Bilateral Remote Ischemic Conditioning in Children:a two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery

Objective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis.Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants.Results: Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 μg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 μg/L/h, n = 58) (mean difference, 13.2 μg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups.Conclusions: Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery

Subcomplex Iλ Specifically Controls Integrated Mitochondrial Functions in Caenorhabditis elegans

Complex I dysfunction is a common, heterogeneous cause of human mitochondrial disease having poorly understood pathogenesis. The extensive conservation of complex I composition between humans and Caenorhabditis elegans permits analysis of individual subunit contribution to mitochondrial functions at both the whole animal and mitochondrial levels. We provide the first experimentally-verified compilation of complex I composition in C. elegans, demonstrating 84% conservation with human complex I. Individual subunit contribution to mitochondrial respiratory capacity, holocomplex I assembly, and animal anesthetic behavior was studied in C. elegans by RNA interference-generated knockdown of nuclear genes encoding 28 complex I structural subunits and 2 assembly factors. Not all complex I subunits directly impact respiratory capacity. Subcomplex Iλ subunits along the electron transfer pathway specifically control whole animal anesthetic sensitivity and complex II upregulation, proportionate to their relative impairment of complex I-dependent oxidative capacity. Translational analysis of complex I dysfunction facilitates mechanistic understanding of individual gene contribution to mitochondrial disease. We demonstrate that functional consequences of complex I deficiency vary with the particular subunit that is defective

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Multiple sclerosis relapses and depression

Objective The expression of clinically significant depression symptoms during and post multiple sclerosis (MS) relapse was investigated. The point prevalence of possible depression during a confirmed MS relapse and at 2 and 6 months post-relapse was examined and the influence of disability on the time course of depression symptoms post-relapse determined. Methods 132 sequential patients were recruited from an open access relapse clinic. Clinical data including disability (Expanded Disability Status Scale: EDSS) and depression symptoms (Hospital Anxiety and Depression Scale depression subscale: HADS-D) were recorded at 0, 2 and 6 months post-relapse. Results Prevalence of possible depression (HADS-D score of ≥ 8) was 44.5% during relapse, reducing to 29.2% at 2 months and 34.4% at 6 months post-relapse. HADS-D scores were significantly lower at follow-up than during relapse. Possible depression at relapse was significantly related to a higher likelihood of possible depression at 2 month follow-up (OR 12.12) and improvement in EDSS was related to a lower likelihood (OR 0.51). EDSS at relapse (OR 1.47) and possible depression at relapse (OR 11.87) were significantly associated with possible depression 6 months post-relapse. Conclusions High rates of possible depression were observed during relapse. Although depression scores reduced significantly post-relapse, rates of possible depression at follow-ups remained high. The results suggest that although improvements in disability may influence depression symptoms over the short-term, once depression symptoms are elevated at relapse then depression symptoms become persistent. Further studies are required on the relationship between relapses and depression and whether targeted psychological interventions are beneficial

In-situ observations of volcanic ash clouds from the FAAM aircraft during the eruption of Eyjafjallajökull in 2010

During April–May 2010 the UK Facility for Airborne Atmospheric Measurements (FAAM) BAe-146 aircraft flew 12 flights targeting volcanic ash clouds around the UK. The aircraft observed ash layers between altitudes of 2–8 km with peak mass concentrations typically between 200–2000 μg/m3, as estimated from a Cloud and Aerosol Spectrometer (CAS). A peak value of 2000–5000 μg/m3 was observed over Scotland on 14 May 2010, although with considerable uncertainty due to the possible contamination by ice. Aerosol size distributions within ash clouds showed a fine mode (0.1–0.6 μm) associated with sulphuric acid and/or sulphate, and a coarse mode (0.6–35 μm) associated with ash. The ash mass was dominated by particles in the size range 1–10 μm (volume-equivalent diameter), with a peak typically around 3–5 μm. Electron-microscope images and scattering patterns from the SID-2H (Small Ice Detector) probe showed the highly irregular shape of the ash particles. Ash clouds were also accompanied by elevated levels of SO2 (10–100 ppbv), strong aerosol scattering (50–500 × 10−6 m−1), and low Ångstrom exponents (−0.5 to 0.4) from the 3-wavelength nephelometer. Coarse-mode mass specific aerosol extinction coefficients (kext), based on the CAS size distribution varied from 0.45–1.06 m2/g. A representative value of 0.6 m2/g is suggested for distal ash clouds (∼1000 km downwind) from this eruption.Peer reviewe