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PubMed2026

A prospective pharmacokinetic interaction study between rifampicin and fusidic acid for the treatment of staphylococcal infections.

OBJECTIVE: Fusidic acid with rifampicin is used for the treatment of severe staphylococcal infection, particularly prosthetic joint infections. Previous studies using twice daily fusidic acid showed rifampicin increases fusidic acid clearance, potentially causing sub-therapeutic concentrations. It is uncertain whether this occurs with three-times daily dosing. This study sought to re-evaluate this potential drug-drug interaction. METHODS: In this prospective, open-label drug-drug interaction population pharmacokinetic (PK) study, participants were randomized to receive fusidic acid or rifampicin for 24 hours, followed by combination therapy for the duration of treatment. Drug concentration assays used liquid-chromatography mass spectroscopy on dried blood spots. Population PK models were built for fusidic acid, rifampicin and 25-desacetyl rifampicin. RESULTS: Ten participants were recruited. Inter-individual variability for both absorption (98.1%) and clearance (77.8%) were high for fusidic acid. A population pharmacokinetic model for fusidic acid revealed that early autoinhibition dominated over later rifampicin-mediated induction, resulting in a net decrease in fusidic acid clearance. The mean fusidic acid area under the curve during each dosing interval (AUCτ) at steady state was 1.76-fold [0.049, 34.918] higher relative to Day 1, despite high uncertainty.Large inter-individual (110%) variability in absorption was observed for rifampicin. There was no apparent effect on rifampicin metabolism by fusidic acid co-administration, however, fusidic acid decreased clearance of 25-desacetyl rifampicin. CONCLUSION: In patients treated with fusidic acid three times daily in combination with rifampicin, autoinhibition potentially counteracted rifampicin induction such that fusidic acid concentrations were not reduced. Rifampicin clearance was not affected by fusidic acid, but 25-desacetyl rifampicin clearance was decreased. There was large inter-individual variability in the observed concentrations and final parameter estimates.

Fusidic Acid↗

PubMed2026

Phase 1 Study Evaluating Gefurulimab Pharmacokinetics and Safety Following Delivery Via Autoinjector or Prefilled Syringe With Needle Safety Device in Healthy Adults.

PURPOSE: Gefurulimab, a novel dual-binding nanobody targeting complement component 5 (C5), is in clinical development for anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. Gefurulimab has a low molecular weight, enabling subcutaneous (SC) self-administration by autoinjector (AI) or prefilled syringe with needle safety device (PFS-SD). We compared gefurulimab pharmacokinetic (PK) exposure and safety in healthy adults following a single SC dose administered by AI versus PFS-SD. METHODS: In this phase 1, open-label, randomized, parallel-group study (NCT06208488), healthy participants aged 18 to 65 years were stratified by weight and randomized equally to 1 of 6 combination groups of device and injection site (abdomen/thigh/upper arm). Participants received a single SC dose of gefurulimab on day 1 and were assessed throughout the 92-day evaluation period. Primary endpoints were PK parameters for each device: maximum observed concentration (Cmax) and area under the serum concentration-time curve (AUCinf, AUClast). PK across injection sites, pharmacodynamics, safety, immunogenicity, and device performance were also assessed. FINDINGS: Overall, 175 participants were randomized: AI (n = 87), PFS-SD (n = 88). Geometric least squares mean ratios (90% CI) comparing AI/PFS-SD for Cmax, AUCinf, and AUClast were 97.6% (94.5-100.8), 99.6% (96.1-103.3), and 98.8% (95.2‒102.6), respectively. Secondary analyses found no meaningful differences in PK parameters across injection sites. Serum-free C5 concentrations over time, treatment-emergent adverse event (TEAE) profiles, and antidrug antibody responses were similar between cohorts. Most TEAEs were mild; none led to study discontinuation. IMPLICATIONS: SC administration of gefurulimab by AI and PFS-SD was well tolerated with comparable exposure, meeting bioequivalence criteria.

Humans↗

PubMed2026

Clinical Outcomes and Genomic Epidemiology of Multidrug-Resistant Methicillin-Resistant Staphylococcus aureus Keratitis.

