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Abstract Objective This study aimed to explore the impact of co‐antiseizure medication (co‐ASM) optimization on the effectiveness and tolerability of adjunctive cenobamate (CNB) in patients with drug‐resistant epilepsy in a real‐world setting. Methods This unicentric, retrospective, observational study included adults with focal‐onset seizures who had received ≥2 previous ASMs. The main effectiveness endpoints included responder rates and seizure frequency reduction at 3, 6, and 12‐month visits. The number of co‐ASMs and defined daily dose (DDD) were analyzed at every visit. Safety endpoints included adverse drug reactions (ADRs). Results Thirty‐four patients with a median epilepsy duration of 22 years and a median of 15.5 seizures/month were analyzed. The median number of prior ASMs was 12, and the mean number of co‐ASMs was 2.9 (SD 1). There was a reduction in seizure frequency/month from baseline to the last visit (p

Abstract The Addictions Neuroclinical Assessment (ANA) is a neurobiologically-informed framework designed to understand the etiology and heterogeneity of Alcohol Use Disorder (AUD). Previous studies validated the three neurofunctional domains of ANA: Incentive Salience (IS), Negative Emotionality (NE) and Executive Function (EF) using secondary data. The present cross-sectional observational study assessed these domains in an independent, prospective clinical sample. Adults across the drinking spectrum (N = 300) completed the ANA battery, a standardized collection of behavioral tasks and self-report assessments. Factor analyses were used to identify latent factors underlying each domain. Associations between identified domain factors were evaluated using structural equation models. Receiver operating characteristics analyses were used to determine factors with the strongest ability to classify individuals with problematic drinking and AUD. We found (1) two factors underlie the IS domain: alcohol motivation and alcohol insensitivity. (2) Three factors were identified for the NE domain: internalizing, externalizing, and psychological strength. (3) Five factors were found for the EF domain: inhibitory control, working memory, rumination, interoception, and impulsivity. (4) These ten factors showed varying degrees of cross-correlations, with alcohol motivation, internalizing, and impulsivity exhibiting the strongest correlations. (5) Alcohol motivation, alcohol insensitivity, and impulsivity showed the greatest ability in classifying individuals with problematic drinking and AUD. Thus, the present study identified unique factors underlying each ANA domain assessed using a standardized assessment battery. These results revealed additional dimensionality to the ANA domains, bringing together different constructs from the field into a single cohesive framework and advancing the field of addiction phenotyping. Future work will focus on identifying neurobiological correlates and identifying AUD subtypes based on these factors.

The field of cholangioscopy is undergoing rapid evolution, marked by continuous innovation. The advent of SpyGlass cholangioscopy has initiated a new chapter, transforming the practice with advancements that include single-operator procedures and the introduction of disposable cholangioscopes. Despite these strides, significant needs remain, including enhancement of optical imaging, improving maneuverability, and expansion of therapeutic channels. This article delves into the recent progress within cholangioscopy, with a particular focus on the clinical applications of the Leinzett Lan-EP-3516 cholangioscope for the management of portal biliopathy. We present a detailed case study demonstrating how this cutting-edge cholangioscope—distinguished by its various sizing options and compatibility with portable devices for immediate imaging—played an important role in the successful treatment of a distal common biliary duct stricture and choledocholithiasis. The device's cost-effectiveness and superior imaging quality signify a notable advancement in cholangioscopic technology, facilitating enhanced treatment pathways for patients with complex biliary disorders. This case exemplifies the dynamic and expanding utility of cholangioscopy in therapeutic interventions and underscores its escalating significance in clinical settings.

