Use of negative pressure wound therapy in patients with fracture-related infection more than doubles the risk of recurrence

Purpose: Fracture-related infection (FRI) is one of the most serious complications in orthopedic trauma surgery. Despite its widespread use, the role of Negative Pressure Wound Therapy (NPWT) remains controversial in the management pathway of FRI. The aim of this study was to assess the relationship between the application of NPWT and its duration and recurrence of infection in operatively treated FRI patients. Patients and Methods: This is a retrospective cohort study based on the FRI database of three level 1 Trauma Centres. Included patients had to be at least 16 years of age and surgically treated for FRI between January 1st 2015 and September 1st 2020. Patients were subdivided in either the NPWT group, when NPWT was applied as part of the FRI treatment, or in the control group, when no NPWT had been applied. To limit confounding, patients were excluded if they (also) underwent NPWT prior to the diagnosis of FRI. The relation between the duration of NPWT during FRI treatment and the recurrence rate of infection was analyzed using a multivariable logistic regression model. Results: A total of 263 patients were included, 99 in the NPWT group and 164 in the control group. The median duration of NPWT was 18.0 (IQR 15.8) days. In the NPWT group, 28 patients (28.3%) developed a recurrent FRI. In the control group, 19 patients (11.6%) had a recurrent FRI (p = 0.001, 95% CI [0.174 – 0.635]). In the NPWT group there were no significant differences in baseline characteristics between the recurrence and non-recurrence group. The duration of NPWT was associated with a higher risk of recurrence of infection (p = 0.013, OR 1.036, 95% CI [1.008 – 1.066]). Conclusion: Delayed wound closure with the application of NPWT increased the risk of recurrence of infection in patients with soft tissue defects after FRI treatment. Therefore, it is advised to consider NPWT only as a short-term (e.g. few days) necessity to bridge the period until definitive wound closure can be established

Electrospinning repellents in polyvinyl alcohol-nanofibres for obtaining mosquito-repelling fabrics

Recently, the use of repellents for preventing the transmission of mosquito-borne diseases is getting increasingly more attention. However, most of the current repellents are volatile in nature and must be frequently re-applied as their efficacy is only limited to a short period of time. Therefore, a slow release and abrasion-resistant mechanism is needed for prolonging the protection time of the repellents. The focus of this study is on the direct micro-encapsulation of repellents from an emulsion and integration of already encapsulated repellents into nanofibres via electrospinning. Different repellents were electrospun in polyvinyl alcohol (PVA) nanofibrous structures, namely p-menthane-3,8-diol micro-capsules, permethrin, chilli and catnip oil. The repellents were successfully incorporated in the nanofibres and the tensile properties of the resulting samples did not have a significant change. This means that the newly created textiles were identical to current PVA nanofibrous textiles with the added benefit of being mosquito repellent. Principally, all incorporated repellents in the nanofibrous structures showed a significantly reduced number of mosquito landings compared to the control. Consequently, the currently described method resulted in a new and very effective repelling textile material that can be used in the prevention against mosquito-associated diseases

Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis

Abstract Objective MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature in the serum of systemic sclerosis (SSc) patients and we further assessed their expression in early stages of the disease. Methods The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Three miRNAs were examined in an additional cohort of 107 SSc patients and 24 healthy donors by single qPCR. MiR-483-5p expression was further analysed in the serum of patients with localized scleroderma (LoS) (n = 22), systemic lupus erythematosus (SLE) (n = 33) and primary Sjogren's syndrome (pSS) (n = 23). The function of miR-483-5p was examined by transfecting miR-483-5p into primary human dermal fibroblasts and pulmonary endothelial cells. Results 30 miRNAs were significantly increased in patients with SSc. Of these, miR-483-5p showed reproducibly higher levels in an independent SSc cohort and was also elevated in patients with preclinical-SSc symptoms (early SSc). Notably, miR-483-5p was not differentially expressed in patients with SLE or pSS, whereas it was up-regulated in LoS, indicating that this miRNA could be involved in the development of skin fibrosis. Consistently, miR-483-5p overexpression in fibroblasts and endothelial cells modulated the expression of fibrosis-related genes. Conclusions Our findings showed that miR-483-5p is up-regulated in the serum of SSc patients, from the early stages of the disease onwards, and indicated its potential function as a fine regulator of fibrosis in SSc