PURPOSE: To characterize the clinical features, management, antimicrobial resistance patterns, and genomic epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) keratitis at two North American centers. DESIGN: Retrospective interventional case series combined with laboratory investigation PARTICIPANTS: Seventy eyes of 67 patients presenting laboratory-confirmed MRSA keratitis were included METHODS: We performed a multicenter retrospective case series of patients with culture-proven MRSA keratitis treated between 2005 and 2022. Demographic and clinical data were collected. Antimicrobial susceptibility testing was conducted, and multidrug resistance (MDR) was defined as resistance to ≥3 antibiotic classes. A subset of isolates underwent whole-genome sequencing with core genome multilocus sequence typing. Vancomycin susceptibility, heteroresistance screening, and tolerance testing were performed on available isolates. MAIN OUTCOME MEASURES: Antimicrobial susceptibility and multidrug resistance rates, vancomycin phenotypic profiles, MRSA genotypic distribution, and final best-corrected visual acuity RESULTS: Median age was 63.5 years, and 61.4% were female. Ocular surface disease (67.7%) and prior ocular surgery (65.2%) were common. Only 25.4% had significant healthcare exposure in the preceding year. Most isolates (85.7%) were MDR. Fluoroquinolone susceptibility was low (moxifloxacin 19.7%). All isolates were susceptible to vancomycin (MIC₉₀ 2 µg/mL), and no vancomycin-intermediate, heteroresistant, or tolerant phenotypes were identified. Whole genome sequencing (n = 41) demonstrated predominance of clonal complexes 5 (68.3%) and 8 (29.2%). Visual outcomes were poor, with most patients (85.2%) having a final visual acuity worse than 20/60 among those with follow-up. CONCLUSIONS: MRSA keratitis is associated with high rates of multidrug resistance and poor visual outcomes despite guideline-based therapy. Infections were predominantly caused by CC5 MDR strains despite limited recent healthcare exposure. These findings highlight the persistence of highly resistant MRSA lineages in community-associated corneal infection and underscore the need for ongoing antimicrobial surveillance and optimized treatment strategies.

Humans↗

PubMed2026

The Efficacy of Erector Spinae Plane Block Versus Subcostal Transversus Abdominis Plane Block in Laparoscopic Nephrectomy: A Randomized Clinical Trial.

OBJECTIVES: This study compared the efficacy and safety of erector spinae plane block (ESPB) versus subcostal transversus abdominis plane (TAP) block in reducing postoperative pain among patients undergoing laparoscopic nephrectomy. METHODS: This randomized clinical trial enrolled 70 adult patients, ASA physical status I or II, who underwent total (radical) laparoscopic nephrectomy under general anesthesia. Patients were randomly assigned to 2 groups. Group ESPB received an ultrasound-guided ESPB at the T7 transverse process level, while group TAP received an ultrasound-guided subcostal TAP block. The primary outcome was the total amount of morphine consumed at 6 and 24 hours postoperatively. Secondary outcomes included the incidence of patients requiring opioid analgesia, time to rescue analgesia, visual analog scale of pain intensity, time to postoperative ambulation, intraoperative and postoperative hemodynamics, arterial partial pressure of oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 or P /F) ratio, and incidence of complications. RESULTS: Compared with the TAP group, the ESPB group exhibited significantly lower median morphine consumption at 24 hours ( P =0.032), prolonged time to first analgesic rescue ( P =0.049), and lower incidence of rescue morphine requirement (OR=0.23; 95% CI=0.06-0.94; P =0.031), with lower visual analog scale pain scores at 12, 18, and 24 hours postoperatively ( P <0.001). The mean arterial blood pressure and heart rates were comparable between groups. No significant adverse effects from either approach. DISCUSSION: In laparoscopic nephrectomy, ultrasound-guided ESPB may safely and effectively be used to improve pain management and reduce pain intensity, with stable hemodynamics and a comparable risk of postoperative complications to the ultrasound-guided subcostal TAP block.

Humans↗

PubMed2026

Urinary Small Extracellular Vesicle DNA as a Biomarker for the Non-Invasive Diagnosis of Bladder Cancer.

