Publications by Year: 2026

IMPORTANCE: Docetaxel has been a standard treatment for metastatic castration-resistant prostate cancer (mCRPC) since 2004. Cabazitaxel, a related taxane, was approved in 2010 for patients with mCRPC who had been previously treated with docetaxel. The comparative effectiveness of docetaxel rechallenge vs switching to cabazitaxel after prior docetaxel for mCRPC remains unclear.

OBJECTIVE: To compare the clinical outcomes associated with docetaxel rechallenge vs cabazitaxel in patients with mCRPC who did not experience disease progression during prior administration of docetaxel in the mCRPC setting.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted in the nationwide Veterans Affairs health care system, using inverse probability of treatment weighting to control for potential confounders. Patients who were diagnosed with chemonaive mCRPC between January 1, 2010, and December 31, 2023, received initial docetaxel treatment, and did not experience disease progression were eligible to participate.

EXPOSURES: Treatment with docetaxel rechallenge or cabazitaxel.

MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival (OS) from the initiation of the second course of taxane, which was compared in patients treated with docetaxel rechallenge vs cabazitaxel using weighted Kaplan-Meier analysis and Cox proportional hazards regression models. Secondary outcomes included prostate-specific antigen response, time to next systemic treatment or death, and subsequent treatments received.

RESULTS: A total of 669 patients (407 receiving cabazitaxel and 262 receiving docetaxel rechallenge) with a median age of 72 (IQR, 67-77) years were included. Patients treated with docetaxel rechallenge had a significantly longer OS (median, 12.3 [IQR, 10.5-13.8] months) compared with those treated with cabazitaxel (median, 9.6 [IQR, 8.6-11.1] months), with a hazard ratio of 0.81 (95% CI, 0.55-0.99; P = .04). Descriptive analysis of secondary outcomes was consistent with this finding, including prostate-specific antigen response (weighted 9.8% achieving reduction of 90% or more in the docetaxel rechallenge group vs 3.0% in the cabazitaxel group) and time to next treatment or death (median, 10.7 [IQR, 7.8-12.7] months in the docetaxel rechallenge group vs 8.9 [IQR, 7.1-10.5 months] in the cabazitaxel group). Use of platinum, immunotherapy, or poly (ADP-ribose) polymerase inhibitors was similar between patients treated with cabazitaxel and docetaxel rechallenge.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with mCRPC, docetaxel rechallenge was associated with improved OS compared with cabazitaxel among patients who did not experience disease progression during prior docetaxel for mCRPC. These findings support docetaxel rechallenge as a treatment option for patients in this scenario.

Posttraumatic stress disorder (PTSD) is a disruptive, multifaceted disorder with an estimated lifetime prevalence of 8.3% in the U.S. population. Yoga has been shown to reduce PTSD symptoms overall, though little is known about its efficacy relative to specific PTSD symptom clusters. In this systematic review and meta-analysis, we examined the associations between yoga and symptom change in each DSM-5 PTSD symptom cluster. We hypothesized that yoga participation would be associated with significant reductions in each cluster, particularly alterations in arousal and reactivity/hyperarousal (AAR/H), relative to controls. We searched PubMed, PsycInfo, CINAHL, and SPORTDiscus for eligible studies published through October 2025. Studies that were yoga intervention randomized controlled trials, enrolled trauma survivors, and reported PTSD subscale scores were included. We computed standardized mean difference scores and used an NIH tool to assess risk of bias. In direct models (k = 9 studies), yoga led to small-medium reductions in intrusions, d = -0.31, p = .027, and total PTSD symptoms, d = -0.29, p = .030. When including age as a moderator, yoga also improved avoidance, d = -2.28, p = .003, and AAR/H symptoms, d = -1.92, p = .007. There was a substantial risk of bias across studies. Yoga showed the most robust effects for reducing intrusions and total PTSD symptoms, with efficacy in reducing avoidance and AAR/H symptoms when age was added as a moderator. Yoga's emphasis on mindfulness in the present moment may allow for attentional awareness that is protective against intrusions.

