Fertility-preserving treatments for young women with endometrioid endometrial carcinoma (EEC) have limited effectiveness, with only ∼50% of patients responding to first-line progesterone therapy. The absence of reliable methods to predict clinical response during the six-month treatment window creates substantial clinical uncertainty. Here, we developed EEC patient-derived tumor-like cell clusters (PTCs). Utilizing label-free hyperspectral stimulated Raman scattering microscopy in PTCs, we identified cholesteryl ester as an independent biomarker for progesterone response, achieving 86.2% predictive accuracy in a retrospective clinical cohort. Strikingly, progesterone-insensitive patients receiving progesterone-statin combination therapy exhibited a significantly higher 6-month complete response rate compared to those treated with progesterone alone (66.67% vs. 7.69%; HR = 13.00, 95% confidence interval (CI): 2.80-60.28, P < 0.001), including one documented case of post-treatment conception culminating in live birth. Mechanistically, fibroblast-specific cholesteryl ester accumulation was strongly associated with progesterone insensitivity. These results present a biomarker-guided strategy to optimize personalized fertility-preserving therapies in EEC.

INTRODUCTION:We aimed to assess the safety of continuous uterus-preserving treatment among patients with endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) who gave birth after progestin-based fertility-sparing treatment (FST). MATERIAL AND METHODS:From January 2005 to June 2020, we conducted a retrospective cohort study at Peking University People's Hospital, China, comprising 212 patients with EC or AEH who underwent FST. The participants were categorized into two groups based on the reproductive outcome of live birth. Risk factors were analyzed for disease recurrence in the entire cohort, and additional analysis was conducted on postpartum recurrence specifically in the live birth group. RESULTS:Of 212 eligible patients, 73 had a live birth, and 139 did not have a live birth after FST. Multivariable Cox analysis showed that live birth significantly reduced the risk of disease recurrence (HR 0.326, p = 0.011), while insulin resistance was identified as an adverse factor (HR 3.216, p = 0.014). Except for two patients who underwent hysterectomy, among 71 patients undergoing uterus preservation after live birth, five (7%) patients experienced disease relapse (two EC and three AEH) after a median follow-up of 26 (11, 47.5) months. Four out of these five patients with recurrence achieved a complete response after a second round of FST. Eight other patients (11.3%) experienced hyperplasia without atypical (EH) after live birth. Potential risk factors for postpartum recurrence of EC/AEH included irregular menstruation (80% vs. 39%; p = 0.153), abnormal ultrasonographic findings (60% vs. 18.6%; p = 0.065), and increased endometrial thickness (0.82 cm vs. 0.55 cm; p = 0.017). While postpartum maintenance therapy was identified as a protective factor against recurrence (0% vs. 62.5%; p = 0.012). Notably, patients with postpartum recurrence may achieve a complete response with repeat FST. CONCLUSIONS:Although live birth was associated with improved recurrence-free survival in patients with EC or AEH receiving FST, postpartum recurrence remains a concern. Irregular menstruation and abnormal ultrasound findings were identified as key risk factors for recurrence, while maintenance therapy exhibited a protective effect. These findings highlight the need for vigilant postpartum monitoring in this population.

Introduction Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) affects around 35%–50% of men during their lifetime. The efficacy of current oral medication for CP/CPPS remains limited. Recent studies demonstrated that vagus nerve stimulation may improve chronic pelvic and abdominal pain. Accordingly, transcutaneous auricular vagus nerve stimulation (taVNS) might represent a promising, non-invasive therapeutic approach for the clinical management of CP/CPPS.Methods and analysis The trial of Transcutaneous Auricular vagus nerve Stimulation for moderate to severe Chronic Prostatitis/CPPS is a prospective, randomised, sham-controlled trial with a 1:1 allocation ratio. Participants will be assigned randomly to either the taVNS group or the sham-taVNS group. The intervention period will consist of a 4-week treatment (a total of 40 sessions), followed by an 8-week follow-up period. The primary outcome is the change from baseline in the National Institutes of Health Chronic Prostatitis Symptom Score Index total score at week 4. Secondary outcomes include the International Prostate Symptom Score Scale, European Quality of Life 5-Dimensions-5-Levels questionnaire, Self-Rating Anxiety Scale and Self-Rating Depression Scale. Safety assessments will be conducted throughout the entire study period.Ethics and dissemination This study protocol and informed consent documents were reviewed and approved by the Institutional Review Board of Guang’anmen Hospital, China Academy of Chinese Medical Sciences (approval number: 2023-250 KY). Written informed consent will be obtained from all participants and/or their legal guardians prior to trial participation. The findings will be disseminated through publication in a peer-reviewed journal and presentations at scientific conferences. The research data will be made available on reasonable request.Trial registration number NCT06287970.

