Heart rate variability (HRV) is a predictor of mortality and morbidity after non-lethal cardiac ischemia, but the relation between preoperatively measured HRV and intra- and postoperative complications is sparsely studied and most recently reviewed in 2007. We, therefore, reviewed the literature regarding HRV as a predictor for intra- and postoperative complications and outcomes. We carried out a systematic review without meta-analysis. A PICO model was set up, and we searched PubMed, EMBASE, and CENTRAL. The screening was done by one author, but all authors performed detailed review of the included studies. We present data from studies on intraoperative and postoperative complications, which were too heterogeneous to warrant formal meta-analysis, and we provide a pragmatic review of HRV indices to facilitate understanding our findings. The review was registered in PROSPERO (CRD42021230641). We screened 2337 records for eligibility. 131 records went on to full-text assessment, 63 were included. In frequency analysis of HRV, low frequency to high frequency ratio could be a predictor for intraoperative hypotension in spinal anesthesia and lower total power could possibly predict intraoperative hypotension under general anesthesia. Detrended fluctuation analysis of HRV is a promising candidate for predicting postoperative atrial fibrillation. This updated review of the relation between preoperative HRV and surgical outcome suggests a clinically relevant role of HRV but calls for high quality studies due to methodological heterogeneity in the current literature. Areas for future research are suggested.

Background Illicit use of anabolic androgenic steroids (AAS) is frequently observed in men and is associated with subsequent testosterone deficiency although the long-term effect on gonadal function is still unclear. Serum insulin-like factor 3 (INSL3) has been suggested to be a superior biomarker of Leydig cell secretory capacity compared to testosterone. The objective of this study was to investigate serum INSL3 concentrations in AAS users. Methods This community-based cross-sectional study included men aged 18 – 50 years, involved in recreational strength training and allocated to one of three groups: never-AAS users as controls (n=44), current (n=46) or former AAS users (n=42) with an average duration since AAS cessation of 32 (23;45) months. Results Serum INSL3 was lower in current AAS users and former AAS users than in controls, median (IQR), 0.04 (ND – 0.07) and 0.39 (0.24 – 0.62) versus 0.59 (0.45 – 0.72) µg/L, P<0.001. Former AAS users exhibited lower serum INSL3 levels than controls in a multivariate linear regression even after adjusting for serum total testosterone and other relevant confounders, (B) (95%CI), -0.16 (-0.29;-0.04) µg/L, P=0.011. INSL3 and total testosterone were not associated in the model, P=0.821. Longer accumulated AAS duration (log2) was associated with lower serum INSL3 in former AAS users, (B) (95%CI), -0.08 (-0.14;-0.01), P=0.022. Serum INSL3, but not inhibin B or testosterone, was associated with testicular size in a multivariate linear regression, (B) (95%CI); 4.7 (0.5 ; 8.9), P=0.030. Conclusions Serum INSL3 is reduced years following AAS cessation in men, independently of testosterone, suggesting persistently impaired Leydig cell capacity.

Aim To investigate whether the mineralocorticoid receptor antagonist eplerenone has beneficial effects on liver fat and metabolism in patients with type 2 diabetes (T2D), the mineralocorticoid receptor antagonist in type 2 diabetes (MIRAD) trial. Material and methods In this 26‐week, double‐blind, randomized, placebo‐controlled trial, we enrolled 140 patients with T2D and high risk of cardiovascular disease. Patients were randomized 1:1 to either eplerenone with a target dose of 200 mg/day for patients with estimated glomerular filtration rate (eGFR) of 60 mL/min per 1.73 m2 or more and 100 mg/day for patients with eGFR between 41 and 59 mL/min per 1.73 m2 or placebo. The primary outcome measure was change in liver fat by proton magnetic resonance spectroscopy at week 26 from baseline; secondary outcomes were changes in metabolism, and safety by incident hyperkalaemia. Results No changes in liver fat in the eplerenone group 0.91% (95% CI −0.57 to 2.39) or the placebo group −1.01% (−2.23 to 0.21) were found. The estimated absolute treatment difference was 1.92% (−3.81 to 0.01; P = 0.049). There was no beneficial impact on supporting secondary outcome variables of metabolism as fat mass distribution, lipid metabolism or insulin resistance. Despite a high dosage of eplerenone 164 versus 175 mg in patients treated with placebo (P = 0.228), the number of patients with incident hyperkalaemia (≥5.5 mmol/L) was low, with six in the eplerenone versus two in the placebo group (P = 0.276). Conclusion The addition of high doses of eplerenone to background antidiabetic and antihypertensive therapy does not show beneficial effects on liver fat and metabolism in patients with T2D.

