Time-course of heart rate variability after total hip arthroplasty.

Heart rate variability (HRV) is a measure of the autonomic nervous system function and possibly related to postoperative outcome. Despite several HRV studies in different surgical settings, optimal indices and timepoints for measuring have not been adequately determined. Consequently, there is a need for detailed descriptive procedure-specific studies on the time-course of perioperative HRV within a modern fast-track surgical setting. We measured HRV continuously in 24 patients from 4 days before until 9 days after total hip arthroplasty (THA). Statistical methods included mainly ANOVA and t-tests or Kruskal-Wallis and pairwise Wilcoxon test. Patients completed the Orthostatic Discriminant and Severity Scale five times during the study describing autonomic nervous system dysfunction. Standard deviation between normal-to-normal beats and the total power of HRV were reduced for at least 9 days following THA, with a trend towards increased HRV leading up to the day of surgery. The balance between low- and high-frequency power of HRV was reduced in the postoperative evenings. There was increased orthostatic intolerance symptoms on the first postoperative day, with symptoms of pain, fatigue and weakness decreasing after the first postoperative day. Median hospital stay was 1 day. We provide the first detailed description of perioperative time-course of HRV and orthostatic symptoms in fast-track THA, showing reduced HRV after surgery for at least a week, and that HRV changes are sensitive to time of day and timing before and after surgery. These results are helpful in designing future HRV studies in perioperative risk assessment and outcome.

Days alive and out of hospital after video-assisted thoracoscopic surgery wedge resection in the era of enhanced recovery.

BACKGROUND: Days alive and out of hospital is proposed as a valid and patient-centred quality measure for perioperative care. However, no procedure-specific data exist after pulmonary wedge resection. The aim of this study was to assess the first 90 days alive and out of hospital after video-assisted thoracoscopic surgery wedge resection in an optimized enhanced recovery programme. METHODS: A retrospective analysis of prospectively collected data of consecutive patients undergoing enhanced recovery thoracoscopic wedge resections from January 2021 to June 2022 in a high-volume centre was carried out. All factors leading to hospitalization, readmission, and death were evaluated individually. A logistic regression model was used to evaluate predictors. Additionally, a sensitivity analysis was performed. RESULTS: A total of 433 patients were included (21.7% (n = 94) with non-small cell lung cancer, 47.6% (n = 206) with metastasis, 26.8% (n = 116) with benign nodules, and 3.9% (n = 17) with other lung cancers). The median duration of hospital stay was 1 day. The median of postoperative 30 and 90 days alive and out of hospital was 28 and 88 days respectively. Air leak (112 patients) and pain (96 patients) were the most frequent reasons for reduced days alive and out of hospital from postoperative day 1 to 30, whereas treatment of the original cancer or metastasis (36 patients) was the most frequent reason for reduced days alive and out of hospital from postoperative day 31 to 90. Male sex, reduced lung function, longer dimension of resection margin, pleural adhesions, and non-small cell lung cancer were independent risks, confirmed by a sensitivity analysis. CONCLUSION: Days alive and out of hospital within 90 days after enhanced recovery thoracoscopic wedge resection was only reduced by a median of 2 days, mainly due to air leak and pain.

Higher Myonuclei Density in Muscle Fibers Persists Among Former Users of Anabolic Androgenic Steroids.

CONTEXT: No information exists on the long-lasting effects of supraphysiological anabolic androgenic steroids (AASs) usage on the myocellular properties of human skeletal muscle in previous AAS users. OBJECTIVE: We hypothesized that former AAS users would demonstrate smaller myonuclei domains (ie, higher myonuclei density) than 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 = .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 = .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 = .024. Type I fibers in current AAS users exhibited a higher amount of satellite cells per myofiber (P = .031) than controls. CONCLUSION: Muscle fibers in former AAS users demonstrated persistently higher myonuclei density and DNA to cytoplasm ratio 4 years after AAS cessation suggestive of enhanced retraining capacity.

Continuous perioperative heart rate variability monitoring in video-assisted thoracoscopic surgery lobectomy-a pilot study.

Heart rate variability (HRV) is a measure of cardiac autonomic modulation and is potentially related to hypotension, postoperative atrial fibrillation, and orthostatic intolerance. However, there is a lack of knowledge on which specific time points and indices to measure. To improve future study design, there is a need for procedure-specific studies in an enhanced recovery after surgery (ERAS) video-assisted thoracic surgery (VATS) lobectomy setting, and for continuous measurement of perioperative HRV. HRV was measured continuously from 2 days before until 9 days after VATS lobectomy in 28 patients. After VATS lobectomy, with median length of stay = 4 days, the standard deviation between normal-to-normal beats and the total power of HRV were reduced for 8 days during the night and day times, while low-to-high frequency variation and detrended fluctuation analysis were stable. This is the first detailed study to show that HRV measures of total variability were reduced following ERAS VATS lobectomy, while other measures were more stable. Further, preoperative HRV measures showed circadian variation. The patch was well tolerated among participants, but actions should be taken to ensure proper mounting of the measuring device. These results demonstrate a valid design platform for future HRV studies in relation to postoperative outcomes.