Pathogenic variants in the SLC34A1 gene, which encodes the sodium-phosphate cotransporter NaPi-IIa, lead to a spectrum of renal tubular disorders, including infantile hypercalcemia type 2, nephrolithiasis/osteoporosis-hypophosphatemia type 2, and Fanconi renotubular syndrome type 2. Despite increasing recognition of SLC34A1-related disorders, data on genotype-phenotype correlations and treatment response remain limited due to the rarity of the condition. We retrospectively analyzed the clinical, biochemical, and molecular features of 11 patients from unrelated families carrying 12 pathogenic or likely pathogenic SLC34A1 variants, three of which were novel. Next-generation sequencing and ACMG-AMP criteria were used for variant classification. Biochemical parameters including serum phosphate, calcium, parathyroid hormone, urinary calcium, and TmP/GFR were evaluated. Treatment response to oral phosphate supplementation was longitudinally assessed. All patients exhibited hypercalciuria and nephrocalcinosis at diagnosis. Oral phosphate supplementation (5-20 mg/kg/day) resulted in normalization of urinary calcium excretion in 10 of 11 cases, regardless of baseline serum phosphate status. Linear growth improved in all but one patient. The identified mutations clustered primarily within functional domains of the NaPi-IIa protein, particularly amino acid residues 109-205 and 375-487. Several splice-site and codon-specific variants-such as those affecting Gly153 and Gly194-were highlighted as potential pathogenic hotspots. Our findings expand the mutational and phenotypic spectrum of SLC34A1-related disease and reinforce the utility of oral phosphate supplementation in managing hypercalciuria and promoting growth. Functional domain mapping and variant clustering analyses enhance understanding of disease mechanisms and support the importance of early diagnosis and long-term surveillance.

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is the most common chronic liver disease worldwide, with a particularly high incidence among individuals with type 2 diabetes and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as effective weight loss agents, with growing evidence suggesting potential benefits in MASH. This study aimed to evaluate the efficacy and safety of GLP-1RAs in improving the histologic features of MASH.

METHODS: This study is a meta-analysis of randomized controlled trials evaluating the effect of FDA-approved GLP-1RAs in patients with biopsy-confirmed MASH, up to May 2025. The primary outcomes were resolution of MASH without worsening of fibrosis and a ≥1 improvement in fibrosis stage without worsening of MASH at 12-18 months. Secondary outcomes included ≥1-point improvements in the nonalcoholic fatty liver disease activity score, changes in liver histologic features, and the incidence of serious adverse events.

RESULTS: A total of 6 randomized controlled trials with 1555 patients (1082 GLP-1RA and 473 placebo) with MASH were included. At 18 months, a significantly greater proportion of patients in the GLP-1RA group achieved MASH resolution without worsening fibrosis compared with the placebo group (OR: 4.16, 95% CI: 2.33-7.42, p<0.001). A subgroup analysis excluding studies with patients with cirrhosis showed a significant benefit on fibrosis regression (OR: 2.02, 95% CI: 1.56-2.62, p=0.01). GLP-1RAs significantly improved nonalcoholic fatty liver disease activity scores and liver histologic features, including balloon degeneration, lobular inflammation, and steatosis, compared with placebo. The pooled serious adverse event rate for GLP-1RAs was comparable to placebo.

CONCLUSIONS: In patients with noncirrhotic MASH, GLP-1RAs appear to be associated with both MASH resolution without fibrosis worsening and ≥1-stage fibrosis regression without MASH worsening.

