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HIV-associated tuberculosis is a leading cause of mortality. Mycobacterium tuberculosis bloodstream infection (MTB-BSI) is complicated by diagnostic difficulty and severe illness. We assessed whether MTB-BSI continues to be common in the era of widespread antiretroviral therapy and whether it continues to result in increased risk of early mortality. We enrolled inpatients from medical wards irrespective of tuberculosis symptoms and outpatients with tuberculosis symptoms. All participants had HIV and were ≥18 years old, and all were recruited from 7 countries: Malawi, South Africa, Tanzania, Thailand, Uganda, Vietnam, and Zambia. Participants also had <3 doses of antituberculosis treatment in the past 60 days and no isoniazid preventive therapy in the past 6 months. We estimated the prevalence of MTB-BSI. In Bayesian survival models, we estimated the hazards of mortality for inpatients with MTB-BSI vs those without. Between 2019 and 2021, 1703 participants were included: 44% were hospitalized, the median CD4 count was 361 cells/μL, and 77% reported using antiretroviral therapy. Crude prevalence of MTB-BSI varied by country but was 4.4% (32/723) among all inpatients, 22.5% (32/142) among inpatients with microbiologically confirmed TB, and 0.2% (2/913) among all outpatients. Among all inpatients, those with MTB-BSI had 2.65-times (95% credible interval, 1.06-5.01) increased hazard of death by 30 days and 1.79-times (95% credible interval, .81-3.11) increased hazard by 70 days. Lower CD4 and older age were strongly associated with mortality. MTB-BSI is far more common for inpatients than outpatients with HIV. Across multiple settings with high tuberculosis prevalence, MTB-BSI was strongly associated with heightened risk of early mortality in PWH. Novel optimized diagnostic and treatment strategies are still needed for HIV-associated MTB-BSI.
Pediatric migrant health has been identified by the World Health Organization as a critical area for interdisciplinary research to improve care for children and adolescents with migration experience. Nevertheless, research agendas have rarely been shaped systematically by individuals with lived and professional experience, limiting relevance and impact. To identify and prioritize the most important unanswered research questions in pediatric migrant health in Europe through a structured, participatory priority-setting process. This multiphase survey study (April 2024 to June 2025), led by migrants and clinicians using the James Lind Alliance participatory priority-setting methodology, comprised 2 online consultations informed by Delphi procedures and a final in-person consensus workshop using a modified nominal group technique. Participants residing in multiple European countries included migrant caregivers, former migrant children and adolescents, health care workers in pediatric migrant health, and double experts with combined lived and professional experience. They were recruited via professional networks, community organizations, and open calls. The final in-person consensus workshop convened in Basel, Switzerland, in June 2025. The primary outcome was a ranked list of the top 10 unanswered research priorities in pediatric migrant health based on participant-generated questions and consensus methods. In consultation 1, 256 participants (156 [61.0%] with lived migration experience; 25 countries of residence, 41 countries of origin; 115 aged <35 years [44.9%], 138 aged ≥35 years [53.9%]; 158 female [61.7%]) submitted 1589 questions and comments, which were consolidated into 53 unanswered summary questions after qualitative content analysis and evidence checking. In consultation 2, rankings from 576 participants (214 [37.2%] with lived migration experience; 31 countries of residence, 50 countries of origin; 193 aged ≤35 years [33.5%], 364 aged ≥35 years [63.2%]; 412 female [71.5%]) yielded a short list of 25 questions. During the final consensus workshop, participants selected the top 10 research priorities. The 3 highest ranked priorities focused on universal access to health care, the health impact of racism and discrimination, and barriers to accessing care. Remaining priorities addressed health effects of migration, social determinants of health, needs of at-risk groups (including unaccompanied or undocumented minors and children with medical complexities), professional language support, training of health care workers, and family involvement in care. The research priorities identified in this survey study could provide a roadmap for future multidisciplinary and participatory research to improve health equity for pediatric migrants in Europe.
