Citations

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.

Background Intracranial occlusions in embolic stroke of undetermined source are histopathologically similar to cardiac sources of embolism. Whether patients with embolic stroke of undetermined source and intracranial occlusion benefit from anticoagulation is unknown. Methods A multicenter retrospective cohort of adults with cryptogenic stroke was queried for patients with proximal or medium/distal vessel occlusion. The primary outcome was recurrent ischemic stroke, which was assessed in unadjusted and adjusted Cox proportional hazards models and repeated following 1:1 propensity score matching and biweight kernel density matching. Results Of the 2328 patients who were followed over a median of 1.31 years (interquartile range, 0.34–2.85), 999 (42.6%) had an intracranial occlusion. When compared with patients without an intracranial occlusion, those with an occlusion had fewer atherosclerotic vascular risk factors, more severe symptoms, and less severe cerebral microvascular disease. The rate of recurrent stroke was similar between patients with versus without an intracranial occlusion (6.8%/year [95% CI, 5.7–8.2] versus 7.0%/year [95% CI 6.0–8.1]; adjusted hazard ratio [HR], 1.09 [95% CI, 0.77–1.55]). There was no association between occlusion and recurrent stroke in the adjusted propensity score matching (HR, 1.01 [95% CI, 0.64–1.59]) or kernel density models (HR, 0.95 [95% CI, 0.62–1.45]). There was no interaction between occlusion and treatment with anticoagulation, sex, age, or high‐risk sources of embolism for the primary outcome in the unmatched and matched analyses. Conclusions Intracranial occlusion in patients with embolic stroke of undetermined source is not associated with a greater risk of recurrence when compared with patients without an intracranial occlusion. There was no difference in rate of recurrent stroke with anticoagulation when stratified by presence or absence of occlusion.

Objectives To compare survival and oncological outcomes of cisplatin‐ineligible patients (Cis‐I) and cisplatin‐eligible (Cis‐E) patients with muscle‐invasive bladder cancer (MIBC) undergoing immediate radical cystectomy (IRC), as IRC is currently considered the standard‐of‐care for Cis‐I patients with MIBC. Patients and Methods Data from patients with clinical (c)T2–4cN0–1M0 MIBC undergoing IRC, between 2006 and 2021, were retrospectively analysed from four tertiary care centres in the United States. Overall, recurrence‐free and event‐free survival were described using the Kaplan–Meier method and tested using the log‐rank test. For context, we compared survival outcomes against those in Cis‐E patients with MIBC undergoing IRC from the Southwest Oncology Group (SWOG)‐8710 trial. Results Overall, 379 Cis‐I and 125 Cis‐E patients with cT2–4cN0–1M0 MIBC who underwent IRC were included. Cis‐I patients included 44.8% cT3/4 vs 60% cT3/4 in the Cis‐E group. Overall, 83.3% of Cis‐I and 79.2% of Cis‐E patients died during follow‐up. The median event‐free and overall survival were 12.1 and 14.5 months for the Cis‐I group and 28.8 and 60.1 months for the Cis‐E group ( P < 0.001). [Correction added on 10 October 2025, after first online publication: The preceding sentence has been revised in this version.] Limitations include retrospective comparison of contemporary multi‐institutional data with that of a randomised control trial. Conclusions The Cis‐I patients with MIBC undergoing IRC fared poorly, with a median overall survival of 14.5 (95% confidence interval 11.1–17.9) months, mostly due to non‐cancer‐related deaths. These results provide a benchmark for clinical trials exploring novel agents or alternative chemotherapy regimens in Cis‐I patients with MIBC.

Importance Multiparametric magnetic resonance imaging (MRI), with or without prostate biopsy, has become the standard of care for diagnosing clinically significant prostate cancer. Resource capacity limits widespread adoption. Biparametric MRI, which omits the gadolinium contrast sequence, is a shorter and cheaper alternative offering time-saving capacity gains for health systems globally. Objective To assess whether biparametric MRI is noninferior to multiparametric MRI for diagnosis of clinically significant prostate cancer. Design, Setting, and Participants A prospective, multicenter, within-patient, noninferiority trial of biopsy-naive men from 22 centers (12 countries) with clinical suspicion of prostate cancer (elevated prostate-specific antigen [PSA] level and/or abnormal digital rectal examination findings) from April 2022 to September 2023, with the last follow-up conducted on December 3, 2024. Interventions Participants underwent multiparametric MRI, comprising T2-weighted, diffusion-weighted, and dynamic contrast–enhanced (DCE) sequences. Radiologists reported abbreviated biparametric MRI first (T2-weighted and diffusion-weighted), blinded to the DCE sequence. After unblinding, radiologists reported the full multiparametric MRI. Patients underwent a targeted biopsy with or without systematic biopsy if either biparametric MRI or multiparametric MRI was suggestive of clinically significant prostate cancer. Main outcomes and measures The primary outcome was the proportion of men with clinically significant prostate cancer. Secondary outcomes included the proportion of men with clinically insignificant cancer. The noninferiority margin was 5%. Results Of 555 men recruited, 490 were included for primary outcome analysis. Median age was 65 (IQR, 59-70) years and median PSA level was 5.6 (IQR, 4.4-8.0) ng/mL. The proportion of patients with abnormal digital rectal examination findings was 12.7%. Biparametric MRI was noninferior to multiparametric MRI, detecting clinically significant prostate cancer in 143 of 490 men (29.2%), compared with 145 of 490 men (29.6%) (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points; P = .50). Biparametric MRI detected clinically insignificant cancer in 45 of 490 men (9.2%), compared with 47 of 490 men (9.6%) with the use of multiparametric MRI (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points). Central quality control demonstrated that 99% of scans were of adequate diagnostic quality. Conclusion and relevance In men with suspected prostate cancer, provided image quality is adequate, an abbreviated biparametric MRI scan, with or without targeted biopsy, could become the new standard of care for prostate cancer diagnosis. With approximately 4 million prostate MRIs performed globally annually, adopting biparametric MRI could substantially increase scanner throughput and reduce costs worldwide. Trial registration ClinicalTrials.gov Identifier: NCT04571840