Physical manipulatives (PMs) are concrete objects used during hands-on learning activities (e.g., building blocks, fraction tiles, counters), and are widely used in primary-school teaching, especially during maths instruction. This scoping review collated studies that have examined the effectiveness of educational PM interventions with pre-primary and primary-age children. A total of 102 studies met the inclusion criteria and were synthesised in the review. Most studies included a sample of children aged 4-6 years and were conducted in a school setting. They spanned 26 different countries, but almost all took place in high- or middle-income contexts, mainly in the USA. Interventions were grouped into three main learning domains: maths, literacy and science. Considerable heterogeneity was identified across the review studies in terms of the PMs and hands-on activities used (e.g., block building, shape sorting, paper folding, enactment with figurines). Evidence relating to effectiveness of the intervention programmes was synthesised, with the most promising findings identified in the maths domain. Benefits to children's spatial, literacy and science skills were also reported. Overall, however, the evidence was mixed: other studies found that PMs were not associated with learning benefits, and many were hindered by methodological shortcomings. This calls for caution when drawing conclusions about the overall effectiveness of PM interventions. Nevertheless, the findings illustrate the many ways hands-on PM activities can be incorporated into children's early learning experiences. Recommendations for further research and for using PMs in practice are made.

The first Asia-Pacific consensus recommendations for endoscopic and interventional management of hilar cholangiocarcinoma were published in 2013. Since then, new evidence on the role of endoscopy for management of malignant hilar biliary obstruction (MHBO) has emerged. To update the recommendation, we reviewed the literature using a PICO (population/intervention/comparison/outcomes) framework and created consensus statements. The expert panel voted anonymously using the modified Delphi method and all final statements were evaluated for the quality of evidence and strength of recommendation. The important points with inadequate supporting evidence were classified as key concepts. There were seven statements and five key concepts that reached consensus. The statements and key concepts dealt with multiple aspects of endoscopy-based management in MHBO starting from diagnosis, strategies and options for biliary drainage, management of recurrent biliary obstruction, management of cholecystitis after biliary stenting, and adjunctive treatment before stenting. Although the recommendations may assist physicians in planning the treatment for MHBO patients, they should not replace the decision of a multidisciplinary team in the management of individual patients.

Background: This study aims to evaluate the effectiveness of the OSCEai, a large language model-based platform that simulates clinical encounters, in enhancing undergraduate medical education. Methods: A web-based application, OSCEai, was developed to bridge theoretical and practical learning. Following use, medical students from the University of Calgary Class of 2026 completed an anonymized survey on the usability, utility, and overall experience of OSCEai. Results: A total of 37 respondents answered the anonymized survey. The OSCEai platform was highly valued for its ability to provide data on demand (33/37), support self-paced learning (30/37), and offer realistic patient interactions (29/37). The ease of use and medical content quality were rated at 4.73 (95% CI: 4.58 to 4.88) and 4.70 (95% CI: 4.55 to 4.86) out of 5, respectively. Some participants (8/37) commented that few cases were not representative and needed clarification about app functionality. Despite these limitations, OSCEai was favorably compared to lecture-based teaching methods, with an overall reception rating of 4.62 (95% CI: 4.46 to 4.79) out of 5. Interpretation: The OSCEai platform fills a gap in medical training through its scalable, interactive, and personalized design. The findings suggest that integrating technologies, like OSCEai, into medical curricula can enhance the quality and efficacy of medical education.

Stress plays a well-documented role in alcohol consumption and the risk for developing alcohol use disorder. The concept of resilience - coping with and successfully adapting to stressful life experiences – has received increasing attention in the field of addiction research in recent decades, and there has been an accumulation of evidence for resilience as a protective factor against problematic alcohol consumption, risk for alcohol use disorder, disorder severity, and relapse. The conceptual and methodological approaches used in the generation of this evidence vary considerably across investigations, however. In light of this, we carried out this review in order to provide a more thorough understanding of the meaning and scope of resilience, what factors contribute to resilience, how it is measured, and how it relates to alcohol-associated phenotypes. Implications for treatment through the use of resilience-building interventions are likewise discussed, as well as implications for future research on the role of resilience in the etiology and clinical outcomes of alcohol use disorder.

