Smoke water (SW), a liquid by-product of wood pruning waste pyrogasification, was investigated for its nematicidal potential. We evaluated SW's efficacy against adult Aphelenchus avenae and the egg and second-stage juveniles (J2) of the root-knot nematode Meloidogyne javanica under controlled laboratory conditions. Five concentrations (100 mL/L, 10 mL/L, 1 mL/L, 0.1 mL/L) and a sterile water control were tested over four days. Undiluted SW caused complete apparent mortality of M. javanica j2 within 24 h, while 100 mL/L achieved full mortality by day 2. The 10 mL/L treatment also showed significant activity, exceeding 50% mortality by day 4. Similar responses were observed in A. avenae, with undiluted and 100 mL/L SW reaching full mortality within 1 and 4 days, respectively. Egg hatching of M. javanica was completely inhibited at undiluted and 100 mL/L SW and markedly reduced at 10 mL/L. These findings indicate that SW may represent a promising natural alternative to synthetic nematicides.
Extracranial carotid artery aneurysms (ECAAs) are exceedingly rare in children, with only a limited number of cases reported worldwide. Surgical reconstruction in infancy poses unique challenges owing to vascular fragility and the need for long-term growth compatibility. We report the case of a 1-year-old boy with a large right ECAA who was treated with graft-free internal-to-external carotid artery (ICA-to-ECA) transposition. The aneurysm was completely resected, the proximal ICA was ligated, and the distal ICA was anastomosed adjacent to the ECA. Microsurgical reconstruction was performed under temporary clipping, with an occlusion time of 22 min. Postoperative angiography confirmed excellent flow through the transposed vessel. Serial imaging over a 13-year follow-up period demonstrated persistent patency without stenosis or proportional diameter growth of the reconstructed ICA, with no neurological complications or ischemic events. The anastomotic segment enlarged proportionally to the patient's cervical growth, indicating successful long-term biological integration. This case represents one of the longest documented follow-ups of pediatric ECAA reconstruction using native arterial tissues. Direct ICA-to-ECA transposition provides a durable, infection-free, and growth-adaptive solution superior to prosthetic or vein graft repair. This outcome underscores the central tenet of pediatric neurosurgery: surgical innovation must harmonize with a child's lifelong development.
Surfactant-free microemulsions (SFMEs) are unique microemulsions, which form from immiscible liquids (generally called oil and water components) in the presence of amphi-solvents rather than traditional surfactants. Our understanding of SFMEs is still limited. One of the questions to be explored is whether the surfactant-free systems can form the middle-phase (or Winsor III) microemulsions like the surfactant-containing systems. In the current work, the phase behavior of the ternary mixture of n-hexadecane (HDA), n-butanol (BuOH), and water was investigated at different temperatures (20-90 °C), where amphi-solvent BuOH is completely miscible with HDA (oil) but partially miscible with water. The single-phase, two-phase, and three-phase patterns were observed for the ternary mixture, depending on its composition. The area of the three-phase region in the ternary phase diagram decreases with an increase in T (20-55 °C). The mesoscale structuring of the ternary mixture samples with different existing states was determined using dynamic light scattering, electrical conductivity, and cryogenic and negative-staining transmission electron microscopy techniques. The middle phase of the three-phase systems was identified as the bicontinuous (BC) microemulsion, demonstrating that the middle-phase (or Winsor III) microemulsion can be formed without traditional surfactants. In addition, the Winsor I, II, and IV microemulsion systems were also identified in the ternary mixture. This work provides a better understanding of the features of SFMEs.