Existing diagnostic technologies for bladder cancer (BC) suffer from low sensitivity, low specificity, or a lack of validation. Therefore, validated, non-invasive diagnostic biomarkers with high sensitivity and specificity for early detection of BC are needed to complement and improve upon the limitations of existing diagnostic methods. We used low-pass whole genome sequencing (LP-WGS) technology to detect copy number variations (CNVs) in small extracellular vesicle (sEV) DNA isolated from urine samples of patients. Based on these results, we constructed and validated a diagnostic model to differentiate between benign and malignant bladder lesions. We conducted a receiver operating characteristic analysis and calculated the area under the curve (AUC) to evaluate the performance of the diagnostic model. The urine sEV-DNA LP-WGS data revealed CNV differences between benign and malignant samples. The diagnostic model achieved an AUC of 0.953, a sensitivity of 86.7%, and a specificity of 100% in the training cohort and an AUC of 0.985, a sensitivity of 90%, and a specificity of 100% in the validation cohort. Even at the lowest coverage depth of 0.01X, the performance of the diagnostic model remained relatively robust. Notably, the performance of this diagnostic model surpassed that of the biomarker neuron-specific enolase (sensitivity: 85.7% vs. 64.3%; specificity: 100% vs. 87.5%) and urinary cytology (sensitivity: 100% vs. 66.7%; specificity: 100% vs. 94.1%). Our study demonstrates that urine sEV-DNA exhibits high discriminatory power in distinguishing between benign and malignant bladder lesions, making it a promising tool for auxiliary diagnosis of BC.

Humans↗

PubMed2025

Preoperative Patient Education on Opioid Use and Pain After Surgery: A Randomized Trial.

OBJECTIVE: To evaluate the impact of preoperative analgesic education on postoperative opioid consumption, pain scores, and patient satisfaction with analgesia. BACKGROUND: Effective postoperative pain management is crucial for patient recovery and satisfaction, yet opioid use poses risks of tolerance and addiction. Preoperative patient education offers a potential avenue to mitigate opioid reliance and improve pain management outcomes. METHODS: This single-center randomized trial was conducted at the Cleveland Clinic Main Campus between October 2021 and October 2023. Adult patients scheduled for hip arthroplasty or laparoscopic-assisted abdominal surgery with an ASA physical status of 1 to 4 were eligible. Patients with a history of prolonged opioid use, planned regional block or epidural analgesia, or limited English fluency were excluded. Participants were randomized 1:1 to receive either an analgesic educational video or a generic video about surgery and hospitalization. The primary outcome was opioid consumption during the initial 72 postoperative hours. Secondary outcomes included time-weighted average pain scores and patient satisfaction with analgesia. RESULTS: Among 957 analyzed patients, preoperative analgesic education did not significantly reduce opioid consumption (adjusted ratio of geometric means, 1.01; 95% CI, 0.86-1.18; P =0.890) or improve pain scores (adjusted mean difference, -0.1; 95% CI, -0.3 to 0.2; P =0.617). Patient satisfaction scores also did not differ significantly between groups (adjusted mean difference, -0.1; 95% CI, -0.3 to 0.2; P = 0.611). CONCLUSIONS: Preoperative analgesic education did not result in clinically meaningful reductions in opioid consumption or improvements in pain management outcomes. Further research may explore more intensive educational interventions to optimize postoperative pain management strategies.

Humans↗

PubMed2026

A Qualitative Analysis of Cancer Survivors' Experience in a Time-Restricted Eating vs Control Clinical Trial to Address Cancer-Related Fatigue.

