Search

Background: Clinically important perioperative atrial fibrillation (POAF) is a common cardiac complication after noncardiac surgery. Little is known about how patients with POAF are managed acutely and whether practices have changed over time. Methods: We conducted an observational substudy of patients who had POAF, were at elevated cardiovascular risk, and were enrolled in the PeriOperative Ischemic Evaluation (POISE)-1, 2 and 3 trials between 2002 and 2021. POAF was defined as new, clinically important atrial fibrillation occurring within 30 days after surgery. We assessed the use of rhythm-control and anticoagulation treatment in response to POAF, at hospital discharge and at 30 days after surgery. We assessed for temporal trends using multivariable logistic regression. Results: Of the 27,896 patients included, 545 (1.9%) developed clinically important POAF. Patients received rhythm-control treatment in 48.6% of cases. The level of use of rhythm-control treatment increased over the course of the trials (POISE-1 vs POISE-2 vs POISE-3; 40.9% vs 49.5% vs 59.1%). A later randomization date was associated independently with use of rhythm-control treatment (odds ratio, 1.05 per year; 95% confidence interval, 1.01-1.09). Anticoagulation treatment was prescribed in 21% of POAF cases. The level of anticoagulation treatement use was higher in POISE-3, compared to that in the 2 previous trials (POISE-1 vs POISE-2 vs POISE-3—16.4% vs 16.5% vs 33.6%). A later randomization date was associated independently with use of anticoagulation treatment (odds ratio, 1.06 per year; 95% confidence interval, 1.02-1.11). Conclusions: Despite the absence of randomized controlled trials, the level of use of rhythm-control and anticoagulation treatment for POAF is rising. High-quality trials are needed urgently to determine whether these interventions are safe and effective in this population. Résumé: Contexte: En chirurgie non cardiaque, la fibrillation auriculaire postopératoire (FAPO) d’importance clinique est une complication cardiaque fréquente. La prise en charge ponctuelle des patients présentant une FAPO est mal connue et on ne sait pas précisément si les pratiques ont évolué au fil du temps. Méthodologie: Nous avons mené une sous-étude d’observation auprès de patients ayant présenté une FAPO et dont le risque cardiovasculaire était élevé, et qui avaient participé aux études 1, 2 ou 3 du programme d’essais cliniques POISE (PeriOperative Ischemic Evaluation) entre 2002 et 2021. La FAPO était définie comme un nouvel épisode de fibrillation auriculaire (FA) d’importance clinique au cours des 30 jours suivant une intervention chirurgicale. Nous avons évalué l’utilisation d’un traitement visant à régulariser le rythme cardiaque et de l’anticoagulothérapie dans la prise en charge d’une FAPO, au moment du congé de l’hôpital, puis 30 jours après l’intervention chirurgicale. Nous avons procédé à l’évaluation des tendances temporelles par régression logistique multivariée. Résultats: Sur les 27 896 patients inclus dans l’analyse, 545 (1,9 %) ont présenté une FAPO d’importance clinique. Dans 48,6 % des cas, les patients ont reçu un traitement visant à régulariser le rythme cardiaque. Le taux d’utilisation d’un traitement visant à régulariser le rythme cardiaque a augmenté d’une étude à l’autre (étude POISE-1 vs étude POISE-2 vs étude POISE-3; 40,9 % vs 49,5 % vs 59,1 %, respectivement). Une date plus tardive de la répartition aléatoire était un facteur indépendant de l’utilisation d’un traitement visant à régulariser le rythme cardiaque (rapport de cotes = 1,05 par an; intervalle de confiance [IC] à 95 % : 1,01-1,09). Une anticoagulothérapie a été prescrite à 21 % des patients ayant présenté une FAPO. Le taux d’utilisation d’une anticoagulothérapie était plus élevé dans l’étude POISE-3, comparativement aux deux essais précédents (étude POISE-1 vs étude POISE-2 vs étude POISE-3; – 16,4 % vs 16,5 % vs 33,6 %, respectivement). Une date plus tardive de la répartition aléatoire était un facteur indépendant d’utilisation d’une anticoagulothérapie (rapport de cotes = 1,06 par an; IC à 95 % : 1,02-1,11). Conclusions: Malgré l’absence d’essais comparatifs avec répartition aléatoire, le taux d’utilisation d’un traitement visant à régulariser le rythme cardiaque ou d’une anticoagulothérapie chez les patients présentant une FAPO est en augmentation. Il existe un besoin urgent de réaliser des études cliniques de grande qualité afin de déterminer si ces interventions sont sûres et efficaces dans cette population de patients.

