Research Spotlight

Packer, M. (2017). “Heart failure with a mid-range ejection fraction: A disorder that a psychiatrist would love.” JACC Heart Fail 5(11): 805-807.

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Over the past 5 decades, cardiologists have become obsessed with the ejection fraction. The term can be found in the abstracts of more than 52,000 papers; 10s of 1,000s of additional papers refer to it in their texts. The measurement yields important prognostic information in patients without heart failure, yet the field of heart failure has been particularly consumed by its assessment. We rarely find a paper about heart failure that does not mention it, guidelines mandate its evaluation in all patients, and it has been an entry criterion for every heart failure trial over the past 30 years. Its importance seems odd, however, because ejection fraction is not related to or associated with any specific clinical feature or pathophysiological abnormality of heart failure.

Stewart, R. J., B. Flannery, J. R. Chung, M. Gaglani, M. Reis, R. K. Zimmerman, M. P. Nowalk, L. Jackson, M. Jackson, A. S. Monto, E. T. Martin, E. A. Belongia, H. McLean, A. M. Fry and F. Havers (2017). “Influenza antiviral prescribing for outpatients with an acute respiratory illness and at high risk for influenza-associated complications during five influenza seasons-united states, 2011-2016.” Clin Infect Dis: 1-20.

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Background: Influenza causes millions of illnesses annually; certain groups are at higher risk for influenza-associated complications. Early antiviral treatment can reduce the risk of complications and is recommended for outpatients at increased risk. We describe antiviral prescribing among high-risk outpatients for 5 influenza seasons and explore factors that may influence prescribing. Methods: We analyzed antiviral prescription and clinical data for high-risk outpatients aged >/= 6 months with an acute respiratory illness (ARI) and enrolled in the US Influenza Vaccine Effectiveness Network during the 2011-2012 to 2015-2016 influenza seasons. We obtained clinical information from interviews and electronic medical records and tested all enrollees for influenza with rRT-PCR. We calculated the number of patients with ARI that must be treated to treat 1 patient with laboratory-confirmed influenza. Results: Among high-risk outpatients with ARI who presented to care within two days of symptom onset (early), 15% (718/4861) were prescribed an antiviral medication, including 472/1292 (37%) of those with rRT-PCR-confirmed influenza. Less than half (40%) of high-risk outpatients with influenza presented to care early. Earlier presentation to care was associated with antiviral treatment (OR: 4.1, CI: 3.5-4.8), as was fever (OR: 3.2, CI: 2.7-3.8), although 25% of high-risk outpatients with influenza were afebrile. Empiric treatment of 4 high-risk outpatients with ARI was needed to treat 1 patient with laboratory-confirmed influenza. Conclusion: Influenza antiviral medications were infrequently prescribed for high-risk outpatients with ARI who would benefit most from treatment. Efforts to increase appropriate antiviral prescribing are needed to reduce influenza-associated complications.

Shahbazov, R., B. Naziruddin, K. Yadav, G. Saracino, G. Yoshimatsu, M. A. Kanak, E. Beecherl, P. T. Kim and M. F. Levy (2017). “Risk factors for early readmission after total pancreatectomy and islet auto transplantation.” HPB (Oxford): 1-9.

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BACKGROUND: Little published data exist examining causes of hospital readmission following total pancreatectomy with islet autotransplantation (TPIAT). METHODS: A retrospective analysis was performed of a prospectively collected institutional TPIAT database. Primary outcome was unplanned readmission to the hospital within 30 days from discharge. Reasons and risk factors for readmission as well as islet function were evaluated and compared by univariate and multivariate analysis. RESULTS: 83 patients underwent TPIAT from 2006 to 2014. 21 patients (25.3%) were readmitted within 30 days. Gastrointestinal problems (52.4%) and surgical site infection (42.8%) were the most common reasons for readmission. Initial LOS and reoperation were risk factors for early readmission. Patients with delayed gastric emptying (DGE) were three times more likely to get readmitted. In multivariate analysis, patients undergoing pylorus preservation surgery were nine times more likely to be readmitted than the antrectomy group. CONCLUSION: Early readmission after TPIAT is common (one in four patients), underscoring the complexity of this procedure. Early readmission is not detrimental to islet graft function. Patients undergoing pylorus preservation are more likely to get readmitted, perhaps due to increased incidence of delayed gastric emptying. Decision for antrectomy vs. pylorus preservation needs to be individualized.

Schiattarella, G. G., A. Sannino, E. Toscano, G. Giugliano, G. Gargiulo, A. Franzone, B. Trimarco, G. Esposito and C. Perrino (2017). “Gut microbe-generated metabolite trimethylamine-n-oxide as cardiovascular risk biomarker: A systematic review and dose-response meta-analysis.” Eur Heart J 38(39): 2948-2956.

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Aims: Gut microbiota-derived metabolite trimethylamine-N-oxide (TMAO) is emerging as a new potentially important cause of increased cardiovascular risk. The purpose of this meta-analysis was to systematically estimate and quantify the association between TMAO plasma levels, mortality, and major adverse cardio and cerebrovascular events (MACCE). Methods and results: MEDLINE, ISI Web of Science, and SCOPUS databases were searched for ad hoc studies published up to April 2017. Associations between TMAO plasma levels, all-cause mortality (primary outcome) and MACCE (secondary outcome) were systematically addressed. A total of 17 clinical studies were included in the analytic synthesis, enrolling 26 167 subjects. The mean follow-up in our study population was 4.3 +/- 1.5 years. High TMAO plasma levels were associated with increased incidence of all-cause mortality [14 studies for 16 cohorts enrolling 15 662 subjects, hazard ratio (HR): 1.91; 95% confidence interval (CI): 1.40-2.61, P < 0.0001, I2 = 94%] and MACCE (5 studies for 6 cohorts enrolling 13 944 subjects, HR: 1.67, 95% CI: 1.33-2.11, P < 0.00001, I2 = 46%,). Dose-response meta-analysis revealed that the relative risk (RR) for all-cause mortality increased by 7.6% per each 10 mumol/L increment of TMAO [summary RR: 1.07, 95% CI (1.04-1.11), P < 0.0001; based on seven studies]. Association of TMAO and mortality persisted in all examined subgroups and across all subject populations. Conclusions: This is the first systematic review and meta-analysis demonstrating the positive dose-dependent association between TMAO plasma levels and increased cardiovascular risk and mortality.

Strober, B. E., R. G. B. Langley, A. Menter, M. Magid, B. Porter, T. Fox, J. Safi, Jr. and C. Papavassilis (2017). “No elevated risk for depression, anxiety, or suicidality with secukinumab in a pooled analysis of data from 10 clinical studies in moderate-to-severe plaque psoriasis.” Br J Dermatol: 2017 Oct [Epub ahead of print].

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Concerns have emerged over the potential for brodalumab, a monoclonal antibody that binds to the human interleukin (IL)-17 receptor A and blocks the activity of multiple IL-17 isoforms, to increase risk of suicidal ideation and behaviour. Although the validity of this association has been questioned,1,2 brodalumab has a boxed warning regarding suicidality in its US label and is only available through a Risk Evaluation and Mitigation Strategy. Regardless of the true association between suicidality and brodalumab, the demonstrated adverse impact of psoriasis on mental health necessitates careful assessment for possible psychiatric adverse effects of psoriasis therapies, including those that inhibit the IL-17 pathway.