Citations

Abstract Extramedullary disease (EMD) is increasingly recognized in relapsed/refractory multiple myeloma (MM), with central nervous system involvement (CNS-MM) representing a rare but highly aggressive manifestation associated with dismal outcomes. Data on its incidence and optimal management, particularly in the era of cellular and bispecific therapies, remain limited. We conducted a retrospective analysis of patients with MM with pathology-confirmed EMD treated at our institution between January 2000 and December 2023. CNS-MM was defined by parenchymal or leptomeningeal involvement. Clinical features, cytogenetics, treatments, and outcomes were analyzed, with predictors of CNS involvement evaluated among patients with EMD. Among 304 patients with EMD, 20 (6.5%) had CNS-MM. CNS involvement occurred a median of 19.2 months after MM diagnosis, though 15% presented at diagnosis. CNS-MM was strongly associated with high-risk cytogenetics (odds ratio [OR], 3.7) and additional visceral EMD (OR, 4.6). Median overall survival (OS) from CNS-MM diagnosis was 4.2 months. Outcomes were significantly improved in patients receiving chimeric antigen receptor T-cell therapy or bispecific antibodies, with a median OS of 19.2 months vs 1.2 months in those who did not receive immune effector therapies. Intrathecal (IT) chemotherapy demonstrated limited and transient benefit. In conclusion, CNS-MM is an aggressive complication enriched in high-risk, multifocal EMD with extremely poor prognosis. Cellular and bispecific therapies show promising activity and may meaningfully improve survival, whereas IT therapy appears to have limited efficacy. Prospective studies are needed to define optimal treatment strategies for CNS-MM.

ABSTRACT Background & Aims Metabolic dysfunction‐associated steatotic liver disease (MASLD) is highly prevalent and increasingly recognized as a multisystem cardiometabolic disorder. The global burden, incidence and prognostic implications of coexisting chronic kidney disease (CKD) in MASLD remain uncertain. Methods In this meta‐analysis, we searched MEDLINE and EMBASE from inception through September 25, 2025, for observational studies reporting CKD prevalence and/or incidence among adults (≥ 18 years) with MASLD. The primary outcomes were pooled CKD prevalence, estimated using random‐effects models on the logit scale with the Hartung–Knapp adjustment, and pooled CKD incidence (per 1000 person‐years), estimated using random‐effects models with exact Poisson confidence intervals. Secondary outcomes included all‐cause mortality and cardiovascular, renal and cancer outcomes. Results From 2811 records, 36 observational studies met the inclusion criteria. Twenty‐three studies contributed prevalence estimates (575 615 participants; 56 248 CKD cases) and thirteen studies contributed incidence estimates (27 996 new events). The pooled global CKD prevalence among individuals with MASLD was 15.22% (95% CI 9.69–23.12). The pooled CKD incidence was 22.17 per 1000 person‐years (95% CI 11.44–32.89) in the MASLD population. Hypertension (OR 1.49, 95% CI 1.29–1.72), dyslipidaemia (OR 1.22, 95% CI 1.20–1.24) and diabetes (OR 1.94, 95% CI 1.69–2.22) were associated with higher odds of CKD in the MASLD population. All‐cause mortality rates were 18.28 per 1000 person‐years (95% CI 3.45–33.11) in coexistent MASLD and CKD, more than double those in the MASLD‐only population (7.26 per 1000 person‐years (95% CI 2.97–11.56)). Conclusions Coexistent CKD affects one in seven individuals with MASLD worldwide, conferring a more than two‐fold increased risk of all‐cause mortality compared with individuals with MASLD alone.

Sleep is an active period of profound autonomic fluctuation, cycling between the parasympathetic dominance of nonrapid eye movement sleep and the sympathetic/parasympathetic volatility of rapid eye movement sleep. Sleep-disordered breathing, a spectrum of disorders marked by recurrent ventilatory instability and intermittent hypoxia during sleep, particularly obstructive sleep apnea, pathologically amplifies this volatility, transforming sleep into a nightly cascade of severe autonomic and hemodynamic stress. The cardinal features of sleep-disordered breathing, intermittent hypoxia, recurrent arousals, and marked intrathoracic pressure swings, act synergistically to drive chronic, 24-hour sympathetic overactivity, chemoreflex sensitization, and maladaptive neuroplasticity. These effects are mediated at a cellular level by oxidative stress, systemic inflammation, endothelial dysfunction, and neuroendocrine dysregulation. This persistent autonomic reset provides a direct mechanistic link to cardiovascular consequences. It is likely a primary driver of hypertension, blunting the nocturnal blood pressure dip and promoting sustained 24-hour sympathoexcitation. It fosters a proarrhythmic substrate for atrial fibrillation through mechanical stress, which drives atrial remodeling and autonomic conflict. Furthermore, sleep-disordered breathing contributes to myocardial ischemia by increasing myocardial oxygen demand and promoting a prothrombotic state. Beyond chronic disease, sleep-related autonomic shifts can act as acute triggers for malignant arrhythmias in individuals with vulnerable substrates, such as inherited channelopathies, a risk that may be significantly amplified by comorbid sleep-disordered breathing. This review delineates the critical neural and cellular pathways connecting sleep, autonomic dysregulation, and cardiovascular risk.