PURPOSE: To describe cancer survivors' lived experiences in a clinical trial that tested an individualized nutrition counseling with or without time-restricted eating to address cancer-related fatigue. METHODS: The Fatigue REDuction After cancer study was a two-arm, randomized controlled trial. Participants were adult cancer survivors who were 2 months to 2 years post-treatment. All participants received individualized nutrition counseling; those in the time-restricted eating group self-selected a consistent 10-hour eating window for 12 weeks. After the study, semi-structured exit interviews were conducted to gauge participants' experiences in the trial. Interviews were transcribed and two independent coders thematically analyzed the interviews using inductive and deductive coding. NVivo software was used for data organization and analysis. RESULTS: Participants (n = 24; TRE = 11; Control = 13) were 55 ± 13 years old, 75% were female, and they had a variety of cancer types. The majority of participants found that being in the study helped them to set and achieve lifestyle goals and would therefore recommend the study to others. Participants in the time-restricted eating group noted that time-restricted eating helped them set a better routine, providing a positive sense of control. However, some noted difficulty switching to a 14-hour fasting schedule, as it can interfere with their regular routine or employment schedules. Many participants noted they were happy that cancer-related fatigue was gaining more attention, hoping to find solutions for persistent cancer-related fatigue. CONCLUSION: The majority of participants found the study useful and, regardless of their group assignment or the intervention's impact on their fatigue, found the study helped them to gain better control of their dietary habits.

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PubMed2026

Patient-reported outcomes with tarlatamab in extensive-stage small cell lung cancer after platinum-based chemotherapy: results from the phase 3 DeLLphi-304 trial.

BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) is associated with a high symptom burden and impaired health-related quality of life (HRQoL). This prespecified analysis from the phase 3 DeLLphi-304 trial evaluated patient-reported outcomes (PROs) for tarlatamab versus standard-of-care (SoC) chemotherapy following first-line platinum-based therapy. METHODS: DeLLphi-304 is a multicenter, open-label, randomized phase 3 study in adults with ES-SCLC. PROs were assessed using validated instruments, including the EORTC QLQ-C30, EORTC QLQ-LC13, FACT-G GP5, BPI-SF, and the EQ-5D-5L visual analogue scale. Change from baseline, response rates, and time to deterioration in these PROs were analyzed. RESULTS: PRO data from all 509 patients enrolled were evaluated. Compliance with QLQ-C30 and QLQ-LC13 assessments remained above 69% through 19 weeks. A higher proportion of patients receiving tarlatamab achieved symptom or functional improvement at 19 weeks compared with SoC in chest pain (19% vs 10%), cough (35% vs 26%), dyspnea (22% vs 7%), physical functioning (13% vs 8%), and global health status (23% vs 15%), respectively. Tarlatamab also delayed deterioration in symptoms, physical functioning, and pain at worst relative to SoC. FACT-G GP5 results indicated that patients receiving tarlatamab were less bothered by treatment side effects over time. CONCLUSIONS: In addition to its previously reported antitumor activity, tarlatamab demonstrated clinically meaningful improvements in symptoms and HRQoL compared with SoC. These findings support a favorable benefit-risk profile of tarlatamab in patients previously treated for ES-SCLC.

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PubMed2025

Impact of subthreshold troponin levels and temporal trends on short term adverse cardiovascular outcomes in patients discharged from the emergency department: a RACE-IT trial substudy.

BACKGROUND: High-sensitivity cardiac troponin I assays enable early exclusion of myocardial infarction in the emergency department. However, the clinical implications of detectable troponin values below the 99th percentile upper reference limit (4-18 ng/L) remain unclear. OBJECTIVE: To assess the association between subthreshold troponin levels and 30-day outcomes in patients from the RACE-IT trial, using exact troponin values when available. METHODS: This post-hoc analysis of the RACE-IT stepped-wedge randomized controlled trial included patients with troponin ≤ 18 ng/L across nine EDs. Patients were stratified by initial troponin, peak value, absolute change, and percent change. The primary outcome was a 30-day composite of all-cause death, acute MI, percutaneous coronary intervention, and coronary artery bypass grafting. Logistic regression analysis after adjusting for age, sex, race, and coronary artery disease was performed. RESULTS: Among 19,194 patients with troponin ≤ 18 ng/L, 117 (0.6%) experienced the composite outcome. Higher troponin levels were associated with increased event rates in unadjusted analyses. Adjusted analyses showed no independent associations overall, though patients whose highest troponin values fell within the ≥ 11- ≤ 18 ng/L range continued to demonstrate significantly worse outcomes than those with lower peak levels. Elevated troponin values correlated with older age, male sex, and greater comorbidity burden. CONCLUSION: In this post-hoc analysis of patients with troponin values below the 99th percentile URL, absolute levels and temporal changes were not independently associated with 30-day adverse outcomes. These findings support the use of subthreshold troponin values in rapid rule-out protocols, emphasizing the need to consider clinical context and comorbidities in risk assessment.