This randomized clinical trial investigates if intra-arterial alteplase improves clinical outcomes in patients with acute ischemic stroke (AIS) of the posterior circulation within 24 hours of symptom onset and after successful mechanical recanalization. QuestionAmong patients with acute basilar artery occlusion treated within 24 hours of symptom onset and achieving successful mechanical recanalization, does intra-arterial alteplase improve clinical outcomes?FindingsIn this randomized clinical trial including 246 patients, functional independence at 90 days was achieved in approximately half of patients in both the intra-arterial alteplase and control groups. Rates of symptomatic intracranial hemorrhage were similar across groups.MeaningStudy results show that adjunctive intra-arterial alteplase after successful endovascular recanalization for acute stroke due to basilar artery occlusion seems safe but did not improve functional outcomes at 90 days. ImportanceThe impact of adjunctive intra-arterial alteplase after successful endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) in the posterior circulation requires further investigation.ObjectiveTo assess the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation.Design, Setting, and ParticipantsThis was a multicenter, prospective, randomized, open-label, blinded-end point (PROBE design) clinical trial. The study was conducted between September 5, 2023, and November 29, 2024, with the 3-month follow-up completed on February 18, 2025. The trial was conducted in 37 comprehensive stroke centers in China. Patients in China with acute basilar artery occlusion presenting within 24 hours of the time last known well were randomly assigned to the treatment group or control group. Eligible participants were adults who achieved successful recanalization after EVT.InterventionsEligible patients were randomly assigned to the intra-arterial alteplase group (0.225 mg/kg, maximum dose limit 22.5 mg infused at a concentration of 1.0 mg/mL within 15 minutes distal to the origin of posterior inferior cerebellar artery) or control group (no intra-arterial thrombolysis).Main Outcomes and MeasuresThe primary efficacy outcome was the proportion of patients achieving functional independence (modified Rankin Scale score of 0-2) at 90 days. The primary safety outcomes were mortality at 90 days and incidence of symptomatic intracranial hemorrhage within 48 hours.ResultsA total of 247 patients were enrolled, and 1 patient was excluded from the full analysis set due to basilar artery reocclusion before intra-arterial alteplase. The remaining 246 patients (median [IQR] age, 65.0 [56.0-72.0] years; 176 male [71.5%]) were included in this analysis, 124 (50.4%) in the treatment group and 122 (49.6%) in the control group. Among the patients recruited and followed up, functional independence at 90 days was achieved in 52 (41.9%) in the intra-arterial alteplase group and 57 (46.7%) in the control group (adjusted risk ratio, 0.93; 95% CI, 0.73-1.18; P = .55). Mortality at 90 days (29.6% vs 27.0%, respectively; adjusted hazard ratio, 1.07; 95% CI, 0.71-1.61; P = .75) and incidence of symptomatic intracranial hemorrhage (2.4% vs 2.5%, respectively; unadjusted risk ratio, 0.98; 95% CI, 0.20-4.74; P = .97) were similar across groups.Conclusions and RelevanceResults of this randomized clinical trial reveal that in patients with posterior circulation stroke due to acute basilar artery occlusion, intra-arterial alteplase after successful endovascular recanalization appeared to be safe but was not associated with improvement of functional outcomes at 90 days.Trial RegistrationClinicalTrials.gov Identifier: NCT05897554

