confirm.
JAMA

When you lose your stethoscope during a rapid response

Things are tough to find in an emergency, so an evidence-guided approach can help. A retrospective study found that CT angiogram (CTA) localized the site of acute lower GI bleeds in a greater proportion of patients than red blood cell scintigraphy (tagged RBC scan), even though scintigraphy was used more frequently. CTA also took less time to complete. Clinical outcomes were similar in both groups. 
Am J Roentgenol

Brush up

Diabetic ketoacidosis (DKA)

It may still be dinner without bread and butter, but it’s definitely not medicine residency without DKA. Insulin deficiency leads to blood sugar elevation, fatty acid breakdown, ketone production, and life-threatening acidosis. Look for blood glucose > 250 mg / dL, pH < 7.3, bicarbonate < 18 mEq / L, and the presence of serum or urine ketones for diagnosis. Treat with IV fluids, insulin, electrolyte replacement, and correction of any underlying trigger (commonly infection).

What's the evidence

For bicarbonate administration in DKA?  While the buildup of ketoacids may tempt you to reach for a buffer, DKA is more complicated than your freshman chemistry lab. A systematic review found only transient improvements in pH after bicarbonate infusion, without an improvement in glucose control or duration of hospitalization. Bicarbonate may also paradoxically worsen ketosis and delay its resolution by up to six hours.

What your nutrition friends are talking about

You love cheese, cheese loves you, and it's possible that regular fat cheese does not raise your LDL cholesterol. It may even give your HDL cholesterol a boost.

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