Background. The patency of the pharyngeal airway has a far-reaching impact on craniofacial development. Conversely, the position of the maxillofacial skeletal components in certain disorders may lead to a compromised airway. Therefore, the evaluation of the airway is an essential step in treatment planning. Objectives. The basic aim of this study was to measure the pharyngeal air space volume in the patients with maxillofacial skeletal abnormalities (like Class II, Class III malocclusion, TMJ Ankylosis, Condylar abnormalities and Syndromic cases) and those without any skeletal abnormalities. The objectives were to assess the Linear, Cross-sectional, and Volumetric dimensions of the pharyngeal airway in patients with and without maxillofacial skeletal abnormalities. (Study and Control group) Materials and methods. The Study group included 49 patients with maxillofacial Skeletal abnormalities like Class II and Class III malocclusion, Temporomandibular Joint Ankylosis, Condylar abnormalities, Syndromic cases. 49 Control group patients did not present with any skeletal abnormalities. The Linear, Cross-sectional, and Volumetric dimensions of the pharyngeal airway in the Study group and Control group were calculated and compared within the groups. Statistical Analysis: Unpaired t -test, ANOVA test and Tukey’s Post Hoc analysis test were for the data analysis of the above study. Outcomes. The Anteroposterior dimension of the airway at the Superiormost level was found to be significantly greater in Class II (p-value-0.039), Class III (p-value-0.002), and Control groups (p-value

Resumen: Introducción-objetivos: Analizar los resultados clínicos y la supervivencia tras el implante de asistencia ventricular de larga duración en pacientes pediátricos en situación de insuficiencia cardiaca terminal. Métodos: Entre enero de 2006 y noviembre 2021 se implantaron 34 dispositivos Berlin Heart EXCOR® en pacientes pediátricos. Analizamos las características preoperatorias, las intraoperatorias y las complicaciones tras el implante, así como la evolución de los pacientes (trasplante o fallecimiento). Estudio estadístico con STATA IC 15. Resultados: Edad media 51 ± 53 meses (1-180), peso medio 17 ± 16 kg (2,2-65). La cardiopatía de base fue miocardiopatía en el 68% y cardiopatía congénita en el 32%. Inicialmente el Berlin Heart EXCOR® implantado fue univentricular en el 65% de los pacientes. La indicación de implante fue puente a trasplante en el 97%. Duración media de soporte 92 ± 105 días (1-511). Complicaciones frecuentes: 62% infecciosas, 44% neurológicas (29% isquémicas y 15% hemorrágicas). Mortalidad de ictus hemorrágicos 80% y de isquémicos 20%. A partir de 2019, cuando se sustituyó la heparina por bivalirudina, los eventos neurológicos disminuyeron y no ha habido muertes por causa neurológica. El 71% han sido trasplantados y el 29% han fallecido. Conclusiones: Ante el creciente número de pacientes pediátricos en situación de insuficiencia cardiaca terminal, ha aumentado el uso del dispositivo Berlin Heart EXCOR®, especialmente como puente a trasplante. Los eventos neurológicos, sobre todo hemorrágicos, son los más temidos por su alta mortalidad. Por eso, la terapia antitrombótica continúa siendo el principal reto. A pesar de ello, supone una alternativa esperanzadora como asistencia de larga duración en población pediátrica, y permite llegar al trasplantarse al 71% de ellos. Abstract: Background and aim: The aim is to analyse clinical and survival results after the implant of a long-term mechanical assist device in pediatric patients in the end stages of heart failure. Methods: Between January 2006 and November 2021 34 Berlin Heart EXCOR® devices were implanted in pediatric patients. We analysed preoperative and intraoperative characteristics, together with complications after implant. Outcomes were also evaluated (transplant vs. death). Statistical analysis with STATA IC 15. Results: The mean age was 51 ± 53 months (1-180), mean weight 17 ± 16 kg (2.2-65). Underlying heart disease was myocardiopathy in 68% and congenital heart disease in 32%. The Berlin Heart EXCOR® device was univentricular in 64% of the patients. Surgical indication was bridge to transplant in 97%. Mean duration of mechanical support was 92 ± 105 days (1-511). Postoperative complications were common: 62% infectious and 44% neurological (29% ischaemic and 15% haemorrhagic). Mortality of haemorrhagic strokes 80%, ischaemic 20%. Since 2019, when heparin was changed to bivalirudin, no mortal strokes were observed. 71% of the patients has been transplanted, 29% has died. Conclusions: As a response to the increasing number of paediatric patients in end stages of congestive heart failure, the use of the Berlin Heart EXCOR® device has spread, especially if the intention is to use it as bridge to transplant. Neurological events, mostly haemorrhagic, are the most feared because of high mortality. Nevertheless, it is an encouraging alternative as a long-term mechanical assist device in children, allowing them to reach the transplant in 71% of the cases.

