🎉  Happy 2018! We're so excited to begin another year with you 

Jan 5, 2018

Engine on

The story

You know from every time you tell a patient "I'll be back later" that it's one thing to promise and another to deliver. We've got the latest on attempts to bring CAR T cell therapy to the masses.

The cells

Like the intern who seems designed-from-birth to shred through her to-do list, chimeric antigen receptor (CAR) T cells are laboratory engineered to find and attack cancer. The patient's own T cells are collected via leukapheresis and genetically modified to go ape-sh*t on B cell malignancies, then re-infused into the patient and set loose. But while CAR Ts have shown tremendous promise in refractory lymphoma, many have questioned whether a patient-tailored gene therapy can be manufactured by big pharma for use outside of ultra-specialized treatment centers.

The study

ZUMA-1 evaluated the use of anti-CD19 CAR T-cell therapy in 100 patients with refractory large B-cell lymphoma, where median survival is 6 months. A central manufacturing facility was used to supply treatments to 22 centers. Overall survival at 18 months was 52% in the phase II study, including 40% of patients who had a persistent complete response. Median collection-to-infusion time, of critical importance for patients with rapidly progressing disease, was 17 days. Over 90% of patients had the dreaded cytokine release syndrome, but only 13% had severe symptoms.

The takeaway

ZUMA-1 is a blueprint for the use of commercial CAR Ts in large B-cell lymphoma. The treatment is already FDA-approved and will be marketed under the brand name Yescarta.

Say it on rounds

When you want to challenge your attending but fear repercussion 

Does risk outweigh reward? An analysis of the oft-cited SPRINT trial found that adding a new antihypertensive drug class to a patient's existing regimen led to an average systolic blood pressure decrease of 14 mmHg without any increase in major adverse events. Measuring the effect of additional anti-hypertensives is typically prone to bias because sicker patients receive more meds, but the authors escaped this trap by performing an instrumental variable analysis on the different blood pressure target groups in SPRINT.

When your old iPhone still gets the job done

New is overrated (and upgrading takes cash). Even though recent models are designed to be compliant, every resident has to deal with MRI restrictions for patients with old pacemakers or ICDs. A prospective trial of 1,500 patients with legacy devices found no long-term adverse events or significant device failures after 2,100 MRI exams. All pacemakers had to undergo temporary programming changes prior to imaging, so make sure to call cardiology if you plan on sending these patients to MRI. 

When you'll graduate before three AFBs are collected

Try a dipstick. Researchers have pioneered a urine test that allows for fast, cheap, and accurate diagnosis of active pulmonary tuberculosis (TB). The test detects a cell wall compound called lipoarabinomannan that is secreted into the blood and ultimately the urine during active TB. In 48 HIV-negative, Peruvian patients with confirmed disease, the urine test had a sensitivity > 95% and specificity > 80%. With tinkering, the researchers hope to develop a rapid test similar to urine beta-hCG in pregnancy.
Sci Transl Med

Brush up


Suspect acute pyelonephritis in patients with flank pain and white cells or bacteria in the urine. Patients may or may not have fever, and illness severity can vary widely. Admit patients with sepsis, immunocompromise, or tenuous psychosocial situations for fluid resuscitation and empiric antibiotics (see this algorithm for more). A positive urine culture is the gold standard for confirmation.

What's the evidence

For imaging in pyelonephritis? Think about imaging when you're worried about kidney stones or abscess. A prospective 2010 trial of 350 patients with febrile urinary tract infections found that renal injury (GFR < 40 mL / min), urine pH > 7.0, or a history of urolithiasis predicted need for imaging with a positive predictive value of 24% and a negative predictive value of 93%. Patients without these findings were unlikely to have urgent urologic disorders.

What your East Coast friends are talking about

We're not meteorologists and we're guessing neither are you. But for the scientifically-inclined, here are the nuts and bolts behind the bomb cyclone that closed your clinics and gave your non-medicine friends a snow day.

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