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PubMed2026

Smart crutch tipsTM real-time feedback improves adherence to partial weight-bearing protocols following lower extremity fracture surgery: a pilot study.

PURPOSE: To evaluate the effectiveness of Smart Crutch Tips™ in promoting adherence to prescribed early partial weight-bearing (PWB) protocols and to assess patient experience with real-time weight-bearing feedback during home rehabilitation. METHODS: Twenty patients with lower extremity fractures prescribed partial weight-bearing (PWB) were randomized into two groups utilizing real-time feedback crutch tips (RFC). The Intervention group (n = 10) used Smart Crutch Tips™ (ComeBack Mobility Inc., Kiev, Ukraine), which provided real-time feedback on weight-bearing compliance. The Control group (n = 10) also used crutches equipped with Smart Crutch Tips™, but notifications were disabled, allowing passive data collection without patient feedback. Weight-bearing compliance was defined as the percentage of steps within ± 10% of the prescribed target. Secondary outcomes included patient satisfaction and device usability assessed using the System Usability Scale (SUS) throughout the home rehabilitation period. RESULTS: The Intervention group demonstrated significantly greater PWB compliance compared with the Control group (73.6% vs. 21.1%, p < 0.01). The Intervention group reported a mean SUS score of 84.25, indicating excellent usability. No device-related complications or adverse events were observed. Patient satisfaction, assessed through video interviews, was high, with participants in the Intervention group expressing a strong willingness to recommend the device to others with similar injuries and rating it 10 out of 10. CONCLUSION: Smart Crutch Tips™ significantly improved adherence to prescribed partial weight-bearing protocols following lower extremity fracture surgery. The RFC device demonstrated high usability, excellent patient satisfaction, and no device-related complications during home rehabilitation throughout the study period.

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PubMed2026

Dealcoholized muscadine wine improved skin elasticity and oxidative stress biomarkers without affecting gut microbiome in women over 40 in a randomized controlled trial.

Muscadine wine has a unique polyphenol profile distinct from that of common wine, and limited research exists on its health benefits. This study aimed to investigate the effects of intake of dealcoholized muscadine wine (DMW) on skin health, oxidative stress, inflammatory biomarkers, and the gut microbiome. Seventeen healthy women were randomly assigned to consume 300 mL of DMW or a placebo daily for 6 weeks, separated by a 3-week washout period, in a randomized, single-blinded, crossover design. Skin health parameters were measured on the face and forearm. Oxidative stress and inflammatory biomarkers were assessed in plasma. Fecal bacterial DNA was sequenced using shotgun sequencing. DMW did not affect UVB-induced erythema compared to placebo. However, it significantly decreased transepidermal water loss and increased facial gross elasticity. Skin elasticity significantly improved on the forearm, whereas other skin parameters were not affected. DMW significantly decreased plasma levels of matrix metalloproteinase-9 and advanced glycation end products compared with placebo. However, the abundance, diversity, and functions of the gut microbiome were not affected. Polyphenol-rich DMW administered for six weeks improved certain skin health parameters and reduced oxidative and inflammatory stress, without affecting the gut microbiome in healthy women.

Humans↗

PubMed2026

Ablative radiotherapy in castration-resistant prostate cancer.