β-cells maintain glucose homeostasis by adjusting insulin secretion to meet the demands of (patho)physiological triggers; yet, they also undergo energy-dependent transitions between proliferation, differentiation and maturation that underlie function across the lifespan. There are energy costs to prioritizing distinct cell states within β-cells. As such, specific metabolic programming is likely essential for distinct β-cell states as they toggle between immaturity and maturity. Transcriptional, nutritional, hormonal and stress-based cues coordinately regulate the development of native β-cells in vivo. These steps are mirrored in protocols to differentiate human pluripotent stem cells (hPSCs) into β-like cells, but these cells remain functionally immature. Understanding how metabolic programs drive β-cell state transitions may reveal strategies to accelerate sc-islet maturation, restore β-cell function in diabetes, and improve cell-based therapies. Here we outline the known and unknown metabolic physiology of β-cells throughout development in vivo and in vitro.

STUDY OBJECTIVES: Large long-term assessments of opioid effectiveness and dose stability for those with dopamine agonist augmentation of restless legs syndrome (RLS) are lacking. We present 5-year longitudinal findings from the National RLS Opioid Registry.

METHODS: Five-hundred participants taking opioids for RLS were interviewed at baseline about RLS symptoms, opioid medications and doses, sleep and mental health. Participants subsequently completed online surveys every 6 months. Changes from baseline to 5-year follow-up in morphine milligram equivalents (MME), excluding those taking buprenorphine, were evaluated by group-based trajectory modeling. Independent associations with opioid dose changes were determined using multiple logistic regression.

RESULTS: At 5-years of follow-up, 410 (364 excluding any taking buprenorphine) participants remained for this analysis. Most participants are female (57.1%) and white (98.3%), with an average age of 64.7 (±10.6) and 88.8% had a history of dopamine agonist augmentation. The median daily MME at 5-years was 37.5 (equivalent to methadone 8.0 mg or oxycodone 25.0 mg), an increase of 7.5 MME from baseline. Opioid doses increased from baseline to 5-years in 49.5% of participants and decreased in 20.0% of participants. Group-based trajectory analysis identified four distinct groups: decrease (3.4% of participants; average MME change=-15.7±12.4), no/little change (66.1% of participants; average MME change=1.5±8.0), small increase (23.9% of participants; average MME change=22.0±11.6), and large increase (3.4% of participants; average MME change=49.2±18.7). RLS severity was stable from baseline (13.3±9.6) to 5-years (13.1±9.0) according to the IRLS severity scale.

CONCLUSIONS: Opioid doses in augmented RLS remain largely stable over five years of follow-up. Low-dose opioids provide an effective long-term option for augmented RLS.

AIM: White matter (WM) alterations in the corpus callosum (CC) and visual cortex have been implicated in early psychosis, with the visual regions particularly linked to psychotic symptoms. Whether similar WM patterns occur in early-onset bipolar disorder (EOBD) remains unclear. This study investigated WM alterations in EOBD and their associations with psychiatric symptoms.

METHODS: Eighty-seven individuals with EOBD and 57 healthy controls (HCs) underwent diffusion magnetic resonance imaging (dMRI) and psychiatric assessments. Whole-brain WM changes between groups were examined using TractSeg and tract-based spatial statistics. Partial correlations with multiple comparison corrections assessed associations between altered tracts and symptoms.

RESULTS: Compared with HCs, EOBD showed widespread lower fractional anisotropy (FA) and altered other WM parameters, particularly in the CC and visual-related tracts. Lower FA in the anterior midbody CC (r = -0.307, q = 0.038), right superior longitudinal fascicle I (r = -0.305, q = 0.038), thalamo-parietal (r = -0.315, q = 0.038), and parieto-occipital pontine tracts (r = -0.329, q = 0.038) correlated with greater depressive symptoms. Lower FA in the left inferior fronto-occipital fascicle (r = -0.371, q = 0.030), left optic radiation (r = -0.381, q = 0.030), and left thalamo-occipital tract (r = -0.392, q = 0.030) were associated with greater positive symptoms. These visual-related lower FAs were found more frequently in individuals with visual hallucinations.

CONCLUSION: EOBD was associated with WM abnormalities in the CC and visual pathways linked to depressive symptoms and visual hallucinations, supporting its characterization as a neurodevelopmentally distinct subtype with persistent WM dysconnectivity.

