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BACKGROUND: Tebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive for HLA-A*02:01 and have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported a long-term survival benefit associated with the drug. METHODS: We report the 3-year efficacy and safety results from our open-label, phase 3 trial in which HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma were randomly assigned in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigators choice of therapy with pembrolizumab, ipilimumab, or dacarbazine (control group), with randomization stratified according to the lactate dehydrogenase level. The primary end point was overall survival. RESULTS: At a minimum follow-up of 36 months, median overall survival was 21.6 months in the tebentafusp group and 16.9 months in the control group (hazard ratio for death, 0.68; 95% confidence interval, 0.54 to 0.87). The estimated percentage of patients surviving at 3 years was 27% in the tebentafusp group and 18% in the control group. The most common treatment-related adverse events of any grade in the tebentafusp group were rash (83%), pyrexia (76%), pruritus (70%), and hypotension (38%). Most tebentafusp-related adverse events occurred early during treatment, and no new adverse events were observed with long-term administration. The percentage of patients who discontinued treatment because of adverse events continued to be low in both treatment groups (2% in the tebentafusp group and 5% in the control group). No treatment-related deaths occurred. CONCLUSIONS: This 3-year analysis supported a continued long-term benefit of tebentafusp for overall survival among adult HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. (Funded by Immunocore; IMCgp100-202 ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.).

We describe a 9-year-old male who suffered a linear, non-displaced scaphoid fracture following a pedestrian motor vehicle accident. Initially, X-ray imaging failed to detect the fracture, but MRI confirmed the diagnosis, highlighting the challenges in identifying scaphoid fractures in pediatric patients due to the bone's cartilaginous nature in this age group. The patient was treated with immobilization using a Plaster of Paris cast, consistent with standard management for non-displaced fractures in children. He experienced pain improvement and achieved bone union after eight weeks, returning to normal activities without complications. The discussion emphasizes the rarity of scaphoid fractures in children under 10 and underscores the increasing incidence of such injuries in pediatric populations due to sports participation. A comparative analysis of similar cases in children of different ages is included, demonstrating variations in fracture types, treatment approaches, and outcomes, providing valuableinsights into the management of pediatric scaphoid fractures.

Our case details the atypical presentation of postpartum pituitary apoplexy in a 20-year-old female, who exhibited general weakness, dizziness, and brief loss of consciousness following an uncomplicated vaginal delivery. Despite normal vital signs except for bradycardia, imaging revealed a pituitary hemorrhage, leading to the diagnosis of pituitary apoplexy. Managed conservatively with IV hydrocortisone and intensive care, the patient experienced persistent bradycardia and severe abdominal pain, requiring transfer to another ICU. This case highlights the diagnostic challenges posed by the rarity and complexity of pituitary apoplexy during pregnancy and the postpartum period, emphasizing the importance of early diagnosis and tailored treatment strategies. The discussion further contrasts this case with existing literature, particularly in the context of postpartum pituitary apoplexy, and explores the broader implications for managing such rare cases, reinforcing the viability of conservative management in the absence of visual field disturbances.

Introduction: Leiomyosarcoma (LMS) is a malignancy with smooth muscle differentiation. Metastatic LMS is associated with poor prognosis and limited efficacy of systemic treatment. Novel treatment modalities are desperately needed for this entity. Case Presentation: We report the first use of pembrolizumab plus pharmacologic ascorbate in 3 patients with metastatic LMS. All cases resulted in persistent objective responses and disease control significantly better than has been reported with chemotherapy or other immunotherapeutic approaches. Three patients with metastatic LMS, one each of uterine, vascular, and soft tissue origin, were treated with pembrolizumab plus pharmacologic ascorbate. The patient with uterine LMS received combination therapy at presentation and had persistent response for 12 months, which is ongoing. The patient with metastatic LMS of the inferior vena cava received combination therapy at presentation and had persistent response for 12 months, at which time new metastases were found. The patient with soft tissue LMS had disease progression on pembrolizumab monotherapy prior to the addition of ascorbate, after which she had a 17-month response, which is ongoing. No side effects attributed to treatment were reported. Conclusion: Pembrolizumab plus pharmacologic ascorbate is a novel immunotherapeutic approach and warrants further study in LMS.

Abstract Background Diabetes mellitus (DM) is a major public health concern with considerable morbidity and mortality. DM affects patients’ quality of life and can lead to multiple complications, including chronic kidney disease (CKD) and the need for dialysis. Higher patient activation can improve health outcomes in hemodialysis patients with DM. This study aimed to explore the factors associated with higher patient activation and health-related quality of life (HRQoL) among hemodialysis patients with DM. Methods This was a cross-sectional, questionnaire-based study conducted on hemodialysis patients with DM in Palestine. The quota sampling method was utilized to draw samples from six dialysis centers. The questionnaire consists of three sections. The first section includes demographic, socioeconomic and clinical questions. The second section utilizes the patient activation measure-13 (PAM-13) to measure patient activation, while the third section assesses HRQoL using the EQ-5D-5 L tool and the visual analog scale (VAS). Mann‒Whitney and Kruskal‒Wallis tests were employed to examine the relationships between variables at the bivariate level, and multiple regression analysis was employed at the multivariate level. Results Of the 200 patients who were approached, 158 were included. The median PAM, EQ-5D index, and VAS score were low at 51.0, 0.58, and 60.0, respectively. A higher PAM score was independently associated with a higher household income level and taking medications independently. A higher EQ-5D index was associated with taking more than eight medications, taking medications independently, living with fewer than three comorbid conditions, and having a higher PAM. A higher VAS score was associated with being married, and receiving less than 3.5 hours of hemodialysis. Conclusions A higher patient activation level was associated with a higher income level and independence in taking medications. Interventions designed to improve patient activation, such as medication management programs, should address these factors among the target population. Longitudinal studies are needed to assess the time effect and direction of causation between health status and patient activation.

