Primecuts-This Week in the Journals

October 19, 2015

File:Lincoln Douglas Debates 1958 issue-4c.jpgBy Abinav Baweja, MD

This past week we witnessed the first democratic national debate, where Hillary Rodham Clinton quieted doubters with her strong showing and minimized talk regarding her e-mail account. Meanwhile, ex-NBA player Lamar Odom was found unconscious in a brothel in Las Vegas where he had been using herbal analogs of Viagra and cocaine, and is presently in critical condition. Amidst all this news, we move on to some of the latest findings in the medical literature…

Is remote ischemic preconditioning beneficial for cardiac surgery?
Remote ischemic preconditioning (RIPC) involves inducing transient ischemia and reperfusion of non-vital tissues and may play a role in protecting vital organs from a prolonged period of ischemia, such as during cardiac surgery. Initial studies of RIPC focused on assessing biomarkers in patients undergoing cardiovascular surgery. While these studies demonstrated a potential protective effect of RIPC, they were limited by lack of primary end points and inadequate sample sizes [1].

In this prospective, multi-center, randomized, double-blinded trial, 1403 participants were included and RIPC involved performing 4 cycles of occlusion of the upper arm with a blood pressure cuff for 5 minutes after the induction of anesthesia. No significant differences were observed in the primary end points (14.3% in the RIPC group and 14.6% in the control group), which included death, myocardial infarction, stroke and acute renal failure. Further, no differences were seen in troponin release, new onset of atrial fibrillation, duration of mechanical ventilation, and length of hospital stay [2].

This study demonstrates that there was no difference between upper-limb RIPC and control in patients undergoing cardiac surgery with respect to primary end-points. Although initial laboratory investigations suggested organ-protective effects of RIPC, this may not directly translate to the clinical realm given that patients undergoing cardiac surgery tend to have multiple comorbidities (e.g. diabetes, hyperlipidemia, and peripheral vascular disease), thereby precluding them from any possible benefits of ischemia/reperfusion.
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Bioresorbable Scaffolds for Coronary Artery Disease
While the use of drug-eluting stents has provided monumental benefit in reducing morbidity and mortality in patients with acute myocardial infarction, the occurrence of stent thrombosis and in-stent restenosis is not entirely eliminated [3]. The use of resorbable stents has been investigated to circumvent the issue of occlusive stent failure, and in this multicenter trial, Ellis and colleagues randomized 2008 patients (in a 2:1 ratio) to receive a bioresorbable vascular scaffold (Absorb group) or an everolimus-eluting stent (Xience group). The primary end point assessed was target-lesion failure at 1 year, which included cardiac death, target-vessel infarction, and requirement for target-lesion revascularization.

Target-lesion failure (7.8% vs. 6.1%) and device thrombosis (1.5% vs. 0.7%) at 1 year were not significantly different between the two groups. There also were no differences in rate of cardiac death (0.6% in the Absorb group vs. 0.1% in the Xience group). Furthermore, no significant differences were observed in rates of target-vessel myocardial infarction or requirement for target revascularization due to ischemia between both groups [4].

Compared with the traditional drug-eluting stent, this study demonstrates non-inferiority of the bioresorbable scaffold in coronary disease. While non-significant differences in device thrombosis were seen between the Absorb and Xience stents at 1 year, longer-term studies will be needed to assess the potential benefits of such resorbable stents in coronary disease.

What are the trends in cancer incidence over time among persons with HIV?
Although antiretroviral therapy has prolonged the lifespan of individuals affected by human immunodeficiency virus (HIV), the cumulative incidence of certain cancers is increasing in this population, thereby presenting additional challenges to their medical care. In a cohort study by Silverberg and colleagues published in the Annals of Internal Medicine, cumulative cancer incidence was measured in 86,620 HIV-infected adults and 196,987 uninfected adults in North America between 1996 and 2009. They present the cumulative cancer incidence for various malignancies by age 75, which approximates the lifespan of patients effectively treated with HIV and thus may provide a more valuable metric of disease burden as compared with static incidence at a single point in time.