ABSTRACT Beyond the arboviruses they transmit to humans and animals, mosquitoes harbour diverse viral communities that shape infection and immunity dynamics. Understanding how these communities shift within mosquito populations across time and space has important implications for how we anticipate and manage arboviral disease epidemics. Here, we examined the viromes of rural and sylvatic mosquito species sampled longitudinally across two years from countries representing South America, Africa, and Southeast Asian geographies to quantify the relative contributions of host and ecological factors in shaping their virome dynamics. We found that virus diversity and virome composition are strongly influenced by host phylogeny and spatial factors and show limited temporal variation. By examining virus similarity networks across mosquito species and biogeographies, we observed frequent instances of within- and cross-genus Culex - Anopheles virus sharing in Madagascar. Taken together, these findings inform the development and implementation strategies of any virome-based vector control technology and raise new evolutionary questions on how host generalism shapes the spatial prevalence of viruses and their potential for disease emergence.

Abstract Uterine fibroids (leiomyomas) and adenomyosis are among the most common benign gynecological conditions affecting women of reproductive age. These disorders are frequently associated with abnormal uterine bleeding, pelvic pain, pressure symptoms on adjacent pelvic organs, and potential infertility. The incidence of fibroids increases as women enter their third and fourth decades of life. In parallel, recent trends in delayed childbearing have further emphasized the need for fertility‐preserving treatment options. Notably, fibroids have a higher prevalence in African‐American women, highlighting a significant disparity in health needs compared to white women. Historically, hysterectomy and myomectomy were considered definitive treatments. However, these procedures carry inherent surgical risks, longer recovery periods, and, in the case of hysterectomy, a complete loss of reproductive potential. Consequently, there is increasing demand for uterus‐sparing, minimally invasive alternatives that provide effective symptom control with lower morbidity and preservation of fertility. Among the evolving treatment options, three image‐guided, minimally invasive therapies have gained particular attention: Uterine Artery Embolization (UAE), Radiofrequency Ablation (RFA), and High‐Intensity Focused Ultrasound (HIFU). Uterine Artery Embolization (UAE), also known as uterine fibroid embolization (UFE), is a well‐established endovascular procedure in which embolic agents are introduced via catheterization of the uterine arteries, inducing ischemia and infarction of fibroids. Performed under conscious sedation or regional anesthesia, UAE has demonstrated significant reductions in fibroid volume and symptom relief in over 80% of appropriately selected patients. All image‐guided techniques are especially beneficial for women who desire uterine preservation, have contraindications to surgery, or wish to avoid major operative interventions. In comparison with UAE, Radiofrequency Ablation (RFA) uses targeted thermal energy to induce coagulative necrosis within fibroid tissue. This approach can be delivered via laparoscopic, transcervical, or transvaginal routes, depending on the platform. The Sonata® System integrates intrauterine ultrasound guidance with energy delivery, enabling precise fibroid targeting with minimal myometrial damage. RFA is associated with shorter recovery and less intraoperative blood loss, though it is more suitable for smaller or fewer fibroids and may be less ideal for extensive disease. Together, these advancements reflect a paradigm shift in fibroid management—driven by demographic trends, racial disparities, patient preferences, and technological innovations—toward evidence‐based, uterus‐preserving therapies tailored to individual patient needs. This article discusses details of each technique including the procedure, benefits and complications and also the impact on particular situations such as pregnancy. Some key points common to each technique are also mentioned.