Abstract Background Adipocytokines play a pivotal role in maintaining adipose tissue homeostasis by regulating cellular metabolism, proliferation, differentiation, and secretory activity. These soluble factors are relevant components for healthy adipose tissue, while their deficiency is closely associated with the development of obesity and related metabolic diseases, e.g., chronic inflammation. In human adipose tissue, inter-α-trypsin inhibitor heavy chain 5 (ITIH5) is expressed in proportion to the development of adipose tissue, i.e., the individual’s BMI. Thus, ITIH5 has been proposed to be an inert marker of human obesity. However, when applied to adipose stem cells in vitro, recombinant (r)ITIH5 protein inhibited proliferation and adipogenesis, suggesting that ITIH5 negatively affects the development of fat mass. We now tested the role of ITIH5 in vivo and compared ITIH5 +/+ wildtype with ITIH5 −/− knockout mice. Results Genetic deletion of ITIH5 significantly increased adipose tissue mass relative to animal bodyweight (p

Introduction The rise of opioid-free anaesthesia (OFA) aims to reduce postoperative pain while reducing opioid-related side effects during surgery. However, the various adjuvant agents used in OFA complicate the evaluation of their effectiveness and risks. Recent reviews question the clinical benefits of OFA, highlighting the need for thorough evaluation. This protocol describes a network meta-analysis to compare the effectiveness of OFA with opioid-based anaesthesia and will identify key components for optimal postoperative outcomes.Methods and analysis We will perform a systematic search of literature published in English without time restriction in Embase, The Cochrane Library, MEDLINE (via PubMed) and CINAHL, along with Google Scholar for grey literature. The final search will be performed on 1 October 2024. We will include randomised controlled trials with adult patients undergoing surgery with general anaesthesia, excluding preclinical, observational, regional anaesthesia-only and prolonged anaesthesia outside the operating room studies. The primary outcome is postsurgical pain scores, with secondary outcomes including quality of recovery, opioid consumption, adverse effects and long-term events. We will assess bias using the Cochrane risk of bias 2 tool and conduct Bayesian network meta-analyses for pooled estimates. We will report effect estimates as ORs and standardised mean differences with 95% credible intervals and assess certainty using GRADE methodology.Ethics and dissemination Ethics approval is not required for this systematic review. Results will be published in a peer-reviewed journal and presented at national and international anaesthesia and pain management conferences.PROSPERO registration number CRD42024505853.

Abstract Background Pressure ulcers account for a substantial fraction of hospital-acquired pathology, with consequent morbidity and economic cost. Treatments are largely focused on preventing further injury, whereas interventions that facilitate healing remain limited. Intermittent electrical stimulation (IES) increases local blood flow and redistributes pressure from muscle-bone interfaces, thus potentially reducing ulcer progression and facilitating healing. Methods The Pressure Injury Treatment by Intermittent Electrical Stimulation (PROTECT-2) trial will be a parallel-arm multicenter randomized trial to test the hypothesis that IES combined with routine care reduces sacral and ischial pressure injury over time compared to routine care alone. We plan to enroll 548 patients across various centers. Hospitalized patients with stage 1 or stage 2 sacral or ischial pressure injuries will be randomized to IES and routine care or routine care alone. Wound stage will be followed until death, discharge, or the development of an exclusion criteria for up to 3 months. The primary endpoint will be pressure injury score measured over time. Discussion Sacral and ischial pressure injuries present a burden to hospitalized patients with both clinical and economic consequences. The PROTECT-2 trial will evaluate whether IES is an effective intervention and thus reduces progression of stage 1 and stage 2 sacral and ischial pressure injuries. Trial registration ClinicalTrials.gov NCT05085288 Registered October 20, 2021.