A contemporary standard of care for patients with metastatic androgen pathway modulator-naive/sensitive (APMN/S) prostate cancer (also known as metastatic hormone-sensitive prostate cancer) is androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) until progression. PSMAddition aimed to evaluate the efficacy and safety of [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) combined with ADT plus ARPI in prostate-specific membrane antigen (PSMA)-positive metastatic APMN/S prostate cancer. PSMAddition is an ongoing, randomised, controlled, phase 3 superiority trial conducted at 169 sites across 20 countries, including hospitals, medical centres, and specialist cancer centres. Eligible male patients had treatment-naive or minimally treated metastatic APMN/S prostate cancer diagnosed by CT, MRI, or bone scan and one or more PSMA-positive metastatic lesion on centrally read baseline [68Ga]Ga-PSMA-11 PET. Patients were randomly assigned 1:1 to open-label, intravenous 177Lu-PSMA-617 (7·4 GBq [200 mCi] ±10% every 6 weeks for up to six cycles) with ADT plus ARPI (177Lu-PSMA-617 arm) or ADT plus ARPI (control arm). ADT and ARPI were investigator-chosen according to local authorisation and administered per local product labelling. Control arm patients with centrally confirmed radiographic progression could cross over to 177Lu-PSMA-617. The primary endpoint was radiographic progression-free survival (centrally assessed per Prostate Cancer Clinical Trials Working Group 3-modified RECIST 1.1 or death); secondary endpoints included safety and tolerability. We report the second interim analysis of radiographic progression-free survival in the intention-to-treat population (all randomly assigned participants; data cutoff Jan 13, 2025). Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04720157, and is ongoing. From June 15, 2021, to July 25, 2023, 1529 patients were screened and 1144 were randomly assigned (n=572 per arm; 1144 [100%] male, 572 [50%] with de novo metastatic APMN/S prostate cancer, 779 [68%] with high-volume disease; median age 68·0 years [IQR 62·0-73·0]). Baseline characteristics were balanced between arms. At second interim analysis for radiographic progression-free survival (median time from randomisation to data cutoff 23·6 months [IQR 20·3-29·2]; median radiographic progression-free survival follow-up time 19·6 months [IQR 14·0-24·1]), 139 (24%) of 572 participants in the 177Lu-PSMA-617 arm and 172 (30%) of 572 participants in the control arm had radiographic disease progression or death. Radiographic progression-free survival was significantly improved in the 177Lu-PSMA-617 arm versus the control arm, with a 28% reduction in the relative risk of radiographic progression or death (HR 0·72 [95% CI 0·58-0·90]; p=0·0021; median radiographic progression-free survival not reached in either arm). The primary endpoint was thus met. Grade 3 or worse adverse events occurred in 286 (51%) of 564 patients in the 177Lu-PSMA-617 arm and 243 (43%) of 565 patients in the control arm. Serious adverse events occurred in 180 (32%) of 564 patients in the 177Lu-PSMA-617 arm and 162 (29%) of 565 in the control arm; of which 17 (3%) in the 177Lu-PSMA-617 arm were 177Lu-PSMA-617-related. The most common adverse event was dry mouth, in 258 (46%) patients in the 177Lu-PSMA-617 arm and 21 (4%) patients in the control arm; all were grade 1 or 2 and none were serious. Other common adverse events with higher incidence in the 177Lu-PSMA-617 arm included cytopenias and gastrointestinal disturbances. Combining 177Lu-PSMA-617 with ADT plus ARPI prolonged radiographic progression-free survival in patients with PSMA-positive metastatic APMN/S prostate cancer. Although adverse events were more frequent, there were no unexpected safety findings associated with the drug combination. Therefore, combining 177Lu-PSMA-617 with ADT plus ARPI might be a new treatment option in metastatic APMN/S prostate cancer. Novartis.
To explore the experiences and challenges associated with genetic testing decisions among untested individuals from hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS) families. Qualitative descriptive study. Semi-structured telephone interviews were conducted between 2022 and 2024 with 56 untested at-risk relatives drawn from the Israeli CASCADE cohort of HBOC and LS families, which comprises carriers of pathogenic/likely pathogenic variants, true negatives (non-carriers) and untested individuals. Interview narratives were analysed using thematic analysis. Two overarching themes were generated. (1) Illusion of Mastery, encompassing four categories reflecting internal coping strategies participants employed to maintain perceptions of control, resulting in avoidance of genetic testing: choosing uncertainty as a psychological shield; avoiding anxiety; controlling health through lifestyle; and protecting life stages. (2) Lost in the System, encompassing five categories across two subthemes: (2.1) perceived deficiencies in informational, emotional and familial guidance from the healthcare system; and (2.2) active withdrawal from the system to avoid medical entrapment and preserve personal values, both resulting in avoidance of genetic testing. Findings suggest avoidance rather than denial or outright refusal of genetic testing, reflecting active decision-making. This avoidance was shaped by a convergence of personal,familial and systemic factors, centered on autonomy, uncertainty management and psychological self-protection, in the context of inadequate informational and emotional support. These findings highlight nurses' potential to support informed, person- and family-centered genetic testing decision-making. Given their accessibility to at-risk families across diverse clinical settings, nurses can address emotional needs, provide clear guidance and acknowledge the psychological complexity underlying testing avoidance. Future studies should explore nurse-led interventions that facilitate informed decision-making while respecting individual autonomy. This study adhered to the Consolidated Criteria for Reporting Qualitative Studies (COREQ) guidelines. No patient or public contribution.
