Citations

Abstract Background Imaging-based glioma monitoring is confounded by treatment-related changes. D-2-hydroxyglutarate (D-2-HG), produced by the isocitrate dehydrogenase (IDH) mutation, is detectable in cerebrospinal fluid (CSF), which can be sampled from cranial or lumbar compartments. We evaluated CSF D-2-HG as a serially accessible biomarker for IDH-mutant gliomas, including the optimal compartment for longitudinal sampling. Methods Lumbar and cranial CSF samples were collected from patients with IDH-mutant gliomas or IDH-wild-type central nervous system pathologies via surgical field collection, lumbar punctures, and CSF access devices. CSF D-2-HG was quantified via our CLIA-certified gas chromatography mass spectrometry assay. Results D-2-HG was significantly higher in cranial than lumbar CSF from IDH-mutant glioma patients. Consistent with low D-2-HG abundance in lumbar CSF, lumbar samples could not discriminate IDH-mutant gliomas from IDH-wild-type lesions. In contrast, cranial CSF D-2-HG was significantly higher in IDH-mutant gliomas than wild-type lesions, providing an adequate baseline for initial evaluations of monitoring capabilities. Across 75 samples from 7 consecutive patients with grade 4 IDH-mutant astrocytomas, serial cranial CSF D-2-HG decreased with cytoreduction, remained unchanged with stable disease, and increased with disease progression, but not pseudoprogression. Conclusions Serial cranial CSF D-2-HG shows promise as a monitoring biomarker for IDH-mutant gliomas.

Background Area‐based deprivation indices have been linked to hypertension and diabetes outcomes, but limited information exists about their relative performance. We compared 2 area‐based deprivation measures (Area Deprivation Index and Yost Index) as risk factors for hypertension and diabetes control. Methods This cohort study identified adults with hypertension or diabetes in a 19‐county region of Southeast Minnesota covered by the Rochester Epidemiology Project. The deprivation indices were operationalized as quintiles for state and national ranks. We assessed agreement using the weighted kappa statistic. We used modified Poisson regression to evaluate associations of the deprivation indices with blood pressure or diabetes control in 2022. We compared relative model fit using the area under the receiver operating characteristic curve. Results We identified 67 386 individuals with hypertension and 30 435 with diabetes. There was moderate to substantial agreement between indices, but the agreement was higher for the state rank (weighted kappa 0.68 for both cohorts) than the national rank (0.54 for both). Although the indices were not associated with hypertension control, greater deprivation was associated with worse diabetes control for the Yost Index (relative risk [RR], 1.21 [95% CI, 1.07–1.38]) and Area Deprivation Index (RR, 1.39 [95% CI, 1.12–1.73]) national ranks. The full‐model area under the receiver operating characteristic curve was similar across indices but differed across cohorts with worse fit for hypertension (0.53 for both) than diabetes (0.63 for both). Conclusions Two common area‐based deprivation indices had similar strength of association with diabetes control, suggesting that either index would be appropriate for researching and developing interventions for diabetes control.

Background Pulmonary hypertension (PH) and sensitization adversely affect heart transplant outcomes. Although left ventricular assist devices may reduce PH, they can increase sensitization. We examined the impact of sensitization on heart transplant outcomes in left ventricular assist device‐bridged patients and whether precapillary PH modifies this effect. Methods Adults bridged to heart transplant with an left ventricular assist device between 2005 and 2020 were identified from the United Network for Organ Sharing database. Patients with available panel‐reactive antibody (PRA) and hemodynamic data were included. Associations between PRA and survival and treated rejection were analyzed. Results Among 2469 patients, 1053 had precapillary PH (pulmonary vascular resistance [PVR] >2 Wood units [WU]) and 1416 had PVR ≤2 WU. Elevated PRA (>10%) occurred in 566 patients (24.8% with PVR >2 WU; 21.5% with PVR ≤2 WU). Overall, PRA >10% was associated with increased mortality (adjusted hazard ratio [aHR], 1.28 [95% CI, 1.04–1.58], P =0.022), driven by patients with PVR >2 WU (aHR, 1.82 [95% CI, 1.34–2.50], P <0.001), with no association in those with PVR ≤2 WU (aHR, 0.99 [95% CI, 0.47–1.32], P =0.92). PRA >10% was also associated with treated rejection overall (adjusted odds ratio [aOR], 1.41 [95% CI, 1.09–1.82], P =0.008), confined to the PVR >2 WU group (aOR, 1.87 [95% CI, 1.26–2.76], P =0.002) and absent in the PVR ≤2 WU group (aOR, 1.13 [95% CI, 0.80–1.59], P =0.49). Conclusions Elevated PRA predicts worse outcomes in LVAD‐bridged transplant recepients with precapillary PH, but not in those without precapillary PH.

