Citations

Currently, the vasopressin V2 receptor antagonist tolvaptan is the only approved treatment for autosomal dominant polycystic kidney disease (ADPKD). It has been suggested that vasopressin acting on V1a or V1b receptors may also affect its development. We show that a V1aR antagonist has no effect in an ADPKD mouse model (Pkd1RC/RC), whereas a V2R antagonist has a modest attenuating effect in female mice only. Neither potentiates or hinders the beneficial effect of tolvaptan when administered in combination with this drug.

Abstract Background and Aims Accurate differentiation of cardiac amyloidosis (CA) from phenotypic mimics remains challenging using current clinical and echocardiographic techniques. The accuracy of a novel artificial intelligence (AI) screening algorithm for echocardiography-based CA detection was assessed. Methods Utilizing a multisite, multiethnic dataset (n = 2612, 52% CA), a convolutional neural network was trained to differentiate CA from phenotypic controls using transthoracic apical four-chamber video clips. External validation was conducted globally across 18 sites including 597 CA cases and 2122 controls. Classification accuracy was assessed on the entire external validation dataset, and subgroup analyses were performed both on technetium pyrophosphate scintigraphy referrals, and individuals matched for age, sex, and wall thickness. Model accuracy was also compared with the transthyretin CA score and the increased wall thickness score within a subset of older heart failure with preserved ejection fraction patients with increased wall thickness. Results Cardiac amyloidosis patients and controls displayed similar age, sex, race, and comorbidities. After the removal of uncertain AI predictions (13%), model discrimination and classification were excellent for the entire external validation dataset [area under the receiver operating characteristic curve (AUROC) 0.93, sensitivity 85%, specificity 93%], irrespective of CA subtype (sensitivity: light-chain = 84%, wild-type transthyretin = 85%, and hereditary transthyretin = 86%). Performance was maintained in subgroup analysis in patients clinically referred for technetium pyrophosphate scintigraphy imaging (AUROC 0.86, sensitivity 77%, specificity 86%) and matched patients (AUROC 0.92, sensitivity 84%, specificity 91%). The AI model (AUROC 0.93) also outperformed transthyretin CA score (AUROC 0.73) and increased wall thickness (AUROC 0.80) scores. Conclusions This AI screening model—using only an apical four-chamber view—effectively differentiated CA from other causes of increased left ventricular wall thickness.

Increased intracranial pressure (ICP) is increasingly recognized in myelin oligodendrocyte glycoprotein antibody-associated disease but has not been systematically explored in other demyelinating conditions. This cross-sectional study examines the features of raised ICP in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). Lumbar puncture opening pressure (OP) done within 30 days of an attack was identified in 41 NMOSD patients and 37 MS patients. Raised OP was present in 7 (17.1%) NMOSD patients and 4 (10.8%) MS patients who were largely asymptomatic, partially explained by obesity, and did not require ICP lowering medications beyond acute treatment with corticosteroids.

Abstract Brain-derived extracellular vesicles (BDEVs) carry tau filaments and promote tau transmission in Alzheimer’s disease (AD). However, how APOE ε4 allele, a key genetic risk factor for AD, may change BDEV molecular structures thereby facilitate disease progression is poorly understood. Here we report comprehensive analyses of BDEVs isolated from human E3/3 and E4/4 AD brains with a biological multi-omics approach. E4/4 BDEVs significantly enhanced tau propagation in aged human MAPT (Tau) knock-in and APPNL-G-F: Tau double knock-in mouse brains in vivo and increased neuronal uptake and excitability in induced pluripotent stem cell-derived neurons (iNeurons) compared to E3/3 BDEVs in vitro. Notably, correlation analysis of BDEV-lipidome and proteome exhibited synergistic enrichment in unsaturated free fatty acid (FFA)18:2, a precursor of inflammatory w6 FFA, and neural cell adhesion molecule 1 (NCAM1). Treatment of iNeurons with FFA 18:2 induces NCAM1 expression, recruits tau into EVs and enhance their tau seeding activity, which is blocked by NCAM1 antibody in vitro . Finally, intracerebroventricular injection of NCAM1 antibody significantly alleviated pathological tau accumulation and glial inflammation in PS19 tauopathy mouse brains, which had previously been reported to exhibit increased level of 18:2 FFA. This highlights novel pathological mechanism in tau transfer mediated by E4/4 BDEVs and emphasizes strong therapeutic potential of targeting EV molecules in AD progression.

Sustained measles elimination requires high herd immunity, maintained through vaccination and verified by global serosurveillance. Comparing measles neutralizing antibody titres in US and Indian populations, we identified distinct age-specific and country-specific trends. These findings highlight the urgent need for tailored strategies to strengthen population immunity and global measles control efforts.

Purpose To compare the outcomes of standard combined Phaco-Kahook Dual Blade (KDB) surgery (GI) with those of the extended technique (GII). Methods This retrospective, comparative, multicenter, case-control study enrolled patients with one-year follow-up. GI removed 90° of the trabecular meshwork (TM) extension during KDB, whereas GII removed 150°. The successful criteria were based on a modification of the AAO PPP recommendations - Reporting Clinical Endpoints in Studies of Minimally Invasive Glaucoma Surgery. Qualified success was achieved with or without medication, while absolute success was achieved without the use of any ocular hypotensive medication. Results A total of 72 eyes (36 in both groups) were included. The IOP was similar between groups preoperatively (GI: 17.0 ± 2.7 mmHg vs. GII: 17.5 ± 4.2 mmHg, p = 0.5), and at 12 months postoperatively (GI: 13.5 ± 2.8 mmHg vs. GII: 12.3 ± 2.7 mmHg, p = 0.06). The number of glaucoma medications was reduced from 1.7 ± 0.9 to 0.4 ± 0.8 in GI ( p < 0.001) and from 2.1 ± 0.8 to 0.4 ± 0.7 in GII ( p < 0.001). At 12 months, both groups reduced comparable glaucoma medications ( p = 0.9). Qualified success was achieved in 77.1% of the eyes with GI and 94.4% with GII ( p = 0.03), whereas complete success was achieved in 68.6% of the eyes with GI and 69.4% with GII ( p = 0.7). No serious complications were observed in any of the groups. Conclusion Extended combined Phaco-KDB surgery showed greater relative success than the Standard Phaco-KDB technique. Both techniques achieved similar IOP reduction at 12 months postoperatively.

AbstractPatients with resectable Ewing sarcoma (ES) in select sites, such as the pelvis or chest wall, have a higher risk of positive microscopic margins following surgery. AEWS1031 was the first North American/Australasia ES cooperative group trial allowing standardized preoperative radiotherapy, intended to minimize the morbidity of combined modality local tumor control as well as improve the likelihood of clear surgical margins. In this study, we found that the use of low‐dose preoperative radiation to a smaller target volume resulted in a high rate of R0 resection. The robust pathologic response rate strengthens existing evidence illustrating the radiosensitivity of Ewing sarcoma.