Lasers have wide applications in medicine but are associated with pain and anxiety, particularly in younger patients. Pain mitigation is often limited to topical anesthetics in the outpatient setting. Distraction techniques are limited by the need for ocular protection, which can include eye patches that completely occlude vision. Virtual reality (VR) is effective at managing procedural pain and anxiety during other short medical procedures and is a promising tool for this population. This trial aims to assess the safety, feasibility, and efficacy of the virtual reality pain alleviation therapeutic (VR-PAT) for pain management during outpatient laser procedures. A total of 40 patients requiring outpatient laser therapy for at least 2 sessions will be recruited from a pediatric hospital in the Midwestern United States for this crossover randomized, 2-arm clinical trial. During the first laser visit, the participants will be randomly assigned to either play the VR-PAT game during their procedure or wear the headset with a dark screen. Participants will answer questions about their pain (Numeric Rating Scale 0-10), anxiety (State-Trait Anxiety Inventory for Children, Numeric Rating Scale 0-10, and Modified Yale Preoperative Anxiety Scale), and pain medication usage. Those playing the VR-PAT will report simulator sickness symptoms and their experience playing the game. At their second laser visit, participants will cross over to the opposite intervention. The primary outcomes are the differences in self-reported pain and anxiety between the 2 interventions. Feasibility outcomes include the proportion of screened patients who were eligible, have given consent, and completed both visits, as well as adverse events reported. To evaluate the efficacy of pain reduction, composite pain scores, and pain medication usage will be calculated for each laser visit. To evaluate the efficacy of anxiety reduction, the change in Modified Yale Preoperative Anxiety Scale scores will be compared between control and VR groups at each visit using the Wilcoxon rank sum tests. All statistical analyses will follow the intention-to-treat principle with regard to intervention assignment at each visit. The study was funded in January 2023 and began enrollment at that time. A total of 44 participants were recruited, and data collection was completed in November 2025, with 40 participants completing both visits. The sample was balanced, with 40 participants using the intervention and participating in the control condition. The age range of the complete sample was 6 to 21 years at recruitment, and 22 (55%) were female. Data analysis is in progress with final results planned for June 2026. Findings from this innovative randomized clinical trial will provide early evidence on the efficacy of the VR-PAT in reducing self-reported pain and anxiety during outpatient laser procedures. The results from this trial will inform a large-scale, multisite study.
Chromosomal abnormalities involving the sex chromosomes constitute critical genetic factors influencing fertility in horses. Nevertheless, a substantial proportion of individuals carrying sex chromosomal abnormalities exhibit normal reproductive phenotypes, which complicates their identification until adulthood. Here, we present four mares carrying a complex deletion/translocation rearrangement with the karyotype formula 64, X, del(X)(p∼25),t(X; Y)(p∼25; q∼15). The cases analyzed belong to three unrelated families of Pura Raza Española (PRE), all presenting the same chromosomal abnormality. Two of the individuals analyzed were a fertile mare and her foal, demonstrating vertical transmission of the rearrangement to the next generation. The animals were initially flagged for sex chromosome abnormalities due to incompatibilities between phenotypic and genotypic sex detected during STR analysis for parentage. They were subsequently analyzed for copy number abnormalities and sex chromosome assessment using an equine commercial SNP-array-based methodology, detecting a large heterozygous 10 Mb deletion located at the distal part of the ChrX p-arm, as well as the existence of a genomic region associated with ChrY. Fluorescence in situ hybridization (FISH) further confirmed that ChrY-derived material was translocated to the same distal part of the ChrX p-arm. Finally, bioinformatic tools were used to evaluate the abundance of CpG islands and to perform a functional analysis of the genes located in the affected regions. These results may suggest that reproductive competence in the fertile mare could be explained by the production of euploid zygotes carrying at least one copy of the intact X chromosome. This study highlights the importance of accurate detection and characterization of chromosomal abnormalities in horses, particularly in individuals with apparently normal reproductive phenotypes. Genetic changes in the sex chromosomes, the structures that determine an animal’s biological sex, play an important role in fertility. While these abnormalities often reduce reproductive ability, some animals appear completely normal until adulthood. This makes such conditions difficult to detect without specialized genetic testing. In this study, we describe four cases of a complex chromosomal abnormality in Pura Raza Española horses. Among these is the first known report of a fertile mare that successfully passed the genetic rearrangement to her foal. The condition was first suspected when routine parentage testing showed inconsistencies between the animals’ physical sex and their genetic markers. To better understand the abnormality, we used advanced genetic techniques to examine the horses’ chromosomes in detail. We identified a structural change in one of the X chromosomes of the four mares, including a large missing segment, and the relocation of small fragments from the Y chromosome to the X. Despite these alterations, the only mare of reproductive age remained fertile. We hypothesize that this reproductive competence could be due to the presence of an intact X chromosome in her genome, which compensates for the deletion. Our findings highlight the importance of genetic screening in horses, even when animals show normal reproductive characteristics, allowing for better management of genetic health.