Abstract Carbaporphyrin dimers, investigated for their distinctive electronic structures and exceptional properties, have predominantly consisted of systems containing identical subunits. This study addresses the associated knowledge gap by focusing on asymmetric carbaporphyrin dimers with Janus-like characteristics. The synthesis of a Janus-type carbaporphyrin pseudo-dimer 5 is presented. It displays antiaromatic characteristics on the fused side and nonaromatic behavior on the unfused side. A newly synthesized tetraphenylene (TPE) linked bis-dibenzihomoporphyrin 8 and a previously reported dibenzo[g,p]chrysene (DBC) linked bis-dicarbacorrole 9 were prepared as controls. Comprehensive analyses, including 1H NMR spectral studies, single crystal X-ray diffraction analyses, and DFT calculations, validate the mixed character of 5. A further feature of the Janus pseudo-dimer 5 is that it may be transformed into a heterometallic complex, with one side coordinating a Cu(III) center and the other stabilizing a BODIPY complex. This disparate regiochemical reactivity underscores the potential of carbaporphyrin dimers as versatile frameworks, with electronic features and site-specific coordination chemistry controlled through asymmetry. These findings position carbaporphyrin dimers as promising candidates for advances in electronic structure studies, coordination chemistry, materials science, and beyond.

ABSTRACT: Generation of transgenic birds can be achieved by temporal suppression of endogenous spermatogenesis in males prior to primordial germ cell implantation. One of many established methods to induce male sterility is the intraperitoneal injection of busulfan, an alkylating agent. Nevertheless, the use of busulfan injections, which may also affect hematopoietic stem cells, carries the risk of potential lethality in animals. Given their safety and non-toxic nature, it has been demonstrated that intratesticular busulfan injections in mammals are less effective than intraperitoneal injections. This study aimed to compare, for the first time, the sterility and toxicity effects of intraperitoneal vs. intratesticular busulfan injections in quail and chickens. Our experimental design involved a previously established single intraperitoneal busulfan injection of 40 mg/kg of body weight (BW). In quail, busulfan was then administered intratesticularly at 3 different concentrations (6, 12, and 20 mg/kg BW), while in chickens, the working concentration was 20 mg/kg BW. We found that a single intraperitoneal busulfan injection of 40 mg/kg of BW resulted in 100% mortality in the treated roosters. In quails, however, this concentration only caused a temporary suppression of fertility for a 15-d period. Moreover, we found that a higher dose of intratesticular injection of busulfan is required to suppress spermatogenesis in quail (20 mg/kg BW) compared to mammals (4 mg/kg BW). Following these findings, we further confirmed that intratesticular injection of 20 mg/kg BW busulfan into roosters did not affect their overall viability. However, it induced a temporary state of male sterility, consistent with the effects observed with intraperitoneal injections. Hence, our data demonstrate that quail and chicken respond differently to busulfan administration. Furthermore, the present study provides evidence that direct injection into the rooster testes causes less physiological stress than intraperitoneal injection.

Objective:. To determine timing and risk factors associated with readmission within 30 days of discharge following noncardiac surgery. Background:. Hospital readmission after noncardiac surgery is costly. Data on the drivers of readmission have largely been derived from single-center studies focused on a single surgical procedure with uncertainty regarding generalizability. Methods:. We undertook an international (28 centers, 14 countries) prospective cohort study of a representative sample of adults ≥45 years of age who underwent noncardiac surgery. Risk factors for readmission were assessed using Cox regression (ClinicalTrials.gov, NCT00512109). Results:. Of 36,657 eligible participants, 2744 (7.5%; 95% confidence interval [CI], 7.2–7.8) were readmitted within 30 days of discharge. Rates of readmission were highest in the first 7 days after discharge and declined over the follow-up period. Multivariable analyses demonstrated that 9 baseline characteristics (eg, cancer treatment in past 6 months; adjusted hazard ratio [HR], 1.44; 95% CI, 1.30–1.59), 5 baseline laboratory and physical measures (eg, estimated glomerular filtration rate or on dialysis; HR, 1.47; 95% CI, 1.24–1.75), 7 surgery types (eg, general surgery; HR, 1.86; 95% CI, 1.61–2.16), 5 index hospitalization events (eg, stroke; HR, 2.21; 95% CI, 1.24–3.94), and 3 other factors (eg, discharge to nursing home; HR, 1.61; 95% CI, 1.33–1.95) were associated with readmission. Conclusions:. Readmission following noncardiac surgery is common (1 in 13 patients). We identified perioperative risk factors associated with 30-day readmission that can help frontline clinicians identify which patients are at the highest risk of readmission and target them for preventive measures.