Importance:The impact of adjunctive intra-arterial alteplase after successful endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) in the posterior circulation requires further investigation. Objective:To assess the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation. Design, Setting, and Participants:This was a multicenter, prospective, randomized, open-label, blinded-end point (PROBE design) clinical trial. The study was conducted between September 5, 2023, and November 29, 2024, with the 3-month follow-up completed on February 18, 2025. The trial was conducted in 37 comprehensive stroke centers in China. Patients in China with acute basilar artery occlusion presenting within 24 hours of the time last known well were randomly assigned to the treatment group or control group. Eligible participants were adults who achieved successful recanalization after EVT. Interventions:Eligible patients were randomly assigned to the intra-arterial alteplase group (0.225 mg/kg, maximum dose limit 22.5 mg infused at a concentration of 1.0 mg/mL within 15 minutes distal to the origin of posterior inferior cerebellar artery) or control group (no intra-arterial thrombolysis). Main Outcomes and Measures:The primary efficacy outcome was the proportion of patients achieving functional independence (modified Rankin Scale score of 0-2) at 90 days. The primary safety outcomes were mortality at 90 days and incidence of symptomatic intracranial hemorrhage within 48 hours. Results:A total of 247 patients were enrolled, and 1 patient was excluded from the full analysis set due to basilar artery reocclusion before intra-arterial alteplase. The remaining 246 patients (median [IQR] age, 65.0 [56.0-72.0] years; 176 male [71.5%]) were included in this analysis, 124 (50.4%) in the treatment group and 122 (49.6%) in the control group. Among the patients recruited and followed up, functional independence at 90 days was achieved in 52 (41.9%) in the intra-arterial alteplase group and 57 (46.7%) in the control group (adjusted risk ratio, 0.93; 95% CI, 0.73-1.18; P = .55). Mortality at 90 days (29.6% vs 27.0%, respectively; adjusted hazard ratio, 1.07; 95% CI, 0.71-1.61; P = .75) and incidence of symptomatic intracranial hemorrhage (2.4% vs 2.5%, respectively; unadjusted risk ratio, 0.98; 95% CI, 0.20-4.74; P = .97) were similar across groups. Conclusions and Relevance:Results of this randomized clinical trial reveal that in patients with posterior circulation stroke due to acute basilar artery occlusion, intra-arterial alteplase after successful endovascular recanalization appeared to be safe but was not associated with improvement of functional outcomes at 90 days. Trial Registration:ClinicalTrials.gov Identifier: NCT05897554.

Background: In the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS), we found no significant difference between the bypass surgery group and the medical group with respect to the primary composite outcome of stroke or death within 30 days or any subsequent ipsilateral ischemic stroke within 2 years of follow-up. We now extend the long-term follow-ups to 10 years. Methods: We randomly assigned symptomatic patients with hemodynamically compromised internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion to extracranial-intracranial (EC-IC) bypass surgery plus medical treatment or medical treatment alone at 13 centers in China. We extended the follow-ups from the original 2 years to 10 years to assess long-term outcomes. The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days after randomization. Results: 324 patients were assigned to the surgery (n=161) or medical group (n=163); the median duration of follow-up was 7.6 years (interquartile range [IQR], 2.3 to 9.2). The primary outcome occurred in 18 of 161 patients (11.2%) in the surgical group, significantly lower than that in the medical group (32 out of 163 patients [19.6%]; relative risk [RR], 0.57; 95% confidence interval [CI], 0.33 to 0.97; P=0.04). The risk of any stroke was 16.1% in the surgical group vs 23.3% in the medical group (RR, 0.76; 95% CI, 0.52 to1.13; P=0.15); the all-cause mortality was 8.1% in the surgical group vs. 8.6% in the medical group (RR, 0.94; 95% CI, 0.46 to 1.94]; P=0.93). Conclusions: Among symptomatic ICA or MCA occlusion patients with hemodynamic insufficiency, the addition of extracranial-intracranial bypass surgery to medical treatment was safe and led to a lower risk of recurrent stroke through 7 years of follow-up than medical treatment alone. (ClinicalTrials.gov number, NCT01758614.)