Continuous quality improvement rounds (CQIRs) play an important role in medical education, quality assurance, and accreditation in Canadian hospitals. This study aimed to establish a more thorough understanding of their specific application and perceived value in general surgery departments within hospitals in British Columbia (BC), Canada. A 27-item (and one additional optional item) cross-sectional survey was conducted between August-December 2023 amongst general surgery department heads across BC hospitals, with the goal of obtaining information on CQIR logistics such as scheduling, format, and content, as well as surgeons' subjective assessments of impact on quality improvement, educational value, and barriers to participation. Thirteen complete responses representing surgical departments across the province were qualitatively analyzed. Most reported monthly or every 4 months CQIR meetings, lasting at least one hour, with strong attendance by attending surgeons. Noted areas for improvement included the absence of specific inclusion criteria, the need for standardized error classification, and lack of post-CQIR engagement for learning assessment. Respondents expressed satisfaction with CQIR effectiveness but communicated a desire for more in-person meetings and increased structure. CQIRs in BC are effective but occur less frequently than is ideal for medical education and quality improvement. This study suggests an increase in meeting frequency and organization in case selection and analysis may enhance the delivery and application of key learning objectives. Future research in this area is needed.
Telerobotic surgery allows expert surgical care delivery across large distances using robotic systems and high-speed, low-latency networks. However, concerns regarding technical safety, clinical workflow and outcomes - particularly in settings without on-site surgical expertise - limit its global adoption. To evaluate the feasibility, safety, efficacy, workflow and technical requirements of long-distance telerobotic cholecystectomy in India using the indigenous SS Innovations (SSI) MantraSync robotic system and Multiprotocol Label Switching (MPLS)-based dedicated connectivity. Two female patients underwent an elective telerobotic cholecystectomy with the surgeon located at Gurugram and the patient at Guwahati, separated by ~ 1950 km. A pre-established surgical workflow with a modified surgical safety checklist was followed. A strict contingency protocol, multilayered network security and backup conversion plans were implemented. Technical requirements included a dedicated 40 Mbps MPLS line, ultra-low latency video and control data paths and the RASCOW2 protocol for stable streaming. Perioperative and network parameters were prospectively recorded. Both surgeries were completed successfully without intraoperative complications, conversions or technical failures. Console times were 51 and 30 mins, blood loss was minimal (10-15 mL), Visual Analogue Scale pain score at 24 h was 1-2 and uneventful discharge occurred on day 2. Network transmission latency was 35-40 ms, round-trip latency 250-260 ms, with jitter <10 ms and packet loss <0.1%. All values were within recommended global benchmarks for telerobotic safety (<320 ms round-trip). Functional handover to local control was verified and could be achieved in 2-3 min if needed. Telerobotic cholecystectomy using the SSI MantraSync platform and a robust network infrastructure is safe, feasible and effective, with technical and clinical outcomes comparable to in-person robotic surgery. Adherence to multidisciplinary workflow, safety checklists and redundancy protocols is critical. These results support expanded adoption of telerobotic surgery in resource-limited and remote environments, enabling broader access to advanced surgical care.
Chronic low back pain is notoriously challenging to diagnose and manage, especially when imaging fails to reveal a cause. Superior cluneal nerve entrapment is an increasingly recognized, but often overlooked, source of pain that can mimic lumbosacral radiculopathy. We describe a 43-year-old woman with longstanding chronic low back pain unresponsive to physical therapy, extracorporeal shockwave therapy, and targeted sacroiliac joint injections. A physical examination revealed focal tenderness along the posterior iliac crest, a positive Tinel sign, and pain over the iliac crest. Lumbar magnetic resonance imaging was unremarkable. She underwent fluoroscopic and ultrasound-guided superior cluneal nerve blocks in separate sessions; each block produced immediate and complete pain resolution. Superior cluneal nerve entrapment should be considered when a patient has axial low back pain with negative imaging. Ultrasound-guided superior cluneal nerve blocks are a safe and effective alternative to fluoroscopic guidance, offering real-time visualization without radiation exposure.
