Citations

Background: Statins have been associated with a reduced risk of primary liver cancer (PLC), primarily hepatocellular carcinoma (HCC). However, the optimal use for effective protection and whether benefits vary by patient characteristics remain unclear. We evaluated the association between statin use and PLC risk in metabolic-dysfunction-associated steatotic liver disease (MASLD), considering cumulative exposure and potential effect modifiers. Methods: We conducted a retrospective cohort study using the Veteran Affairs electronic health records. Patients with chronically elevated liver enzymes and metabolic dysfunction, without other chronic liver diseases, were identified between 2007 and 2009 and followed through 2019 for incident PLC. Statin exposure was assessed at baseline and during the follow-up, with dose standardization by LDL-lowering potency (simvastatin-equivalent units). Time to PLC was analyzed using Cox models adjusted for covariates, considering potential interactions. Results: Among 329,577 patients (92% male; median age 62 years), 0.82% developed PLC (median follow-up of 9.7 years). Baseline statin use showed a significantly lower PLC risk (adjusted hazard ratio 0.64; 95% CI, 0.57–0.71; p < 0.0001). No significant interaction was observed with age, sex, metabolic syndrome, or cirrhosis. Higher cumulative statin exposure demonstrated a dose-dependent risk reduction, remaining significant at simvastatin-equivalent doses > 15,561 mg annually after accounting for incident cirrhosis. Atorvastatin/rosuvastatin use provided comparable protection, despite different lipophilicity, and demonstrated stronger effects than others. Conclusions: In MASLD, statin therapy was associated with a dose-dependent PLC risk reduction. High-intensity therapy (simvastatin-equivalent > 40 mg daily) conferred substantial protection regardless of age, sex, insulin resistance, or cirrhosis, supporting a potential statin-based PLC chemoprevention in MASLD.

ABSTRACT Background Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors improve glycemic and cardiovascular outcomes in type 2 diabetes mellitus (T2DM). However, their impact on quality of life (QoL) and patient‐reported outcomes (PROs) has not been systematically evaluated. We conducted a systematic review and meta‐analysis to assess the effect of SGLT2 inhibitors on QoL in patients with T2DM. Methods MEDLINE, Embase, Scopus, Cochrane and ClinicalTrials.gov were searched until 18 August 2025 for randomised controlled trials and post hoc analyses of SGLT2 inhibitors reporting validated QoL or PRO outcomes in adults with T2DM. A random‐effects model was used to estimate mean differences (MD) or odds ratios (OR) with 95% CIs. Subgroup analyses compared SGLT2 inhibitors with placebo and active comparators. Risk of bias was assessed using the Cochrane RoB‐2 tool. Results Ten studies including 5294 patients (SGLT2i: 2807; control: 2487) were included. SGLT2 inhibitors significantly improved: EQ‐5D Index score versus placebo (MD: 0.04, p = 0.008), DTR‐QoL against active comparators (MD: 6.99; p = 0.0006), DTSQ compared to active comparators (MD: 0.54; p = 0.006) and IWQoL (MD: 1.44; p = 0.005) versus placebo. Improvements were also observed in SHIELD WQ‐9 overall QoL (OR: 2.11; p = 0.005), emotional health (OR: 2.16; p = 0.006), self‐esteem (OR: 2.26; p = 0.006) and work performance (OR: 1.99; p = 0.04) compared with placebo. Conclusion Randomised evidence suggests SGLT2 inhibitors enhance EQ‐5D Index score, diabetes‐specific QoL and several PROs in T2DM, particularly in physical, emotional and treatment satisfaction domains, supporting their earlier use in this population.

