Citations

Chronic left bundle branch block (LBBB) has been associated with adverse cardiac remodeling and the development of cardiomyopathy. This retrospective cohort study evaluated the impact of angiotensin II receptor blocker (ARB) therapy on cardiovascular outcomes in adults with isolated LBBB with no known heart failure (HF), cardiomyopathy, or ischemic heart disease. Using the TriNetX global research network, patients were stratified by ARB use and followed for up to 5 years. Propensity score matching was performed to balance characteristics. Three thousand two hundred sixty-six patients were included in each group with comparable baseline characteristics. The ARB therapy was not associated with a reduction in new-onset acute HF events (4.9% vs 4.4%; hazard ratio (HR) 1.05 (95% CI 0.84–1.32)). Similarly, there were no significant differences in rates of all-cause hospitalizations, cardiac arrest, or ventricular tachycardia. However, ARB use was associated with a significantly lower, all-cause mortality rate (8.6% vs 12.1%; HR 0.67 (95% CI 0.57–0.77)). This is the first real-world study examining ARB use in a cohort with isolated LBBB, highlighting a potential mortality benefit, despite no difference in acute HF risk. While ARBs are not effective in preventing LBBB-induced cardiomyopathy based on these findings, the observed survival advantage warrants further investigation. Prospective studies are needed to elucidate mechanisms underlying this mortality benefit and to determine whether ARBs should be considered in the management of patients with isolated LBBB.

ABSTRACT Precision medicine approaches have gained attention for their potential to more effectively manage obesity by tailoring diagnosis and treatment strategies to individual characteristics, including genetic background, phenotypes, metabolic profiles, and environmental exposures. The current review evaluates the evidence for precision medicine in weight management by summarizing the proceedings of a Pennington Biomedical Scientific Symposium titled “Precision Prevention, Diagnostics, and Treatment of Obesity: Pipedream or Reality?” This review discusses the extent to which we can classify and predict obesity risk based on individual‐level factors; whether we have the diagnostic capability to prospectively identify people who will benefit most from specific interventions; whether prospective trials demonstrate superior prevention and treatment of obesity when precision approaches are applied; and whether evidence is sufficient to guide policy decisions. Expert opinions were presented on the current evidence of precision medicine for obesity to collectively evaluate key barriers and opportunities for implementation of precision approaches in clinical and public health settings.

Glioblastoma (GBM) is an aggressive brain tumor with a highly immunosuppressive microenvironment that promotes tumor progression and therapy resistance. Tumor-associated macrophages (TAMs), comprising up to 50% of the tumor mass, are recruited via chemokine axes such as CCL2/CCR2, CX3CL1/CX3CR1, and CXCL12/CXCR4 and adopt an M2-like immunosuppressive phenotype, facilitating immune escape and angiogenesis. Key signaling pathways, including CSF1R, STAT3, NF-κB, PI3K/Akt, and HIF-1α, regulate TAM function, making them promising therapeutic targets. Strategies such as TAM depletion, reprogramming, and immune checkpoint blockade (PD-1/PD-L1, and CD47-SIRPα) have shown potential in preclinical models. Emerging approaches, including CAR-macrophage (CAR-M) therapy, nanotechnology-based drug delivery, and exosome-mediated modulation, offer new avenues for intervention. However, clinical translation remains challenging due to GBM’s heterogeneity and adaptive resistance mechanisms. Future research should integrate multi-omics profiling and AI-driven drug discovery to refine TAM-targeted therapies and improve patient outcomes. This review provides a comprehensive analysis of TAM-mediated immune regulation in GBM and explores evolving therapeutic strategies aimed at overcoming its treatment barriers.