The effectiveness of a digital training (DT) system in which patients receive individually tailored physiotherapeutic elbow-specific training (PEST) delivered via a digital platform remains unclear. This study determines the effectiveness of a DT system in which patients receive individually tailored PEST supervision and guidance via the Joymotion Intelligent Rehabilitation System and educational videos, compared with conventional training (CT) conducted by qualified physiotherapists at outpatient clinics and unsupervised home-based PEST in patients following arthroscopic release for posttraumatic elbow stiffness. This single-center, noninferiority randomized controlled trial was conducted at the Rehabilitation Department of Shanghai Sixth People's Hospital between September 2020 and June 2024. Patients aged 16-65 years undergoing arthroscopic release for posttraumatic elbow stiffness were randomized to receive either a 12-week DT program or conventional outpatient clinic-based training. Outcome measures included elbow flexion-extension range of motion (primary outcome); forearm rotation; isometric and dynamic muscle strength; American Shoulder and Elbow Surgeons (ASES) and Disabilities of the Arm, Shoulder, and Hand (DASH) scores; EQ-5D-5L; cost-effectiveness; adherence; and adverse events, assessed at 4, 12, and 24 weeks postoperatively. At 12 weeks, the mean elbow flexion-extension range of motion improved similarly in the DT and CT groups (between-group difference -1.6°, 95% CI -8.2° to 4.9°; P=.53), confirming noninferiority. Forearm rotation gains were slightly greater with DT (difference 14.2°, 95% CI 2.9°-25.6°). Patient-reported outcomes were equivalent between groups: ASES function (difference 0.6, 95% CI -0.3 to 1.5; P=.39) and pain (difference 0, 95% CI -8.3 to 8.5; P=.68) subscores, DASH (difference 0.23, 95% CI -1.54 to 1.99; P=.68), and EQ-5D-5L index (difference 0.001, 95% CI -0.012 to 0.015; P=.56) showed no significant between-group differences. Nearly all patients completed the 12-week program in both arms (104/106, 98.1%, vs 101/102, 99%, adherence; odds ratio 0.52, 95% CI 0.05-5.77). Adverse events occurred in 29 out of 106 (27.4%) participants in the DT group and 32 out of 102 (31.4%) participants in the CT group (odds ratio 0.82, 95% CI 0.45-1.50). Total rehabilitation costs per patient were lower in the DT group by an average of CNY -7418.58, and incremental cost-effectiveness analysis indicated that DT provided comparable outcomes at lower cost. Individually tailored PEST delivered via a DT system is a viable, cost-effective, and safe alternative to conventional outpatient clinic-based training following arthroscopic release for posttraumatic elbow stiffness. These findings support its integration into routine postsurgical care, particularly for patients facing barriers to traditional therapy. Chinese Clinical Trial Registry Chictr2400093415; https://www.chictr.org.cn/showprojEN.html?proj=240693.
Haemodialysis patients are especially vulnerable to blood-borne viral infections because of repeated exposure to invasive procedures and the dialysis care environment. This study aimed to determine the HBV-positive status of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus among haemodialysis patients and to identify factors associated with HBV seropositivity. A cross-sectional analytical study was conducted among haemodialysis patients in Morocco. A total of 305 haemodialysis patients were included. Sociodemographic, clinical, and serological data were collected using a structured form. Serological status for HBV, HCV, and HIV was assessed by ELISA and confirmed using specific confirmatory assays. Statistical analysis used: Univariate and multivariable logistic regression analyses were performed to identify factors associated with HBV seropositivity. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and statistical significance was set at p < 0.05. The overall seroprevalence was 2.62% for HBV, 0.33% for HCV, and 0.66% for HIV. Multivariable analysis showed that use of an arteriovenous fistula and complete HBV vaccination (3-4 doses) were significantly associated with lower odds of HBV infection (OR = 0.012, 95% CI: 0.010-0.286, p = 0.007; OR = 0.008, 95% CI: 0.000-0.511, p = 0.023, respectively). In contrast, longer haemodialysis duration was significantly associated with increased HBV seropositivity (OR = 1.036, 95% CI: 1.012-1.061, p = 0.004). Despite the low prevalence of HBV, HCV, and HIV, prevention, surveillance, and strengthened vaccination strategies remain necessary in haemodialysis settings.