Abstract Objective: Antibiotics are frequently prescribed for acute sinusitis despite national guidelines recommending antibiotics only if specific symptom criteria are met. We aimed to define the proportion of acute sinusitis encounters meeting criteria for antibiotic prescribing, characterize prescribing practices, and identify factors associated with guideline-discordant prescribing. Design: This retrospective cohort study included 1,000 randomly selected adult ambulatory encounters with a primary diagnosis of acute sinusitis between January 1, 2024 and March 31, 2024. Encounter notes were reviewed for appropriate antibiotic prescribing criteria as per national guidelines. Encounters were evaluated for drug selection and duration concordance based on local guidelines. A multivariable logistic regression analysis was performed to identify predictors of inappropriate antibiotic prescribing. Setting: Emergency departments, urgent care centers, and primary care clinics. Results: Antibiotic prescribing criteria were met for 67.6% of included encounters. Antibiotics were prescribed in 93.5% of encounters that met prescribing criteria, and 80.2% of encounters that did not. Both drug selection and duration were guideline-concordant in 49.2% of total encounters. On multivariable analysis, predictors of inappropriate antibiotic prescribing included cough (OR 2.15, 95% CI 1.08–4.29; P = 0.03) and symptom duration between 7 and 9 days (compared to <6 days; OR 7.70, 95% CI 3.24–18.31; P < 0.001). Electronic encounters were associated with lower odds of prescribing compared to in-person encounters (OR 0.03, 95% CI 0.01–0.09; P < 0.001). Conclusions: Most encounters for acute sinusitis result in an antibiotic prescription, despite prescribing criteria not being met. These findings may aid antimicrobial stewardship programs in benchmarking and optimizing antibiotic prescribing for acute sinusitis.

Summary: Microsurgery is a specialized field within plastic surgery constrained by the high cost and limited availability of surgical microscopes, particularly in resource-limited settings. This lack of access hinders trainees from developing essential microsurgical skills. Previous efforts have explored smartphone-based alternatives, but there remains a need for high-fidelity, accessible training microscopes. This study presents a novel, low-cost, travel-friendly surgical microscope designed for microsurgery training. Modified binocular objective lenses enable near-field stereoscopic viewing using a dual-mirror array. A 3D-printed chassis provides the correct top-down orientation, and an integrated light source operates on standard or battery power, ensuring usability in low-resource environments. Initial testing demonstrated a fixed 6.5× magnification, allowing trainees to perform end-to-end anastomoses on 2-mm vessels. Prototypes were deployed for microsurgery training in the United States, Rwanda, Ethiopia, and Vietnam through the SHARE (Surgeons in Humanitarian Alliance for Reconstruction, Research and Education) plastic surgery organization, Nuoy Reconstructive International, and the senior author’s home institution. The authors’ investigation continues to assess the effectiveness of the microscope compared with state-of-the-art surgical microscopes. By offering a low-cost, portable solution without compromising image quality, this innovation has begun to transform microsurgical education and operating room–based microscopy worldwide, increasing accessibility for trainees and patients in diverse settings.

Abstract Background: Although some vaccines seem to be associated with a lower risk of lymphoma, their impact on outcomes is largely unknown. Methods: Data from a large prospective lymphoma cohort study were utilized to estimate associations of self-reported history of vaccination against hepatitis A, hepatitis B, influenza, and yellow fever with event-free survival (EFS) and overall survival (OS) using Cox proportional hazard models. Results: None of the vaccines were associated with EFS [hazard ratio (HR) 0.77–1] or OS (HRs 0.96–1.04). Similarly, there were no significant associations between the vaccines and outcomes for each lymphoma subtype. Conclusions: Prior vaccination against selected viruses was not associated with EFS or OS among patients with lymphoma. Impact: We did not find evidence for an impact of prior vaccination on lymphoma prognosis.

Abstract The impact of microglia antigen presentation on CNS infiltrating CD8 T cells responses during neurotropic virus infection remains undefined. Using Theiler’s murine encephalomyelitis virus (TMEV) infection of neurons as a model system, we generated H-2K b and H-2D b Tmem119 conditional knockout mice. During TMEV infection, we determined using Tmem119 K b cKO mice that microglia H-2K b contributes to antiviral CD8 T cell proliferation in the brain. Meanwhile, using Tmem119 D b cKO mice we determined that microglia H-2D b increased antiviral CD8 T cell perforin levels and the capacity to induce blood-brain barrier (BBB) disruption. Furthermore, microglial H-2D b was essential for antigen-specific reactivation of CD8 tissue resident memory (TRM) cell recall responses and BBB disruption long after virus had been cleared. These findings demonstrate discrete roles of individual MHC class I genes on microglia in CD8 T cell proliferation, effector functions, memory recall and neuropathology.

