Primecuts – This Week In The Journals

May 11, 2016

1280px-2006-12-09_Chipanzees_D_BruyereBy Tania Ruiz-Maya, MD

Peer Reviewed

This past week there was great news for all animal advocates and conservationists when the world’s largest chimpanzee research facility, Louisiana’s New Iberia Research Center (NIRC), announced that it will release all 220 of its chimps to a sanctuary in what it is calling the largest resettlement of chimpanzees from a U.S. research center [1]. The transfer to Project Chimps, a 95-hectare sanctuary in the mountains of northern Georgia, will be completed in the next 3 to 5 years. In sports news, Golden State Warriors guard Stephen Curry became the first unanimous NBA Most Valuable Player, winning the award for a second straight season. Curry joins Tom Brady (2010 NFL MVP) and Wayne Gretzky (1982 Hart Trophy winner) as the only unanimous MVP’s in their respective leagues [2]. The fire that has already prompted the evacuation of 88,000 people from the city of Fort McMurray was on its way to doubling in size after 1 week. This is expected to be the costliest natural disaster in Canada’s history [3]. And now on to updates in the medicine world.

Ventilator associated pneumonia can be identified earlier with lung ultrasound

Bedside ultrasound is emerging as a minimally invasive, low cost clinical tool that can help physicians make quick and accurate diagnoses. A new multicenter prospective study published in Chest assessed whether lung ultrasound (LUS) could improve the early diagnosis of ventilator-associated pneumonia. (VAP) [4]. The study enrolled patients with suspected VAP at 3 different ICUs in France, Italy and Canada. Suspicion of VAP was based on mechanical ventilation ≥ 48hrs, a new or evolving infiltrate on chest x-ray, and two or more clinical signs or symptoms of pneumonia (temperature ≥ 38.5C or < 36.5C  leukocytosis >/ml or leukopenia <4./ml, purulent tracheal secretions, PaO2/FiO2 < 300mmHg). Patients with ongoing pneumonia or contraindication for fiber-bronchoscopy were excluded.

LUS findings including subpleural consolidation, lobar consolidation and dynamic air bronchogram were aggregated into the ventilator-associated pneumonia lung ultrasound score (VPLUS). VAP diagnosis was confirmed by positive results on BAL (≥1 microorganism with a concentration ≥ 104 CFU/mL) or simultaneous presence of all clinical criteria with negative result on BAL if antibiotics had been modified/introduced in the previous 48 hours.

In this study, LUS was a reliable tool for early VAP diagnosis at the bedside, showing that subpleural consolidation and a dynamic arborescent/linear air bronchogram had a positive predictive value of 86% with a positive likelihood ratio of 2.8. Two dynamic linear/arborescent air bronchograms produced a positive predictive value of 94% with a positive likelihood ratio of 7.1. A VPLUS score ≥ 2 had 69% specificity and 71% sensitivity. Endotracheal aspirate (EA) data was also integrated with VPLUS to assess whether combining these tests could improve the diagnostic accuracy (VPLUS-EAgram). A VPLUS-EAgram score ≥ 3 had 77% specificity and 78% sensitivity. Both performed better than the clinical pulmonary infection score (CPIS), which integrates various signs and symptoms of pneumonia and has been used in the diagnosis of VAP.

From this study, it appears that if used consistently, LUS could be a relatively sensitive and specific, noninvasive method to improve early detection of VAP. However, LUS is operator dependent and LUS findings may be difficult to interpret in patients with differences in body habitus. Additionally, VAP is a difficult diagnosis to confirm. BAL and the clinical diagnostic criteria used in the study have their own limitations. Also, the study included patients with relatively high pre-test probability of pneumonia. Whether ultrasound can be used for patients in which suspicion for pneumonia is lower remains unclear. Lastly further studies will be needed to test whether early diagnosis with ultrasound has meaningful impact on clinical outcomes.

Prevention of late MI after coronary stenting in diabetic patients with double antiplatelet therapy 

Patients with diabetes mellitus (DM) who undergo coronary stenting have higher rates of death and myocardial infarction (MI) than patients without DM [5]. Therefore, whether continued dual antiplatelet therapy after 1 year can improve outcomes after coronary stenting in diabetics remains unclear. A new study published in Circulation looked at the effects of continued thienopyridine therapy among patients with DM participating in the Dual Antiplatelet Therapy (DAPT) Study using a prespecified analysis [6]. In this study, 11,648 patients with coronary stents who had received 12 months of thienopyridine plus aspirin were randomly assigned to continued thienopyridine or placebo for 18 more months. Aspirin was continued in both groups. As expected, diabetics were at increased risk of death, MI or stroke compared to non-diabetics.  When diabetics were continued on dual antiplatelet therapy for an additional 18 months there was a significantly decreased rate of stent thrombosis (0.5% vs. 1.1%, P=0.06) and MI (3.5% vs. 4.8%, P=0.058). The NNT to prevent stent thrombosis was 167 and it was 77 to prevent MI. Bleeding rates were not significantly higher between the 2 groups, although the study was not powered to detect this difference. From this study, it seems reasonable to continue diabetics on thienopyridine beyond 1 year after coronary stenting. One of the limitations of the study is that the subgroups of patients with and without DM were not powered for comparison between randomized treatment arms. Further studies are needed to identify the optimal duration of dual antiplatelet therapy after coronary stenting in patients with DM and its mortality benefit vs. risk of bleeding. 