Abstract Early life stress (ELS) significantly increases susceptibility to alcohol use disorder (AUD) by affecting the interplay between the executive and the salience networks (SNs). The link between AUD and higher body-mass index (BMI) is known, but we lack understanding of how BMI impacts the relationship between ELS and brain connectivity in individuals with AUD. To bridge this gap, we investigated the main and interaction effects of ELS and BMI on brain connectivity in individuals with AUD compared to non-AUD participants (n = 77 sex-matched individuals per group). All participants underwent resting-state functional magnetic resonance imaging, revealing intriguing positive functional connectivity between SN seeds and brain regions involved in somatosensory processing, motor coordination and executive control. Examining the relationship of brain connectivity with ELS and BMI, we observed positive associations with the correlations of SN seeds, right anterior insula (RAIns) and supramarginal gyrus (SMG) with clusters in motor [occipital cortex, supplementary motor cortex]; anterior cingulate cortex (ACC) with clusters in frontal, or executive, control regions (middle frontal gyrus; MFG, precentral gyrus) that reportedly are involved in processing of emotionally salient stimuli (all |β | > 0.001, |p |

Abstract Background and Objectives Ethanol has been reported to improve tremor severity in approximately two thirds of patients with essential tremor (ET), but the accuracy of that proportion is not certain and the mechanism of action is unknown. The goal of this study was to investigate alcohol response on tremor by applying an a priori objective response definition and subsequently to describe the responder rate to a standardized ethanol dose in a cohort of 85 ET patients. A secondary analysis evaluated other tremor and nontremor features, including demographics, tremor intensity, breath alcohol concentration, nontremor effects of alcohol, self‐reported responder status to ethanol, and prior ethanol exposure. Methods This was a prospective, open‐label, single‐dose challenge of oral ethanol during which motor and nonmotor measurements were obtained starting immediately prior to ethanol administration and subsequently every 20 min for 120 min. We defined tremor reduction as a 35% decline in power in the patient's tremor frequency recorded during spiral drawing 60 min after ethanol administration. Results In total, 80% of patients were considered alcohol responsive using our objective definition. Responder status and change in the objective tremor metrics were significantly correlated with the change in breath alcohol concentration levels after ethanol administration, but no other relationships to nontremor metrics were found. Discussion A high percentage of patients actually respond to acute ethanol. However, their self‐reported response does not correlate well with their objective response. Objective response correlates with breath alcohol level but not with sedation, indicating a specific effect of ethanol on tremor.

Some styles of alcohol consumption are riskier than others. How the level and rate of alcohol exposure contribute to the increased risk of alcohol use disorder is unclear, but likely depends on the alcohol concentration time course. We hypothesized that the brain is sensitive to the alcohol concentration rate of change and that people at greater risk would self-administer faster. We developed a novel intravenous alcohol self-administration paradigm to allow participants direct and reproducible control over how quickly their breath alcohol concentration changes. We used drinking intensity and the density of biological family history of alcohol dependence as proxies for risk. Thirty-five alcohol drinking participants aged 21-28 years provided analytical data from a single, intravenous alcohol self-administration session using our computer-assisted alcohol infusion system rate control paradigm. A shorter time to reach 80 mg/dl was associated with increasing multiples of the binge drinking definition (p = 0.004), which was in turn related to higher density of family history of alcoholism (FHD, p = 0.04). Rate-dependent changes in subjective response (intoxication and stimulation) were also associated with FHD (each p = 0.001). Subsequently, given the limited sample size and FHD range, associations between multiples of the binge drinking definition and FHD were replicated and extended in analyses of the Collaborative Study on the Genetics of Alcoholism database. The rate control paradigm models binge and high-intensity drinking in the laboratory and provides a novel way to examine the relationship between the pharmacokinetics and pharmacodynamics of alcohol and potentially the risk for the development of alcohol use disorders.