Interleukin-1 Receptor-Associated Kinase-3 Is a Key Inhibitor of Inflammation in Obesity and Metabolic Syndrome

BACKGROUND: Visceral obesity is associated with the rising incidence of type 2 diabetes and metabolic syndrome. Low-grade chronic inflammation and oxidative stress synergize in obesity and obesity-induced disorders. OBJECTIVE: We searched a cluster of molecules that support interactions between these stress conditions in monocytes. METHODS: RNA expressions in blood monocytes of two independent cohorts comprising 21 and 102 obese persons and 46 age-matched controls were determined by microarray and independently validated by quantitative RT-PCR analysis. The effect of three-month weight loss after bariatric surgery was determined. The effect of RNA silencing on inflammation and oxidative stress was studied in human monocytic THP-1 cells. RESULTS: Interleukin-1 receptor-associated kinase-3 (IRAK3), key inhibitor of IRAK/NFκB-mediated chronic inflammation, is downregulated in monocytes of obese persons. Low IRAK3 was associated with high superoxide dismutase-2 (SOD2), a marker of mitochondrial oxidative stress. A comparable expression profile was also detected in visceral adipose tissue of the same obese subjects. Low IRAK3 and high SOD2 was associated with a high prevalence of metabolic syndrome (odds ratio: 9.3; sensitivity: 91%; specificity: 77%). By comparison, the odds ratio of high-sensitivity C-reactive protein, a widely used marker of systemic inflammation, was 4.3 (sensitivity: 69%; specificity: 66%). Weight loss was associated with an increase in IRAK3 and a decrease in SOD2, in association with a lowering of systemic inflammation and a decreasing number of metabolic syndrome components. We identified the increase in reactive oxygen species in combination with obesity-associated low adiponectin and high glucose and interleukin-6 as cause of the decrease in IRAK3 in THP-1 cells in vitro. CONCLUSION: IRAK3 is a key inhibitor of inflammation in association with obesity and metabolic syndrome. Our data warrant further evaluation of IRAK3 as a diagnostic and prognostic marker, and as a target for intervention

Adjusting for time-varying confounding in the subdistribution analysis of a competing risk

Despite decades of research in the medical literature, assessment of the attributable mortality due to nosocomial infections in the intensive care unit (ICU) remains controversial, with different studies describing effect estimates ranging from being neutral to extremely risk increasing. Interpretation of study results is further hindered by inappropriate adjustment (a) for censoring of the survival time by discharge from the ICU, and (b) for time-dependent confounders on the causal path from infection to mortality. In previous work (Vansteelandt et al. Biostatistics 10:46-59), we have accommodated this through inverse probability of treatment and censoring weighting. Because censoring due to discharge from the ICU is so intimately connected with a patient's health condition, the ensuing inverse weighting analyses suffer from influential weights and rely heavily on the assumption that one has measured all common risk factors of ICU discharge and mortality. In this paper, we consider ICU discharge as a competing risk in the sense that we aim to infer the risk of 'ICU mortality' over time that would be observed if nosocomial infections could be prevented for the entire study population. For this purpose we develop marginal structural subdistribution hazard models with accompanying estimation methods. In contrast to subdistribution hazard models with time-varying covariates, the proposed approach (a) can accommodate high-dimensional confounders, (b) avoids regression adjustment for post-infection measurements and thereby so-called collider-stratification bias, and (c) results in a well-defined model for the cumulative incidence function. The methods are used to quantify the causal effect of nosocomial pneumonia on ICU mortality using data from the National Surveillance Study of Nosocomial Infections in ICU's (Belgium)

Functional outcome and general health status after plate osteosynthesis of posterior malleolus fractures - The quest for eligibility