Background: Longitudinal genomic profiling through serial circulating tumor DNA (ctDNA) testing offers a noninvasive method to monitor clonal evolution in advanced prostate cancer. This study evaluated the frequency and nature of newly emergent and potentially actionable genomic alterations detected through serial testing in a real-world setting. Methods: We conducted a retrospective analysis of advanced prostate cancer patients who underwent multiple Guardant360 ctDNA tests between October 2020 and March 2023. The study focused on identifying new genomic alterations absent in the initial test, with particular attention to alterations relevant for on-label therapies, therapies approved in other oncologic indications (i.e., off-label), or a clinical trial. Results: Among 479 patients with at least two ctDNA tests, the median interval between the first and second evaluable tests was 207 days. New and potentially actionable alterations emerged in 57.8% of patients, including potential targets for on-label therapies (16.7%), off-label therapies (16.5%), and clinical trials (55.7%). Tumor mutational burden (TMB) increased from “low” to “high” in 11% of patients, although none had microsatellite instability or mismatch repair deficiency. In a Mayo Clinic subset, ten patients received olaparib based on treatment-emergent alterations, but none achieved a prostate-specific antigen (PSA) response. Two patients who transitioned from low to high TMB received pembrolizumab, both with progressive disease as best response. Conclusions: In a large real-world cohort, serial ctDNA testing frequently identified new alterations that were not detected at baseline and are potentially actionable therapeutic targets, highlighting the value of serial genomic profiling for capturing clonal dynamics. Additional research is needed to better establish a framework for retesting and to clarify how these results should influence subsequent treatment decisions.

ABSTRACT Objective The optimal treatment for neurosarcoidosis myelitis is uncertain. We characterize incident neurosarcoidosis myelitis and assess treatment response by MRI and clinical scales. Methods Incident probable or definite neurosarcoidosis myelitis in adults was retrospectively identified from 13 academic medical centers. Cases were analyzed by initial treatment. The primary outcome was T1 post‐contrast gadolinium enhancement resolution at 6 months post‐treatment. Secondary outcomes were changes in modified Rankin scale (mRS) and Expanded Disability Status Scale (EDSS) from nadir to final follow‐up. Results Two hundred two patients were identified (median diagnosis age: 47 years (IQR 39–55); male: female 1.3:1). Median nadir mRS and EDSS were 2 (IQR 2–3) and 4 (IQR 2.5–6). At initial treatment, 129 (63.9%) received prolonged corticosteroids ≥ 4 weeks (group A 1 ), 36 (17.8%) received corticosteroids < 4 weeks (B 1 ), 21 (10.4%) received corticosteroids plus sarcoidosis‐directed immunosuppressant (E), and 16 (7.9%) received corticosteroids plus non‐sarcoidosis‐directed agents (F). In 167 cases with sufficient imaging, there were no significant differences in contrast enhancement resolution at 6 months (A 1 27/106 (25.5%), B 1 9/28 (32.1%), E 5/19 (26.3%), F 5/14 (35.7%); Fisher's exact p = 0.76). There were no significant differences in changes in mRS or EDSS among treatment groups (Kruskal–Wallis p = 0.69 and 0.63, respectively) after median follow‐up of 46.5 months (IQR 18–91.3). Interpretation Different initial immunosuppression strategies did not correlate with MRI contrast enhancement resolution at 6 months or clinical scales (mRS, EDSS). However, conclusions are limited by retrospective design, imbalanced cohorts, and insensitivity of binary MRI outcomes and available clinical scales for treatment response in neurosarcoidosis.

Objectives. Allergic rhinitis (AR) can substantially compromise daily functioning and well-being, and many patients require more than a single agent to obtain satisfactory symptom control. This study examined whether adding montelukast to antihistamine could manage AR symptoms and quality-of-life outcomes effectively.Methods. A review was performed in PubMed, Embase, Medline, Scopus, the Cochrane Library, and Google Scholar to identify eligible studies reported through April 2025. Eligible studies compared combination therapy with montelukast plus antihistamine against antihistamine monotherapy and reported nasal symptoms or rhinoconjunctivitis quality of life questionnaire (RQLQ) scores. Treatment effects were further examined by antihistamine class.Results. Fifteen studies including 2,882 subjects were analyzed. Combination therapy significantly improved daytime nasal symptoms (standardized mean difference [SMD] [95% CI], 0.44 [0.21–0.67]), nighttime nasal symptoms (0.12 [0.01–0.23]), and RQLQ scores (0.14 [0.00–0.27]) versus monotherapy. Individual nasal or ocular symptoms, sneezing, nasal obstruction, and rhinorrhea improved significantly, while nasal itching and ocular symptoms did not. Combinations with desloratadine and levocetirizine showed greater benefits than those with loratadine or fexofenadine.Conclusion. Montelukast–antihistamine combination therapy reduced overall symptoms and improved quality of life versus antihistamine monotherapy. The magnitude of benefit appears to vary depending on the specific antihistamine used, highlighting the possible value of individualized treatment strategies in the treatments of AR.