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OBJECTIVES Days alive and out of hospital (DAOH) integrates overall information of hospitalization, readmissions, and mortality that have been applied as a new outcome measure. However, DAOH after video-assisted thoracoscopic surgery (VATS) in an established enhanced recovery after surgery (ERAS) programme has not been reported. METHODS Patients aged ≥18 years with non-small-cell lung cancer undergoing VATS lobectomy in an established ERAS programme were eligible. The primary and secondary outcomes were DAOH during the first postoperative 365 days and reasons for reduced DAOH. RESULTS A total of 316 consecutive patients with well-defined inclusion criteria and complete follow-up were assessed retrospectively. The median length of stay was 3 days (IQR 2–6). The medians (IQR) of postoperative 30, 60, 90, 180 and 365 DAOH were 27 (22–28), 57 (51–58), 86 (80–88), 176 (169–178) and 359 (349–363) days, respectively. Air leak was the dominant factor for reduced DAOH from postoperative day (POD) 0–30 (47.2%) and 0–365 (38.3%). Side effects of adjuvant chemotherapy were dominant from POD 31–60 and 61–90 (23.5% and 47.1%) and recurrence/metastases from POD 91–180 and 181–365 (25.6% and 50.0%). A low diffusing capacity for carbon monoxide (odds ratios 1.28, 95% confidence interval 1.07–1.53; P=0.007) and prior surgical history (odds ratios 1.80, 95% confidence interval 1.08–2.99; P=0.023) were predictors for low DAOH. CONCLUSIONS DAOH after 1 year with an established VATS lobectomy ERAS programme was only reduced with a median of 6 days. The main factors reducing DAOH were air leak, adjuvant chemotherapy and recurrence. DAOH may be an important patient-centred outcome to define future improvement strategies.

Background and objective No information exists on the long-lasting effects of supraphysiological anabolic androgenic steroids (AAS) usage on the myocellular properties of human skeletal muscle in previous AAS users. We hypothesized former AAS users would demonstrate smaller myonuclei domains (i.e., higher myonuclei density) compared to matched controls. Methods A community-based cross-sectional study in men aged 18-50 years engaged in recreational strength training. Muscle biopsies were obtained from the m. vastus lateralis. Immunofluorescence analyses were performed to quantify myonuclei density and myofiber size. Results Twenty-five males were included: 8 current and 7 previous AAS users and 10 controls. Median (25th-75th percentiles) accumulated duration of AAS use was 174 (101–206) and 140 (24–260) weeks in current and former AAS users, respectively (P = 0.482). Geometric mean (95%CI) elapsed duration since AAS cessation was 4.0 (1.2; 12.7) years among former AAS users. Type II muscle fibers in former AAS users displayed higher myonuclei density and DNA-to-cytoplasm ratio than controls, corresponding to smaller myonuclei domains (P = 0.013). Longer accumulated AAS use (weeks, log2) was associated with smaller myonuclei domains in previous AAS users, beta-coefficient (95%CI), -94 (-169; -18), P = 0.024. Type I fibers in current AAS users exhibited a higher amount of satellite cells per myofiber (P = 0.031) compared to controls. Conclusion Muscle fibers in former AAS users demonstrated persistently higher myonuclei density and DNA-to-cytoplasm ratio four years after AAS cessation suggestive of enhanced retraining capacity.

Background Anabolic androgenic steroid (AAS) abusers are considered at increased risk of cardiovascular morbidity and mortality. We hypothesized that current and former AAS abuse would induce a procoagulant shift in the haemostatic balance. Methods Men 18 to 50 years of age were included as current AAS abusers, former AAS abusers or controls. Morning blood samples were collected after overnight fasting. Thrombin generation (lag time, time to peak, peak height, and endogenous thrombin potential [ETP]) and coagulation factor II (prothrombin), VII and X, antithrombin, protein C, free protein S and tissue factor pathway inhibitor (TFPI) were assessed. Groups were compared by ANOVA or Kruskal–Wallis test and probabilities were corrected for multiple comparisons. Associations were evaluated using linear regression models. Results ETP was increased around 15% in current (n = 37) and former (n = 33) AAS abusers compared with controls (n = 30; p < 0.001). Prothrombin and factor X were increased ≥10% in AAS abusers and prothrombin was a predictor of ETP (p < 0.0005). Lag time and time to peak were increased 10 to 30% in current AAS abusers (p < 0.001) and associated with higher concentrations of TFPI, antithrombin, protein C and protein S (p < 0.0005; = 0.005). Multivariate linear regression, with all coagulation inhibitors as covariates, identified TFPI to be independently associated with lag time and time to peak (p < 0.0005). Conclusion Thrombin generation is augmented in current and former AAS abusers, reflecting a procoagulant state, with altered concentrations of coagulation proteins. Prospective studies are needed to clarify whether these findings translate into an increased thrombotic risk in AAS abusers potentially even after cessation.

Objectives The purpose of this study was to describe the incidence and reasons for early (0–30 days) and late (31–90 days) readmission after enhanced recovery video-assisted thoracoscopic surgery lobectomy. Methods We performed a retrospective analysis of prospectively collected consecutive VATS lobectomy data in an institutional database from January 2019 until December 2020. All reasons for readmission with complete follow-up were individually evaluated. Univariable and multivariable analyses were used to assess predictors. Results In total 508 patients were included and median length of stay after surgery was 3 days. Early and late readmission were 77 (15%) and 54 (11%), respectively. Multiple readmissions during postoperative 0–90 days were 33 (7%). Pneumonia (19.8%) and pneumothorax (18.3%) were the dominant reasons for early readmission, and side effects to adjuvant chemotherapy (22.0%) for late readmission. In multivariable analyses, current smoking (P = 0.001), alcohol abuse (P = 0.024) and chronic obstructive pulmonary disease (P = 0.019) were predictors for early readmission, while (Clavien-Dindo I-II grade gastrointestinal complicationspredicted late readmission (P = 0.006) and multiple readmissions (P = 0.007). Early discharge (&lt; 3 days) was not a predictor for readmission. Early readmission does not increase late readmission. Conclusions Early and late readmission are frequent despite of following enhanced recovery programs after video-assisted thoracoscopic lobectomy. Pulmonary complications and adjuvant chemotherapy are the most predominant reasons for early and late readmission.