The efficacy of endovascular treatment for acute large vessel occlusion strokes has been demonstrated, but whether it can improve functional outcomes in patients with acute ischemic stroke (AIS) who only present with severe large vessel stenosis without occlusion has not yet been studied. This study investigates the effectiveness of immediate angioplasty or stenting on functional outcomes in AIS patients with severe intracranial stenosis without occlusion. We retrospectively included patients with AIS with symptom onset within 24 hours and imaging-confirmed severe intracranial stenosis (70%-99%, Warfarin Asprin Symptomatic Intracranial Disease criteria) of the culprit vessel from 7 centers in China between January 1, 2020, and December 31, 2024. We compared patients undergoing immediate angioplasty or stenting with those receiving standard medical treatment (SMT) alone. The primary outcome was the distribution of modified Rankin Scale (mRS) scores at 90 days. The treatment effect was estimated through multivariable adjusted models and inverse probability of treatment weighting (IPTW). Safety outcomes included symptomatic intracranial hemorrhage (sICH) within 24 hours and mortality within 90 days. A total of 242 patients were included, with a mean age of 65.7 years, and 86 patients (35.5%) were female. Ninety-six (39.7%) patients underwent immediate angioplasty or stenting, and 146 (60.3%) received SMT. The median 90-day mRS score was 1 (interquartile range 0-3) in the immediate angioplasty or stenting group and 1 (interquartile range 1-3) in the SMT group. The immediate angioplasty or stenting group showed a shift toward better functional outcomes on the mRS scores (adjusted common odds ratio [OR] 2.73 [95% CI 1.49-5.00], p = 0.001; after IPTW, OR 2.50 [95% CI 1.72-3.63], p < 0.001). There was no significant difference in the incidence of sICH (1.0% vs 1.4%; adjusted risk ratio 0.36 [95% CI 0.02-5.35], p = 0.46) or mortality (2.1% vs 1.4%; adjusted hazard ratio 1.01 [95% CI 0.92-1.11], p = 0.93). Among patients with AIS with severe intracranial stenosis without occlusion, immediate angioplasty or stenting was associated with improved 90-day functional outcomes compared with SMT alone. No significant difference was observed in the incidence of sICH or mortality. This study provides Class III evidence that in AIS patients with severe intracranial stenosis, immediate angioplasty or stenting was associated with improved 90-day functional outcomes compared with SMT.

Molecularly defined oligodendrogliomas are rare tumors whose prognosis has improved over time because of more effective treatments. However, several aspects of management are still controversial, and studies with long-term follow-up are needed. The main aim of this study was to analyze and compare the natural history and management of patients with OG2 and OG3 and define which factors have the strongest effect on outcome. We reviewed an institutional retrospective cohort (1996-2024) of patients with molecularly defined OG2 and OG3 according to World Health Organization 2021. We retrieved information on baseline clinical features, MRI characteristics (i.e., presence and pattern of contrast enhancement), extent of resection, initial treatment modalities after surgery, and management at progression. The relationships of these factors with progression-free survival (PFS) and overall survival (OS) were studied with univariate and multivariate analyses. Among 240 patients with IDH-mutant 1p/19q-codeleted oligodendrogliomas, grade 2 tumors were 149 (62.1%) and grade 3 were 91 (37.9%) with a median age of 42 and 44 years, respectively. Male/female ratio was 73/76 (49%/51%). Among patients with OG3, 70/91 (77%) exhibited a diffuse grade 3 histology (OG3d), whereas 21/91 (23%) had focal grade 3 areas only (OG3f). Overall, patients with OG2 and OG3 had similar median PFS (57.6 months, CI 53.2-61.9, vs 59.8 months, CI 41.9-77.6, p = 0.25), and prolonged median OS (274 months vs not reached). However, patients with OG3 exhibited a shorter time to radiotherapy at progression and their survival probability declined more rapidly within the first decade after surgery. The extent of resection was the only factor that significantly affected both PFS and OS in a multivariate analysis (for PFS, hazard ratio [HR] 0.90, 0.62-0.99, p = 0.026; for OS, HR 0.29, 0.13-0.79, p = 0.016), whereas tumor grade did not. Temozolomide alone as initial treatment of high-risk OG2 and OG3 with large residual tumor after surgery was not detrimental for survival. The same was true for observation in a small group of young patients with nonenhancing OG3 who have undergone complete resection and with only focal areas of malignancy (OG3f). This large retrospective cohort of IDH-mutant 1p/19q-codeleted oligodendrogliomas receiving standard treatments could serve as a benchmark for comparison with new IDH inhibitors in future clinical studies.