Background/Objectives: Among the most common medical conditions of pregnancy, nausea and vomiting of pregnancy (NVP) and its severe form hyperemesis gravidarum (HG) represent a clinically significant and increasingly researched area of maternal health. However, the global evolution, structural organization, and thematic development of this literature remain insufficiently characterized. This bibliometric study maps five decades of global research on therapeutic and supportive interventions for NVP and HG. Methods: Web of Science Core Collection records were searched on 10 May 2026, restricted to English-language articles and reviews published up to 2025, and deduplicated to 1182 unique documents. A secondary thematic filter was subsequently applied to generate a refined obstetric subset for the country collaboration, keyword co-occurrence, and thematic evolution analyses. Bibliometric performance, collaboration networks, source impact, institutional output, PELT-based changepoint detection, metadata completeness, keyword co-occurrence, and thematic evolution were analyzed using VOSviewer, Bibliometrix/Biblioshiny, and custom Python scripts. Results: Publication output increased markedly after 2010 and reached its maximum in 2025. PELT sensitivity analysis localized the principal transitions to the mid-1990s and early 2010s, informing three broad analytical macroperiods: 1975-1994, 1995-2009, and 2010-2025. The United States dominated cumulative output and collaboration intensity, while Canada, England, Australia, Italy, Germany, and China showed substantial scientific influence. Core publication venues were concentrated in obstetrics, gynecology, reproductive safety, and pregnancy-focused clinical medicine. Keyword and thematic analyses showed a transition from early vomiting, Bendectin, exposure, and pregnancy-safety concerns toward pharmacological treatment, complementary interventions, controlled clinical evaluation, maternal-fetal outcomes, and supportive management. Metadata-completeness analysis identified a major pre-1991 indexing discontinuity, requiring caution when interpreting long-range keyword-based trends. Conclusions: These findings outline the trajectory of the field and highlight priorities for future research, including stronger comparative evidence for pharmacological, complementary, and supportive-care strategies, broader international collaboration, and prospective studies to strengthen the evidence base for managing NVP and HG.
Hierarchical composite end points (HCEs) are a promising tool used in randomized clinical trials (RCTs) to integrate multiple outcomes of varying clinical relevance into a single measure. To describe how often HCEs are used as primary outcomes in RCTs, and how they are constructed, analyzed, and reported. MEDLINE, Embase, CENTRAL, and Web of Science were searched on December 9, 2024, complemented by a forward citation search of methodological papers on HCEs. RCTs that used an HCE as their primary outcome were included, defined either by self-declaration (hierarchical composite or outcome ranking) or through use of an HCE-specific analytical approach (win ratio, win odds, probabilistic index, or generalized pairwise comparison). Pilot studies, post hoc analyses, and hierarchically tested coprimary end points were excluded. Data were independently screened and extracted in duplicate. Trial characteristics, end point composition, hierarchy justification, and analytical methods were summarized descriptively. Among 5188 screened records, 92 RCTs were included, with 79 567 planned participants. The use of an HCE as a primary end point has increased, with 72 trials (78.3%) initiating recruitment within the past decade. Most RCTs were drug trials (43.5% [40 of 92]), in cardiology (43.5% [40 of 92]), multicenter (91.3% [84 of 92]), and non-industry sponsored (67.4% [62 of 92]). The 92 HCEs had a median (IQR) of 4 (3-5) components and the highest ranked component was usually mortality (80.4% [74 of 92]). The last hierarchical component was most often a continuous component (64.1% [59 of 92]). The majority of RCTs did not report any information on how the hierarchy was established (82.2% [60 of 73]; excluding RCTs where only information from registries was available). Generalized pairwise comparison was the most frequent analysis approach (57.3% [26 of 45]) among the 45 published RCTs, yet no standardized way for presenting results was observed. This scoping systematic review of 92 RCTs using HCEs found that their use has increased across medical fields, but their construction, analytical approaches, and reporting of results remained highly heterogeneous. By systematically mapping how HCEs are currently implemented, further review is essential for the development of much needed methodological and reporting standards.
