UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER

Biosimilars for adalimumab led to a 45% drop in net spending despite minimal impact on Humira prescriptions. Biosimilar uptake was low, raising concerns about market sustainability. Humira retained 98.65% of the market, with biosimilars at 1.35%.

FDA approved vagus nerve stimulation for treatment-resistant depression in 2007, but limited by lack of insurance coverage. The RECOVER trial, sponsored by LivaNova, aims to provide evidence for CMS and insurers to cover invasive vagus nerve stimulation. The trial, still recruiting, plans to enroll 6,800 participants and observe for a year to assess gradual response to the treatment.

A clinical trial of 4-phenylbutyrate (PBA) shows significant reduction in seizure activity among children with genetic mutations causing severe epilepsy. Some children who failed multiple anti-seizure drugs have become seizure-free. The research is supported by nonprofit patient advocacy organizations, SLC6A1 Connect and Cure GABA-A, founded by mothers of children with genetic epilepsy. The trial is conducted at Vanderbilt University Medical Center, Weill Cornell Medical Center, Children's Hospital Colorado, and the University of Texas Southwestern Medical Center.

The UK Biobank study recruited 500,000 participants aged 40-69 years (2006-2010) with extensive phenotypic and genetic data. Participants were genotyped using two arrays and imputed centrally based on the 1000 Genomes Project phase 3. Adiposity measures, including VAT, WFM, and WHR, were used, with MRI-derived PDFF and liver iron corrected T1 provided by the UK Biobank. Phenotypic prediction models were developed using penalized linear regression and tenfold nested cross-validation. Genome-wide association analysis was conducted using REGENIE, and independent variants were identified through LD clumping and conditional joint SNP analysis. Heritability and genetic correlations were estimated using LD score regression. Functionally informed fine-mapping was performed with PolyFun and SuSiE. Colocalization analysis was conducted between genetic loci and eQTLs from GTEx. Gene mapping and functional enrichment analysis were performed using FUMA and Enrichr. Partitioned polygenic risk scores were defined based on concordant or discordant associations with PDFF and circulating triglycerides. Replication cohorts included NEO, Liver BIBLE, MAFALDA, and Dallas Heart Study. Meta-analysis was performed using inverse-variance weighted fixed-effect models. RNA-seq analysis was conducted on paired liver and VAT samples from MAFALDA. Follow-up analysis tested the longitudinal association of PRS with outcomes using Cox proportional hazard regression. Gene-adiposity interaction analysis was performed in REGENIE. Mediation analysis examined the impact of loci on PDFF or liver iron corrected T1 mediated via adiposity measures. Association analysis with adiposity measures was conducted using REGENIE. bNMF clustering was applied to define clusters of independent loci. Comparison between bNMF and PDFF-TGs pPRS was performed using Wald test and Akaike information criterion.

The Hastings Center announces its 2024 fellows, leaders in bioethics addressing global issues like infectious disease, AI in health, neuroscience, reproductive rights, genetics, and disability.

Altered metabolism in tumors is a hallmark of cancer, detected by imaging techniques like PET, MRI, and CT. APTw imaging shows promise in predicting breast cancer response to neoadjuvant chemotherapy. EPROI-defined hypoxic tumor subvolumes improve radiation therapy efficacy. PSMA PET/CT is crucial for prostate cancer staging, though 18 F-PSMA-1007 uptake in the bladder needs further study. Deuterium metabolic imaging (DMI) offers insights into tumor metabolism and treatment responses, potentially enhancing precision medicine.

Clearside Biomedical presented suprachoroidal delivery tech and pipeline data at APVRS, OIS, and FLORetina, highlighting ODYSSEY wet AMD results and XIPERE real-world data.

The Southwest Forum on Difficult to Treat Depression, chaired by Jordan F. Karp, MD, convened experts to discuss novel mechanisms, evidence-informed algorithms, and access to comprehensive depression care. Topics included advanced treatments like brain stimulation and neurosteroids, challenges in late-life depression, digital mental health treatments, and the role of biomarkers in precision psychiatry. The forum emphasized the need for equitable access and personalized medicine to improve outcomes in treatment-resistant depression.

Perioperative treatment with a targeted agent plus immunotherapy improved tumor outcomes and thrombus control in RCC, with higher tumor necrosis and better PFS. Immuno-oncology followed by a tyrosine kinase inhibitor (TKI) showed better results than IO/IO regimens, though immune-related adverse events were more frequent with IO/IO. Larger studies are needed for statistical significance.

A multicenter study assessed real-world outcomes of ipilimumab and nivolumab in mesothelioma patients, finding results similar to the CheckMate 743 trial. The study, conducted by Dr. Arthi Sridhar, aims to guide patient treatment and plans to expand its sample size.