OBJECTIVE: To prove the oncological benefit of ablative radiotherapy in patients with up to five metastases from castration-resistant prostate cancer (CRPC) a single-centre randomised trial was initiated. PATIENTS AND METHODS: This monocentric, randomised, phase II clinical trial enrolled patients with up to five prostate-specific membrane antigen-positive bone or lymph node metastases developing prostate-specific antigen (PSA) progression during androgen deprivation (ADT) or ADT and androgen-receptor targeted therapy. Participants were randomised (2:1) to receive metastasis-directed therapy (MDT) or observation (OBS) without changing systemic therapy. The primary endpoint was the proportion of patients having PSA progression within 1 year, with statistical analyses conducted using intention-to-treat principles. Here, results of a planned interim analysis of the primary endpoint are reported. RESULTS: A total of 30 patients (12 in the observation arm and 18 in the MDT arm) were enrolled, PSA progression within 1 year occurred in 44% of the MDT group vs 75% in the OBS group (P = 0.14, not significant). The median time to PSA progression was significantly longer in the MDT arm (12.4 months) compared to the OBS arm (2.9 months, P = 0.03). The pre-defined criteria to discontinue the study were not met. Limitations include the single-centre design and small sample size at interim analysis. CONCLUSION: This pre-planned interim analysis of the primary endpoint did not meet the discontinuation criteria of the study protocol, suggesting that MDT in oligometastatic CRPC may extend the time to PSA progression without immediate change of systemic therapy. The continuation of the study in a multicentre setting is planned (Institutional funding by the TU Dresden, ClinicalTrials.gov identifier: NCT04141709).

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PubMed2026

Plasma proteomics reveal SERPINA1 and CD59 as candidate biomarkers for COVID-19 severity stratification and prognosis prediction.

BACKGROUND: COVID-19 has been closely associated with coagulation abnormalities. However, existing biomarkers, including D-dimer and fibrin degradation products (FDP), exhibit limited accuracy in stratifying disease severity and predicting long-term clinical outcomes. OBJECTIVES: This study aimed to use proteomic analysis to identify plasma biomarkers associated with COVID-19 severity and prognosis, and validate their predictive utility for mortality and thromboembolic complications. METHODS: Plasma proteomic profiles were analyzed across three COVID-19 severity classes. Differential expression analysis and functional analysis were performed. Clustering analysis was used to identify proteins correlated with disease severity. Candidate biomarkers were validated in an independent cohort. Predictive performance of the biomarkers for mortality, sepsis and venous thromboembolism was evaluated using bootstrap-corrected ROC analyses and multivariable regression analyses. RESULTS: Proteomic analysis revealed progressive involvement of the coagulation and complement pathway with increasing disease severity. SERPINA1 and CD59 were identified as candidate biomarkers and exhibited significantly higher plasma levels in severe cases. Bootstrap-corrected ROC analyses demonstrated strong predictive performance: SERPINA1 achieved AUCs of 0.775 and 0.924 for 30-day and 12-month mortality, and CD59 achieved AUCs of 0.720 for sepsis; the combined model further improved prediction of 12-month mortality (AUC 0.946) and sepsis (AUC 0.904), outperforming D-dimer and FDP. Multivariable regression confirmed their independent prognostic value. CONCLUSION: This exploratory study identifies SERPINA1 and CD59 as candidate prognostic biomarkers in COVID-19, highlighting the role of coagulation and complement-related pathways in disease severity and warranting further prospective validation.

Humans↗

PubMed2026

A multi-scale fusion model based on multi-phase contrast-enhanced CT for predicting pancreatic cancer resectability.

Purpose.Develop a multi-scale fusion model (MSFM) based on multi-phase contrast-enhanced computed tomography (CECT) to predict pancreatic cancer (PC) resectability, thereby assisting expert decision-making.Methods.This retrospective study enrolled 280 patients with PC from four institutions, which were randomly divided into a training cohort (202 patients) and an independent test cohort (78 patients). Three-phase CECT images (arterial, venous, and delayed phases) were used for modeling. The MSFM comprises two sub-networks: (1) a multi-phase fusion network for extracting cross-phase shared fusion features, (2) a phase-specific branch network for capturing phase-specific features; and a post-fusion strategy to generate the final predictive score by integrating the shared fusion features and three groups of phase-specific features. Additionally, a human-machine fusion deep learning model (HMfDL) was constructed by fusing the predictive score of the MSFM with expert assessments.Results.In the independent test, the MSFM achieved an AUC (area under the receiver operating characteristic curve) of 0.8385 (95% CI: 0.7521-0.9249), accuracy of 84.62%, sensitivity of 72.00%, and specificity of 90.57%. This performance outperformed single-phase models (AUC range: 0.7638-0.7781), two-phase models (AUC range: 0.7826-0.7864), and ten states-of-the-art classifiers (AUC range: 0.7404-0.7796). The HMfDL further improved the performance, reaching an AUC of 0.8626 (95% CI: 0.7853-0.9400), accuracy of 91.03%, sensitivity of 80.00%, and specificity of 96.23%. Notably, the HMfDL corrected 58.82% of misdiagnosis made by experts.Conclusions. The MSFM effectively fuses multi-phase CECT to enable highly accurate predictions of PC resectability, and provides valuable support for expert decision-making through HMfDL.