RATIONALE:The Chemical Optimization of Cerebral Embolectomy (CHOICE) trial suggested that the administration of intra-arterial alteplase after successful endovascular thrombectomy (EVT) may improve neurological outcomes in patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) in the anterior circulation. However, the use of adjunctive intra-arterial alteplase following successful EVT in acute posterior circulation stroke remains unexplored. AIMS:This study aims to investigate the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation. SAMPLE SIZE:To detect an estimated 15% difference in the primary outcome between the two groups, a total of 376 patients will be enrolled. This sample size allows for 80% power and a 5% significance level, with an interim analysis planned after half of the sample (188 patients) has completed a 90-day follow-up. METHODS AND DESIGN:The Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP) trial is a multicenter, prospective, randomized clinical trial using an open-label treatment design with blinded endpoint assessment (PROBE) conducted in China. Patients with acute basilar artery occlusion will be randomly assigned in a 1:1 ratio to receive either intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) or standard care following successful thrombectomy (defined as expanded thrombolysis in cerebral infarction [eTICI] ⩾ 2b50). STUDY OUTCOMES:The primary outcome is the modified Rankin Scale (mRS) score of 0-2 at 90 days. Key secondary outcomes include changes in eTICI scores after intra-arterial thrombolysis (in the experimental group), mRS 0-3 at 90 days, ordinal shift analysis of mRS at 90 days, early neurological improvement at 48 h, and improvement in National Institutes of Health Stroke Scale (NIHSS) scores at 48 h and 7 days or discharge. Safety outcomes include symptomatic intracranial hemorrhage (sICH) rates at 48 h, 90-day mortality, non-intracranial hemorrhagic complications, and non-hemorrhagic serious adverse events. DISCUSSION:The IAT-TOP trial will provide crucial evidence regarding the potential benefits of adjunctive intra-arterial alteplase in patients with AIS-LVO in the posterior circulation following successful thrombectomy. TRIAL REGISTRATION:ClinicalTrials.gov NCT05897554.

Objective: We aim to test the ability of CT perfusion (CTP) for predicting ischemic stroke in patients with symptomatic chronic carotid or middle cerebral artery occlusion. Methods: This was a post-hoc analysis of the CMOSS trial (NCT01758614), a randomized controlled trial comparing extracranial-intracranial (EC-IC) bypass surgery to medical therapy in patients with symptomatic carotid or middle cerebral artery occlusion and hemodynamic insufficiency measured by CTP. Patients treated with medical treatment alone in the trial were included. Mean transit time (MTT) and relative cerebral blood flow (rCBF) from CTP were collected. The primary outcome was defined as ischemic stroke in the territory of the qualifying artery within 2 years after randomization. Results: All 165 per-protocol patients (median age = 53.7 years, 81.2% males) treated with medical treatment alone were analyzed. Sixteen patients (9.7%) suffered from ischemic stroke in the territory of the qualifying artery during two-year follow-ups. Cut-off values of MTT>6.5s (symptomatic side) and rCBF ≤0.5 were suggested to be associated with recurrent stroke. In multivariate Cox regression, MTT (adjusted hazard ratio [HR] = 3.50, 95% CI = 1.19-10.30, p = 0.02) and rCBF (adjusted HR = 7.36, 95% CI = 2.27-23.85, p =0.001) were independently associated with the primary outcome. Conclusion: This study demonstrated CTP-based hemodynamic evaluation had relative accuracy in predicting recurrent ischemic stroke in symptomatic patients with chronic carotid or middle cerebral artery occlusion, which can be potentially used in patient selection for stratified secondary prevention of stroke. Future studies are warranted to verify current findings.

BACKGROUND:Vertebral artery origin stenosis (VAOS) is a common cause of posterior circulation ischemic events, and endovascular treatment serves as an alternative treatment. However, conventional endovascular treatment methods are related to high risk of restenosis. It is unclear whether the drug-coated balloon (DCB) can reduce restenosis risk of VAOS. METHODS:This was a prospective, multicenter, randomized trial conducted from 6 January 2020 to 1 October 2023 in China. Symptomatic patients with severe VAOS were randomly allocated in a 1:1 ratio to undergo either DCB or bare-metal stent (BMS) and followed up for 12 months. The primary safety endpoint was the incidence of transient ischemic attack, stroke, or death related to target vessel within 30 days post-procedure. The primary efficacy endpoint was the rate of 12-month restenosis. RESULTS:A total of 179 patients were enrolled with 91 in the DCB group and 88 in the BMS group. No significant difference was observed in the rates of transient ischemic attack, stroke, or death related to target vessel within 30 days between the DCB and BMS groups (0 (0.0%) vs. 1 (1.1%); P = 0.49). The 12-month restenosis rate was significantly lower in the DCB group compared to the BMS group (10/76 (13.2%) vs. 27/76 (35.5%); risk ratio = 0.37; 95% confidence interval = 0.19 to 0.71; P = 0.001). CONCLUSION:This trial demonstrated that DCB may reduce restenosis risk in symptomatic patients with severe VAOS compared to BMS. REGISTRATION:URL: https://clinicaltrials.gov (unique identifier: NCT03910166).