Background and Aims: Preoperative cognitive function screening can help identify high-risk patients, but resource-intensive testing limits its widespread use. A novel self-administered tablet computer-based Processing Speed Test (PST) was used to assess cognitive 'executive' function in non-cardiac surgery patients, but the relationship between preoperative test scores and postoperative outcomes is unclear. The primary outcome was a composite of 30-day readmission/death. The secondary outcome was a collapsed composite of discharge to a long-term care facility/death. Exploratory outcomes were 1) time to discharge alive, 2) 1-year mortality and 3) a collapsed composite of postoperative complications. Methods: This retrospective study, after approval, was conducted in elective non-cardiac surgery patients ≥65 years old. We assessed the relationship between processing speed test scores and primary/secondary outcomes using multivariable logistic regression, adjusting for potential confounding variables. Results: Overall 1568 patients completed the PST, and the mean ± standard deviation test score was 33 ± 10. The higher PST score is associated with better executive function. A 10-unit increase in the test score was associated with an estimated 19 lower 30-day readmission/death odds, with an odds ratio (OR) and 95 confidence interval (CI) of 0.81 (0.68, 0.96) (P = 0.015). Similarly, 10-unit increase in test score was associated with an estimated 26 lower odds of long-term care need/death, with OR (95 CI) of 0.74 (0.61, 0.91) (P = 0.004). We also found statistically significant associations between the test scores and time to discharge alive and to 1-year mortality, however, not with a composite of postoperative complications. Conclusion: Elderly non-cardiac surgery patients with better PST scores were less likely to be readmitted, need long-term care after discharge or die within 30 days. Preoperative assessment of cognitive function using a simple self-administered test is feasible and may guide perioperative care. Keywords: Cognition, processing speed test, readmission, non-cardiac surgery, Author(s): Kamal Maheshwari (corresponding author) [1,2]; Esra Kutlu Yalcin [2]; Dong Wang [2,3]; Edward J. Mascha [2,3]; Anson Rosenfeldt [4]; Jay L. Alberts [4]; Alparslan Turan [1,2]; Daniel I. Sessler [...]

Abstract Kaplan–Meier (KM) survival analyses based on complex patient categorization due to the burgeoning volumes of genomic, molecular and phenotypic data, are an increasingly important aspect of the biomedical researcher’s toolkit. Commercial statistics and graphing packages for such analyses are functionally limited, whereas open-source tools have a high barrier-to-entry in terms of understanding of methodologies and computational expertise. We developed surviveR to address this unmet need for a survival analysis tool that can enable users with limited computational expertise to conduct routine but complex analyses. surviveR is a cloud-based Shiny application, that addresses our identified unmet need for an easy-to-use web-based tool that can plot and analyse survival based datasets. Integrated customization options allows a user with limited computational expertise to easily filter patients to enable custom cohort generation, automatically calculate log-rank test and Cox hazard ratios. Continuous datasets can be integrated, such as RNA or protein expression measurements which can be then used as categories for survival plotting. We further demonstrate the utility through exemplifying its application to a clinically relevant colorectal cancer patient dataset. surviveR is a cloud-based web application available at https://generatr.qub.ac.uk/app/surviveR , that can be used by non-experts users to perform complex custom survival analysis.