Introduction Translating findings from cell and animal models to the clinic is difficult because these systems insufficiently capture human disease biology. Computational approaches, notably pathways modeling, have overcome interspecies differences by mapping shared signaling pathways between species. We considered whether this approach could be generalized to bridge animal and virtual drug screening data to effects measured in patients. We emphasized translational psychiatry datasets because of the unmet need for effective therapies. Methods We conducted three parallel analyses using published drug screening data in zebrafish, structure-function computational screening data, and clinically-reported efficacy data for experimental and approved antipsychotic drugs and predicted drug pathways using the PathFX algorithm Results Despite choosing screens developed for unique aspects of psychiatry and without careful curation of shared drugs, we found pathways associated with drugs that performed “well” across these distinct platforms—specifically, among drugs measured as favorable (expected to improve disease) or unfavorable (expected to aggravate disease) across screens, these drugs connected to distinct pathway proteins; however, these drugs are connected to similar protein families and shared Gene Ontology functional terms. By comparing screens, we discovered that favorable drugs may influence G-proteins, solute carrier family proteins, adrenoceptors, and steroid hydroxylase activity and that unfavorable drugs affect serotonin receptors and phosphodiesterase activity. Discussion This suggests that predictive platforms could emphasize functional information as features that could overcome differences in distinct screening platforms to eventually improve translational approaches.

Abstract Patients with hypertensive disorders of pregnancy (HDPs) are recommended to attend an early postpartum follow-up visit for blood pressure monitoring. Follow-up frequency for patients with HDPs can vary widely, with some patients requiring multiple office visits. We sought to determine factors associated with multiple postpartum blood pressure visits among patients with HDPs. We retrospectively identified patients with HDPs who delivered at our maternity center in 2019 and compared factors between patients who attended a single blood pressure follow-up appointment without requiring further clinical evaluation for hypertension and patients who required multiple postpartum clinical evaluations for persistent hypertension. Univariate logistic regression models were used to identify factors associated with increased odds of having multiple clinically indicated postpartum visits for blood pressure monitoring. We identified 328 patients with HDPs, of whom 260 (79.3%) attended an initial postpartum blood pressure follow-up appointment and were included in further analyses. Of the 260 patients, 70 (26.9%) had multiple blood pressure visits. Factors associated with multiple blood pressure visits included delivery between 34 and less than 37 weeks of gestation (odds ratio [OR], 3.62; 95% CI, 1.07–12.30), systolic blood pressure before discharge of 140 mm Hg or higher (OR, 5.02; 95% CI, 2.57–9.82), and discharge with blood pressure medication (OR, 3.42; 95% CI, 1.82–6.41). Patients with HDPs who deliver preterm, have persistent hypertension before discharge, or are discharged with antihypertensive medication require continued close postpartum observation and continuity of care.

Background Breast cancer-related lymphedema (BCRL) is a common and life-long adverse event affecting ~20% of breast cancer survivors. As existing non-pharmacologic management is burdensome, expensive, and variably effective, this systematic scoping review aims to identify pharmacologic and herbal agents for prevention and treatment for BCRL. Methods PubMED, Embase, Web of Science Core collection, and the Cumulative Index to Nursing and Allied Health Literature were searched for studies published in English between 1993 and 2025 that investigated the preventative or therapeutic effect of pharmacologic or herbal agents on BCRL among adult stage I-III breast cancer patients. Studies describing interventions with systemically absorbed anti-inflammatories, anti-thrombotics, anti-coagulants, and blood product components were included. Systematic reviews, protocols for ongoing clinical trials, preclinical and non-human studies, editorials, and studies not exclusive to BCRL were excluded. Three reviewers screened and extracted data between June and August 2025. The primary outcomes of interest were reduction in BCRL incidence or severity. Results Of the 217 articles screened, 37 were included in the final review. After full text review, 13 were excluded for repetitive data, non-English language, or irrelevant outcomes. The 24 studies included in the analysis investigated anti-diabetic, herbal, anti-inflammatory, anti-hypertensive, immunomodulatory, and microbiome modifying agents, and venoactive flavinoid derivates. Three studies explored the role of pharmacologic/herbal agents in BCRL prevention. While thiazolidinediones, anti-hypertensives, and non-steroidal anti-inflammatory drugs (NSAIDs) had no effect on BCRL incidence, glucagon-like peptide-1 receptor agonists (GLP-1 RA) were associated with BCRL prevention. In the 21 studies that assessed the effect of pharmacologic/herbal agents in BCRL treatment, NSAIDs/steroids, anti-hypertensives, microbiome/synbiotic supplements, and doxycycline showed no benefit and data for flavonoid-derived venoactive agents and herbal products were inconsistent. Immune-modulating therapies were associated with improved BCRL signs/symptoms in three studies. Conclusion This systematic scoping review found limited evidence suggesting that GLP-1 RAs may reduce the risk of BCRL and that immunomodulatory agents may improve signs/symptoms of BCRL. Rigorous prospective trials using standardized limb volume/edema, quality-of-life (QoL), and symptom measures and longer follow-up are needed to inform clinical practice aimed at preventing and treating BCRL. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251055134.