BACKGROUND:Whether the long-term benefit of stroke prevention when stenting is added to medical therapy (MT) over MT alone for symptomatic severe intracranial artery stenosis offsets the perioperative risks of the stenting has not been directly evaluated in a randomized trial. We aimed to compare the long-term (>3 years) effect of stenting versus MT alone in patients with symptomatic severe intracranial artery stenosis in a randomized trial. METHODS:We extended the follow-up of 358 subjects enrolled in a multicenter, open-label, randomized trial conducted at 8 centers in China. Patients with transient ischemic attack or stroke attributed to severe intracranial stenosis (70% to 99%) were recruited between March 5, 2014, and November 10, 2016. The primary outcome was a composite of stroke or death within 30 days or stroke in the territory of the qualifying artery beyond 30 days. Other secondary outcomes included stroke in the territory of the qualifying artery, as well as disabling stroke or death after enrollment. RESULTS:A total of 358 patients (stenting 176 versus MT 182) were recruited from March 5, 2014, and followed up till January 22, 2024. The median duration of follow-up was 7.4 years (interquartile range, 6.0-8.0). The primary outcome was not significantly different (stenting 14.8% versus MT 14.3%; hazard ratio, 1.02 [95% CI, 0.58-1.77]; P=0.97). No significant difference was found between groups for the secondary outcomes: stroke in the territory of qualifying artery (14.8% versus 14.3%; hazard ratio, 1.02 [95% CI, 0.58-1.77]; P=0.97), disabling stroke or death (16.5% versus 14.3%; hazard ratio, 1.12 [95% CI, 0.66-1.91]; P=0.70), and death (9.1% versus 7.1%; hazard ratio, 1.22 [95% CI, 0.58-2.58]; P=0.60). CONCLUSIONS:This study provides compelling evidence that, even over prolonged observed periods, the addition of stenting to MT does not confer additional benefits to MT alone in patients with symptomatic severe intracranial artery stenosis. These results underscore the importance of MT as the cornerstone of long-term stroke prevention in this patient population. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01763320.

BACKGROUND AND OBJECTIVES: Intermittent reports of spinal cord arteriovenous shunts (SCAVSs)-induced paralysis during pregnancy and puerperium have raised significant concerns. This study aimed to assess whether women with SCAVSs are at an elevated clinical risk during this period. METHODS: Consecutive female patients with SCAVSs from 10 referral centers were included. Only clinical data within reproductive age were analyzed. The primary outcome was the occurrence of clinical deterioration associated with SCAVSs, categorized into acute and gradual patterns based on the modified Aminoff and Logue scale. RESULTS: A total of 480 patients were included. Before initial treatment, 262 patients experienced pregnancy. Both acute (17.88%/y vs 4.87%/y, P < .0001) and gradual (9.67%/y vs 3.27%/y, P < .0001) deterioration during pregnancy and puerperium were significantly elevated. In the matched cohort of 72 pregnant patients with untreated SCAVSs and their nonpregnant control, acute deterioration was significantly higher in the pregnant patients (26.09%/y vs 6.97%/y, P = .013). After partial SCAVSs obliteration, acute (33.74%/y vs 5.15%/y, P < .0001) and gradual (18.40%/y vs 2.61%/y, P = .0008) deterioration rates during this period were still significantly elevated. In the matched cohort of 23 pregnant patients with residual SCAVSs and their nonpregnant control, acute deterioration was still significantly higher in the pregnant patients (39.50%/y vs 6.25%/y, P = .043). In addition, no significant decrease in the clinical deterioration was observed after partial treatment compared with nontreated patients during this period. CONCLUSION: The risk of clinical deterioration associated with SCAVSs is significantly elevated during pregnancy and puerperium.

This study examines extracranial-intracranial bypass surgery plus medical treatment vs medical treatment alone in symptomatic patients with hemodynamically compromised internal carotid artery or middle carotid artery occlusion.