Prostate cancer often requires frequent in-person clinical visits, imposing substantial travel, financial, and time burdens for patients. Combining telehealth with in-home monitoring (enhanced telehealth) has the potential to make care more patient centered and efficient. To assess the feasibility and implementation context of enhanced telehealth for patients with prostate cancer. Adult patients with prostate cancer receiving androgen deprivation therapy (ADT) were enrolled in this multiphase quality improvement study of enhanced telehealth from June 1, 2023, to June 30, 2024, and followed up for 8 months. The study was conducted at 7 ambulatory oncology practice sites at Memorial Sloan Kettering, an academic comprehensive cancer center. Phase 1 included semistructured interviews with key stakeholders to assess implementation considerations of enhanced telehealth. Phase 2 piloted an enhanced telehealth program offering remote blood pressure (BP) monitoring, mobile phlebotomy, and injections at home; patients could choose to participate in any available component. Enhanced telehealth, a care delivery model that augments routine telehealth encounters with (1) home phlebotomy, (2) remote BP monitoring, and/or (3) at-home administration of ADT or other injectable therapies. The primary outcome was feasibility, assessed by completion rates for each enhanced telehealth component at the patient and visit levels. Patient and clinician satisfaction was assessed using the Net Promotor Score. Acceptability, appropriateness, and feasibility were measured using validated measures on a 5-point Likert scale. Thirty-eight patients participated; the median age was 70.0 years (IQR, 61.5-76.7 years) and 24 (63.2%) had metastatic castration-sensitive prostate cancer. Patient-level completion rates for at least 1 service were telehealth, 68.4% (26 of 38); remote BP monitoring, 91.9% (34 of 37); home phlebotomy, 96.3% (26 of 27); and at-home injections, 90.0% (9 of 10). Visit-level completion rates were high for telehealth (92.3% [60 of 65]), phlebotomy (95.4% [145 of 152]), and injections (84.6% [11 of 13]) but lower for BP monitoring (65.0% [343 of 528]). Patients rated all components as acceptable (mean [SD] score, 4.8 [0.4]; range, 3.25-5), appropriate (mean [SD] score, 4.8 [0.4]; range, 3.75-5), and feasible (mean [SD] score, 4.7 [0.5]; range, 3.25-5). Enhanced telehealth had high patient and clinician satisfaction (Net Promotor Score: patients, 82.4%; clinicians, 80.0% for telehealth, 80.6% for remote BP monitoring, 84.6% for home phlebotomy, and 75.0% for home injections). In this quality improvement study, enhanced telehealth was feasible, with greater than 60% completion for all scheduled visits, with strong endorsement of benefits from patients with prostate cancer as well as clinicians. These findings support further development of enhanced telehealth.
Hard-to-heal (chronic) diabetic foot ulcers (DFUs) are a major healthcare challenge worldwide. A combinatorial strategy may offer effective therapeutic potential. The present study investigated the effectiveness of a repairing gel containing platelet-rich plasma-fibrin glue (PRP-FG) and oral methylene blue (MB, administered as leucomethylene blue (LMB)) for hard-to-heal DFUs. This single-centre, self-controlled pilot study was conducted on patients with DFUs who met the inclusion criteria. All patients had not responded to standard therapies for at least four weeks. For 12 weeks, they received the repairing gel dressing and 35mg of MB dissolved in 200ml of infant formula milk (administered as LMB). Participants had weekly follow-up visits to assess their wound healing progress. A total of six patients took part; four participants completed the 12 weeks of treatment. At the end of the treatment period, the new intervention was compared to previous standard care. Participants demonstrated a reduced wound area and improved wound bed condition. A significant increase in transcutaneous oxygen tension was observed, indicating improved tissue oxygenation (p=0.034). Additionally, participants experienced reductions in wound exudate, pain and malodour within the first week of treatment. No serious adverse events were reported during the follow-up period. The findings of this pilot study suggest that combined therapy using a PRP-FG-containing repair gel and oral MB (as LMB) may provide a safe and effective approach to treating hard-to-heal DFUs. Further research is warranted to confirm these findings.
Introduction Ticagrelor is a widely used potent P2Y12 inhibitor in patients aged ≥75 years with acute coronary syndromes. Despite its widespread use, data on ticagrelor's safety in older adults remain limited. Material & methods We performed a retrospective pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) from 2010 to 2024. Disproportionality analysis compared ticagrelor with clopidogrel, assessing predefined adverse events in adults (<75 years) and older adults (≥75 years). For each group, reporting odds ratios (RORs) with 95% confidence intervals (CI) were calculated, and differences between age groups were evaluated interaction analysis. Results A total of 6,476 ticagrelor-related adverse event reports were included: 4,795 (74%) adults and 1,681 (26%) older adults. In older adults, ticagrelor was not associated with increased reporting of dyspnea, intracranial hemorrhage, complete atrioventricular block, or gout. Acute kidney injury (AKI) was the only event reported more frequently in older adults (ROR 2.3 [95% CI 1.5-3.6] vs. 0.6 [95% CI 0.4-0.9]; p<0.001). Ticagrelor was associated with lower reporting of gastrointestinal bleeding, hematuria, hemoptysis, and anemia in both age subgroups. Bradycardia and syncope were reported more frequently among adults (p=0.002 and p<0.001, respectively). Conclusion Ticagrelor appears generally safe in older adults (≥75 years), with no excess reporting of major adverse events compared to younger adults, aside from a higher reporting of AKI. Keywords ACS, anti-platelets, Ticagrelor, elderly, adverse effect.