PURPOSE OF REVIEW: This narrative review synthesizes advances from the past 18 months on the etiology of autism spectrum disorder (ASD), integrating findings from genetics, neurobiology, environmental epidemiology, and developmental psychiatry. Given the profound clinical heterogeneity of ASD, improved etiologic clarity is essential for risk stratification, early identification, and targeted intervention.

RECENT FINDINGS: Extensive genomic and multiancestry studies are now further clarifying how both common polygenic and rare high-impact variants contribute to ASD. These studies reveal different patterns of genetic liability that underlie distinct ASD subgroups. In parallel, functional and multiomic research is highlighting shared pathways involving synaptic signaling, gene regulation, immune processes, and the balance between excitatory and inhibitory signals. Environmental research, especially on maternal immune activation and maternal metabolic factors, uses causal inference methods to clarify modest but plausible causal effects, tempering earlier claims. Longitudinal imaging and infant cohort studies continue to show that atypical connectivity and social-brain differences occur before behavioral diagnosis. Sex differences and global diversity underscore the need for etiology models to incorporate sex-specific genetic architecture and address significant gaps in ancestral representation.

SUMMARY: ASD arises from a dynamic interplay of genetic liability, early neurodevelopmental processes, and environmental exposures. Etiologic progress now depends on integrating multilevel and multiomic data - including genomic, transcriptomic, epigenetic, imaging, and epidemiologic information - toward stratified developmental models and better-tailored interventions.

Protectin DX (PDX) is a member of the superfamily of specialized proresolving mediators and exerts anti-inflammatory actions in animal models; however, its signaling mechanism remains unclear. Here, we demonstrate the analgesic actions of PDX in a mouse model of tibial fracture-induced postoperative pain (fPOP). Intravenous early- and late-phase treatment of PDX (100 ng/mouse) effectively alleviated fPOP. Compared with protectin D1 (PD1)/neuroprotectin D1, DHA, steroids, and meloxicam, PDX provided superior pain relief. While dexamethasone and meloxicam prolonged fPOP, PDX shortened the pain duration. The analgesic effects of PDX were abrogated in Gpr37-/- mice, which displayed deficits in fPOP resolution. PDX was shown to bind GPR37 and induce calcium responses in peritoneal macrophages. LC-MS/MS-based lipidomic analysis revealed that endogenous PDX levels were approximately 10-fold higher than those of PD1 in muscle at the fracture site. PDX promoted macrophage polarization via GPR37-dependent phagocytosis and efferocytosis through calcium signaling in vitro, and it further enhanced macrophage viability and efferocytosis in vivo via GPR37. Finally, PDX rapidly modulated nociceptor neuron responses by suppressing C-fiber-induced muscle reflex in vivo and calcium responses in DRG neurons ex vivo and by reducing TRPA1/TRPV1-induced acute pain and neurogenic inflammation in vivo. Our findings highlight multiple benefits of PDX to manage postoperative pain and promote perioperative recovery.

OBJECTIVES: Extracting sections from clinical notes is crucial for downstream analysis but is challenging due to variability in formatting and labor-intensive nature of manual sectioning. This study develops a pipeline for automated note sectioning using open-source large language models (LLMs), focusing on three sections: History of Present Illness, Interval History, and Assessment and Plan.

MATERIALS AND METHODS: We fine-tuned three open-source LLMs to extract sections using a curated dataset of 487 progress notes, comparing results relative to proprietary models (GPT-4o, GPT-4o mini). Internal and external validity were assessed via precision, recall, and F1 score.

RESULTS: Fine-tuned Llama 3.1 8B (F1 = 0.92) outperformed GPT-4o. On the external validity test set, performance remained high (F1 = 0.85).

DISCUSSION: While proprietary LLMs have shown promise, privacy concerns limit their utility in medicine; fine-tuned, open-source LLMs offer advantages in cost, performance, and accessibility.

CONCLUSION: Fine-tuned, open-source LLMs can surpass proprietary models in clinical note sectioning.