The cumulative incidences of cancer by age 75 revealed higher rates of the following cancers for persons with HIV compared to those without: Kaposi’s sarcoma (4.4% vs. 0.01%), non-Hodgkin lymphoma, (4.5% vs. 0.7%), lung cancer (3.4% vs. 2.8%), and anal cancer (1.5% vs. 0.05%) [5].

The high cumulative incidences by age 75 for these cancers argue for earlier actionable and preventive efforts in the HIV population. Promotion of early antiretroviral therapy, smoking cessation, and screening for these malignancies with high cumulative occurrence must be considered. Further studies with the aging HIV population will be necessary to better risk stratify patients based upon more concrete risk factors such as CD4 cell count, viral co-infection (e.g. hepatitis B or C), and substance use (alcohol, tobacco).

Do proton-pump inhibitors increase risk for C. difficile infection by altering the gut microbiome?
Broad-spectrum antimicrobial therapy is a known risk-factor for Clostridium difficile infection (CDI), causing alteration of host gut flora allowing for overgrowth of this microbe. Interestingly, proton-pump inhibitors (PPI) have been associated with CDI as well, though the mechanism is not clear.

In this open-label crossover trial, investigators tested whether PPI therapy can affect the gastrointestinal microbiome in ways that facilitate C difficile infection. 12 healthy volunteers donated baseline fecal samples at weeks 0 and 4, and then took PPI therapy (40 mg omeprazole twice daily) for 4 weeks. Fecal samples were again collected at completion of the course of therapy (week 8). Six of the individuals continued PPI therapy for an additional 4 weeks and additional stool samples were taken at week 12. Stool samples were analyzed by 16S ribosomal RNA sequencing. The investigators found that there were no significant differences with regards to microbiome diversity for each individual on PPI therapy as compared to their baseline samples. However, significant changes in organisms associated with C difficile infection were seen with PPI use, including increased Enterococcaceae and Streptococcaceae, and decreased Clostridia. Furthermore, PPI use in this study demonstrated an increase in organisms associated with gastrointestinal bacterial overgrowth, such as increased Micrococcaceae and Staphylococcaceae [6].

Hence, while 4 weeks of PPI therapy alone did not alter the diversity of the fecal microbiome, there were significant effects on specific organisms associated with C. difficile and bacterial overgrowth, suggesting a potential mechanism by which PPI therapy can predispose the gut microbiome to opportune microbial colonization.

1. Cancer resistance in elephants may be linked to the evolution of multiple copies of the TP53 tumor suppressor gene and altered DNA damage responses [7].

2. In a randomized, double-blind, placebo-controlled trial of daily supplementation with vitamin D, calcium, or both after removal of colorectal adenomas, there was no reduction in the risk of recurrent colorectal adenomas over 3-5 years [8].

3. The SPLIT clinical trial assesses the effect of a buffered crystalloid compared with normal saline in patients admitted to the intensive care unit, demonstrating no differences in the development of acute kidney injury [9].

4. A study of primary care appointment “no-shows” identifies high-risk patients based upon the no-show propensity factor [10].


1. Meybohm P, Bein B, Brosteanu O, et al. A multicenter trial of remote ischemic preconditioning for heart surgery. N Engl J Med 2015; 373:1397-1407

2. Hausenloy DJ, Yellon DM. The therapeutic potential of ischemic conditioning: an update. Nat Rev Cardiol. 2011; 8:619-629

3. Ellis SG, Kereiakes DJ, Metzger DC, et al. Everolimus-eluting bioresorbable scaffolds for coronary artery disease. N Engl J Med. DOI: 10.1056/NEJMoa1509038

4. Kirtane AJ, Gupta A, Iyengar S, et al. Safety and efficacy of drug-eluting and bare metal stents: comprehensive meta-analysis of randomized trials and observational studies. Circulation. 2009; 119:3198-3206

5. Silverberg MJ, et al. Cumulative Incidence of Cancer Among Persons With HIV in North America: A Cohort Study Ann Intern Med. 2015; 163(7):507-518

6. Freedberg, DE, et al. Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial. Gastroenterology. 149; 4:883 – 885.e9

Abinav Baweja, MD is a first year internal medicine resident at NYU Langone Medical Center

Peer Reviewed by Anish Parikh, MD, Associate Editor, Clinical Correlations

Picture courtesy of Wikimedia Commons