BackgroundWomen's futsal has experienced significant growth, highlighting the importance of understanding psychological need satisfaction and burnout as key determinants of athlete well-being. Basic psychological needs satisfaction, according to Self-Determination Theory, and athlete burnout are key constructs in promoting healthy and sustainable sports environments. Foot injuries are also prevalent in high-intensity sports such as Futsal and may be related to psychological outcomes in athletes.ObjectivesThis study aimed to examine the relationship between psychological need satisfaction and burnout in female futsal players, and to explore associations between foot and ankle injuries (podiatric pathology), age, and sport experience with these psychological variables.DesignObservational, cross-sectional, descriptive study.MethodsNinety-four adult female futsal players from first and second national divisions participated. Participants completed a sociodemographic and injury questionnaire, the Athlete Burnout Questionnaire (ABQ), and the Psychological Needs in Sport Questionnaire (PNSQ-15). Injury history included ankle sprains, plantar fasciitis, Achilles tendinopathy, fifth metatarsal fractures, and anterior cruciate ligament ruptures. Data were analyzed using descriptive and correlational statistics.ResultsThe majority of players (85%) reported previous injuries, with ankle sprains (73.4%) and plantar fasciitis (35.1%) being most common. PNSQ-15 scores indicated high activation and concentration, with moderate confidence and motivation. Greater age and sport experience were associated with higher concentration and motivation. ABQ scores were moderate overall; more weekly training hours were associated with lower burnout in the dimensions of reduced sense of accomplishment and sport devaluation. Players with plantar fasciitis showed higher burnout scores, particularly in reduced sense of accomplishment (p=0.036).ConclusionFemale futsal players showed favorable psychological skills and moderate levels of burnout. Age, sport experience, and training load were associated with some psychological dimensions, while the presence of certain foot injuries was related to higher burnout scores. These findings suggest that psychological need satisfaction, training load, and injury history are interrelated factors influencing burnout and psychological well-being in female futsal players. Female futsal is growing rapidly, making it important to understand the psychological and physical factors that affect players’ well-being and performance. This study looked at how satisfaction of basic psychological needs such as feeling competent, connected, and autonomous relates to burnout, a state of emotional and physical exhaustion caused by prolonged stress. We also examined whether foot and ankle injuries influence burnout or psychological well-being. Ninety-four adult female futsal players completed questionnaires about their psychological skills, burnout levels, and previous injuries. Most players (85%) had experienced injuries, with ankle sprains and plantar fasciitis being the most common. Overall, players reported good psychological skills, especially in concentration and motivation. More experienced players showed better psychological outcomes. Players who trained more hours per week tended to have lower burnout, suggesting that regular engagement in sport can be protective. However, players with chronic foot injuries, like plantar fasciitis, showed higher burnout levels, indicating that persistent pain may negatively affect well-being. These findings highlight the importance of supporting both the psychological and physical health of female futsal players. Coaches and sports organizations should consider strategies that promote psychological skills, prevent injuries, and provide support for players dealing with chronic pain to maintain well-being and enhance performance.
Long-term (> 24 weeks) real-world evidence of eptinezumab's effectiveness is limited. We evaluated ≥ 50% and ≥ 75% response rates over 48 weeks in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM). EMBRACEIII (NCT05570149) is a prospective, multicenter, observational study. Adults with HFEM or CM who experienced ≥ 3 preventive treatment failures received eptinezumab 100 mg intravenously every 12 weeks, with optional 300 mg escalation after week 12 for inadequate response. Co-primary endpoints were ≥ 50% and ≥ 75% reductions in monthly migraine/headache days (MMD/MHD) at weeks 45-48 versus baseline. Secondary endpoints were changes in MMD/MHD, monthly analgesic intake (MAI), pain intensity (assessed using the numeric rating scale [NRS]), migraine-related disability and impact (assessed using the Headache Impact Test-6 [HIT-6], Migraine Disability Assessment [MIDAS], the Migraine Interictal Burden Scale-4 [MIBS-4]), patient-reported global treatment response (assessed using the Patient Global Impression of Change [PGI-C] questionnaire), and 100% response. Exploratory analyses assessed dose escalation, prior anti-calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) treatment failures, responders without adverse events, ≥ 30% reduction in the NRS during residual attacks, and clinically complex subgroups. Among the 261 patients (safety population) included in the study, 124 completed ≥ 48 weeks of treatment with eptinezumab. At week 48, the response rates for ≥ 50%, ≥ 75%, and 100% were 82.3%, 51.6%, and 9.7%, respectively. All secondary endpoints improved significantly (p < 0.001), with significant reductions from baseline: MMD/MHD, - 15.5; MAI, - 14.9; NRS, - 3.3; HIT-6, -  20.6; MIDAS, - 74; and MIBS-4, - 4.3. Also, 94.8% of patients reported PGI-C improvement. Dose escalation occurred in 69.4% of patients. Patients receiving ≥ 3 doses of 300 mg eptinezumab achieved outcomes comparable to responders receiving 100 mg. Among patients with prior anti-CGRP mAb treatment failures (51.6%), ≥ 50% and 100% responders were similar to mAb-naïve patients, whereas ≥ 75% response was lower (37.5%; p = 0.002). Response rates of ≥ 50%,  ≥ 75% and 100% were achieved by 81.2%, 50.4%, and 8.5%, respectively, in patients without adverse events; 85.7%, 51.4%, and 8.6% in patients with psychiatric comorbidities; 87.8%, 54.9%, and 7.3% in patients with CM with medication overuse; and 89.2%, 50.0%, and 7.1% in patients with CM with both conditions. Eptinezumab demonstrated sustained 48-week effectiveness, with high response rates of ≥ 75% and 100% in a difficult-to-treat population. Effectiveness was preserved in patients with prior anti-CGRP mAb failures after 300 mg escalation and in clinically complex subgroups. Many patients achieved ≥ 30% reduction in NRS during residual migraine attacks. ClinicalTrials.gov: NCT05570149.
