Citations

ObjectiveThis study assessed the relationship between speech and language impairment and outcome in a multicenter cohort of isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD).MethodsPatients with iRBD from 7 centers speaking Czech, English, German, French, and Italian languages underwent a detailed speech assessment at baseline. Story‐tale narratives were transcribed and linguistically annotated using fully automated methods based on automatic speech recognition and natural language processing algorithms, leading to the 3 distinctive linguistic and 2 acoustic patterns of language deterioration and associated composite indexes of their overall severity. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow‐up. The Cox proportional hazard was performed to evaluate the predictive value of language patterns for phenoconversion over a follow‐up period of 5 years.ResultsOf 180 patients free of parkinsonism or dementia, 156 provided follow‐up information. After a mean follow‐up of 2.7 years, 42 (26.9%) patients developed neurodegenerative disease. Patients with higher severity of linguistic abnormalities (hazard ratio [HR = 2.35]) and acoustic abnormalities (HR = 1.92) were more likely to develop a defined neurodegenerative disease, with converters having lower content richness (HR = 1.74), slower articulation rate (HR = 1.58), and prolonged pauses (HR = 1.46). Dementia‐first (n = 16) and parkinsonism‐first with mild cognitive impairment (n = 9) converters had higher severity of linguistic abnormalities than parkinsonism‐first with normal cognition converters (n = 17).InterpretationAutomated language analysis might provide a predictor of phenoconversion from iRBD into synucleinopathy subtypes with cognitive impairment, and thus can be used to stratify patients for neuroprotective trials. ANN NEUROL 2024;95:530–543

Background Distal transradial artery access (dTRA) has received increasing consideration for performing diagnostic cerebral angiography and neurointerventional procedures. In this meta-analysis, we aim to evaluate the safety and efficacy of dTRA compared to conventional transradial access (cTRA) for cerebral angiography and neurointerventions. Method A systematic review and meta-analysis were conducted on studies investigating outcomes of dTRA and cTRA in neurointerventions. The primary outcome was technical success rates. Secondary outcomes included access site complication rates, crossover rates to alternative vessels, fluoroscopy time, and contrast volume. The random effects model was used to calculate the mean difference (MD) and odds ratios (OR) with 95% confidence intervals (Cl). Results Eight retrospective observational studies with a total of 1477 patients who underwent 1175 diagnostic cerebral angiography and 516 neurointerventional procedures using 546 dTRA and 1164 cTRA approaches were included in our meta-analysis. The technical success rate was similar between dTRA and cTRA groups (95.8% vs 91.4%; OR:1.65; 95% Cl: 0.52 to 5.22; P = 0.40). Similarly, no difference was seen in dTRA and cTRA regarding access site complications (2% vs 1.4%; OR: 1.31; 95% CI: 0.47 to 3.61; P = 0.61) and access site crossover (2.1% vs 5.3%; OR: 0.55; 95% Cl: 0.28 to 1.05; P = 0.07). After resolving heterogeneity among included studies, dTRA was associated with a shorter fluoroscopy time (MD: −0.91 min; 95% CI: −1.74 to −0.09; P = 0.03) and lower contrast volume (MD: −8.32 mL; 95% CI = −14.7 to −1.94; P = 0.011). Conclusion Our findings suggest that the dTRA approach is a safe and effective alternative to the cTRA approach in patients undergoing cerebral angiography and neurointerventions.

Key Clinical MessagePre‐bariatric surgery dietary recommendations should take into account daily protein intake and other risk factors for kidney injury. This is important because a high protein intake can potentially lead to kidney injury.AbstractBariatric surgery has been shown to be a highly effective intervention for achieving weight loss and reducing obesity related‐comorbidities. Acute kidney injury (AKI) is considered one of the common complications in perioperative and post‐bariatric surgery. However, pre‐bariatric surgery AKI has never been reported. Several studies demonstrated that pre‐bariatric surgery weight loss improved surgical outcomes and decrease postoperative complications. Some diet regimens have been introduced including low‐caloric diet (LCD), very‐low caloric diet (VLCD), and very‐low caloric ketogenic diet (VLCKD). We present a patient who develops AKI after 10 days of having a high‐protein diet from a pre‐bariatric weight loss strategy.