Importance Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a substantial burden. Standardized global prevalence estimates and data on associated sociodemographic and risk factors are lacking. Objective To estimate the global prevalence of HS and study differences in prevalence by age, sex, geographical location, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), smoking status, gross domestic product (GDP), and Human Development Index (HDI). Data Sources and Study Selection Included studies were conducted using the standardized Global Hidradenitis Suppurativa Atlas methodology with finalized data collection before May 19, 2023. Studies were required to use a population-based sampling method and conduct clinical confirmation of HS diagnosis following a screening questionnaire. Data Extraction and Synthesis Data were independently extracted from relevant studies by 2 reviewers (D.B. and C.E.M.) using a standardized form. Extracted variables included geographic location, age, sex, BMI (median and BMI &amp;gt;30), smoking status, HS prevalence estimates (with 95% CIs), GDP, and HDI. A proportional meta-analysis using a random-effects model was conducted on the included studies. Main Outcomes and Measures The primary outcome was the point prevalence of HS, confirmed by clinical examination. Secondary outcomes included differences in HS prevalence by sex, age, BMI category, smoking status, and country-level socioeconomic indicators (GDP and HDI). All outcomes were prespecified before data analysis. Results The sample included 22 743 participants, identifying 247 patients with HS, across 25 studies in 23 countries spanning 6 continents. The median proportion of female patients with HS was 55.6%, and the median age was 34.5 years. While the prevalence estimates showed considerable inconsistency ( I 2 &amp;gt; 75%; τ 2 = 0.747), the overall random-effects global prevalence of HS was 0.99% (95% CI, 0.67%-1.46%). Female sex was the only factor observed to be associated with the prevalence estimates (β = 1.02; 95% CI, 1.01-1.03). Conclusions and Relevance In this meta-analysis, an estimated global prevalence of HS between 0.67% and 1.46% surpassed previous global estimates. Substantial global variations in HS prevalence were also observed. Female sex was the only factor associated with prevalence in this sample. Future studies assessing genetic, environmental, and etiological factors are warranted to explain the heterogeneity in prevalence.

Chronic pain affects nearly 100 million adults in the U.S., yet few novel therapeutics have emerged in recent decades. P2X4 receptor (P2X4R), implicated in pain signaling, represents a promising target. We evaluated a humanized single-chain variable fragment (hscFv) targeting P2X4R for its ability to reduce ATP-induced currents and modulate excitability in human dorsal root ganglion (hDRG) neurons. Voltage-clamp recordings confirmed that human P2X4R (hP2X4R) hscFv significantly reduced ATP-evoked currents in HEK-293T cells expressing human P2X4, likely by relocalization of the receptor to the perinuclear region after hscFv treatment. Immunohistochemistry and transcriptomic analyses demonstrated widespread P2X4R ( P2RX4 ) expression across hDRG neuronal subtypes in both male and female donors. Current-clamp recordings revealed that hP2X4R hscFv selectively increased action potential (AP) threshold in multi-firing hDRG neurons, without affecting single-firing neurons. Spontaneous activity at rest and depolarizing spontaneous fluctuation (DSF) amplitude were also reduced. Analysis confirmed consistent effects of hP2X4R hscFv on excitability parameters. These findings suggest that hP2X4 hscFv exerts modest but targeted effects on human sensory neurons, supporting its potential as a novel therapeutic for chronic pain.

ABSTRACT Background and Aims Steroid supplementation remains controversial in septic shock, partly due to the heterogeneity of the populations studied. Cirrhotic patients with sepsis frequently develop relative adrenal insufficiency, showing poor response to vasopressors and poor prognosis. Early administration of low‐dose hydrocortisone might facilitate shock reversal and reduce mortality in this population. Methods Double‐blind, randomised, placebo‐controlled multicentre trial, enrolling adult cirrhotic patients with septic shock. Patients were assigned to receive i.v. hydrocortisone (100 mg followed by a continuous infusion of 200 mg/24 h) or placebo, for at least 3 days, followed by a tapering period of 3–7 days, depending on the time of shock resolution. Primary endpoint was 28‐day all‐cause mortality. Results After enrolment of 83 patients the trial was stopped early due to slow inclusions. Most patients required low‐to‐moderate doses of vasopressors. There was no difference in 28‐day mortality (35% vs. 39.5%; p = 0.84) between hydrocortisone and placebo groups. Shock resolution (85% vs. 72.1%; p = 0.25) and days to shock resolution [3 days (2.2–4; IQR) vs. 4 (2–7.5; IQR)] were also similar between groups. More patients receiving placebo died of refractory shock (47.6% vs. 8.7%). No significant differences between treatment arms were observed in shock relapse, new shock episodes or bacterial or fungal superinfections during hospital stay. Hypo‐ and hyperglycaemias were more frequent in the hydrocortisone arm. Severity of ACLF at inclusion and inadequacy of empirical antibiotic therapy (HR = 6.40; 95% CI: 3.21–12.79) independently predicted 28‐day mortality. Conclusions Supplemental hydrocortisone did not improve short‐term survival in cirrhotic patients with septic shock requiring low‐to‐moderate doses of vasopressors. Trial Registration S‐number University Hospitals Leuven, Belgium: S55168; EUDRACT: 2010–024273‐38; Clinicaltrials.gov id: NCT02602210