Citations

Purpose Genitourinary syndrome of menopause (GSM) describes the symptoms and physical changes that result from declining estrogen and androgen concentrations in the genitourinary tract during the menopausal transition. This guideline provides information to clinicians regarding identification, diagnosis, counseling, and treatment for patients with GSM to optimize symptom control and quality of life while minimizing adverse events. Methods The systematic review used in the creation of this guideline is based on research conducted by the Minnesota Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality and funded by the Patient Centered Outcomes Research Institute. The EPC synthesized effectiveness and/or harms outcomes from 68 publications. An additional 66 articles evaluating 46 nonhormonal interventions were described in an evidence map. Results Clinicians diagnose GSM based on symptoms, with or without related physical findings, and after ruling out other etiologies or co-occurring pathologies. There is a large body of evidence examining the use of hormonal and nonhormonal treatment options to manage the symptoms of GSM; however, the local low-dose vaginal estrogen has the most robust evidence base. Conclusion The strategies defined in this document were derived from evidence-based and consensus-based processes. Given that there is insufficient information to recommend one hormonal therapy over another, this guideline is not meant to support a stepwise progression through different hormonal approaches. The clinician should make treatment decisions in the context of shared decision-making, considering patient goals and preferences, using the evidence of efficacy and adverse events of each possible intervention as a guide.

Abstract Chronic widespread pain (CWP) remains challenging due to its heterogeneous causes and complex mechanisms. A total of 2920 plasma proteins are analyzed from 29,254 UK Biobank participants. A total of 256 proteins are identified as cross‐sectionally correlated with CWP. A simple (top 10 proteins) and comprehensive (all significant proteins) proteomic‐based score (ProtS) is created for CWP diagnosis, both outperforming and improving the existing clinical score (area under the curve, AUC: 0.801, 0.723, and 0.791 alone, and 0.856 and 0.880 in combination). In addition, the protein score predicted 13‐years risk of pain‐related traits over the body, including pain onset, progression, and intensity; Moreover, it has stronger associations with nociplastic pain and fibromyalgia compared to nociceptive and neuropathic pain, implying a unique protein signature of different pain mechanisms. Finally, among 434 candidate proteins prioritized in the observational analysis, 18 are corroborated with causal relevance by Mendelian randomization, and importantly, four (CA14, DPEP1, LGALS3, and TNF) showed potential as novel drug targets repurposed for treating CWP.

ABSTRACT Introduction Sinonasal sarcomas are exceedingly rare entities, constituting less than 7% of head and neck sarcomas. Their complex histology needs specialized treatment, which is often based on multimodal approaches including surgery, radiation therapy, and/or chemotherapy. This manuscript aims to gather expert opinions to establish common management principles for sinonasal sarcomas. Methods This international consensus followed a modified Delphi method in seven steps, including statements definition by the core group, expert panel recruitment, and a two‐round survey. Sixty‐two statements on sinonasal sarcoma management were developed. Experts from multiple continents participated, and results were anonymized and analyzed between March and May 2025. Results A total of 44 invited experts were recruited, 43.2% otorhinolaryngologists/head and neck surgeons, 31.8% medical oncologists, and 25% radiation oncologists. Participants varied in age and experience, representing Europe (70.5%), North America (18.2%), South America (6.8%), and Asia (4.5%). Among all histologies, biphenotypic sarcoma, chondrosarcoma, leiomyosarcoma, and myofibrosarcoma are principally treated with an upfront surgical management, differently from Ewing sarcoma and rhabdomyosarcoma in which chemotherapy, eventually associated with radiotherapy, is often chosen. In the remaining histologies (angiosarcoma, liposarcoma, malignant peripheral nerve sheath tumor [MPNST], osteosarcoma, and synovial sarcoma), a precise multimodal treatment is less standardized and needs to be discussed on a case‐by‐case basis. Conclusion Sinonasal sarcomas require a histology‐driven approach to determine upfront treatment, whether surgical, medical, or multimodal. Despite this structured strategy, prognosis remains highly variable across subtypes. Multidisciplinary evaluation and individualized management in referral centers are crucial to address the biological diversity and anatomical complexity of these rare malignancies.

Background A classification system describing clinical presentation before aortic valve replacement (AVR) has recently been proposed (stable valve syndrome [SVS]), mildly symptomatic (progressive valve syndrome), or with acute and severe signs and symptoms (acute valve syndrome [AVS]). We aimed to evaluate the clinical impact, health care costs, and resource use associated with the mode of clinical presentation at the time of AVR among patients presenting with aortic stenosis. Methods Using the Market Clarity database (2017–2023), patients >18 years old with aortic stenosis and undergoing AVR (transcatheter or surgical) were included. Patients were categorized as SVS, progressive valve syndrome, or AVS based on their clinical presentation during the 1 year before AVR. All‐cause death, heart failure hospitalization, total health care costs (index hospitalization plus 1‐year follow‐up), and resource use were compared across clinical presentation groups using adjusted regression models. Results Of the 24 075 patients undergoing AVR for aortic stenosis, 270 (1.1%) had SVS, 10 195 (42.3%) progressive valve syndrome, and 13 610 (56.5%) AVS. Compared with SVS, AVS presentation was associated with increased risk of 1‐year death (adjusted hazard ratio [aHR], 2.93 [95% CI, 1.1–7.8]; P =0.03) and heart failure hospitalization (aHR, 4.15 [95% CI, 1.6–11.1]; P <0.01) after AVR. The total costs of AVR and 1‐year follow‐up were significantly higher in both the progressive valve syndrome (difference $27 410 [$13 507–$41 314]) and AVS groups (difference $36 267 [$22 302–$50 232]) compared with patients with SVS. Conclusions AVS was frequent among patients undergoing AVR and was associated with increase in death, heart failure hospitalization, health care costs, and resource use 1 year after AVR, and SVS presentation was associated with the best clinical and economic outcomes.

ABSTRACT Background Obeticholic acid (OCA) was conditionally approved in 2016 as a second‐line therapy for patients with primary biliary cholangitis (PBC) and incomplete response to ursodeoxycholic acid (UDCA) monotherapy. We aimed to evaluate the impact of OCA add‐on therapy on biochemical outcomes and safety in those patients. Methods We systematically searched MEDLINE, Embase, and Cochrane CENTRAL for papers published up to October 29, 2024, evaluating OCA in patients with PBC at the 12‐month timepoint. Pooled analyses of liver enzymes were performed using the standard mean difference (SMD) and 95% confidence interval (CI) from the OCA baseline. Side effects and the achievement of criteria for adequate response are presented in percentages (95% CI). Results We included 1285 patients from 10 studies, two of which were RCTs. The addition of OCA significantly reduced alkaline phosphatase (ALP) (SMD −0.86; −1.15 to −0.56; p < 0.001) and total bilirubin (SMD −0.29; −0.43 to −0.15; p < 0.001). Overall, 37.23% of the patients (95% CI 31.47–43.39) responded to OCA (POISE criteria). The response rate was greater in the POISE trial results compared with real‐world data (46.15% vs. 30.54%, respectively; p = 0.0089). Pruritus was the most common adverse event (40.23%; 24.65–58.07). Approximately one‐fifth of the patients stopped OCA (18.05%; 12.72–24.99), with pruritus being the main reason for discontinuation (47.70%; 34.15–61.60). Conclusion Adding OCA improves ALP, bilirubin, and biochemical remission rates in patients with PBC who did not respond well to UDCA monotherapy. Real‐world data show an attenuated response. Pruritus is the most common side effect and the leading cause of drug discontinuation.