Background Hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSDs) are heritable connective tissue disorders characterized by widespread fragile soft connective tissue affecting the skin, ligaments, joints, vasculature, and internal organs. Although hEDS and HSD are autosomal-dominant conditions and would be expected to display a 1:1 sex ratio, studies report higher prevalence in women. Objectives The purpose of this exploratory study was to determine whether self-reported sexual problems differed between females and males diagnosed with hEDS or HSD compared with controls with chronic pain but no hypermobility. Methods In this exploratory retrospective study, we examined 1,407 patients diagnosed with hEDS or HSD according to the 2017 diagnostic criteria for eight indicators of sexual problems based on a validated screening tool. Results Patients in each diagnosis primarily self-reported as White, non-Hispanic females (90%). Of the 1,407 patients who attended the EDS Clinic, 976 (69%) were diagnosed with HSD, 240 (17%) with hEDS, and 191 (14%) were chronic pain controls with neither diagnosis. For HSD, 937 (96%) were females vs. 39 (4%) males (24:1 females to males), while for hEDS, 210 (88%) were females vs. 30 (13%) males (7:1 females to males), and controls were 165 (86%) females vs. 26 (14%) males (6:1 females to males). Females with hEDS reported significantly higher rates of sexual issues than chronic pain controls, including sexual problems (69%, p = 0.018), problems with sexual interest (41%, p = 0.023), sexual pain (45%, p = 0.006), and orgasm difficulty (34%, p = 0.022) compared with males with hEDS or males or females with HSD. In contrast, males diagnosed with hEDS did not report any sexual problems over controls, and males and females diagnosed with HSD reported only one issue—more problems with sexual interest—compared with controls (females p = 0.019, males p = 0.018). However, the small number of males in this study limits conclusions that can be drawn for them. Conclusions This study is unique because we examine sex differences in sexual problems in patients with hEDS and HSD. Our findings indicate a higher percentage of sexual problems in females with hEDS than chronic pain controls without hypermobility, but this was not observed for females with HSD.

Background Current literature has shown benefit of radial pressure wave (RPW) and focused shockwave (FSW) for management of proximal hamstring tendinopathy (PHT), although there remains a lack of consensus on treatment parameters and optimal patient positioning. Purpose The purpose of this narrative review and clinical commentary is to report what has been described for patient positioning during treatment of PHT with RPW or FSW and propose an alternative side lying approach. Methods A search was conducted of MEDLINE/PubMed and EMBASE electronic databases for studies published from January 2005 to January 2026. Key search terms included proximal hamstring tendinopathy, shockwave therapy, extracorporeal shockwave treatment, radial pressure wave, hamstring tendinosis, hamstring tendinitis, and hamstring pain. Studies were included if they evaluated RPW or FSW for the treatment of PHT. Results Six manuscripts were identified for inclusion, two randomized controlled trials (RCT), two retrospective reviews, and two case reports; a total of 217 patients (145 female, 72 male) with PHT were treated with RPW and/or FSW. One RCT provided an in-depth description of patient positioning during shockwave treatment with the patient supine, with the hip and knee flexed, compared to other manuscripts detailing clinical focusing techniques only. One case report involving a para swimmer included a figure of treatment with the patient in a prone position. Improvement in patient reported outcomes with RPW and/or FSW was noted, with one RCT showing no differences between physiotherapy compared to RPW and FSW treatment. Conclusion RPW and FSW have some evidence regarding their benefits for treatment of PHT but controlled studies are limited and no consensus on treatment protocols or patient positioning during treatment have been determined. The authors’ preferred approach in treating PHT involves having the patient side lying with the hip and knee flexed to allow patient and clinician comfort while also creating compression of the proximal hamstring about the ischial tuberosity. It remains unclear how variance in patient positioning affects patient-reported outcomes. Future studies using RPW and FSW should include documentation of patient positioning when evaluating RPW and FSW efficacy. Level of Evidence 5