Objective: To explore the efficacy of the implementation of quality control (QC) program for children with fulminant myocarditis (FM) on improving the survival rate, reducing mortality and complication rates, and to evaluate the feasibility of the QC protocol. Methods: A retrospective cohort study was conducted. A Clinical Medical Quality Control Scoring Scale for Pediatric Fulminant Myocarditis (the QC Scale) was implemented since January 2021. Clinical data and the QC Scale data of 187 children with FM admitted to 8 tertiary hospitals capable of pediatric extracorporeal membrane oxygenation (ECMO) treatment over 6 years were collected, including the pre-QC group (January 2018 to December 2020) and the post-QC group (January 2021 to December 2023). Independent-samples t-test, Mann-Whitney U test, Chi-square test or Fisher's exact test were used for intergroup comparisons; and multivariate Logistic regression was performed for risk factor analysis. The clinical characteristics of pediatric FM and the feasibility and clinical efficacy of the QC protocol were evaluated. Results: A total of 187 children with FM were enrolled, including 82 cases in the pre-QC period and 105 cases in the post-QC period. The age was (8±4) years, and the weight was (28±14) kg. There were 104 female cases (55.5%) and 83 male cases (44.5%). A total of 156 children survived and 31 died, with an overall in-hospital mortality rate of 16.6% (31/187). The completion rates of electrocardiogram or cardiac monitoring and echocardiography or non-invasive hemodynamic monitoring within 30 min after admission were 98.7% (81/82) and 92.6% (72/82) in the pre-QC group, compared with 96.2% (101/105) and 90.5% (95/105) in the post-QC group. The post-QC group showed significantly higher completion rates of blood lactate measurement and Glasgow Coma Scale assessment within 60 min of admission than the pre-QC group (86.5% (71/82) vs. 98.1% (103/105), 62.2% (51/82) vs. 81.9% (86/105), χ²=9.43, 8.72; P=0.002, 0.003). The pre-QC completion rates of reaching blood lactate ≤5 mmol/L, central venous oxygen saturation ≥65%, and urine output≥1 ml/(kg·h) at 12 h after treatment were 82.1%(46/56), 72.1%(31/43) and 72.7%(48/66), respectively, compared with 81.1%(77/95), 69.1%(47/68) and 80.9%(76/94) in the post-QC group. The time from admission to ECMO initiation was shorter in the post-QC group than in the pre-QC group ((11±17) vs. (7±10) h, t=2.09, P=0.037). The mortality rates were 22.0% (18/82) in the pre-QC group and 12.4% (13/105) in the post-QC group. Compared with the pre-QC group, the post-QC group presented decreased rates of pre-ECMO cardiopulmonary resuscitation, cerebral injury and severe renal injury (51.2% (42/82) vs. 28.6% (30/105), 19.5% (16/82) vs. 8.6% (9/105), 19.5% (16/82) vs. 8.6% (9/105); χ²=9.97, 4.76, 4.76, all P<0.05). Conclusions: The implementation of the QC protocol for pediatric FM improves the ability of organ injury identification and standardized treatment, facilitates timely ECMO initiation, reduces the occurrence of cardiac arrest and major complications, and is of great significance for improving long-term quality of life. The pilot hospitals achieves high completion rates of QC indicators, indicating good feasibility of the protocol.

