Sana Klinikum

Arthrofibrosis is a frequent complication after total knee arthroplasty (TKA) and remains difficult to diagnose early due to the lack of reliable biomarkers. Excessive extracellular matrix (ECM) remodeling is driven by core signaling cascades, notably the Transforming Growth Factor-beta 1 (TGF-ß1) and Wnt/ß-catenin pathways. Xylosyltransferase-I (XT-I), a key enzyme regulating proteoglycan biosynthesis, has emerged as a critical downstream effector and potential indicator of early fibrotic activity. This narrative review summarizes clinical and experimental findings on XT-I in joint fibrosis, with emphasis on its role within the molecular network of key pro-fibrotic signaling and its diagnostic and translational potential in knee arthrofibrosis. XT-I is consistently upregulated in fibrotic synovial fibroblasts and synovial fluid of arthrofibrotic knees, correlating with ECM remodeling and myofibroblast activation induced by both TGF-ß1and Wnt/ß-catenin signaling. XT-I demonstrates local rather than systemic diagnostic value and may serve as an early fibrosis indicator. XT-I holds promise as a synovial biomarker and potential therapeutic target in arthrofibrosis. Targeting XT-I, potentially in combination with core pathway inhibitors (e.g., Wnt/ß-catenin inhibitors), may offer a refined strategy for early diagnosis and postoperative management in TKA patients.

Abstract BACKGROUND Patients with CNS-WHO G2 and G3 IDH-mutant glioma commonly achieve long survival after chemoradiotherapy. Proton beam therapy (PBT) can be used for this group to reduce the dose to uninvolved brain and, consequently, late toxicity involving mostly deterioration of neurocognitive functioning. In the present study we analyzed the disease control and patient-reported outcomes (PROs) from our institution. MATERIAL AND METHODS This prospective observational study included 30 patients with IDH1/2-mutant CNS-WHO G2 and G3 glioma treated with pencil beam scanning PBT between 2017 and 2021. The total dose was 54.04 Gy (RBE)/28 fractions for G2 and 60 Gy (RBE)/30 fractions for G3 disease. 25 patients (83.6%) received concomitant and/or adjuvant chemotherapy. PROs included quality of life (QoL) questionnaires (EORTC QLQ-C30 and EORTC QLQ-BN20) and a battery of neurocognitive tests: Hopkins verbal learning test - revised, trail making test and controlled oral word association. The assessments were routinely performed at baseline, end of treatment, at 3, 6, 12 months post PBT and afterwards annually. RESULTS The median follow-up was 62.5 months (range: 33.8 - 85.6). The actuarial 5-year progression-free and overall survival were 65.8% and 89.7%, respectively. The presence of MGMT promoter methylation corresponded to reduced risk of progression (HR = 0.24, 95%CI: 0.06-0.9, p = 0.034) and death (HR = 0.05, 95%CI: 0.005-0.56, p = 0.015). No other significant clinical risk factors were identified, including the tumor grade. The rates of acute and late ≥G3 complications were 6.6% and 0%, respectively. For QoL assessment, statistically significant longitudinal differences were seen in form of improvement of social functioning (Χηι2 = 17.8, p = 0.037) and future uncertainty (Χηι2 = 23.35, p = 0.006) as well as hair loss (Χηι2 = 27.9, p = 0.001) and itchy skin (Χηι2 = 17.22, p = 0.045), where after an expected initial symptom increase throughout the treatment, a full resolution was subsequently seen. No significant longitudinal changes were seen for neurocognitive assessment with high p-values of all scales (0.48 - 0.86) indicating a stable course of neurocognitive functioning. CONCLUSION Proton therapy is an effective and safe treatment modality of IDH1/2-mutant grade 2 and 3 glioma. It offers satisfactory disease control and does not lead to any long-term decline of quality of life and neurocognitive functioning. Comparable results for grade 2 and 3 tumors suggest that the reimbursement schemes should routinely involve both of these groups.

