A MicroRNA Linking Human Positive Selection and Metabolic Disorders

Postponed access: the file will be accessible after 2021-10-14Positive selection in Europeans at the 2q21.3 locus harboring the lactase gene has been attributed to selection for the ability of adults to digest milk to survive famine in ancient times. However, the 2q21.3 locus is also associated with obesity and type 2 diabetes in humans, raising the possibility that additional genetic elements in the locus may have contributed to evolutionary adaptation to famine by promoting energy storage, but which now confer susceptibility to metabolic diseases. We show here that the miR-128-1 microRNA, located at the center of the positively selected locus, represents a crucial metabolic regulator in mammals. Antisense targeting and genetic ablation of miR-128-1 in mouse metabolic disease models result in increased energy expenditure and amelioration of high-fat-diet-induced obesity and markedly improved glucose tolerance. A thrifty phenotype connected to miR-128-1-dependent energy storage may link ancient adaptation to famine and modern metabolic maladaptation associated with nutritional overabundance.acceptedVersio

Estimates of new and total productivity in central Long Island Sound from in situ measurements of nitrate and dissolved oxygen

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Estuaries and Coasts 36 (2013): 74-97, doi:10.1007/s12237-012-9560-5.Biogeochemical cycles in estuaries are regulated by a diverse set of physical and biological variables that operate over a variety of time scales. Using in situ optical sensors, we conducted a high-frequency time-series study of several biogeochemical parameters at a mooring in central Long Island Sound from May to August 2010. During this period, we documented well-defined diel cycles in nitrate concentration that were correlated to dissolved oxygen, wind stress, tidal mixing, and irradiance. By filtering the data to separate the nitrate time series into various signal components, we estimated the amount of variation that could be ascribed to each process. Primary production and surface wind stress explained 59% and 19%, respectively, of the variation in nitrate concentrations. Less frequent physical forcings, including large-magnitude wind events and spring tides, served to decouple the relationship between oxygen, nitrate, and sunlight on about one-quarter of study days. Daytime nitrate minima and dissolved oxygen maxima occurred nearly simultaneously on the majority (> 80%) of days during the study period; both were strongly correlated with the daily peak in irradiance. Nighttime nitrate maxima reflected a pattern in which surface-layer stocks were depleted each afternoon and recharged the following night. Changes in nitrate concentrations were used to generate daily estimates of new primary production (182 ± 37 mg C m-2 d-1) and the f-ratio (0.25), i.e., the ratio of production based on nitrate to total production. These estimates, the first of their kind in Long Island Sound, were compared to values of community respiration, primary productivity, and net ecosystem metabolism, which were derived from in situ measurements of oxygen concentration. Daily averages of the three metabolic parameters were 1660 ± 431, 2080 ± 419, and 429 ± 203 mg C m-2 d-1, respectively. While the system remained weakly autotrophic over the duration of the study period, we observed very large day-to-day differences in the f-ratio and in the various metabolic parameters.This work was supported by the Yale Institute for Biospheric Studies, the Sounds Conservancy of the Quebec-Labrador Foundation, and the Yale School of Forestry and Environmental Studies Carpenter-Sperry Fund.2014-01-0

Postoperative atrial fibrillation is associated with increased resource utilization after cardiac surgery: a regional analysis of the Southeastern United States

Aim: Postoperative atrial fibrillation (POAF) is a known risk factor for morbidity and mortality following cardiac surgery though contemporary resource utilization data is limited. We hypothesize that POAF increases the length of stay, hospital cost, and discharges to facilities, though this trend may be tempering over time.Methods: Records were extracted for all patients in a regional database who underwent coronary artery bypass grafting, aortic valve replacement, or both (2012-2020). Patients without a history of atrial fibrillation were stratified by POAF for univariate analysis. Patients were propensity-score matched to account for baseline, operative, and postoperative differences.Results: Of the 27,307 cardiac surgery patients, 23% developed POAF. Matching resulted in 5926 well-balanced pairs of patients with and without POAF. Every metric of resource utilization was higher for patients with POAF, including ICU length of stay (58 h vs. 49 h, P < 0.0001), postoperative length of stay (7 days vs. 5 days, P < 0.0001), discharge to a facility (27% vs. 23%, P < 0.0001), and readmission (11% vs. 8%). The mean additional total hospital cost attributable to POAF was $6705 by paired analysis. A sensitivity analysis of only patients without major complications demonstrated similarly increased resource utilization for patients with POAF.Conclusions: POAF was associated with an increased 9 additional ICU hours, 2 postoperative days, 18$6705 is associated with POAF. These conservative estimates demonstrate the broad impact of POAF on in and out of hospital resource utilization that warrants future efforts at containment and quality improvement