Abstract Malignant histiocytic neoplasms (MHNs) are rare tumors derived from the mononuclear phagocyte system (MPS), encompassing histiocytic sarcoma, Langerhans cell sarcoma, interdigitating dendritic cell sarcoma, and other high-grade MPS lineage tumors. Despite advances in understanding histiocytic neoplasms, MHNs remain diagnostically challenging and lack standardized treatment algorithms. Current classification systems differ in lineage framing and fail to address mixed or ambiguous phenotypes, contributing to diagnostic uncertainty and inconsistent care. To address these gaps, the Histiocyte Society convened an international working group of pathologists and oncologists, including World Health Organization and International Consensus Classification contributors, to harmonize nomenclature, define minimum diagnostic criteria, and develop pragmatic treatment recommendations. Using a modified Delphi process and case-based review, the group formulated &gt;40 consensus statements spanning classification, pathology, molecular testing, clinical evaluation, and therapeutic strategies. Key recommendations include the adoption of a unified MHN designation, use of a minimum immunophenotypic panel, integration of broad molecular profiling, and the documentation of previous hematopoietic malignancy. Treatment algorithms emphasize surgical resection for unifocal disease and targeted therapy or immune checkpoint inhibition for multifocal disease when actionable mutations or programmed death ligand 1 expression are present. These consensus recommendations aim to reduce diagnostic ambiguity, standardize reporting, and improve outcomes for both pediatric and adult patients. Future priorities include international registries to refine risk stratification and biomarker-driven trials exploring targeted therapy, immunotherapy, and combination approaches.

Abstract Objectives Patients referred for specialized care often arrive with outside medical records (OMRs) compiled into multi-report PDFs that include imaging, pathology, and clinical notes in unstructured formats. Reviewing these records is time consuming and mentally taxing, increasing the risk of delayed care, clinician frustration, and missed information affecting quality of care. This study aimed to automate the segmentation, classification, and date extraction of scanned OMRs, with a focus on records relevant to breast cancer care. Materials and Methods We used optical character recognition (OCR) to extract machine-readable text from 1303 scanned PDF documents from 116 distinct external institutions. Gemini 1.5, a large language model (LLM), was then used to segment multi-report files into individual documents, classify them into clinically meaningful categories such as mammograms and pathology reports, and extract study dates to build diagnostic timelines. Document categories were informed by clinical workflows in a breast cancer center. Results The system achieved an F1 score of 0.95 for segmentation, 0.96 for classification, and 0.90 for date extraction. In a pilot of 45 records reviewed by clinicians, only 2 classification errors and 1 date error were reported. Clinicians estimated that the tool reduced OMR review time by 40%, improved workflow efficiency, and increased satisfaction. Discussion Our findings demonstrate that combining OCR with LLMs can significantly enhance the processing of unstructured medical records, reducing manual burden and supporting timely clinical decision-making. Conclusion This study demonstrates the successful application of OCR and LLMs for organizing scanned OMRs within a specialty clinic. By automating a previously manual process, the approach supports scalable review of incoming outside records and has potential for adaptation to other clinical workflows. Future work will focus on evaluating the system across additional specialties and institutions.

Background and Aims: Metabolic dysfunction–associated steatohepatitis (MASH) is a progressive liver disease that poses significant public health challenges. Although liver biopsy remains the gold standard for diagnostic and prognostic use in patients with MASH, its invasiveness limits its practical application in routine care and large-scale trials. This narrative review explores the growing role of noninvasive tests in the assessment of disease progression and treatment efficacy in MASH. Approach and Results: This review represents expert opinion synthesizing current literature on the most widely used noninvasive tests being assessed as frontline biomarkers for identification of patients with metabolic dysfunction–associated steatotic liver disease at risk of outcomes and/or in need of pharmacological intervention, and that are being used to assess treatment response in the context of clinical trials, and how they may be translated into clinical practice. Among these, elastography and the enhanced liver fibrosis test are highlighted for their potential to replace liver biopsy in clinical settings and trials. These methods are analyzed for their accuracy and ability to monitor therapeutic response, emphasizing their growing importance in providing reliable measures of clinical improvement as drug development efforts for MASH intensify. Conclusions: This synthetic review aims to provide a roadmap for federal regulators updating and potentially revising the requirements for demonstrating histologic improvement in MASH clinical trials, and for practitioners to translate this information into clinical practice. The ultimate goal is to reduce the reliance on liver biopsy while maintaining the rigor necessary to evaluate therapeutic efficacy, thus accelerating the path to approval for new MASH treatments.