Ablation versus Escalation of Antiarrhythmic Drugs for ventricular tachycardia 

Up to 15% of patients with ICDs are initially treated with a concomitant antiarrhythmic drug and up to 38% receive an appropriate shock for ventricular arrhythmia within 5 years [7]. The Ventricular Tachycardia Ablation versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease (VANISH) trial was a multicenter, randomized control trial that compared catheter ablation with escalated antiarrythmic drugs (AAD) therapy in patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia (VT) despite first line ADD therapy [7]. This study enrolled patients with an episode of VT during treatment with amiodarone or another class I or class III AAD within the previous 6 months.

Patients were randomly assigned to receive either catheter ablation with continuation of baseline AAD or escalated AAD therapy. During a mean (±SD) of 27.9±17.1 months of follow-up, ventricular arrhythmias occurred significantly less frequently in the ablation group (59.1% versus 68.5%). The NNT to prevent a ventricular arrhythmia was 11 for ablation instead of additional antiarrhythmics.

The rate of the composite outcome of death at any time or VT storm or appropriate ICD shock after 30 days was lower in patients who underwent ablation compared to patients that received escalated AAD therapy. There was no significant difference in mortality between the groups. Treatment associated adverse events were also more frequent in the escalated therapy group (51 vs 22 P=0.25) and occurred in more patients (39 vs 20 P=0.003).

Similar to previous ablation studies [8,9], this data suggests that catheter ablation should be preferred over escalation of AAD therapy for the reduction of recurrent VT in this population.

Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease (COPD) after withdrawal of inhaled corticosteroids

Can eosinophil counts predict COPD exacerbations after withdrawal of inhaled glucocorticoids? Post-hoc analysis of the WISDOM trial published this week shows that patients with higher blood eosinophil counts at screening were more likely to develop exacerbations after inhaled corticosteroids (ICS) treatment was withdrawn, suggesting an effect size related to eosinophil counts [10]. Patients were separated into parallel groups that received tiotropium, salmeterol and fluticasone daily for 6 weeks and were then randomly assigned to receive either continued or reduced ICS over 12 weeks. The rates of exacerbations after ICS withdrawal were compared in both groups as well as time to exacerbation outcomes on the basis of blood eosinophil subgroups.

This is the first analysis to investigate eosinophil subgroups in the presence of a long acting muscarinic antagonist (LAMA) plus a long acting beta2 agonist (LABA). This is of particular interest for clinicians since most patients with exacerbations are on these therapies in addition to ICS. The mechanism underlying the association between blood eosinophils and ICS response remains unclear. According to this study, any association between blood eosinophil counts and exacerbation rate is only seen when the baseline eosinophil count is greater than 4% or 300 cells per μL. The positive signal seen when a lower cutoff is used reflects the effect of withdrawal of ICS on those with higher eosinophil counts. These findings need to be confirmed in appropriately stratified prospective clinical trials. In the meantime, there is a plausible argument that long-acting bronchodilator use is at least as effective as ICS/LABA in preventing exacerbations in patients with severe COPD on maintenance treatment with a LABA and a LAMA [10]. 

Mini cuts: 

Impact of timing of Metoprolol during STEMI on infarct size and ventricular function.

IV administration of metoprolol before primary angioplasty reduces infarct size in patients with STEMI, and earlier administration is associated with smaller infarct size and higher residual LVEF [11].

Phase 1 trials of rVSV Ebola vaccine in Africa and Europe.

The replication-competent recombinant vesicular stomatitis virus (rVSV)–based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa [12].

Physical Fitness Among Swedish Military Conscripts and Long-Term Risk for Type 2 Diabetes Mellitus: A Cohort Study

Low aerobic capacity and muscle strength at age 18 years were associated with increased long-term risk for type 2 DM, even among those with normal body mass index [13].

Dr. Tania Ruiz-Maya is a resident at NYU Langone Medical Center

Peer reviewed by Matthew Dallos, MD, Chief Resident, Internal Medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons


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  5. Ritsinger V, Saleh N, Lagerqvist et al High event rate after a first percutaneous coronary intervention in patients with diabetes mellitus: results from the Swedish coronary angiography and angioplasty registry. Circulation Cardiovascular Interventional. 2015;8:e002328.
  6. Meredith I, Tanguay JF, Kereiakes D, et al. Diabetes Mellitus and Prevention of Late Myocardial Infarction After Coronary Stenting in the Randomized Dual Antiplatelet Therapy Study. Circulation 2016;133:1772-1782.
  7. Sapp JL, Wells GA, Parkash R, et al. Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs. New England Journal of Medicine. May 5, 2016
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  13. Crump C, Sundquist J, Winkleby MA, et al. Physical Fitness Among Swedish Military Conscripts and Long-Term Risk for Type 2 Diabetes Mellitus: A Cohort Study. Ann Intern Med. 2016;164:577-584