Post-traumatic stress symptoms (PTSSs) are associated with an imbalanced time perspective (TP) as well as with unhealthy substance use. Although neurodevelopmental processes during adolescence may impact PTSS, most etiological models of post-traumatic stress disorder (PTSD) are derived from studies with adults and neglect possible distinctive characteristics in adolescent PTSD. This study examined possible direct and mediated relations between exposure to potentially traumatic experiences (EPTEs) and PTSS with TP as a potential mediator. In addition, the study investigated the direct and indirect effects of EPTE, TP, and PTSS on cannabis use. The aim of this study was to investigate whether findings from adult studies can be transferred to adolescent PTSD. One hundred and five patients between 14 and 20 years of age were recruited from child and adolescent psychiatric units. They answered questionnaires to assess EPTE, PTSS, TP, and cannabis use. Participants with clinically relevant PTSS showed imbalanced TP with a high orientation to negative past and a low orientation to positive past and future. Higher EPTE was associated with higher level of PTSS, but TP mediated the level of PTSS in this relation. PTSS predicted the frequency of cannabis use. It may therefore be beneficial to consider TP in PTSD therapy with the aim of reducing deviation from balanced TP and PTSS and preventing comorbid substance use.

Thigh-lift surgery is considered a complication-prone operation, with publications reporting complication rates between 35% and 74%. These studies have not specifically evaluated the effects of each technique on the complication rates. This study presents complication rates for the 3 most common surgical techniques (T, L, and I thigh lifts) and evaluates possible causes in the largest reported cohort of patients with massive weight loss. A retrospective cohort study of 750 thigh lifts in 375 patients from 2008 through 2023 was performed. The data collected were collated into the 3 thigh-lift techniques and analyzed according to preoperative risk factors and postoperative complications. The overall complication rate was the lowest for I thigh lifts (40.3%), followed by T thigh lifts (66.6%) and then L thigh lifts (73.9%). An analysis of major complications revealed rates of 9.5%, 33%, and 39.1%, respectively. Smoking, a body mass index of 30 or above, higher temperatures, and prolonged operative duration were found to increase the risk of complications. The I incision technique for thigh-lift surgery after massive weight loss has fewer complications, reduces scarring and operating times, and has a low revision rate.

BackgroundThe number of CIEDs implantations has steadily increased over the past decade and is one of the most common procedures in cardiology. There are approximately 230 actively implanting hospitals in the German federal state North Rhine-Westphalia (NRW) with 17.9 million inhabitants. A large variation in implantation numbers exists between hospitals, from < 10 to 1,234 cases per year. Peri-/post-operative complications (C) such as pneumothorax, hemothorax, pericardial effusion, pocket hematoma, wound infection and lead problems (dislocation and dysfunction) are not uncommon after pacemaker (PM) and defibrillator (ICD) implantation. We analyzed whether the C rate depends on the number of implantations in the hospital which has not been clarified statistically for such a wide variability of implantation procedures.MethodsThe analysis is based on the data of all first implantation of CIEDs (including CRT systems) performed between January 1st, 2010 and December 31st, 2020 in any hospital in NRW. All peri-/post-operative C documented as part of the mandatory quality assurance were recorded. A potential association between implantation volume and quality (VOR) was evaluated using the statistical software R, based on the report on "Data evaluation on minimum quantities" (IQTIG 2020). The method includes risk adjustment and takes into account the high statistical uncertainty with small case numbers.ResultsA total of 249,615 cases were examined (PM 73.4%, ICD 26.6%, male 61.3%). ICD patients (pts) were younger (66 y) than PM pts (76 y, p < 0.001). The total number of C was 2.4% (PM 2.6%, ICD 1.6, p<0.001). The most C was lead related at 1.5% (PM 1.7%, ICD 0.7%, p<0.001). Pts with C were older (median 78 y vs 76 y, p<0.001). The forest plot analysis of the general risk factors resulted in an odds ratio (OR) in PM/ICD pts for the ASA class 3 of 1.7/2.1 and the class 4 of 4.2/6.1 (reference ASA class 1). ORs for the type of PM-system were 1.5/2.2 for DDD and 1.0/2.1 for CRT (reference VVI). The VOR revealed a statistically significant relationship between the number of implantations and the occurrence of C, especially for PM patients (p<0.001, AUC 0.7) (see figure). Further evaluation showed that, for example, with a cut-off of 50 annual implantations ~59 of 377 (~16%) C could be avoided and ~2,500 of 16,073 (~16%) pts would have to be redirected to other hospitals. In case of cut-off of 25 annual implantations ~30 of 377 (~8%) C could be avoided and ~850 of 16,073 (~5%) pts. would have to be redirected to other hospitals.ConclusionIn addition to the risk factors that have been analyzed in the literature, such as age, high ASA class or type of system, the VOR demonstrated a significant influence of the implantation volume. With a relevant number of possibly avoidable C, minimum quantities can be justified and consequences can be estimated.VOR for PM implantations in 2010-2020