Interhospital failure to rescue after coronary artery bypass grafting

OBJECTIVE: We evaluated whether interhospital variation in mortality rates for coronary artery bypass grafting was driven by complications and failure to rescue. METHODS: An observational study was conducted among 83,747 patients undergoing isolated coronary artery bypass grafting between July 2011 and June 2017 across 90 hospitals. Failure to rescue was defined as operative mortality among patients developing complications. Complications included the Society of Thoracic Surgeons 5 major complications (stroke, surgical reexploration, deep sternal wound infection, renal failure, prolonged intubation) and a broader set of 19 overall complications. After creating terciles of hospital performance (based on observed:expected mortality), each tercile was compared on the basis of crude rates of (1) major and overall complications, (2) operative mortality, and (3) failure to rescue (among major and overall complications). The correlation between hospital observed and expected (to address confounding) failure to rescue rates was assessed. RESULTS: Median Society of Thoracic Surgeons predicted mortality risk was similar across hospital observed:expected mortality terciles (P = .831). Mortality rates significantly increased across terciles (low tercile: 1.4%, high tercile: 2.8%). Although small in magnitude, rates of major (low tercile: 11.1%, high tercile: 12.2%) and overall (low tercile: 36.6%, high tercile: 35.3%) complications significantly differed across terciles. Nonetheless, failure to rescue rates increased substantially across terciles among patients with major (low tercile: 9.1%, high tercile: 14.3%) and overall (low tercile: 3.3%, high tercile: 6.8%) complications. Hospital observed and expected failure to rescue rates were positively correlated among patients with major (R = 0.14) and overall (R = 0.51) complications. CONCLUSIONS: The reported interhospital variability in successful rescue after coronary artery bypass grafting supports the importance of identifying best practices at high-performing hospitals, including early recognition and management of complications

Association Between Postoperative Pneumonia and 90-Day Episode Payments and Outcomes Among Medicare Beneficiaries Undergoing Cardiac Surgery

Background Postoperative pneumonia is the most common healthcare-associated infection in cardiac surgical patients, yet their impact across a 90-day episode of care remains unknown. Our objective was to examine the relationship between pneumonia and 90-day episode payments and outcomes among Medicare beneficiaries undergoing cardiac surgery. Methods and Results Medicare claims were used to identify beneficiaries with episodes of coronary artery bypass grafting (CABG; n=56 728) and valve surgery (n=56 377) across 1045 centers between April 2014 and March 2015. Using a published diagnosis code-based algorithm, we identified pneumonia in 6.4% CABG episodes and 6.6% of valve surgery episodes. We compared price-standardized 90-day episode payments and outcome measures (postoperative length of stay, discharge to postacute care, mortality, and readmission) between beneficiaries with and without pneumonia using hierarchical regression models, adjusting for patient factors and hospital random effects. Pneumonia was associated with 24.5% higher episode payments for CABG ($46 723 versus$37 496; P\u3c0.001) and 26.5% higher episode payments for valve surgery ($61 544 versus$48 549; P\u3c0.001). For both cohorts, pneumonia was significantly associated with longer postoperative length of stay (CABG: +4.1 days, valve: +5.6 days), more frequent discharge to postacute care (CABG: odds ratio [OR]=1.99, valve: OR=2.17), and higher rates of 30-day mortality (CABG: OR=2.42, valve: OR=2.57) and 90-day readmission (CABG: OR=1.20, valve: OR=1.25), all P\u3c0.001. We compared episode payments and outcomes across terciles of pneumonia rates and found that high pneumonia rate hospitals had higher episode payments and poorer outcomes compared with episodes at low pneumonia rate hospitals in both CABG and valve surgery cohorts. Conclusions Postoperative pneumonia was associated with significantly higher 90-day episode payments and inferior outcomes at the patient and hospital level. Future work should examine whether reducing pneumonia after cardiac surgery reduces episode spending and improves outcomes, which could facilitate hospital success in value-based reimbursement programs