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PubMed2026

Meningioma methylation profiling as a complement to WHO grading: a single-center experience.

OBJECTIVE: The methylation profile of meningiomas is a promising predictive tool that may improve risk stratification beyond WHO grading. This study aimed to evaluate the clinical relevance and real-world applicability of routine epigenetic testing in meningioma management. METHODS: The authors retrospectively analyzed patients who underwent meningioma resection between January 2021 and December 2023. Histopathological grading (WHO 2021) and methylation profiling (methylation class [MC]) with the MethylationEPIC v1.0 (850k) chip were performed by an independent neuropathologist. RESULTS: A total of 106 patients were included; 81 tumors (76%) were classified as WHO grade 1, 20 (19%) as grade 2, and 5 (5%) as grade 3. Epigenetically, 55 tumors (52%) were classified as benign, 18 (17%) as intermediate, and 2 (2%) as malignant; 31 (29%) could not be classified. Discordances between WHO grading and methylation profiling were observed in 18 of 74 cases. Tumor board decisions were made after a median of 8 days postoperatively, guided by WHO grading; however, the epigenetic report was only available after a median of 23 days. During follow-up, 20 patients experienced tumor progression. Progression was significantly associated with the MC (r = -0.4, p < 0.001) and tumor volume (r = 0.4, p = 0.0005), but not with WHO grading (r = 0.17, p = 0.084). However, the relatively high rate of unclassified tumors and delayed result availability limited the direct impact of MC profiling on immediate clinical decision-making. Interestingly, progression-free survival in MC-unclassified tumors mirrored that of the intermediate group. CONCLUSIONS: Methylation profiling demonstrates superior predictive accuracy for meningioma progression and complements WHO grading, especially in identifying malignant meningiomas. However, its current clinical utility is constrained by technical and logistical limitations. In real-world practice, epigenetic classification should therefore be considered a complementary tool rather than a replacement for established histopathological assessment.

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PubMed2026

Bioepidemiology of cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis, primarily due to immunoglobulin light chain (AL) or transthyretin (ATTR) amyloid, is an increasingly recognized cause of heart failure. Modern diagnostic advances suggest that ATTR, particularly in older adults, may be more prevalent than historically reported. METHODS: All Olmsted County decedents aged ≥40 years from 1970 to 1976 were identified. Available ventricular myocardium from retained paraffin blocks was screened histologically for amyloid using sulfated Alcian blue staining; positive cases underwent grading and proteomic typing by laser microdissection coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Beyond prevalence estimation, this analysis characterizes amyloid type, deposition grade and distribution, associated comorbidities, and cause-of-death patterns, comparing amyloid-positive decedents with age- and sex-matched controls. RESULTS: Of 2,566 eligible deaths, 1,028 autopsy cases with evaluable myocardium formed the study cohort (mean age 70.5 years; 61.1% male; 97% White). Cardiac amyloid was present in 52 cases giving an overall prevalence of 5.1% (95% CI: 3.8-6.6, which rose from 0% under age 60 to 37.5% (95% CI: 21.1-56.3) in those ≥90 years (p < 0.001). While prevalence estimates were higher in men above age 80 compared to women, there was no evidence of an interaction of age and sex (p = 0.90). The quantity of amyloid was sufficient for typing in 38 cases: ATTR (84.2%), AL (7.9%), serum amyloid A (5.3%), and apolipoprotein A-IV (2.6%). Adjusted estimates assuming untyped mild cases were ATTR-type increased ATTR prevalence to 4.5% (95% CI: 3.3-5.9) overall. Comorbidity profiles were similar between amyloid-positive and negative groups, though syncope and leg weakness were more common in amyloid-positive decedents. CONCLUSIONS: In an unselected autopsy cohort, cardiac amyloid was common, particularly ATTR in older adults. Prevalence increased steeply after age 80. These findings suggest that ATTR amyloidosis is not rare and is likely underdiagnosed and has similar prevalence in women and men, despite the male predominance reported in the literature.

