Research Spotlight

Papaconstantinou, H. T., R. Ricciardi, D. A. Margolin, R. Bergamaschi, R. C. Moesinger, W. E. Lichliter and E. H. Birnbaum (2018). “A Novel Wound Retractor Combining Continuous Irrigation and Barrier Protection Reduces Incisional Contamination in Colorectal Surgery.” World J Surg 42(9): 3000-3007.

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BACKGROUND: Surgical site infection (SSI) remains a persistent and morbid problem in colorectal surgery. Key to its pathogenesis is the degree of intraoperative bacterial contamination at the surgical site. The purpose of this study was to evaluate a novel wound retractor at reducing bacterial contamination. METHODS: A prospective multicenter pilot study utilizing a novel wound retractor combining continuous irrigation and barrier protection was conducted in patients undergoing elective colorectal resections. Culture swabs were collected from the incision edge prior to device placement and from the exposed and protected incision edge prior to device removal. The primary and secondary endpoints were the rate of enteric and overall bacterial contamination on the exposed incision edge as compared to the protected incision edge, respectively. The safety endpoint was the absence of serious device-related adverse events. RESULTS: A total of 86 patients were eligible for analysis. The novel wound retractor was associated with a 66% reduction in overall bacterial contamination at the protected incision edge compared to the exposed incision edge (11.9 vs. 34.5%, P < 0.001), and 71% reduction in enteric bacterial contamination (9.5% vs. 33.3%, P < 0.001). The incisional SSI rate was 2.3% in the primary analysis and 1.2% in those that completed the protocol. There were no adverse events attributed to device use. CONCLUSIONS: A novel wound retractor combining continuous irrigation and barrier protection was associated with a significant reduction in bacterial contamination. Improved methods to counteract wound contamination represent a promising strategy for SSI prevention (NCT 02413879).

Packer, M. (2018). “Risk of heart failure in diabetic patients receiving sulfonylureas: reply.” Eur J Heart Fail 20(9): 1372.

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I sincerely appreciate the comments of Vaccaro et al. regarding their experience in the TOSCA.IT trial. It seems clear that theTOSCA.IT investigators took specifc steps to enroll a population of patients with type 2diabetes, who were at low risk of developingheart failure during follow-up. As a result, very few heart failure events were recorded in the trial, and consequently, the trial did not have adequate statistical power to determine if the risks of heart failure were truly similar inpatients taking sulfonylureas and pioglitazone. In order to validly conclude that the two classes of drugs were associated with similar risks of heart failure, the TOSCA.IT trial would have had to record 10timesasmanyheart failure events. Given the low risk of the population that was studied, achievement of this target number of events would have required the enrolment of substantially more patients and a far longer period of follow-up. Since this w as not practical, the results ofTOSCA.IT cannot provide reliable information concerning comparative risks of heart failure related to the use of sulfonylureas and pioglitazone. Even if additional data were to show that the increased risks of heart failure with sulfonylureas and pioglitazone were similar, it is important to worry about whether any increase in risk is acceptable, especially since certain antidiabetic medications (i.e. met-formin and sodium–glucose co-transporter 2inhibitors) appear to reduce the risk of heartfailure. Preventing heart failure and other macrovascular complications of diabetes is acritical goal of treatment. For most middle-aged to elderly patients with type 2 diabetes, the heightened risk of macrovascular events is much greater and occurs much earlier than the risk of microvascular events. Further-more, since risk reduction of macrovascular events is not clearly related to glycaemic control, the appropriate choice of an antidiabetic medication must be determined not only by its effects to lower glycated haemoglobin but by its independent actions to reduce the risk of cardiovascular death, myocardial infarction and heart failure. (Reply to Vaccaro’s comment on Packer, Are physicians neglecting the risk of heart failure in diabetic patients who are receiving sulfony-lureas? Lessons from the TOSCA.IT trial. Eur J Heart Fail 2018;20: 49–51.)

Packer, M. (2018). “Questioning the obvious: does dyspnoea really matter in heart failure?” Eur Heart J 39(30): 2822-2824

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Many patients with heart failure continue to exercise despite the experience of dyspnoea, until they feel that their legs can no longer carry them. So do patients with chronic heart failure stop exercising with dyspnoea or because of dyspnoea? If we were able to suppress the sensation of dyspnoea, would patients with heart failure be able to exercise longer? Many investigators who have closely evaluated patients with chronic heart failure believe this is unlikely. Our inability to answer these simple questions highlights how little we know about the factors that influence the capacity of patients with heart failure to perform and enjoy activities of daily living. We have spent several decades prolonging the lives of patients with heart failure, but we have spent little time studying the symptoms that bring them to medical attention in the first place. Since heart failure has become not only the major cause of cardiac death but also the major cause of cardiac disability, this is a conundrum that we can no longer ignore. (Excerpt from text, p. 2224; no abstract available.)