Purpose To compare clinical and functional outcomes (including range of motion, clinical laxity, reoperation/revision rates, and patient‐reported outcome measures) of combined anterior cruciate ligament/posterior cruciate ligament reconstruction (ACLR/PCLR) with and without suture tape (ST) augmentation via a propensity‐matched cohort analysis. Methods A retrospective review was performed to identify all patients who underwent simultaneous primary ACLR/PCLR between 2001 and 2022. A 1:1 propensity match was performed using patient sex, Schenck classification grade, age ±8 years, and body mass index ±10 to produce 2 cohorts: ACLR/PCLR with and without (control) ST augmentation. Clinical outcomes (visual analog scale [VAS], range of motion, Tegner activity scale, Lysholm score, and International Knee Documentation Committee subjective score) were analyzed. Results The propensity match produced a final cohort of 50 ACLR/PCLR patients: 25 with ST augmentation and 25 nonaugmented controls. Most patients had a KD3M injury (12 in each cohort), and no significant differences were noted in concomitant neurovascular, meniscal, or chondral injuries between the groups. Forty patients (80%) completed follow‐up at a mean of 4.7 years for the ST cohort and 8.5 years for the control cohort ( P > .05). Postoperative ST versus control values for outcome measures including VAS at rest (0.9 vs 1.5; P = .71), VAS with use (3.0 vs 2.2; P = .24), International Knee Documentation Committee (75.7 vs 76.3; P = .37), Lysholm (81.8 vs 77.6; P = .91), and Tegner activity (4.8 vs 5.4; P = .37) scores showed no differences ( P > .05 for all). There were no differences in excessive postoperative clinical laxity between ST and control cohorts (ST n = 1 vs control n = 2, Lachman 2+, P = .140; ST n = 3 vs control n = 1, posterior drawer 2+, P = .122). The total number of patients who underwent reoperation was 7 of 25 (28%) for the ST cohort and 8 of 25 (32%) for the control cohort ( P = .76). Conclusions Concomitant ACLR/PCLR utilizing ST augmentation showed similarly satisfactory postoperative clinical outcomes at a minimum 2‐year follow‐up compared to a matched cohort without ST. The use of an independent ST did not limit motion or increase the incidence of complications or revision surgery. Level of Evidence Level III, retrospective comparative case series.

Abstract Introduction The deep inferior epigastric artery perforator (DIEP) flap is widely used for breast reconstruction, with donor site complications influenced by various factors. This study assessed the impact of incisional negative pressure wound therapy (iNPWT) on donor site healing compared to standard dressings (SD). Methods A retrospective review of DIEP flap reconstructions performed between 2017 and 2022 was conducted. Donor sites were managed with either SD or iNPWT (PREVENA PLUS™, 3M). Outcomes assessed included donor-site complications, drain duration, length of stay, and readmissions. Predictors of complications were analyzed using univariable and multivariable logistic regression. Results A total of 320 patients were included; iNPWT was applied in 165 (51.6%) and SD in 155 (48.4%). Baseline demographics and comorbidities were comparable between groups. Complication rates within 30 days were 23.0% for iNPWT and 27.1% for SD (p = 0.401); iNPWT use was associated with significantly earlier drain removal (median 13 vs. 17 days, p = 0.004). Multivariable analysis identified smoking as an independent predictor of donor-site complications (aOR 1.74, 95% CI 1.05–2.86, p = 0.030); iNPWT was not significantly associated with reduced complication rates (OR 1.00, 95% CI 0.64–1.58, p = 0.977). Conclusions Smoking was confirmed as a significant predictor of donor-site morbidity. While iNPWT did not lower overall complication rates, it modestly reduced drain duration. Further prospective studies are warranted to define its role in DIEP flap reconstruction. Level of Evidence Level III, therapeutic study