A Preoperative Risk Model for Postoperative Pneumonia After Coronary Artery Bypass Grafting

BACKGROUND: Postoperative pneumonia is the most prevalent of all hospital-acquired infections after isolated coronary artery bypass graft surgery (CABG). Accurate prediction of a patient\u27s risk of this morbid complication is hindered by its low relative incidence. In an effort to support clinical decision making and quality improvement, we developed a preoperative prediction model for postoperative pneumonia after CABG. METHODS: We undertook an observational study of 16,084 patients undergoing CABG between the third quarter of 2011 and the second quarter of 2014 across 33 institutions participating in the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative. Variables related to patient demographics, medical history, admission status, comorbid disease, cardiac anatomy, and the institution performing the procedure were investigated. Logistic regression through forward stepwise selection (p \u3c 0.05 threshold) was utilized to develop a risk prediction model for estimating the occurrence of pneumonia. Traditional methods were used to assess the model\u27s performance. RESULTS: Postoperative pneumonia occurred in 3.30% of patients. Multivariable analysis identified 17 preoperative factors, including demographics, laboratory values, comorbid disease, pulmonary and cardiac function, and operative status. The final model significantly predicted the occurrence of pneumonia, and performed well (C-statistic: 0.74). These findings were confirmed through sensitivity analyses by center and clinically important subgroups. CONCLUSIONS: We identified 17 readily obtainable preoperative variables associated with postoperative pneumonia. This model may be used to provide individualized risk estimation and to identify opportunities to reduce a patient\u27s preoperative risk of pneumonia through prehabilitation

Effect of Cardiopulmonary Bypass on SARS‐CoV‐2 Vaccination Antibody Levels

Background Adults undergoing heart surgery are particularly vulnerable to respiratory complications, including COVID‐19. Immunization can significantly reduce this risk; however, the effect of cardiopulmonary bypass (CPB) on immunization status is unknown. We sought to evaluate the effect of CPB on COVID‐19 vaccination antibody concentration after cardiac surgery. Methods and Results This prospective observational clinical trial evaluated adult participants undergoing cardiac surgery requiring CPB at a single institution. All participants received a full primary COVID‐19 vaccination series before CPB. SARS‐CoV‐2 spike protein‐specific antibody concentrations were measured before CPB (pre‐CPB measurement), 24 hours following CPB (postoperative day 1 measurement), and approximately 1 month following their procedure. Relationships between demographic or surgical variables and change in antibody concentration were assessed via linear regression. A total of 77 participants were enrolled in the study and underwent surgery. Among all participants, mean antibody concentration was significantly decreased on postoperative day 1, relative to pre‐CPB levels (−2091 AU/mL, P<0.001). Antibody concentration increased between postoperative day 1and 1 month post CPB measurement (2465 AU/mL, P=0.015). Importantly, no significant difference was observed between pre‐CPB and 1 month post CPB concentrations (P=0.983). Two participants (2.63%) developed symptomatic COVID‐19 pneumonia postoperatively; 1 case of postoperative COVID‐19 pneumonia resulted in mortality (1.3%). Conclusions COVID‐19 vaccine antibody concentrations were significantly reduced in the short‐term following CPB but returned to pre‐CPB levels within 1 month. One case of postoperative COVID 19 pneumonia‐specific mortality was observed. These findings suggest the need for heightened precautions in the perioperative period for cardiac surgery patients