Primecuts – This Week In The Journals

July 21, 2015

primecuts 7.20.15By Robin Guo, MD

Peer Reviewed

This week was marked by ground-breaking milestones in the fields of science and engineering, such as the awe-inspiring images of Pluto beamed from several billion miles away and the bioengineering of an organoid human brain to study autism (1, 2). As we sit behind our screens and reminisce about the days when Pluto was still a planet, let us take a look at several news-worthy discoveries from the medical world.

A New Risk-Stratification Index for Pneumonia Patients on Appropriate Antibiotics

Starting off this PrimeCuts is a study that introduces a new method for risk-stratifying pneumonia. In this prospective observational study, 579 hospitalized patients with known pneumonia pathogens who received appropriate antibiotic therapy were followed out to 30 days. The authors found several historical or laboratory variables that were associated with increased mortality, including low albumin (< 3 g/dL), non-ambulatory status, pH less than 7.35, RR greater than 30 breaths per minute, and BUN > 20 mg/dL (3). Using these variables in a predictive model, they were able to show that patients with zero or 1 of these factors had a 1% risk of mortality, whereas those with two or more risk factors were at a significantly increased risk of death (17% for two, 22% for three, 44% for four or five risk factors). This study was a derivation study, therefore, validation studies are needed to confirm the efficacy of this method before we can integrate these rules into our clinical practice. Additionally, the study population was limited to patients with identifiable bacterial pathogens, thus its applicability to all-comers with pneumonia is still unclear. Despite these limitations, keep an eye out for this predictive rule; it could be an incredible tool to help us better triage patients admitted with pneumonia. 

Using Coronary Artery Calcification Tests to Predict 15-year Mortality in Asymptomatic Patients

Calcification of the coronary artery has been known to correlate with coronary artery atherosclerosis, plaque burden, and myocardial infarction (4, 5); however, most studies to date have been limited by their duration of follow-up (mean follow-up of less than 10 years) (6). A recent article from the Annals of Internal Medicine investigated the value of Coronary Artery Calcification (CAC) scoring in predicting long-term mortality for patients without a cardiac history and without symptoms of coronary artery disease. This large, single-center, observational cohort study followed 9715 patients who underwent CAC tests for an average of 14.6 years (7). The authors showed that patients with CAC Scores were independently predictive of 15-year mortality; scores of 0, 1 to 10, 11 to 100, 101 to 399, 400 to 999, and 1000 were associated with overall mortalities of 3%, 6%, 9%, 14%, 21%, and 28%, respectively (P < 0.001). In addition, by adding these CAC scores to current risk calculators, the authors were able to correctly pick up 27.9% more cases of high-risk patients compared to traditional models. The study was lacking, however, in its single-center design and limited demographic diversity (86% white, 8% African American, 4% Hispanic, 2% Asian). In addition, the study was lacking in measures of outcome other than all-cause mortality, including rate of cardiovascular events. Although this study will likely not cause dramatic shifts in the way we screen for heart disease, it nevertheless helps us better understand the long-term predictive value of CAC and its use in CAD screening. 

A New PD-1 Antibody Holds Promise in Patients with Advanced Melanoma

There is also exciting news in cancer treatment. For a long time now, scientists have known that cancer cells evolve different ways to promote their proliferation and disease (8). One way it does this is by overproducing surface molecules that inhibit T-cell-mediated tumor surveillance, known as immune checkpoint molecules (9). In normal cells, these proteins function as roadblocks to prevent inappropriate cell killing and regulate autoimmunity. A new Phase III study published in the New England Journal of Medicine looked at two biologics that inhibited this pathway: a newer drug called pembrolizumab, which targets an immune checkpoint protein called PD-1, and ipilimumab, which targets another checkpoint protein called CTLA-4 (10). In their trial of 834 advanced melanoma patients across 16 countries, the authors compared two regimens of pembrolizumab (once every 2 weeks or once every three weeks) to the control, Ipilimumab. They found that every two weeks or three weeks pembrolizumab significantly prolonged 6-month progression-free survival when compared to Ipilimumab (47.3% or 46.4% vs 26.5%; 95% CI 0.46 to 0.72, P < 0.001 respectively). Data from the second interim analysis showed that the estimated 12-month survival was 74.1% for every 2 weeks pembrolizumab (95% CI 0.47 to 0.83, P < 0.0005), 68.5% for every 3 weeks pembrolizumab (95% CI 0.52 to 0.90; P = 0.0036), compared to 58.2% for ipilimumab and met a pre-determined cut-off for clinical significance. The trial was stopped early to allow patients to have the option of receiving pembrolizumab. Long-term survival data will likely still be needed before pembrolizumab becomes standard of practice, but it is holding promise as first-line treatment for PD-1 ligand positive advanced melanoma in the future.

Finally, take a gander at these other interesting articles in the medical literature…

Volume of Synovial Fluid can be used as a Treatment Target in Patients with Osteoarthritis

A new study from the British Medical Journal found that changes in Synovial Tissue Volume (STV) as measured on MRI were correlated with the level of pain in patients experience with osteoarthritis (11). Further studies with larger patient populations will be needed to better determine the significance of STV, but these findings may help us better differentiate between treatment-responsive and treatment-refractory osteoarthritis in the future. 

Very Early Mobilization for Stroke Patients is Not Better than Standard Therapy

In a recently published large randomized controlled trial, very early mobilization (within 24 hours of stroke) fared worse on the modified Rankin Scale (a measure for degree of disability) when compared to usual care (OR 0.73; 95% CI 0.59-0.90; p = 0.004) (12). The authors noted an insignificant increased risk of harm in patients with intracerebral hemorrhage when mobilized very early (the study was not powered to look at this difference). Further studies will be needed to clarify the underlying pathophysiology.

Cost-effectiveness of 10-Year Risk Thresholds for Initiation of Statin Therapy for Primary Prevention of Cardiovascular Disease

JAMA published a cost-effectiveness study of 10-year ASCVD Risk thresholds and found the current threshold of greater than 7.5% to have an acceptable cost-effectiveness profile ($37,000/QALY), however optimal cost-effectiveness was achieved at even more lenient thresholds of greater than 4% or 3% ($100,000 and $150,000/QALY) respectively.(13) 

Dr. Robin Guo is a 2nd year resident at NYU Langone Medical Center

Peer reviewed by Kerrilynn Carney, MD, 3rd year resident, NYU Internal Medicine Residency Program, NYU Langone Medical Center

Image courtesy of NASA/JHU APL/SwRI


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