In-hospital use of non-invasive ventilation improves outcomes in patients with acute respiratory failure caused by acute exacerbation of chronic obstructive pulmonary disease. Prehospital use of non-invasive ventilation is uncommon due to diagnostic uncertainty and logistical constraints. We hypothesised that prehospital non-invasive ventilation guided by arterial blood gas analysis would improve early physiological outcomes compared with standard medical treatment alone. This investigator-initiated, multicentre trial randomised patients with suspected acute respiratory failure due to acute exacerbation of chronic obstructive pulmonary disease with respiratory acidosis defined as pH < 7.30 and PaCO2 > 6.0 kPa to standard medical treatment alone or standard medical treatment plus non-invasive ventilation. Patients were attended by prehospital physician-manned emergency care units and enrolled without prior consent under emergency trial approval. The primary outcome was the change in arterial pH from enrolment to hospital arrival. The trial was terminated early due to low recruitment. Out of 111 screened patients, 16 were randomised and 14 were included in the analysis. The median prehospital pH change was 0.09 (interquartile range 0.02-0.12) in the non-invasive ventilation + standard medical treatment group and 0.02 (0.01-0.03) in the standard medical treatment alone group. Median on-scene time was 32 min in the non-invasive ventilation + standard medical treatment group versus 28 min in the standard medical treatment alone group. Recruitment was limited by strict inclusion criteria, procedural complexity and challenges related to the implementation of prehospital arterial blood gas analysis and trial procedures. Missing data further limited the assessment of in-hospital outcomes. The clinical effect of prehospital non-invasive ventilation could not be determined due to early termination. This trial highlights important challenges relevant to future clinical trials in the prehospital setting, including patient selection, diagnostic requirements and implementation of complex interventions. NCT06211920.

Targeting PLOD2 induces epithelioid differentiation and improves therapeutic response in sarcomatoid renal cell carcinoma.

AGA Clinical Practice Update on Diagnosis and Treatment of Hemorrhoids: Expert Review.

Glioblastoma (GB) is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after partial surgical resection or resistance to drug treatments. The study aimed to evaluate the predictive values of apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI), plasma levels of placental growth factor (PGF) and glial fibrillary acidic protein (GFAP), and their combination in GB recurrence. The study included 200 patients diagnosed with GB consisting of 136 with tumor recurrence and 64 without. DWI examinations and PGF and GFAP measurements in the plasma were performed preoperatively. The patients with recurrent disease exhibited a lower value of ADC with higher plasma PGF and GFAP levels than those with non-recurrence. The results of Pearson correlation analysis suggested the ADC shared negative correlations with plasma levels of PGF and GFAP in patients with recurrent GB. The plasma level of PGF was also found to be positively correlated with the plasma level of GFAP in patients with recurrent GB. The ADC, plasma levels of PGF and GFAP in predicting recurrent GB presented AUC: 0.75, 0.85, and 0.82, respectively. Combined analysis of two of three to evaluate the prediction showed AUCs of 0.98 (ADC and PGF), 0.96 (ADC and GFAP), and 0.84 (PGF and GFAP). Combined analysis of ADC and plasma PGF, ADC and plasma GFAP, PGF and GFAP to evaluate the prediction showed AUCs of 0.98, 0.96, and 0.84, respectively. Combined analysis of three of them to evaluate the prediction showed AUC as 0.98. The study demonstrates that combined ADC and plasma PGF showed a similar predictive value in recurrent GB after standard treatment as combined ADC, plasma PGF and GFAP together. Considering limited sample size and lack of more sample types in this study, additional value of plasma GFAP in predicting recurrent GB should be further investigated in larger-scale population or different sample sources.

The duality of testosterone in glioblastoma: From targeted therapy to modulation of the tumor microenvironment and neuroprotection.

Patient-derived ovarian cancer organoids as platforms for predicting platinum resistance and screening tumor stem cell inhibitors.

Morphological-biomechanical dual-cornerstone framework: quantitative ultrasound for electrodiagnostically negative carpal tunnel syndrome.

Gastroesophageal reflux disease affects about 20% of children. While proton pump inhibitors are a standard treatment, vonoprazan offers more rapid, potent, and prolonged gastric acid suppression in adults. Despite its promising pharmacological properties, vonoprazan is not yet approved for pediatric use. We aimed to develop and iteratively refine a population pharmacokinetic model to guide pediatric dosing for vonoprazan, characterize its pharmacokinetics in children and adolescents, and evaluate drug exposure across age groups. We developed a two-compartment linear pharmacokinetic model using data from eight adult (18-54 years) studies, one adolescent (≥ 12 to 17 years) study, and one study in children (≥ 6 to < 12 years). The model incorporated delayed absorption via three transit compartments parameterized by mean transit time, along with estimates for absorption rate constant and relative bioavailability. To capture variability, we quantified between-subject differences in clearance and central volume, accounting for correlation, and applied a combined additive and proportional error model to residual variability. Investigating relevant covariate effects allowed us to refine the model further. The model structure remained unchanged as pediatric data were added. The most significant parameter shifts occurred in the age effect on absorption rate and the weight effect on central volume. Predictions aligned closely with observed vonoprazan concentrations across age groups. Model-based simulations demonstrated consistent steady-state exposure among adults, adolescents, and children, with simulated pediatric doses aligning with the reference adult dose. In conclusion, the final two-compartment model successfully predicted vonoprazan pharmacokinetics and confirmed dose selection in children and adolescents aged 6 to 17 years.