Packer, M. (2018). “The CABANA Trial: an honourable view.” Eur Heart J 39(30): 2770.

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The CABANA trial randomized 2204 patients with atrial fibrillation to catheter ablation (n = 1108) or drug therapy to achieve rate or rhythm control (n = 1096). Both groups were anticoagulated, and most patients in the non-ablation group received membrane-active antiarrhythmic drugs. Only 10% had atrial fibrillation for >1 year; 15% had a history of heart failure. The original primary endpoint was all-cause mortality, which was amended to a combined endpoint of death, disabling stroke, serious bleeding, or cardiac arrest. The original trial design anticipated that 25–30% of the patients assigned to drug therapy would receive ablation later in the trial. The investigators pre-specified that success of the trial would be determined by intention-to-treat analysis on the amended primary endpoint. This was an open-label trial; event adjudication was not blinded to the patients’ rhythm. Patients were followed for ≈5 years. According to the reported results, the ablation and non-ablation groups did not differ with respect to the risk of the original primary endpoint (P = 0.377) or the amended primary endpoint (P = 0.303). Ablation did not reduce the risk of any component of the primary endpoint. There was a nominally significant reduction in the combined risk of death or cardiovascular hospitalization, which was likely related to a decrease in admissions for atrial fibrillation in the ablation group. No particular benefit was seen in patients with heart failure. Unfortunately, the investigators showed ‘per-protocol’ and ‘as-treated’ analyses, which converted the randomized trial into an observational study . . . The CABANA trial is an important study that yielded a clear result, i.e. ablation does not prevent the serious consequences of atrial fibrillation. There is little justification to perform confounded observational analyses or rely on derivative subgroup effects. If this were a trial of a new pharmaceutical agent, these questionable analyses would be uniformly rejected as ‘wishful thinking’ and would not influence guidelines. Since ablation procedures are expensive, carry risks and are available to very few, evaluation of their efficacy should not be held to a lower standard of evidence. These thoughts on the CABANA trial are preliminary. We await publication of the full manuscript and a description of the analytical methods to fully understand how the investigators viewed their data. (Excerpt from text, p. 2770; no abstract available.)

Ogola, G. O., M. L. Crandall, K. M. Richter and S. Shafi (2018). “High-volume hospitals are associated with lower mortality among high-risk emergency general surgery patients.” J Trauma Acute Care Surg 85(3): 560-565.

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INTRODUCTION: We have previously demonstrated that Emergency General Surgery (EGS) patients treated at high-volume hospitals experience lower mortality rates than those treated at low-volume hospitals. However, EGS comprises a wide spectrum of diseases. Our goal was to determine which EGS diseases had better outcomes at high-volume hospitals. METHODS: We undertook a retrospective analysis of the National Inpatient Sample database for 2013 (a nationwide representative sample). Patients with EGS diseases were identified using American Association for the Surgery of Trauma definitions. A hierarchical logistic regression model was used to measure risk-adjusted probability of death, adjusting for age, sex, race, ethnicity, insurance type, and comorbidities. Patients were then grouped into 16 risk groups based upon their predicted probability of death. We then compared observed mortality rates at high- versus low-volume hospitals within each risk group. RESULTS: Nationwide, 3,006,615 patients with EGS diseases were treated at 4,083 hospitals in 2013. Patients with predicted risk of death of 4% or higher (275,615 patients, 9.2%) had lower observed mortality rates at high-volume hospitals than at low-volume hospitals (7.7% vs. 10.2%, p < 0.001). We estimated that 1,002 deaths were potentially preventable if high-risk patients who were treated at low-volume hospitals were instead transferred to high-volume hospitals. CONCLUSION: EGS patients with predicted risk of death of 4% or higher experience lower mortality rates at high-volume hospitals than at low-volume hospitals. A regional system of EGS care that enables rapid transfer of high-risk patients to high-volume hospitals may prevent several deaths. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III; Therapeutic/Case Management, level IV.