Abstract Objectives Although countries like Japan and South Korea have implemented nationwide endoscopic screening programs, there is limited evidence on the effectiveness of endoscopy for diagnosing early gastric cancer (EGC) in developing countries such as India. In the present study, we aimed to determine the feasibility of endoscopic detection of EGC from India. Methods The data was prospectively collected for all patients ≥40 years who underwent a diagnostic upper endoscopy from April to September 2021. A single endoscopist who performed the endoscopic procedures completed 1‐month training in advanced endoscopy in Japan. Following the training, the endoscopist continued to engage in internet‐based discussions regarding his cases encountered. Prior to this training, the endoscopist had not detected any EGC cases during his 12‐year gastroenterology practice. Results A total of 1033 patients were included in the study, with males accounting for 65.4% and a mean age 52 years. The average procedural time was 7.13 ± 4.8 min. A total of 25 patients (2.4%) were found to have GC, including 6 patients (0.6%) with EGC. Two patients had synchronous EGC lesions. All EGC patients were males, with an average age of 66 years. All EGCs were detected in the distal stomach in the presence of Helicobacter pylori infection and severe atrophic gastritis. Conclusion Our findings showed that the endoscopic detection of EGC is feasible in India. Optimal training on endoscopic diagnosis of EGC can improve the detection of such lesion. Further studies are warranted to assess the optimization and implementation of an endoscopic screening program for EGC in India.

Abstract Background and Aims Fluoroscopy‐free endoscopic retrograde cholangiopancreatography for common bile duct stone (CBDS) clearance is usually offered only to pregnant patients. We initiated a multicenter, randomized controlled trial comparing clearance of non‐complex CBDSs using fluoroscopy‐free direct solitary cholangioscopy (DSC) to standard endoscopic retrograde cholangiography (ERC) to evaluate the wider applicability of the DSC‐based approach. Here we report the initial results of stone clearance and safety in roll‐in cases for the randomized controlled trial. Methods Twelve expert endoscopists at tertiary care centers in four countries prospectively enrolled 47 patients with non‐complex CBDSs for DSC‐assisted CBDS removal in an index procedure including fluoroscopy‐free cannulation. Successful CBDS clearance was first determined by DSC and subsequently validated by final occlusion cholangiogram as the ERC gold standard. Results Fully fluoroscopy‐free cannulation was successful in 42/47 (89.4%) patients. Brief fluoroscopy with minimal contrast injection was used in 4/47 (8.5%) patients during cannulation. Cannulation failed in 1/47 (2.1%) patients. Fluoroscopy‐free complete stone clearance was reached in 38/46 (82.6%) cases. Residual stones were detected in the validation ERC occlusion cholangiogram in three cases. Overall serious adverse event rate was 2.1% (95% confidence interval 0.1–11.3): postprocedural pancreatitis in one patient. Conclusions In patients with non‐complex CBDS, the fluoroscopy‐free technique is easily transferred to endoscopic retrograde cholangiopancreatography experts with acceptable rates of cannulation and stone clearance and few serious adverse events. (ClinicalTrials.gov number, NCT03421340)

Introduction: Intraoperative squash smear cytology is a useful diagnostic tool in case of CNS lesions. In resource poor countries where frozen section is unavailable, cytology is the mainstay method in giving a rapid intraoperative diagnosis which helps Surgeons regarding the extent of excision. The current study aims to assess the feasibility and accuracy of intraoperative squash cytology in evaluation of CNS tumors. Definitive diagnosis is confirmed by histopathological examination. Materials and methods: This retrospective observational study was carried out at Department of Neuropathology. All patients diagnosed with space occupying lesion (SOL) in CNS were enrolled in the study. Intra-operative cytological diagnosis was compared to histopathological diagnosis. WHO classification of CNS tumors 2021 was used to classify tumors. Results: Total seventy patients with intracranial SOLs were enrolled in this study who were operated for the same and their specimens were examined. Two samples were found to be inadequate and not included in final analysis. Mean age was 38.8 ± 17.85 (SD). Male–female ratio was 1.5:1 with 41 (60.3%) males and 27 (39.7%) females. 58 had neoplastic and rest 10 had non-neoplastic lesions. Complete concordance was achieved in 61 cases (Diagnostic Accuracy-88.2%). 3 (4.4%) cases showed partial concordance and 4 (5.9%) were discordant. For detection of malignant lesions through squash smear cytology overall Sensitivity was 73.9%, Specificity-97.8%, Positive Predictive Value-94.4% and Negative Predictive Value-88%. Conclusions: Squash smear cytology is a simple, rapid and cost-effective method relying solely on the expertise of pathologist. High diagnostic accuracy can be achieved with squash cytology by taking clinical and radiological findings into consideration.

