Predictors of functional improvement in the short term after MitraClip implantation in patients with secondary mitral regurgitation

Background and objectives MitraClip implantation is an established therapy for secondary mitral regurgitation (MR) in high-risk patients and has shown to improve several important outcome parameters such as functional capacity. Patient selection is both challenging and crucial for achieving therapeutic success. This study investigated baseline predictors of functional improvement as it was quantified by the six-minute walk distance (6MWD) after transcatheter mitral valve repair. Methods and results We retrospectively analyzed 79 patients with secondary MR treated with MitraClip implantation at an academic tertiary care center. Before and four weeks after the procedure, all patients underwent comprehensive clinical assessment, six-minute walk tests and echocardiography. 6MWD significantly improved after MitraClip therapy (295 m vs. 265 m, p < 0.001). A linear regression model including seven clinical baseline variables significantly predicted the change in 6MWD (p = 0.002, R-2 = 0.387). Female gender, diabetes mellitus and arterial hypertension were found to be significant negative predictors of 6MWD improvement. At baseline, female patients had significant higher left ventricular ejection fraction (49% vs. 42%, p = 0.019) and lower 6MWD (240 m vs. 288 m, p = 0.034) than male patients. Conclusion MitraClip implantation in secondary MR significantly improves functional capacity in high risk patients even in the short term of four weeks after the procedure. Female gender, diabetes mellitus and arterial hypertension are baseline predictors of a less favourable functional outcome. While further validation in a larger cohort is recommended, these parameters may improve patient selection for MitraClip therapy

Special orthopaedic geriatrics (SOG) - a new multiprofessional care model for elderly patients in elective orthopaedic surgery: a study protocol for a prospective randomized controlled trial of a multimodal intervention in frail patients with hip and knee replacement

Background Due to demographic change, the number of older people in Germany and worldwide will continue to rise in the coming decades. As a result, the number of elderly and frail patients undergoing total hip and knee arthroplasty is projected to increase significantly in the coming years. In order to reduce risk of complications and improve postoperative outcome, it can be beneficial to optimally prepare geriatric patients before orthopaedic surgery and to provide perioperative care by a multiprofessional orthogeriatric team. The aim of this comprehensive interventional study is to assess wether multimorbid patients can benefit from the new care model of special orthopaedic geriatrics (SOG) in elective total hip and knee arthroplasty. Methods The SOG study is a registered, monocentric, prospective, randomized controlled trial (RCT) funded by the German Federal Joint Committee (GBA). This parallel group RCT with a total of 310 patients is intended to investigate the specially developed multimodal care model for orthogeriatric patients with total hip and knee arthroplasty (intervention group), which already begins preoperatively, in comparison to the usual orthopaedic care without orthogeriatric co-management (control group). Patients ≥70 years of age with multimorbidity or generally patients ≥80 years of age due to increased vulnerability with indication for elective primary total hip and knee arthroplasty can be included in the study. Exclusion criteria are age < 70 years, previous bony surgery or tumor in the area of the joint to be treated, infection and increased need for care (care level ≥ 4). The primary outcome is mobility measured by the Short Physical Performance Battery (SPPB). Secondary outcomes are morbidity, mortality, postoperative complications, delirium, cognition, mood, frailty, (instrumental) activities of daily living, malnutrition, pain, polypharmacy, and patient reported outcome measures. Tertiary outcomes are length of hospital stay, readmission rate, reoperation rate, transfusion rate, and time to rehabilitation. The study data will be collected preoperative, postoperative day 1 to 7, 4 to 6 weeks and 3 months after surgery. Discussion Studies have shown that orthogeriatric co-management models in the treatment of hip fractures lead to significantly reduced morbidity and mortality rates. However, there are hardly any data available on the elective orthopaedic care of geriatric patients, especially in total hip and knee arthroplasty. In contrast to the care of trauma patients, optimal preoperative intervention is usually possible

Multiomic ALS signatures highlight subclusters and sex differences suggesting the MAPK pathway as therapeutic target

Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease and lacks effective disease-modifying treatments. This study utilizes a comprehensive multiomic approach to investigate the early and sex-specific molecular mechanisms underlying ALS. By analyzing the prefrontal cortex of 51 patients with sporadic ALS and 50 control subjects, alongside four transgenic mouse models (C9orf72-, SOD1-, TDP-43-, and FUS-ALS), we have uncovered significant molecular alterations associated with the disease. Here, we show that males exhibit more pronounced changes in molecular pathways compared to females. Our integrated analysis of transcriptomes, (phospho)proteomes, and miRNAomes also identified distinct ALS subclusters in humans, characterized by variations in immune response, extracellular matrix composition, mitochondrial function, and RNA processing. The molecular signatures of human subclusters were reflected in specific mouse models. Our study highlighted the mitogen-activated protein kinase (MAPK) pathway as an early disease mechanism. We further demonstrate that trametinib, a MAPK inhibitor, has potential therapeutic benefits in vitro and in vivo, particularly in females, suggesting a direction for developing targeted ALS treatments

Prädiktoren für ein ausbleibendes kardiales reverse remodeling nach perkutaner Mitralklappenreparatur mittels MitraClip Implantation

Die sekundäre Mitralklappeninsuffizienz stellt als schwere kardiale Erkrankung mit steigender Prävalenz bei meist multimorbiden älteren Patienten eine zunehmende Herausforderung dar. Dementsprechend gilt es Therapieoptionen bereitzustellen, die minimalinvasiv und risikoarm bei bestmöglichem Ergebnis für die Patienten sind. Für die Behandlung der schweren fortgeschrittenen Mitralklappeninsuffizienz stellt die perkutane Mitralklappenreparatur mittels MitraClip eine wertvolle Alternative zur konventionellen Operation dar, die in den meisten Fällen aufgrund des hohen Risikos keine reale Therapieoption mehr bietet. Es hat sich gezeigt, dass die MitraClip Implantation einige Monate postinterventionell bei bestimmten Patienten zu kardialem reverse remodeling führt. In der Indikationsstellung ist es bedeutsam, diejenigen Patienten zu identifizieren, die ein höheres Risiko für schlechteres kardiales reverse remodeling nach MitraClip Implantation haben und bei denen ein schlechteres Outcome mit erhöhter Mortalität zu erwarten ist. Reverse remodeling stellt das echokardiographische Korrelat eines sich strukturell regenerierenden Herzens dar. Dieses wird durch Abnahme von LVEDD, LVESD, LVSI, LA-Diameter und LAVI, sowie durch Zunahme der LVEF definiert. In der vorliegenden monozentrischen retrospektiven Studie wurden 125 Patienten mit schwerer funktioneller und gemischter Mitralklappeninsuffizienz auf echokardiographische, laborchemische und klinische Prädiktoren für ein ausbleibendes kardiales reverse remodeling untersucht. Die Datenerhebung erfolgte zu den Zeitpunkten präinterventionell, postinterventionell vor Entlassung aus der Klinik, sowie nach 1, nach 3-6 und nach 12 Monaten. Das Kollektiv war durchschnittlich 74,6 ± 8,5 Jahre alt bei etwa gleicher Geschlechterausgangsverteilung und zu 95% den Herzinsuffizienzklassen NYHA 3 und 4 zugehörig. Durchwegs konnte gezeigt werden, dass sich der Grad der Mitralklappeninsuffizienz und das NYHA-Stadium nach Clip Implantation signifikant besserten. Insbesondere konnten in der Regressionsanalyse hohes NTproBNP vor Intervention (∆LVEDD nach Intervention, ∆LVEDD 12 Monate, ∆LVESD 12 Monate, ∆LVEF 1 Monat), reduzierte Ejektionsfraktion (∆LAVI 3-6 Monate), männliches Geschlecht (∆LVEDD 1 Monat, ∆LVEDD 3-6 Monate, ∆LVESD 3-6 Monate, ∆LVEF nach Intervention, ∆LVEF 3-6 Monate, ∆LAVI 12 Monate) und Z. n. CABG (∆LVEDD 12 Monate, ∆LVESD 12 Monate) als signifikante Prädiktoren für schlechteres kardiales reverse remodeling identifiziert werden (alle p-Werte < 0.05). Die Datenlage zu Prädiktoren eines kardialen reverse remodelings nach MitraClip Implantation ist begrenzt. Die eigenen Ergebnisse machen deutlich, dass Patienten mit den Eigenschaften hohes NTproBNP, Z. n. CABG, reduzierte LVEF und männliches Geschlecht trotz Verbesserung der Klappeninsuffizienz und des NYHA-Stadiums durch die MitraClip Therapie weniger reverse remodeling erreichen können. Diese Erkenntnisse können zu einer verbesserten Patientenselektion bei der Indikationsstellung zur MitraClip Implantation beitragen