This study aimed to evaluate whether preoperative nutritional risk, as measured by the NRS-2002 score, predicts hepatic regeneration after ALPPS in patients with HBV-related HCC. Among the 54 patients who completed both ALPPS stages, intervals to adequate regeneration were dichotomized (≤14 vs. >14 d). Logistic regression identified predictors of prolonged intervals, and a nomogram was developed. Univariable and multivariable logistic analyses revealed that the NRS-2002 score (≥3), resected-side portal vein thrombosis (PVT), and decreased prealbumin (pre-ALB) levels were independently identified as preoperative risk factors for prolonged intervals. The nomogram showed exploratory accuracy in estimating the prolonged interval, with an AUC of 0.905 (95% CI:0.828-0.981). It should be noted that the wide confidence intervals for the predictor odds ratios (e.g., NRS-2002 ≥3: OR = 11.406, 95% CI: 1.481-87.841) reflect the uncertainty inherent to the sample size, and the model may be susceptible to overfitting. However, the relatively wide confidence intervals for key predictors and the modest sample size warrant caution against overfitting, and external validation is required before clinical application. Correlation analysis revealed a statistically significant positive association was observed between standard future liver remnant (sFLR)/standard liver volume (SLV) before stage 1 and sFLR/SLV before stage 2. Patients with lower NRS-2002 scores had better survival outcomes than those with higher scores. Preoperative NRS-2002 score, prealbumin, and portal vein thrombosis may help identify patients with HBV-related HCC at risk for delayed regeneration after ALPPS. However, these findings require validation in intention-to-treat cohorts.
Anxiety and mood disorders, characterized by elevated negative affect (NA) and cognitive impairments, are highly prevalent among college students. Within-person (WP) NA variability, which captures moment-to-moment fluctuations in NA, provides unique insights into emotional processes that are not reflected in mean NA levels. Cognitive variability, particularly reaction time (RT) inconsistency, is increasingly recognized as a sensitive marker of cognitive health and functional integrity. Although prior research links NA to cognitive variability, the short-term dynamics of these associations in naturalistic settings remain understudied. College students provide an ideal population for examining these dynamics using ecological momentary assessment (EMA). This study investigated the association between WP NA and RT inconsistency, hypothesizing that higher WP fluctuations in NA would predict increased RT inconsistency. We also examined the moderating roles of practice effects and covariates, including neuroticism, insomnia, and sex. Using EMA, 99 university students completed morning and evening assessments over 14 days, including a cognitive task measuring RT inconsistency (standard deviation in trial-level RT) and self-reported NA. Multilevel modeling was used to assess WP fluctuations in NA and their impact on RT inconsistency, accounting for time (session number), between-person differences in NA, and covariates such as sleep problems, neuroticism, age, sex, and use of a touch device. WP fluctuations in NA significantly predicted increased RT inconsistency (exp(β)=1.022, 95% CI 1.008-1.037; P=.007), supporting the hypothesis that NA variability disrupts cognitive performance. Male students exhibited lower RT inconsistency than female students, with a small effect size (exp(β)=0.824, 95% CI 0.694-0.977; P=.049). Finally, EMA sessions were inversely associated with RT inconsistency, with a stronger effect up to session 3 (exp(β)=0.930, 95% CI 0.879-0.985; P=.03) than after session 3 (exp(β)=0.986, 95% CI=0.979-0.992; P<.001), indicating practice effects. Momentary fluctuations in NA influence cognitive variability, particularly in the early stages of repeated cognitive tasks, underscoring the role of emotional processes in cognitive performance. Practice effects and individual differences, such as sex and insomnia, influence these associations. These findings highlight the use of EMA for understanding cognitive-affective processes and suggest potential intervention targets, such as addressing NA, to improve cognitive functioning in emotionally vulnerable populations like college students.