Rationale: Uncertainty exists over the optimal treatment for chronic middle cerebral artery occlusion (MCAO). However, with strict perioperative management and surgeon selection, the CMOSS trial exhibited lower perioperative stroke risk than previous trials. In the subgroup analysis, EC-IC bypass exhibited a relatively better effect for patients with hemodynamically impaired MCAO. Aim: We aim to determine the efficacy and safety of EC-IC bypass for patients with hemodynamically impaired MCAO. Methods and Design: The CMOSS-2 trial is a government-funded, multi-center, prospective, randomized, open-label, blinded-endpoint (PROBE) trial, which will recruit patients with symptomatic MCAO (parallel design, 1:1 allocation ratio) and severe hemodynamic insufficiency defined by brain CT perfusion (MTT≥6s or rCBF≤0.8). Thirteen high-volume centers are included. Patients will be randomized to EC-IC bypass surgery plus medical treatment or medical treatment alone. Study Outcomes: The primary outcome is the ischemic stroke in territory of qualifying artery within 2 years after randomization. Key secondary outcomes are: Any stroke or death within 30 days after randomization, ischemic stroke in territory of qualifying artery beyond 30 days to 2 years after randomization, any stroke or death within 30 days, or ischemic stroke in territory of qualifying artery beyond 30 days to 2 years after randomization. Sample Size Estimates: The estimated difference is 10% in proportions of the primary outcome between the EC-IC bypass group and medical group, which requires 420 (210 per group) participants to provide valid data to achieve a statistical power of 80% and two-tailed alpha of 5% significance after 10% loss to follow-up or early withdrawal. Discussion: CMOSS-2 study is expected to confirm the effect of EC-IC bypass surgery for symptomatic MCAO patients through the stricter standard for perioperative risk factors management, surgeon screening, and hemodynamic impairment definition. Trial Registration: ClinicalTrials.gov NCT05899582; registered 15 September 2023. Sponsor: Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (ZLRK202320).

Background The distal transradial access (dTRA) has become an attractive and alternative access to the conventional transradial access (TRA) for cardiovascular interventional diagnosis and/or treatment. There was a lack of randomized clinical trials to evaluate the effect of the dTRA on the long-term radial artery occlusion (RAO). Methods This was a prospective, randomized controlled study. The primary endpoint was the incidence of long-term RAO at 3 months after discharge. The secondary endpoints included the successful puncture rate, puncture time, and other access-related complications. Results The incidence of long-term RAO was 0.8% (3/361) for dTRA and 3.3% (12/365) for TRA (risk ratio = 0.25, 95% confidence interval = 0.07–0.88, P = 0.02). The incidence of RAO at 24 h was significantly lower in the dTRA group than in the TRA group (2.5% vs. 6.7%, P < 0.01). The puncture success rate (96.0% vs. 98.5%, P = 0.03) and single puncture attempt (70.9% vs. 83.9%, P < 0.01) were significantly lower in the dTRA group than in the TRA group. However, the number of puncture attempts and puncture time were higher in the dTRA group. The dTRA group had a lower incidence of bleeding than the TRA group (1.5% vs. 6.0%, P < 0.01). There was no difference in the success rate of the procedure, total fluoroscopy time, or incidence of other access-related complications between the two groups. In the per-protocol analysis, the incidence of mEASY type ≥ II haematoma was significantly lower in the dTRA group, which was consistent with that in the as-treated analysis. Conclusions The dTRA significantly reduced the incidence of long-term RAO, bleeding or haematoma. Trial registration ClinicalTrials.gov identifer: NCT05253820.