Patients with human papillomavirus-associated head and neck squamous cell carcinoma (HPV+ HNSCC) have relatively favorable outcomes, but standard treatments like radiation or chemoradiation frequently result in long-term toxic side effects. Appropriate patient selection has been a barrier to effectively de-escalate therapy for HPV+ HNSCC, and the absence of accurate biomarkers likely contributed to failure of recent promising de-escalation trials that rely on histologic tumor characteristics, history of tobacco use, or tumor response to chemotherapy; This deficiency underlines the need to develop and validate an assay to accurately detect two subtypes of HPV+ HNSCC-one with good prognosis and one with poor prognosis. These two subtypes are distinguished by the activity of NF-κB in tumors. We first developed a DNA-based marker panel consisting of genes that when mutated would lead to NF-κB activation. Additionally, we developed a custom NanoString assay to determine the expression of NF-κB target genes. These assays were tested to determine their accuracy in detecting tumor subtype. We demonstrate that the NF-κB gene signature score, as determined using the NanoString assay, could more accurately classify HPV+ HNSCC as compared with the DNA-based marker panel. Patients with a high NF-κB gene signature score demonstrated significantly increased overall survival, indicating more sensitivity to (chemo)radiation treatment. The NF-κB gene signature score can accurately predict response to standard (chemo)radiation in HPV+ HNSCC. This molecular biomarker holds promise for clinical use in identifying patients who are likely to benefit from treatment de-escalation strategies, potentially reducing long-term side effects without compromising therapeutic efficacy.

Economic Evaluation and Budget Impact Analysis of Secukinumab as a Second-Line Treatment Among Patients With Psoriatic Arthritis Who Were Tumor Necrosis Factor Inadequate Responders in Thailand.

Ecological momentary interventions for depression: A systematic review and meta-analysis.

Impact of hypofractionated radiotherapy schedules on local control in early breast cancer: A five-year study of boost vs. non-boost protocols.

In patients with severe ocular surface disease (OSD) and cornea and cataract-related vision impairment, where the risk of allograft rejection after allogeneic corneal transplantation is unacceptably high and cataract surgery impossible because of corneal opacity, cataract extraction may still offer meaningful improvement in vision-related quality of life. We describe ipsilateral, nonrotational autokeratoplasty (INRA) as option to perform open-sky cataract surgery after removal of the central cornea and prevent immune responses by placing back the original host cornea. This report presents 2 patients with only 1 functional eye, cataract and severe OSD (Lyell syndrome, chemical burn) undergoing INRA to enable cataract surgery as an alternative approach to visual rehabilitation, aiming to avoid high-risk corneal transplantation. Both patients had a small central zone of relative corneal clarity. This is the first report of INRA for concomitant cataract surgery. Postoperatively, both visual acuity and patient-reported visual satisfaction improved. In 1 case, delayed wound healing was noted and successfully managed with standard treatments. No other severe complications, adverse events, or rejection episodes were observed. Although INRA does not address corneal vision impairment, it allows effective cataract management in patients with relative central corneal clarity and otherwise very high risk for corneal allograft failure.

Individual participant-level analysis of four randomized clinical trials examined therapeutic effects of blood pressure lowering on hierarchical kidney outcome using win statistics.

Treatment-related deaths with immune checkpoint inhibitor-based combinations versus tyrosine kinase inhibitor monotherapy in hepatocellular carcinoma: A systematic review and meta-analysis.