Abstract Aims Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce major adverse cardiovascular events in diabetics. This study aimed to investigate the cardiac, cancer, and overall mortality effects of GLP-1 RAs in diabetics treated with anthracyclines. Methods and results We retrospectively identified 1384 diabetics treated with anthracyclines from 2013 to 2023; 56 received GLP-1 RAs between their first and last dose of anthracycline. These patients were propensity score matched 4:1 to 224 controls without concurrent GLP-1 RA use. Because stage was not available for 10 of the 56 patients, a repeat analysis was conducted with additional matching for cancer stage in 46 cases and 92 controls. Major endpoints were rate of all-cause and cancer-related and cardiovascular disease (CVD)–related mortality, no evidence of disease (NED), and hospitalization for CVD including heart failure (HF), over 5 years. Survival analyses were conducted using cause-specific hazards Cox regression. Patients on GLP-1 RAs had a significantly lower 5 year overall mortality (HR 0.46, CI 0.24–0.87, P = 0.007) and cancer-related mortality (HR 0.42, CI 0.19–0.91, P = 0.03). This mortality risk reduction remained significant even when accounting for covariates (HR 0.39, CI 0.20–0.75, P = 0.002). The percentage of patients with NED was higher in the GLP-1 RA than control group (60.9% vs. 38.0%, P = 0.007). A decline in left ventricular ejection fraction was seen in controls but not in patients on GLP-1 RAs. There was no significant difference in CVD hospitalization; the rate of HF-related hospitalization was very low overall. Conclusion GLP-1 RAs may offer survival benefits and better cancer- and cardiac function-related outcomes in diabetics undergoing anthracycline chemotherapy.

Chronic pelvic pain (CPP) represents a complex condition where peripheral nociceptive drivers and central nervous system processes produce symptoms that extend beyond the pelvis. Central sensitization (CS) is a state of heightened neuronal responsiveness with amplified pain signaling and diminished inhibitory control, in which patients experience multifocal pain, fatigue, sleep disturbance, cognitive difficulties, and hypersensitivity to sensory stimuli. Management of CS requires a multimodal and comprehensive approach, including pain neuroscience education, targeted pelvic physical therapy, and behavioral therapies. As the field advances, incorporating sensitization science offers a more accurate, patient-centered framework to reduce symptom burden and improve quality of life.

Abstract Embryonal tumors with multilayered rosettes (ETMR) are rare, highly aggressive tumors of infancy with extremely poor outcomes and no established standard of care therapy. ETMRs were recognized as a distinct molecular entity in 2016, however, the absence of prospective, biology-driven clinical trials has limited translation of these insights into standardized, risk-adapted treatment approaches for this vulnerable population. To address this gap, the Collaborative Network for Neuro-oncology Clinical Trials (CONNECT) developed CURE(Clinical trial advancing Understanding of Rare Embryonal Brain Tumors), an international, multi-institutional, molecularly guided umbrella trial. All patients enroll through the centralized CURE-Screening protocol, which provides rapid comprehensive molecular profiling with real-time central pathology, molecular, and radiographic review to confirm diagnosis, define molecular subtype, and determine eligibility and assignment to disease-specific treatment arms. CURE-ETMR represents the first disease-specific arm to open within this platform. Following centralized screening, children with newly diagnosed ETMR are assigned to clinically defined risk strata using integrated molecular, radiographic, and clinical criteria. Patients will be treated using a risk-adapted multimodal approach in which we prioritize maximal safe surgical resection with consideration of second-look surgery based on centralized imaging review; administer induction chemotherapy followed by consolidation with high-dose chemotherapy and autologous hematopoietic cell rescue or dose-intensified chemotherapy, selectively incorporate radiation sparing approach or early focal radiotherapy for patients with unresectable residual disease or brainstem involvement; deliver intrathecal chemotherapy for leptomeningeal prophylaxis; and include biologically informed maintenance therapy. In parallel, protocol-required longitudinal collection of tumor tissue, cerebrospinal fluid, blood, and advanced neuroimaging supports integrated molecular, liquid biopsy, and imaging biomarker analyses to identify predictors of treatment response, resistance, and relapse. Primary objectives include evaluation of feasibility, safety, progression-free survival, and overall survival compared with molecularly annotated historical cohorts. This centralized screening to assignment framework establishes a scalable model for prospective, biology-driven trials in rare embryonal brain tumors.