Background: Prior randomised trials have shown no benefit of stenting added to medical therapy for patients with symptomatic severe intracranial atherosclerotic stenosis (ICAS). But the potential for stenting to provide benefits over a longer time horizon remains to be explored. We aimed to directly compare the long-term effect of stenting versus medical therapy alone in a randomised trial. Methods: We extended the follow-up of subjects enrolled in a multicentre, open-label, randomised trial conducted at 8 centres in China. Patients with TIA or ischaemic stroke (mRS 0-2) attributed to severe symptomatic ICAS (70%-99%) were enrolled. Eligible patients were randomised in a 1:1 ratio to stenting plus medical therapy vs. medical therapy alone. The primary outcome was a composite of stroke or death within 30 days or stroke in territory of qualifying artery beyond 30 days. Other secondary outcomes included stroke in territory of qualifying artery, as well as disabling stroke or death after enrollment. This trial was registered in ClinicalTrials.gov with identifier NCT01763320. Findings: 358 patients (stenting 176 vs. medical 182) were recruited from Mar 5, 2014 and followed up till Jan 22, 2024. The median duration of follow-up was 7·4 years (IQR 6·0-8·0). The primary outcome was not significantly different (stenting 14·8% vs. medical 14·3%; HR, 1·02 [95% CI, 0·58-1·77]; P = 0·97). No significant difference was found between groups for the secondary outcomes: stroke in territory of qualifying artery (14·8% vs. 14·3%; HR, 1.02 [95% CI, 0·58-1·77]; P = 0·97), disabling stroke or death (16·5% vs. 14·3%; HR, 1·12 [95% CI, 0·66-1·91]; P = 0·70) and death (9·1% vs. 7·1%; HR, 1·22 [95% CI, 0·58-2·58]; P = 0·60). Interpretations: This study provides compelling evidence that, even over prolonged observed periods, the addition of stenting to medical therapy does not confer additional benefits to medical therapy alone in patients with symptomatic severe ICAS. These results underscore the importance of medical therapy as the cornerstone of long-term stroke prevention in this patient population. Trial Registration: This trial was registered in ClinicalTrials.gov with identifier NCT01763320. Funding: This work was supported by a research grant (2011BAI08B04) from the National Health Commission of the People’s Republic of China. Stryker Neurovascular (Stryker neurovascular, Fremont, CA, USA) provided supplemental funding for third-party site monitoring and auditing. This work was supported by a research grant (2011BAI08B04) from the National Health Commission of the People’s Republic of China. Stryker Neurovascular (Stryker neurovascular, Fremont, CA, USA) provided supplemental funding for third-party site monitoring and auditing. Declaration of Interest: CPD reports consultancy to the Penumbra, NoNO, and Euphrates Vascular Inc. Dr Jiao reported receiving grants from the Ministry of Science and Technology of the People’s Republic of China (2011BAI08B04) and Stryker Neurovascular during the conduct of the study, as well as grants from Ministry of Science and Technology of the People’s Republic of China (SQ2016YFSF110141) outside the submitted work. No other disclosures were reported. All other authors declare no competing interests. Ethical Approval: The institutional review board of Xuanwu Hospital reviewed and approved the study ([2013]013).

BackgroundWhether the safety and efficacy of percutaneous transluminal angioplasty and stenting (PTAS) is significantly different from that of medical treatment alone for symptomatic intracranial arterial stenosis (ICAS) is debatable. A study was undertaken to determine the safety and efficacy of both treatments for symptomatic ICAS.MethodsThis preplanned pooled individual patient data analysis included 400 participants treated with PTAS and 409 treated with medical treatment alone in two large multicenter randomized clinical trials (SAMMPRIS and CASSISS). Patients were treated with PTAS using a self-expanding stent or medical treatment alone. The primary outcome was stroke or death within 30 days, or ischemic stroke in the territory of the qualifying artery more than 30 days after enrollment.ResultsIndividual data were obtained for 809 patients, 451 from SAMMPRIS and 358 from CASSISS. 400 participants were randomly assigned to the PTAS group and 409 to the medical group. The risk of the primary outcome was not significant between the PTAS and medical groups (17.5% vs 13.2%; HR 1.37 (95% CI 0.96 to 1.95), P=0.08). However, the risk of stroke or death within 30 days was higher in the PTAS group (10.5% vs 4.2%; HR 2.62 (95% CI 1.49 to 4.61), P<0.001). Patients of white ethnicity (HR 1.97, 95% CI 1.17 to 3.31) and those with hyperlipidemia (HR 2.04, 95% CI 1.27 to 3.26) or a transient ischemic attack (TIA) (HR 2.19, 95% CI 1.08 to 4.45) were at higher risk for PTAS.ConclusionsPTAS poses an increased risk of short-term stroke/death and therefore is not advised as primary treatment for symptomatic ICAS. A balance exists between stroke risks and revascularization benefits. For patients with asymptomatic ICAS of white ethnicity and those with hyperlipidemia or a history of TIA, a thorough assessment is warranted before considering PTAS.Trial registrationClinicalTrials.gov Identifier:NCT00576693,NCT01763320.