Early and late readmissions after enhanced recovery thoracoscopic lobectomy.

OBJECTIVES: The purpose of this study was to describe the incidence of and reasons for early (0-30 days) and late (31-90 days) readmissions 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 through 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; the median length of stay after the operation was 3 days. There were 77 (15%) early and 54 (11%) late readmissions, respectively. There were 33 (7%) multiple readmissions during postoperative days 0-90 ; pneumonia (19.8%) and pneumothorax (18.3%) were the dominant reasons for early readmissions, and the side effects of adjuvant chemotherapy (22.0%), for late readmissions. In multivariable analyses, current smoking (P = 0.001), alcohol abuse (P = 0.024) and chronic obstructive pulmonary disease (P = 0.019) were predictors of early readmissions, whereas Clavien-Dindo I-II grade gastrointestinal complications predicted late readmissions (P = 0.006) and multiple readmissions (P = 0.007). Early discharge (< 3 days) was not a predictor of readmissions. Early readmission did not increase late readmission. CONCLUSIONS: Early and late readmissions after video-assisted thoracoscopic lobectomy are frequent even when enhanced recovery programmes are followed. Pulmonary complications and adjuvant chemotherapy are the most predominant reasons for early and late readmissions.

Days alive and out of hospital after enhanced recovery video-assisted thoracoscopic surgery lobectomy.

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.

Preoperative heart rate variability as a predictor of perioperative outcomes: a systematic review without meta-analysis.

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.

Serum Insulin-like Factor 3 Levels Are Reduced in Former Androgen Users, Suggesting Impaired Leydig Cell Capacity.

CONTEXT: 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. OBJECTIVE: This study aimed to investigate serum INSL3 concentrations in AAS users. METHODS: This community-based, cross-sectional study included men aged 18 to 50 years, involved in recreational strength training and allocated to 1 of 3 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 (interquartile range), 0.04 µg/L (nondetectable [ND]-0.07 µg/L) and 0.39 µg/L (0.24-0.62 µg/L) vs 0.59 µg/L (0.45-0.72 µg/L), P less than .001. Former AAS users exhibited lower serum INSL3 levels than controls in a multivariable linear regression even after adjusting for serum total testosterone (TT) and other relevant confounders, (B) (95% CI), -0.16 µg/L (95% CI, -0.29 to -0.04 µg/L), P equal to .011. INSL3 and TT were not associated in the model, P equal to .821. Longer accumulated AAS duration (log2) was associated with lower serum INSL3 in former AAS users, (B) (95% CI), -0.08 (95% CI, -0.14 to -0.01), P equal to .022. Serum INSL3, but not inhibin B or testosterone, was associated with testicular size in a multivariate linear regression, (B) (95% CI); 4.7 (95% CI, 0.5 to 8.9), P equal to .030. CONCLUSION: Serum INSL3 is reduced years following AAS cessation in men, independently of testosterone, suggesting persistently impaired Leydig cell capacity.

Effect of the mineralocorticoid receptor antagonist eplerenone on liver fat and metabolism in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial (MIRAD trial).

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.

Procoagulant State in Current and Former Anabolic Androgenic Steroid Abusers.

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.

Cost of community integrated prevention campaign for malaria, HIV, and diarrhea in rural Kenya.

BACKGROUND: Delivery of community-based prevention services for HIV, malaria, and diarrhea is a major priority and challenge in rural Africa. Integrated delivery campaigns may offer a mechanism to achieve high coverage and efficiency. METHODS: We quantified the resources and costs to implement a large-scale integrated prevention campaign in Lurambi Division, Western Province, Kenya that reached 47,133 individuals (and 83% of eligible adults) in 7 days. The campaign provided HIV testing, condoms, and prevention education materials; a long-lasting insecticide-treated bed net; and a water filter. Data were obtained primarily from logistical and expenditure data maintained by implementing partners. We estimated the projected cost of a Scaled-Up Replication (SUR), assuming reliance on local managers, potential efficiencies of scale, and other adjustments. RESULTS: The cost per person served was $41.66 for the initial campaign and was projected at $31.98 for the SUR. The SUR cost included 67% for commodities (mainly water filters and bed nets) and 20% for personnel. The SUR projected unit cost per person served, by disease, was $6.27 for malaria (nets and training), $15.80 for diarrhea (filters and training), and $9.91 for HIV (test kits, counseling, condoms, and CD4 testing at each site). CONCLUSIONS: A large-scale, rapidly implemented, integrated health campaign provided services to 80% of a rural Kenyan population with relatively low cost. Scaling up this design may provide similar services to larger populations at lower cost per person.