Large-bore mechanical thrombectomy (LBMT) is a catheter-directed therapy for acute pulmonary embolism (PE). The relationship between aspirated thrombus weight and volume with outcomes remains unclear. The aim was to evaluate the impact of aspirated thrombus weight and volume on outcomes after LBMT. This prospective, open-label, single-arm, single-center registry study included 48 patients undergoing LBMT using the FlowTriever system (Inari Medical/Stryker, Irvine, CA, USA). Thrombus weight and volume were quantified, and clot composition assessed. Associations between thrombus characteristics and clinical, invasive hemodynamics, echocardiographic parameters, and biomarkers were evaluated immediately after the procedure, at hospital discharge, and at 3-month follow-up. Thrombus material was available in 48 patients (31% women), of which 41 presented with intermediate-risk and 7 with high-risk PE. LBMT resulted in significant reductions in systolic pulmonary artery pressures (sPAP) intraprocedurally (- 12.8 ± 8.3 mmHg, p < 0.001), with a further invasively measured decrease through 3 months (- 9.6 ± 10.6 mmHg, p < 0.001). From baseline to discharge, right ventricular coupling improved (+ 0.24, p < 0.001) and right ventricle (RV)/left ventricle (LV) ratio decreased (- 0.23, p < 0.001). NT-proBNP and high-sensitivity cardiac troponin T declined significantly. Neither thrombus weight nor volume correlated with acute changes in sPAP (ρvolume = 0.06; ρweight = 0.10), RV-uncoupling (ρvolume = 0.47; ρweight = 0.46), and RV/LV ratio (ρvolume = - 0.02; ρweight = - 0.005) (p for all > 0.05), nor with outcomes at 3 months. Aspirated thrombus weight and volume were not associated with improvements after LBMT, suggesting that, beyond mechanical obstruction, additional mechanisms potentially including paracrine and endocrine effects of thrombus material may contribute to acute and chronic PE-related cardiopulmonary dysfunction.
Enlarged perivascular spaces (EPVSs) in the basal ganglia (BG-EPVS) are an important marker of cerebral small vessel disease (cSVD), and EPVS in the centrum semiovale (CSO-EPVS) are part of the diagnostic criteria for cerebral amyloid angiopathy. We aimed to investigate associations of EPVS with reduced estimated glomerular filtration rate (eGFR) and glomerular hyperfiltration (higher than normal eGFR), which have scarcely been studied previously. In this cross-sectional study, we used pooled individual patient data from the Microbleeds International Collaborative Network which includes patients with ischemic stroke or transient ischemic attack. We investigated associations of impaired kidney function, defined as an eGFR of 30-60 or <30 mL/minute/1.73 m2, and glomerular hyperfiltration, defined as eGFR above the age-adjusted and sex-adjusted 95th centile, with BG-EPVS and CSO-EPVS severity. EPVS were rated according to a validated 5-point ordinal scale, and combined cSVD burden was rated using a validated 5-point ordinal scale with 1 point assigned for the presence of each of the following: severe white matter hyperintensities, ≥1 cerebral microbleed, ≥1 lacune, and BG-EPVS ≥11. Normal glomerular filtration was defined as eGFR ≥60 without hyperfiltration. We used multivariable ordinal logistic regression models to estimate risk of increased EPVS and cSVD burden severity adjusted for age, sex, and comorbidities. Seven thousand two hundred fifty-four patients (mean age 71 ± 13 years, 43% female) were included in the analysis, 357 with glomerular hyperfiltration, 1,692 with eGFR 30-60, and 256 with eGFR <30. Compared with normal glomerular filtration, hyperfiltration was independently associated with BG-EPVS (adjusted odds ratio [aOR] 1.38, 95% CI 1.11-1.70, p < 0.001) and CSO-EPVS (aOR 1.34, 95% CI 1.08-1.64, p = 0.011). Associations of eGFR 30-60 and eGFR <30 with EPVS were not statistically significant. Compared with normal glomerular filtration, eGFR <30 (aOR 1.27, 95% CI 1.03-1.57) was independently associated with increased cSVD burden, but eGFR 30-60 (aOR 1.06, 95% CI 0.95-1.20) and hyperfiltration (aOR 1.15, 95% CI 0.98-1.34) were not. Glomerular hyperfiltration was independently associated with EPVS severity, in both the basal ganglia and centrum semiovale. eGFR <30 was independently associated with total cSVD burden. A key limitation was a lack of repeated eGFR measurements.