PurposeTo evaluate the gender and racial diversity of plenary session speakers in the annual meetings of Society of Abdominal Radiology (SAR) over 2016 to 2020.Materials and methodsThe brochures of the SAR annual meetings were reviewed for plenary session speakers and titles. Publicly available institutional profiles and social media were reviewed by the investigator in order to infer gender and race. Gender assessments were men, women, transgender men, transgender women or gender non-binary. Race was classified as White, Black or African American, American Indians and Alaskan Natives, Asian, Native Hawaiian and Pacific Islander and Multiracial. Statistical analysis was performed using chi square and T-tests.ResultsBased on self-reported data, the SAR has 64% male and 36% female members. Over 2016-2020, plenary session speakers were more likely to be men [69.6% (183/263)] than women [30.4% (80/263)] (p-value = 0.0007). No speakers could be reliably identified as transgender, gender non-binary or gender expansive. In 2016, there were 24% women plenary speakers. This proportion was 28% in 2017, 33% in 2018 and 36% in 2019, and 30% in 2020. When assessing racial distribution, white speakers accounted for the majority of plenary speakers, ranging from 61 to 78%. Asians speakers accounted for 22 to 35%. There were no Black and African American, American Indian & Alaskan Native, Native Hawaiian & Pacific Islander plenary speakers (0%). Multiracial speakers were represented from 2018 to 2020, accounting for 2-4% speakers (p-value

Hypoplastic left heart syndrome (HLHS) continues to be a challenge in terms of morbimortality. Norwood-Sano surgery has been classically the correction of choice, the introduction of new techniques like biventricular repair, in favorable cases, and hybrid procedures as a step prior to cardiac transplantation have not improved the univentricular results. Technological advances and improvements in anticoagulation therapies have made possible to implant ventricular assist devices (VAD) during the neonatal period. This has motivated us to start a left VAD program in an animal model of HLHS. Our objective is to use long term VAD in a biventricular condition in patients with HLHS as a bridge to cardiac transplantation. Although the conditions have not been met to start a program for patients, the initial results show that the technique is feasible in pigs. We believe that this line of research is worth exploring as cardiac transplant in conditions of biventricular physiology could be less risky and offer better results than the classical univentricular path. Resumen: El síndrome del corazón izquierdo hipoplásico (SCIH) continúa siendo un reto en términos de morbimortalidad. La cirugía clásica de Norwood-Sano continúa siendo de elección y la introducción de nuevas técnicas como la reparación biventricular en los casos más favorables y los procedimientos híbridos para poder optar a un trasplante cardiaco posterior, no han conseguido una mejora en los resultados de la cirugía univentricular clásica. El avance de la tecnología y la terapia anticoagulante en los últimos años ha hecho realidad la asistencia ventricular mecánica (AVM) de larga duración en el periodo neonatal. Por estos motivos hemos iniciado un programa de implante de AVM izquierda en un modelo animal de hipoplasia de SCIH. Con el objetivo de que en un futuro la SCIH se pueda trasplantar en condiciones de biventricularidad, con el implante de una AVM izquierda de larga evolución. Los resultados iniciales muestran que técnicamente es posible en cerdos y, aunque actualmente no se dan las condiciones para iniciar un programa de este tipo en pacientes, pensamos que es una vía para seguir investigando, porque creemos que, el trasplante cardiaco en condiciones de biventricularidad, puede ser una opción con menos riesgos y mejores resultados que la vía univentricular.