Abstract In the development of various strategies of anti-CD19 immunotherapy for the treatment of B-cell malignancies, it remains unclear whether CD19 monoclonal antibody therapy impairs subsequent CD19-targeted chimeric antigen receptor T-cell (CART19) therapy. We evaluated the potential interference between the CD19-targeting monoclonal antibody tafasitamab and CART19 treatment in preclinical models. Concomitant treatment with tafasitamab and CART19 showed major CD19 binding competition, which led to CART19 functional impairment. However, when CD19+ cell lines were pretreated with tafasitamab overnight and the unbound antibody was subsequently removed from the culture, CART19 function was not affected. In preclinical in vivo models, tafasitamab pretreatment demonstrated reduced incidence and severity of cytokine release syndrome and exhibited superior antitumor effects and overall survival compared with CART19 alone. This was associated with transient CD19 occupancy with tafasitamab, which in turn resulted in the inhibition of CART19 overactivation, leading to diminished CAR T apoptosis and pyroptosis of tumor cells.

When students feel successful, they tend to be more confident in their capabilities (i.e., higher self-efficacy), which is associated with improved performance, engagement, and self-regulation. Yet, the way in which learners interpret their experiences is less well-understood. Learners’ views of failure (i.e., failure mindset) are potential lenses through which early adolescent learners perceive and interpret efficacy-relevant information. The relationship between failure mindset and self-efficacy may be particularly important to consider in STEM-related domains like robotics where failure is common. The purpose of this study was to investigate the relationship between young adolescents’ failure mindset and their robotics self-efficacy development. Using mixed methods, we considered how students’ reported failure mindset levels were related to what has made them more or less confident in robotics. We also considered the relationship between failure mindset and robotics self-efficacy. Overall, the findings suggest that early adolescent learners’ failure mindset is related to the efficacy-relevant information they pay attention to in robotics, and, in turn, is associated with their reported robotics self-efficacy. The details of these relationships varied between elementary and middle school students. As there is a social push to normalize failures in educational settings, findings from this study offer an important insight into how students may interpret those failures.

Background: Anthracyclines are highly effective chemotherapeutics, but their use is limited by Anthracycline-Induced Cardiotoxicity (AIC) with notable decline in ejection fraction (EF). Recovery of cardiac function is slow and often only partial, mandating novel and more efficacious treatment approaches to AIC. Hypothesis: Based on high throughput genetic screening in zebrafish we identified autophagy activation, e.g. via Atg7, a key protein in the induction of autophagy, as a potential novel translational therapeutic approach to AIC. Methods: In a mouse model of cardiotoxicity (4 x weekly 5 mg/kg intravenous doxorubicin treatment) two approaches were tested starting one week after the last treatment: 1) AdenoAssociated Viral vector 9-mediated overexpression of Atg7 in the myocardium (AAV9-ATG7, one time injection) and 2) 3 FDA approved autophagy activating (FAA) drugs (pravastatin (40 mg/kg), spironolactone (20 mg/kg) and empagliflozin (10 mg/kg), by daily gavage). Echocardiograms were performed at baseline, before start of therapy and after 28 days before sacrifice. Results: All three FAA drugs were able to rescue AIC and Atg7 overexpression by AAV9 alone sufficed to rescue from AIC (Figure 1). All three FAA drugs were able to either restore Atg7 levels to baseline (pravastatin and empagliflozin) or 2.5 times above baseline levels (spironolactone) versus more than 60fold above baseline by an AAV9-based approach. Conclusion: Atg7 overexpression and autophagy activation suffices to rescue from AIC and can be recapitulated to different levels by pravastatin, empaglifozin and spironolactone.