Background/Objectives: Oral lichen planus (OLP) is a chronic immune-mediated disease of the oral mucosa in which T-cell infiltration, epithelial injury, and stress-related neuroendocrine signaling appear to intersect. Catestatin (CST), a peptide generated from chromogranin A (CgA), modulates catecholamine release and inflammatory cell responses; however, its association with localized mucosal inflammation in OLP has not been clarified. This study aimed to compare serum CST levels between OLP patients and healthy controls and to examine their association with clinical subtype, disease severity, and vitamin D status. Methods: In this cross-sectional study, 51 patients with clinically and histopathologically confirmed OLP and 60 healthy controls were enrolled at the University Hospital of Split. Serum CST was quantified using ELISA. OLP severity was assessed with the REU score by a single experienced oral medicine examiner who was blinded to laboratory results, and pain and burning were recorded separately using 0-10 VASs. Results: Serum CST levels were significantly higher in OLP patients compared to healthy controls (p < 0.001). CST levels showed a strong positive correlation with the REU total score (r = 0.781, p < 0.001), as well as with VAS pain (r = 0.708, p < 0.001) and VAS burning (r = 0.729, p < 0.001). Erosive OLP exhibited significantly higher CST levels compared to the non-erosive subtype (p < 0.001). Furthermore, serum vitamin D levels were significantly lower in OLP patients (p < 0.001), with no significant correlation observed between CST and vitamin D levels. Conclusions: Serum CST levels were higher in OLP patients and showed close associations with REU scores and symptoms, with the strongest signal observed in erosive disease. CST may therefore contribute to the neuroendocrine-immune profile of OLP and may be useful as an adjunctive marker of clinically active or erosive disease. Larger prospective studies including salivary and tissue-based CST measurements are needed before CST can be used for routine monitoring.
Invasive fungal diseases (IFD) pose a major health challenge in Latin America and the Caribbean (LAC), particularly in vulnerable populations. A cross-sectional, survey is distributed between April 2023 and May 2025 to institutions involved in IFD diagnosis or care across LAC. The questionnaire evaluates diagnostic tools, antifungal availability, and therapeutic drug monitoring (TDM). A total of 619 institutions from 23 countries across LAC participate. Candida spp. (92%) and Aspergillus spp. (54%) are most frequently reported as major fungal threats. Culture (90%) is widely available, whereas access to galactomannan (41%), β-D-glucan (29%), and molecular testing (23%) is considerably lower. Availability of antifungals, including liposomal amphotericin B (38%), echinocandins (51%), voriconazole (57%) or posaconazole (33%) is significantly higher in countries with GDP per capita >US$ 10,000, in transplant centres, and in institutions managing people living with HIV. Therapeutic drug monitoring is available in only 36% of centres. Major diagnostic and treatment gaps persist in low-income countries, particularly in access to tools for identifying endemic mycoses. Substantial disparities exist in IFD diagnostic and treatment capacity across LAC, primarily driven by national income and institutional complexity. Strengthening laboratory infrastructure, antifungal access, and integration of fungal disease management into public health systems is urgently needed.