INTRODUCTION: The necessity for reduction and fixation of posterior malleolus fractures remains under debate. Therefore, we assessed the functional outcome and quality after plate osteosynthesis of the posterior malleolus, identified the main drivers of outcome and aimed to determine which patient and fracture type are eligible for plate osteosynthesis of the posterior malleolus. MATERIALS AND METHODS: A prospective patient cohort of 50 patients with an ankle fracture including the posterior malleolus underwent plate osteosynthesis via a posterior approach, and was compared to a retrospective patient cohort of 85 consecutive patients who did not. Twenty-five demographic, operative and postoperative characteristics were assessed. Outcome was recorded using questionnaires: AOFAS, EQ-5D, EQ-5D-VAS, EQ-5D-TTO, sensory nerve-associated complications, and flexion deficit of the hallux. RESULTS: Direct reduction and plate osteosynthesis of posterior malleolus fractures was inferior to non-operative treatment. Subanalysis of trimalleolar fractures revealed that the outcome of plate osteosynthesis was equal. Both fracture type and plate osteosynthesis were independent drivers of the outcome; Haraguchi type 3 posterior malleolus fractures were associated with the best functional outcome and quality of life scores. Comorbidity, age, postoperative complications and reintervention largely determined the outcome. Up to 30% of the patients reported (temporarily) flexion deficit of the hallux and 38% numbness at the lateral side of the foot. CONCLUSIONS: There is no indication for routine plate osteosynthesis of all posterior malleolus fractures. Careful patient selection, less invasive surgery and modified postoperative rehabilitation seem mandatory to improve the outcome and prevent adverse effects.status: publishe

An experiment on the impact of coaches’ and athlete leaders’ competence support on athletes’ motivation and performance

Purpose Grounded in the Cognitive Evaluation Theory, the present experiment aimed to compare the relative impact of competence support provided by coaches versus athlete leaders on players’ competence satisfaction, intrinsic motivation, and performance. Methods We recruited 18 existing competitive male basketball teams (ie, 126 players) to participate in the experiment. Each team was randomly assigned to one of three conditions: (a) the coach provided competence support (ie, by encouraging, providing positive feedback, and expressing team confidence); (b) the athlete leader provided competence support; or (c) neither the coach, nor the athlete leader provided competence support (ie, control condition). Results Teams in which the athlete leader provided competence support reported higher levels of competence satisfaction and intrinsic motivation than teams in the control condition, a difference that did not emerge when the coach provided competence support. Furthermore, teams in which either the coach or the athlete leader supported team members’ competence performed better compared to teams in the control group. Conclusion Our findings highlight the importance of providing competence support to enhance team performance. Given athlete leaders’ unique impact on teammates’ competence satisfaction and motivation, instructing athlete leaders how to provide competence support constitutes an important motivational pathway for coaches to optimize team functioning.status: publishe

Bile Acid Signaling Pathways from the Enterohepatic Circulation to the Central Nervous System

Bile acids are best known as detergents involved in the digestion of lipids. In addition, new data in the last decade have shown that bile acids also function as gut hormones capable of influencing metabolic processes via receptors such as FXR (farnesoid X receptor) and TGR5 (Takeda G protein-coupled receptor 5). These effects of bile acids are not restricted to the gastrointestinal tract, but can affect different tissues throughout the organism. It is still unclear whether these effects also involve signaling of bile acids to the central nervous system (CNS). Bile acid signaling to the CNS encompasses both direct and indirect pathways. Bile acids can act directly in the brain via central FXR and TGR5 signaling. In addition, there are two indirect pathways that involve intermediate agents released upon interaction with bile acids receptors in the gut. Activation of intestinal FXR and TGR5 receptors can result in the release of fibroblast growth factor 19 (FGF19) and glucagon-like peptide 1 (GLP-1), both capable of signaling to the CNS. We conclude that when plasma bile acids levels are high all three pathways may contribute in signal transmission to the CNS. However, under normal physiological circumstances, the indirect pathway involving GLP-1 may evoke the most substantial effect in the brai