Tobacco-cannabis co-use is associated with increased psychosocial and health harms; however, the treatment literature assessing the impact of co-use has been mixed and suffers from critical limitations. To date, no prospective studies have evaluated the degree to which cannabis co-use affects tobacco cessation, nor are there treatment recommendations for those who co-use. The goal of this study was to evaluate and quantify the impact of cannabis co-use on tobacco cessation through a 12-week prospective tobacco cessation trial. This was a multi-site, non-randomized trial. Inverse probability weighted modified Poisson regression models were used to assess the probability of tobacco abstinence between tobacco-only and tobacco-cannabis co-use cohorts. Enrollment occurred at three sites across South Carolina, USA: The Medical University of South Carolina (MUSC) Charleston, Behavioral Health Services of Pickens County and MUSC Florence. Enrolled participants were adults (n = 181; ages 18-40) who (1) smoked tobacco cigarettes and used cannabis regularly (co-use cohort; oversampled) or (2) smoked tobacco cigarettes daily (tobacco-only cohort). Across 3 sites, 181 adults (110 co-using cannabis; 71 tobacco-only) were enrolled (49% female; 19% Black/African American; 6% Hispanic/LatinX). All participants received 12 weeks of first-line tobacco treatment (varenicline, incentives for tobacco abstinence, counseling), while cannabis use was not addressed as part of treatment. The primary outcome was biochemically confirmed 7-day point prevalence tobacco abstinence (PPA) at end of treatment (EOT; Week 12 post-enrollment). Average baseline reported cigarettes per day were not different between tobacco-only or cannabis co-use cohorts [14.9, (standard deviation, SD =7.2) versus 13.4 (SD =7.8); P = 0.25]. Among the co-use cohort, days of cannabis use in the past month at baseline was 23.7 (SD =9.5). In imputed analyses, EOT 7-day PPA tobacco abstinence was achieved in 59% of tobacco-only participants and 33% of the cannabis co-use cohort [Imputed data: relative risk (RR) =1.63, 95% confidence interval (CI) = 1.14-2.33]. Neither baseline daily cannabis use [adjusted relative risk (RRadj) =1.05, 95% CI= 0.63-1.77] nor within-treatment cannabis use frequency (RRadj=0.51, 95% CI = 0.25, 1.06) was associated with EOT PPA for tobacco in the cannabis co-use cohort. This is the first prospective study designed to compare tobacco cessation outcomes by cannabis co-use status. Regular cannabis co-use had a negative impact on tobacco abstinence among younger to middle-aged adults. Addressing cannabis use should be incorporated into standard tobacco treatment to improve cessation outcomes.

For patients with early-stage low-risk uterine cervical cancer ≤2cm, simple hysterectomy is recommended, and this can now be considered the new standard of care.1 However, for patients with cervical cancer >2cm with "non-SHAPE" criteria, radical hysterectomy is still recommended as the standard primary treatment.2. Nerve-sparing radical hysterectomy requires deep knowledge of pelvic neurovascular anatomy. Lack of proper anatomical knowledge and adequate surgical skills are associated with not only the risk of hypogastric nerve injury but also unnecessary bleeding during surgery, which may lead to unintentionally less radical surgery. We performed nerve-sparing radical hysterectomy (Querleu-Morrow classification: type C13) using the following eight steps (Video). In Japan, total laparoscopic radical hysterectomy is performed under the public health insurance system. Step 1: Development of the lateral pararectal space and the paravesical space. Step 2: Isolation of the ureter and separation of the hypogastric nerve. Step 3: Development of the rectovaginal space. Step 4: Dissection of the anterior leaf of the vesicouterine ligament. Step 5: Development of the paravaginal space and dissection of the posterior leaf of the vesicouterine ligament Fig. 1). Step 6: Separation of the cut end of the deep uterine vein from the pelvic splanchnic nerve (Fig. 2). Step 7: Transection of the uterine branch from the inferior hypogastric plexus and ligation of the paracolpium. Step 8: Vaginal cuff creation and transection of the vaginal wall. Surgeons should recognize the importance of developing a retroperitoneal avascular space based on precise anatomical landmarks, and each surgical step must be reproducible. Fig. 1 Anatomical relationships between the posterior leaf of the vesicouterine ligament and the paravaginal space (Left side). (A) and (B) The surgical forceps can easily penetrate the paravesical space. This space is known as the "paravaginal space." (C) After development of the paravaginal space, the posterior leaf of the vesicouterine ligament can be dissected. Fig. 2 Anatomical relationships between deep uterine vein, hypogastric nerve and bladder branch (right side). (A) The bladder branch from the inferior hypogastric plexus can be identified when the cut end of the deep uterine vein is cranially retracted. (B) Dot line: dissection line.