Background: Opportunistic salpingectomy is widely used in gynecological surgery as a preventive measure against ovarian carcinoma. Questions have been raised about the potential impact of salpingectomy on ovarian function, given the possibility of ovarian vascularity disruption through the utero-ovarian arch located in the mesosalpinx. The aim of this study was to evaluate the short-term effects of bilateral salpingectomy on ovarian reserve. Methods: This prospective cohort study included forty premenopausal women, aged 34-50 years, who underwent hysterectomy with bilateral salpingectomy and ovarian preservation for benign uterine conditions. Ovarian reserve was evaluated before surgery and three months postoperatively, using serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and antral follicle count (AFC). Health-related quality of life was assessed using the Women's Health Questionnaire (WHQ). Results: Serum FSH levels increased significantly after surgery, while AMH levels decreased significantly (both p < 0.05). No significant postoperative changes were observed in AFC. The overall WHQ score increased significantly, indicating a mild deterioration in health-related quality of life. The greatest postoperative changes were observed in the depressive, somatic and sexual domains, where menstrual symptoms improved following surgery. No significant correlation was found between WHQ scores and hormonal or ultrasonographic markers of ovarian reserve. Conclusions: Bilateral salpingectomy performed during hysterectomy was associated with significant short-term hormonal changes, while AFC remained stable. Although patient-reported quality of life slightly worsened after surgery, these changes were not correlated with hormonal or ultrasonographic markers of ovarian reserve. Larger controlled studies with longer follow-up are required to determine the long-term clinical significance of these findings.
Wearable devices can measure real-world mobility and generate metrics known as digital mobility outcomes (DMOs). For people with multiple sclerosis (pwMS), these DMOs have not been clinically validated. This study aimed to evaluate the construct (convergent, divergent, and known groups) validity of a comprehensive panel of 24 DMOs in pwMS. PwMS were recruited to the Mobilise-D Clinical Validation Study, which involved 7-days of real-world mobility monitoring with a lower-back-worn wearable device. DMOs of walking amount, pattern, pace, rhythm, and variability domains were assessed. Convergent validity was evaluated against established clinical constructs (Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk, Multiple sclerosis (MS) Walking Scale-12, and Patient-Determined Disease Steps) using a priori hypotheses. Divergent validity was tested against systolic blood pressure. Known-groups validity was assessed across three EDSS strata. An expert panel completed a standardised consensus process. We included 556 participants: 65% women, mean (SD) age of 52.3 (10.7) years, and median (p25-p75) EDSS 5 (4-6). Convergent, divergent, and known-groups validity were supported for 19, 24, and 23 DMOs, respectively. Nineteen DMOs, covering all domains, reached consensus agreement. This study confirms the construct validity of 19 DMOs across all walking domains in pwMS, supporting their use in clinical research and practice. www.isrctn.com/ISRCTN12051706.
Study DesignSystematic review and meta-analysis.ObjectivesWe sought to evaluate the association between pre-treatment symptom duration and outcomes in patients undergoing radiotherapy (RT)/surgery for metastatic epidural spinal cord compression (MESCC).MethodsA systematic review included publications evaluating the association between pre-treatment symptom duration and outcomes after RT/surgery in adults with MESCC. Primary exposure was pre-treatment symptom duration. Outcomes were motor-recovery, ambulation, survival and local control. Pooled-effect-estimates were calculated.Results Of 4639 studies, 37 met the inclusion criteria (26-RT,11-surgery). RT: All studies defined symptom duration as time from motor-weakness onset to RT. Longer symptom duration was associated with improved motor-recovery (Pooled-effect-estimate=2.08, 95%CI:1.68-2.58,p<0.001) and decreased mortality-risk (improved-survival)((Pooled-effect-estimate=0.72, 95%CI:0.69-0.76,p<0.001). Although longer symptom duration was consistently associated with better ambulation and lower local recurrence, few studies precluded meta-analysis. Surgery: Symptom duration was defined as time from neurological-deficit onset to surgery in 7/11 studies; three-studies used ambulatory status, and one-study used both. Longer symptom duration was associated with increased risk-of-death (worse-survival)(Pooled-effect-estimate=1.28, 95%CI:0.54-3.03,p=0.575), though statistically insignificantly. Meta-analysis for motor-recovery wasn't feasible, but most studies found longer symptom duration worsened motor-recovery, while ambulation findings were inconsistent.ConclusionSymptom duration was associated with differing outcome patterns by treatment modality. In RT cohorts, longer symptom duration was associated with improved survival and motor recovery. In surgical cohorts, it trended toward worse survival, though this did not reach statistical significance. Most surgical studies suggested an inverse association between symptom duration and motor recovery. These findings are exploratory, and should be interpreted in context of treatment selection-bias and between-cohort heterogeneity.