PURPOSE This national study was undertaken to determine screening mammography rates among transgender and gender diverse (TGD) individuals. METHODS TGD individuals and cisgender women who qualified to receive screening mammography based on American College of Radiology guidelines were identified in the longitudinal OptumLabs Data Warehouse. The primary end point was the percentage of patients who had high rates of screening (>75% recommended screenings). Multivariable analyses were conducted in a matched population of transgender men to cisgender women to identify and adjust for factors associated with high adherence. Individuals were matched at a 1:4 ratio (transgender men: cisgender women) on age, race/ethnicity, year of enrollment in their health care plan, and duration of follow-up. RESULTS This study focused on 10,478 TGD individuals (3,778 transgender men; 1,294 transgender women; 5,406 with gender dysphoria not meeting other TGD criteria, NMOT) and 6,218,369 cisgender women. For transgender men, transgender women, individuals with gender dysphoria NMOT, and cisgender women, high mammography rates were observed in 41.1% (95% CI, 39.5 to 42.6), 7.4% (95% CI, 6.0 to 8.8), 11.9% (95% CI, 11.0 to 12.7), and 38.3% (95% CI, 38.3 to 38.4), respectively ( P < .0001). When transgender men were compared with 15,112 matched cisgender women, an age-based differential association was observed between sex and high mammography rates (interaction P = .0003); compared with cisgender women, transgender men appeared more likely to manifest high rates of screening at age 40-49 years (odds ratios [ORs], 1.38 [95% CI, 1.28 to 1.50]; P < .0001) and 50-59 years (OR, 1.57 [95% CI, 1.35 to 1.81]; P < .0001) but not in the older age groups. CONCLUSION The relatively high rates of screening mammography in cisgender women and transgender men suggest clinicians are offering mammography to individuals who are at average or high breast cancer risk, as compared with cisgender women, and not to transgender women at low risk.

Abstract Cellular senescence has been implicated in the pathophysiology of radiotherapy-related bone loss. Based on our previous work, clearance of senescent cells using genetic and pharmacological tools alleviates the anomalies associated with radiation-associated bone deterioration. The pro-inflammatory senescence associated secretome referred to as senescence associated secretory phenotype (SASP), is a hallmark of cellular senescence. The modulation of SASP by senomorphic drugs, potentially can suppress the pro-inflammatory secretome of senescent cells, irrespective of the underlying senescence mechanism. In this study we tested a senomorphic drug, ruxolitinib, a Janus kinase inhibitor (JAKi), during acute and chronic radiotherapy related effects on the bone. Our clinical data indicate an early increase in several pro-inflammatory SASP proteins following radiotherapy of spinal metastasis in prostate cancer patients. Longitudinal assessment of SASP-related genes confirmed this acute elevation in several SASP markers in systemic circulation following irradiation of mouse femurs. In a proof-of-concept study, following two preclinical radiotherapy regimens of cumulative doses of 30Gy (5 x 6Gy) and 60Gy (5 x 12Gy), a senomorphic approach of JAKi treatment was more effective in alleviating radiation-related bone loss compared to the senolytic cocktail of D+Q. Early and intermittent suppression of SASP using JAK inhibitors alleviated chronic bone deterioration, diminished telomere dysfunction, lowered senescence and SASP marker expression, reduced bone-marrow adiposity, and mitigated radiation related lymphatic impairment. Overall, our study shows that early targeting of SASP proteins could be a potential therapeutic to prevent radiotherapy-related chronic bone loss and risk of fractures. Lay Summary Radiotherapy as part of cancer treatment is correlated with an acute increase in senescent cells. Here we show that the pro-inflammatory senescence associated secretory phenotype (SASP) becomes much more prominent soon after radiotherapy in both patients and mice. Suppression of the SASP using a Janus kinase inhibitor, ruxolitinib, reduced the overall senescent cell burden, improved bone architecture by promoting bone formation, reduced bone marrow adiposity, and mitigated radiation-induced lymphatic impairment. Overall, these findings suggest that early inhibition of the SASP may help mitigate several bone anomalies and prevent long-term bone loss and fractures after radiotherapy. Graphical Abstract