Humans↗

PubMed2026

Characterizing Submental Neuromuscular Activity of Swallowing Rehabilitation: An Electromyographic Evaluation of Rehabilitative Maneuvers in Healthy Adults.

PURPOSE: The effortful swallow (ES), the Mendelsohn maneuver (MM), and isometric tongue presses (TPs) are widely used swallowing maneuvers/exercises to improve elements of swallowing, such as muscle strength and biomechanics. However, the underlying neuromuscular mechanisms of these exercises remain unclear, potentially limiting our ability to specify treatment targets and improve treatment efficacy. This study aimed to compare submental neuromuscular activation patterns during the ES, MM, TPs, and typical swallows in healthy young and older adults. METHOD: As part of a larger randomized crossover validation study, 60 healthy adults (30 young and 30 older) completed typical swallows and three maneuvers using a wearable submental surface electromyographic (sEMG) system (i-Phagia). Outcome variables included (a) normalized mean sEMG amplitude and (b) time to peak sEMG amplitude. Linear mixed models were used to examine effects of task, age, and sex on both outcomes. RESULTS: Normalized mean amplitude was significantly different across tasks. Post hoc pairwise comparisons confirmed that all three maneuvers produced higher normalized mean sEMG amplitude than typical swallows, with the ES eliciting the highest amplitude across age groups. Time to peak amplitude differed significantly across tasks, with typical swallows requiring the shortest time to reach peak amplitude, followed by the ES, MM, and TP. CONCLUSIONS: The ES required the highest neuromuscular effort with the shortest time to reach peak amplitude, suggesting its potential for targeting submental muscle power. Typical swallows required the least neuromuscular effort with the shortest time to reach peak amplitude, suggesting their potential for training submental muscle speed. The MM and TP may also improve submental muscle strength; however, given their temporal requirements (longer durations), they may be more beneficial for targeting coordination and endurance, though more research in this area is warranted. These findings underscore the importance of task-specific neuromuscular profiling to inform mechanism-based swallowing rehabilitation. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.32948549.

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PubMed2026

Lower androgen sulfate metabolites in women with hypermobile Ehlers-Danlos syndrome may be associated with changed metabolism and disposition.

Hypermobile Ehlers-Danlos Syndrome (hEDS), characterized by joint hypermobility and multisystem involvement, is the most common type of EDS. Its comorbidities are wide-ranging, reflecting the involvement of connective tissue and its role in a multitude of processes. hEDS has been hypothesized to have hormonal aspects since the disorder is diagnosed more often in women and symptom changes closely correlate with hormonal shifts. To better understand the etiology and biochemical changes in hEDS and its comorbidities, a multiple-omics study was performed in women, controls (n = 45) and those with hEDS (n = 45), alongside the collection of questionnaires related to symptom severity. Metabolomic evaluation was performed on serum samples and RNA isolated from fibroblasts cultured from skin punches was analyzed for transcriptomics. Samples from hEDS patients had statistically significantly lower levels of multiple androgen sulfate metabolites, compared with controls, driven largely by participants aged 30-49. Changes to other classes of steroid hormones (corticosteroids, progestogens, and estrogens) were largely not significant between hEDS and control groups. Transcriptomics of skin fibroblasts from hEDS patients revealed downregulation of multiple enzymes involved in biosynthesis, metabolism, and disposition of androgens, compared with controls. Multiple steroid hormones correlated with symptoms surveyed in 18-29 year old participants with hEDS. Shifts in steroid hormone metabolites in hEDS compared with controls may be due to changes to metabolism and disposition, but more validation is necessary to be conclusive. This data provides insights into the unclear links between steroid hormones and hEDS and its comorbidities.

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