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Menopausal sleep disturbances can negatively impact quality of life. Elinzanetant, a dual neurokinin (NK)-1/NK-3 receptor antagonist, reduced self-reported sleep disturbance in postmenopausal women with moderate-to-severe vasomotor symptoms (VMS) in Phase III OASIS trials. NIRVANA explored elinzanetant's effect on multimodal measures of objective and subjective sleep disturbance in postmenopausal women. Postmenopausal women (N = 110; 40-65 years) with moderate-to-severe VMS (≥20/week) and sleep disturbance (polysomnography [PSG] wakefulness after sleep onset [WASO] ≥30 min) were randomized 1:1 to receive elinzanetant 120 mg or placebo for 12 weeks. Sleep disturbance was assessed using PSG; daily Sleep Diary; and nightly contactless home-monitoring (Sleepiz One+ subgroup). The effect of elinzanetant versus placebo was analyzed using mixed-model repeated measures. Elinzanetant was estimated to reduce PSG WASO at Week 4 versus placebo (least square [LS]-mean difference = -22.50 minutes, 90% CI: -35.47, -9.52). Minimal group differences between treatment arms were estimated at Week 12 for PSG WASO (LS-mean difference = -0.94 minutes, 90% CI: -13.96, 12.09). When including all available PSG data across the 12-week period, post hoc random coefficient modeling indicated treatment effects favoring elinzanetant for WASO, total sleep time, sleep efficiency, latency to persistent sleep, number of awakenings, arousal index, and % Stage N2 sleep. Treatment effects on WASO and awakenings favoring elinzanetant were observed with Sleepiz One+ and Sleep Diary across 12 weeks. In this sleep-focused study, elinzanetant reduced WASO at Week 4 and led to estimated improvements in sleep continuity over 12 weeks, supported by multimodal subjective and objective sleep outcomes. A Study to Learn About How Elinzanetant Works and How Safe it is in Women Having Sleep Disturbances Associated With Menopause (NIRVANA), https://clinicaltrials.gov/study/NCT06112756, NCT06112756, date of registration 2023-11-01.
The quadriceps tendon has gained significant momentum as a graft source for knee ligament reconstruction, with the isolated harvest of its superficial layer-the rectus femoris tendon-rapidly emerging as a popular technical refinement. This shift has been driven largely by practical considerations: the cost and limited availability of proprietary instrumentation promoted for partial quadriceps tendon harvesting, combined with the appeal of a familiar, hamstring-like workflow using standard tendon strippers. As a result, numerous surgical technique descriptions have appeared in recent years. However, the enthusiasm surrounding this graft has outpaced the evidence supporting it. This narrative review critically appraises the current state of knowledge regarding the rectus femoris tendon autograft by evaluating its anatomical basis, biomechanical properties and the first available clinical outcomes. Anatomical studies confirm the rectus femoris tendon as a consistent superficial layer separated from the deep vastus intermedius by a distinct cleavage plane, facilitating reproducible harvest. Biomechanically, the isolated graft demonstrates ultimate stress comparable to the patellar tendon, yet exhibits significantly higher elasticity, raising unresolved questions about long-term graft creep and laxity. Early clinical comparative studies report functional outcomes equivalent to hamstring tendon autografts in primary anterior cruciate ligament reconstruction, and folded soft-tissue quadriceps grafts show promising re-rupture rates in the revision setting. Despite these encouraging findings, the existing literature is predominantly Level III and IV evidence with short-term follow-up, and the heterogeneous definitions of 'quadriceps tendon graft' across studies preclude any formal meta-analysis of this specific graft entity. While the rectus femoris tendon autograft holds considerable potential as a versatile option for primary, revision and complex multi-ligament reconstruction, high-powered randomized controlled trials with long-term follow-up are needed to determine whether it truly represents a paradigm shift or merely a technical variation. LEVEL OF EVIDENCE: Level V, narrative review.
Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disease with substantial quality-of-life impact. Accurate measurement of treatment success requires validated instruments capturing both physician-assessed disease activity and patient-reported symptom burden. Despite an expanding toolkit, consensus on defining remission, optimal control, resolution and progression remains elusive. This review provides a comprehensive overview of key clinician- and patient-reported outcome measures in HS, evaluates their psychometric properties and critically addresses minimal clinically important difference, remission, optimal control, resolution and progression. The emerging role of tissue damage, fibrosis assessment, imaging and molecular pathology in redefining treatment success is also discussed. A narrative literature review was conducted via systematic PubMed and MEDLINE searches through March 2026, with emphasis on publications from the EHSF, the HiSTORIC consortium, the Global VOICE project, and recent clinical trial data. HiSCR has been the most widely used primary endpoint but is limited by its exclusion of patients with fewer than three abscess-nodule lesions and inability to capture tunnel improvement. The IHS4 is a robust dynamic scoring system incorporating draining tunnels with fourfold weighting; its derivative IHS4-55 provides a clinically meaningful response threshold regardless of baseline lesion count. HS-IGA demonstrates high test-retest reliability. Among patient-reported outcomes, HiSQOL is the preferred HS-specific quality-of-life instrument (validated MID: 20-21 points), while DLQI remains the most used non-specific tool. The Pain Index effectively evaluates nociceptive pain. Formal definitions of remission, optimal control and progression are being developed through the HiSTORIC treat-to-target initiative. Ultrasound-based fibrosis grading and ultra-high-frequency imaging reveal clinically underscored tissue damage; long-wave infrared thermography may serve as a reproducible inflammatory biomarker. Optimizing HS outcomes requires integration of dynamic physician-reported scores, HS-specific patient-reported outcomes and emerging tissue damage and inflammation metrics. Consensus definitions for remission, minimal disease activity and progression represent the next frontier in HS management.
Training and body composition requirements in elite sports may elevate eating disorder (ED) risk. Current estimates suggest a range of 1-28% prevalence of ED in elite athletes, reflecting methodological heterogeneity, underreporting, and limited research focus. EDs adversely affect physical health (e.g., osteoporosis, fatigue, injury), psychological well-being, and athletic performance, often persisting beyond athletic careers. Sport-specific demands may obscure ED symptoms, making underdiagnoses likely. This longitudinal study's objective is to furnish proof for the theoretical model of disordered eating in elite athletes by examining the role of sport-specific indicators, to improve early identification and psychological diagnostics. Three-hundred elite athletes from weight-sensitive (ballet, bodybuilding) and less weight-sensitive (soccer, racket sports, basketball) sports will complete assessments at four time points. A subgroup of 90 athletes will participate in clinical interviews. Logistic and hierarchical regressions will identify ED risk indicators and estimate the prevalence of EDs in athletes. Receiver Operating Characteristic (ROC) analyses will assess diagnostic accuracy of single and combined indicators with reporting of sensitivity, specificity, and the Area Under the Curve (AUC). Group differences and measurement invariance of ED instruments will be tested between the athlete group and 300 non-athlete controls. Identifying reliable ED indicators in elite sports may support early intervention. This theory-based approach aims to enhance diagnostic accuracy and athletes' care. Prospective registration of the study in the German Clinical Trials Register (DRKS00035100) on 03 February 2025.
The Phase IV MAGNIFY-MS Extension study evaluated the long-term efficacy and durability of cladribine tablets (CladT) in participants with highly active relapsing multiple sclerosis (RMS) during treatment-free Years (Y) 3 and 4. Data were analysed for all participants and by subgroups (treatment-naïve vs experienced). Time to no evidence of disease activity (NEDA-3) and first confirmed Symbol Digit Modalities Test (SDMT) score change (⩾4/8 point improvement or ⩽4/8 point worsening) were assessed using Kaplan-Meier analysis. SDMT changes were confirmed if sustained across two visits ⩾166 days apart; others were classified as stable. Percentage brain volume change (PBVC) was analysed using the SIENA-XL method. Of 270 MAGNIFY-MS participants, 219 entered MAGNIFY-MS Extension (64.8% female; mean age ± standard deviation: 40.4 ± 9.45 years). NEDA-3 rates were 78.6% (Y3), 79.2% (Y4) and 54.2% (Y3-Y4 combined). At Y4, 83.1% had no T1 gadolinium-enhancing lesions, 67.4% had no active T2 lesions, and the annualised relapse rate was 0.09. Mean annualised PBVC was <0.4% in Y4. SDMT scores were 4/8-point stable or improved in 79.0%/88.1% of participants, and 84.5% had no 6-month confirmed disability progression. Two years of short-course CladT provided sustained clinical and cognitive benefits, supporting the potential for treatment-free remission in RMS. gov Identifier: NCT04783935. Date registered: 3 March, 2021.