Tuberculosis preventive treatment (TPT) is essential for tuberculosis elimination; however, evidence on its safety and feasibility in medically complex, high-risk populations is limited. Concerns regarding adverse events frequently hinder treatment initiation and completion in routine clinical practice. The Safety of Preventive Treatment in People at Risk for Tuberculosis (STEP-TB) study aims to generate real-world evidence on the safety of TPT among individuals at high risk of developing active tuberculosis disease and to identify factors associated with adverse events, treatment initiation, adherence, and completion. STEP-TB is a multicenter, prospective observational cohort study conducted at four university-affiliated hospitals in the Republic of Korea. Adults aged ≥19 years who are eligible for latent tuberculosis infection (LTBI) testing or TPT according to national guidelines will be enrolled, including individuals with chronic kidney disease, chronic lung disease, diabetes mellitus, immunosuppressive conditions, malignancy, or occupational risk. LTBI testing will be performed using interferon-gamma release assays, and TPT regimens will follow national guidelines. Participants initiating TPT will be followed for up to 12 months from treatment initiation. Those with negative LTBI results or without TPT will be also followed for up to 12 months. Adverse events, treatment adherence, and completion will be systematically assessed. Blood samples, including volumetric absorptive microsampling, will be collected in a subset of participants for pharmacokinetic and pharmacogenetic analyses. The primary outcome is the occurrence of adverse events during TPT. Secondary outcomes include TPT completion rates, predictors of non-initiation and discontinuation, and progression to active TB. STEP-TB will provide condition-specific, real-world evidence on TPT safety and implementation, informing clinical decision-making, patient-centered care, and national TB control policies to support the safe expansion of LTBI treatment strategies in Korea. CRIS Registration Number: KCT0011063.
A duplicated cystic duct draining a single gall bladder is an exceedingly rare congenital biliary anomaly. Fewer than 25 cases have been described in published literature, and the condition is almost never diagnosed before surgery. We report a 19-year-old male who presented with recurrent right upper quadrant pain. Abdominal ultrasonography confirmed cholelithiasis but revealed no biliary ductal abnormality. During elective laparoscopic cholecystectomy, meticulous dissection of Calot's triangle unexpectedly identified two separate cystic ducts, both draining a single gall bladder. Each duct was individually traced to confirm its distal course, then clipped and divided under direct vision after establishing the critical view of safety. The procedure was completed laparoscopically without complication. The patient was discharged on the post-operative day 2 and remained well at the follow-up. This case underscores that standard pre-operative imaging does not guarantee normal biliary anatomy and that systematic, unhurried dissection with a critical view of safety remains the only reliable safeguard against inadvertent bile duct injury.
To evaluate the oral health status of children with cerebral palsy (CP) in Türkiye and to examine the distribution of caries experience using the Significant Caries (SiC) Index to identify high-risk subgroups. This cross-sectional study included 51 children with CP receiving services from the Spastic Children's Foundation. Clinical examinations assessed dental caries using combined dft + DMFT scores, whilst lesion severity was evaluated using a three-category clinical classification mapped to ICDAS levels. Plaque accumulation was assessed using the Silness-Löe index. Caregivers completed structured questionnaires on oral hygiene practices, feeding habits, and dental attendance. Descriptive statistics were used. Continuous variables were expressed as mean ± SD or median (IQR). Categorical variables were expressed as frequencies and percentages with 95% confidence intervals. ICDAS-mapped lesion prevalence was 94% and the mean dft + DMFT score was 4.12 ± 3.59. Lesion severity distribution based on ICDAS-mapped categories showed a predominance of moderate lesions. The SiC value was 8.41, indicating a subgroup with markedly higher caries burden. Although 86% had a toothbrushing habit, only 43% brushed twice daily. Of those using toothpaste, 59% used fluoride-free children's toothpaste and 34% used adult toothpaste. Nighttime bottle use persisted in 55% and all with this habit had caries. The mean plaque index was 1.25 ± 0.99. No caregiver had received oral health education. Dental caries amongst children with CP in Türkiye are highly prevalent and concentrated in a high-risk subgroup identified by the SiC.