Abstract Background Distal transradial access (dTRA) has been increasingly accepted as an alternative to the transradial access (TRA) for coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). Although the dTRA has been significantly associated with better patient comfort, shorter haemostasis time, and fewer vascular access-related complications, such as haematoma and proximal radial artery occlusion (pRAO), it has also been associated with an increased risk of distal radial artery occlusion (dRAO). Purpose The aim of the present study was to investigate whether the 6-Fr thin-walled sheath was superior to the conventional radial sheath with respect to the incidence of distal radial artery occlusion (dRAO) at 24 h after CAG and/or PCI via dTRA. Methods A prospective, single-centre trial of patients who were randomized to undergo CAG and/or PCI with either a 6-Fr thin-walled sheath or a 6-Fr conventional sheath. The primary endpoint was the incidence of dRAO at 24 h postoperatively, as evaluated by Doppler ultrasound. The second endpoints included the puncture success rate, puncture time, the incidence of pRAO, pain during the sheath placement, and other vascular-associated complications. Results A total of 620 patients were included in the study. The mean age of the patients was 66.6± 9.7 years (median age 69.0 years [interquartile range 60.0- 74.0 years]), and 66.3% were men. The baseline patient and procedural characteristics were similar between the two groups. For the primary endpoint, the incidence of dRAO at 24 h after the procedure was 1.0% (3/314) in the thin-walled sheath group and 3.6% (11/306) in the conventional sheath group (RR= 0.266, 95%CI= 0.075-0.943, P= 0.027) according to the intention-to-treat (ITT) analysis. For secondary endpoints, the incidence of pRAO was 0.3% (1/314) in the thin-walled sheath group and 2.3% (7/306) in the conventional sheath group (P= 0.029). No significant difference was observed between the thin-walled sheath and the conventional sheath groups regarding the puncture success rate (92.4% vs. 92.5%, P= 0.952). The severity of pain experienced during the sheath placement was similar between the two groups (VAS 2 vs. 2 P=0.426). Other secondary endpoints, including procedural outcomes and other puncture-related outcomes and access-related complications, were not significantly different between the two groups. Conclusion A thin-walled sheath can reduce the incidence of early-term dRAO in patients who underwent CAG and/or PCI via the dTRA.The primary endpoint of the trial

Abstract Background The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. Methods Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. Results A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2–78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3–46.7, P < 0.001) and mycobacterial culture (54.2%, 95% CI 48.4–59.9, P < 0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7–50.0), significantly higher than both Xpert (116/961, 12.1%, 95% CI 10.2–14.3, P < 0.001) and mycobacterial culture (154/961, 16.0%, 95% CI 13.8–18.5, P < 0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%. Conclusions The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection. Trial registration The trial was registered on Chictr.org.cn (ChiCTR2000031680, https://www.chictr.org.cn/showproj.html?proj=49316 ).

BackgroundThere is a lack of randomized clinical trials on whether the 6-French (Fr) Glidesheath Slender (GSS; Terumo, Tokyo, Japan) is superior to the 6-Fr conventional radial sheath (CS) with respect to the early-term incidence of distal radial artery occlusion (dRAO) in patients who have undergone coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) via distal transradial access.MethodsThis was a prospective, single-centre trial of patients who were randomized to undergo CAG and/or PCI with either a 6-Fr GSS or a 6-Fr CS. The primary end point was the incidence of dRAO at 24 hours postoperatively, evaluated using Doppler ultrasound.ResultsA total of 620 patients were included in the study. The baseline patient and procedural characteristics were similar among the 2 groups. For the primary end point, the incidence of dRAO at 24 hours after the procedure was 1.0% (3/314) in the GSS group and 3.6% (11/306) in the CS group (risk ratio, 0.266; 95% confidence interval, 0.075-0.943; P = 0.027) according to the intention to treat analysis. For the secondary end points, the incidence of proximal radial artery occlusion was 0.3% (1/314) in the GSS group and 2.3% (7/306) in the CS group (P = 0.029). Other secondary end points, including the puncture success rate, procedural outcomes, other puncture-related outcomes, and access-related complications were not significantly different in the 2 groups.ConclusionsThe use of a thin-walled and hydrophilic coating sheath can reduce the incidence of early-term dRAO in patients who undergo CAG and/or PCI via the distal transradial access.Clinical Trial RegistrationNCT05501925.