This study aims to demonstrate the electronic payment channels applied in Jordanian Islamic banks and their impact on the profitability of these banks during the period 2015-2020. The study used the descriptive analytical approach to reach the objectives of the study. The study included three Jordanian Islamic banks, One of the most important results of the study that there is a statistically significant effect of mobile phone applications, ATMs, and internet banking in Jordanian Islamic banks on the ROA, and that there is no statistically significant effect of all electronic payment channels in Jordanian Islamic banks on the ROE. The study recommended that the Islamic banks should make intensive marketing efforts to attract many dealers to increase the volume of transactions in electronic payment channels, work to increase their banking technological awareness, and encourage innovation in the field of electronic payment.

IntroductionCarotenoids are naturally occurring pigments in plants and are responsible for the orange, yellow, and red color of fruits and vegetables. Carrots are one of the primary dietary sources of carotenoids. The biological activities of carotenoids in higher organisms, including their immunomodulatory activities, are well documented in most tissues but not the large intestine. The gastrointestinal barrier acts as a line of defense against the systemic invasion of pathogenic bacteria, especially at the colonic level.MethodsTo test whether carotenoids in orange carrots can alleviate obesity-associated gut inflammation and strengthen the intestinal barrier function, male C57BL/6J mice were randomized to one of four experimental diets for 20 weeks (n = 20 animals/group): Low-fat diet (LFD, 10% calories from fat), high-fat diet (HFD, 45% calories from fat), HFD with white carrot powder (HFD+WC), or HFD with orange carrot powder (HFD + OC). Colon tissues were harvested to analyze the biochemical effects of carotenoids in carrots. The distal sections were subjected to isobaric labeling-based quantitative proteomics in which tryptic peptides were labeled with tandem mass tags, followed by fractionation and LC-MS/MS analysis in an Orbitrap Eclipse Tribrid instrument.ResultsHigh-performance liquid chromatography results revealed that the HFD+WC pellets were carotenoid-deficient, and the HFD+OC pellets contained high concentrations of provitamin A carotenoids, specifically α-carotene and β-carotene. As a result of the quantitative proteomics, a total of 4410 differentially expressed proteins were identified. Intestinal barrier-associated proteins were highly upregulated in the HFD+OC group, particularly mucin-2 (MUC-2). Upon closer investigation into mucosal activity, other proteins related to MUC-2 functionality and tight junction management were upregulated by the HFD+OC dietary intervention.DiscussionCollectively, our findings suggest that carotenoid-rich foods can prevent high-fat diet-induced intestinal barrier disruption by promoting colonic mucus synthesis and secretion in mammalian organisms. Data are available via ProteomeXchange with identifier PXD054150.

This study examines the impact of Artificial Intelligence (AI) on the field of education, with particular focus on its implications for academic integrity and the adoption of comprehensive assessment approaches. This research fits within the specific setting of university students and faculty members in the Kingdom of Bahrain.MethodsA cross-sectional survey was designed to examine the impact Artificial Intelligence (AI) in field of education, with particular focus on its implications for academic integrity and the adoption of comprehensive assessment approaches. A total of 218 participants were randomly selected from 250 employed in this survey study.ResultsOut of 250 invited participants, 203 responded to the survey. This study evaluated the influence of Educational Impact (EI), Policy and Ethics (PE), and Pedagogical Implications (PI) on Academic Outcomes (AO). Results revealed a significant association between EI → AO with a beta of 0.490, t-value of 4.504, and p

Background In this open-label, randomized, non-comparative, multicenter phase II study (Alliance A091401) we report on three expansion cohorts treated with nivolumab (N) with and without ipilimumab (N+I) and provide a multi-omic correlative analysis of actionable biomarkers.Methods Patients were randomized (non-comparative) to receive either N or N+I. The primary endpoint was a 6-month confirmed response rate (CRR) defined by Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included treatment-related adverse events (TRAEs), progression-free survival, and overall survival. Multi-omic correlative analyses were conducted using samples from both the primary and expansion cohorts.Results A total of 66 patients were evaluated for the primary endpoint with disease including gastrointestinal stromal tumor (GIST, n=18), undifferentiated pleomorphic sarcoma (UPS, n=24), and dedifferentiated liposarcoma (DDLPS, n=24). Neither N nor N+I achieved a complete or partial response in the GIST expansion cohort. In DDLPS and UPS, the primary response endpoint of CRR was met with N+I (both 16.6%, 2/12) but not with N alone (both 8.3%, 1/12). In the GIST cohort, TRAE was higher with N+I treatment, halting enrollment as required per protocol. In a correlative analysis of patients for the expansion cohort and the original cohort (n=86), traditional biomarkers of immunotherapy response were not correlated with response in any histological subtype. Markers of genomic instability including the presence of gene fusions and increased subclonal mutations correlated with improved clinical outcomes.Conclusions This expansion cohort reaffirms the outcomes of A091401. There remains a pressing need to determine the role of and predictive biomarkers for immunotherapy in sarcoma.Trial registration number NCT02500797.

خلفية البحث: تتطلب إمكانية قبول الطعم الجلدي بواسطة سرير الجرح اتصالاً مباشراً بين الاثنين للسماح بالانتشار الأمثل للمواد المغذية. إن تثبيت الطعم مفيد لهذا الغرض في منع تشكل الورم المصلي والتمزق. ومن طرق التثبيت المستخدمة الخياطة باستخدام القطب العابرة، تتضمن الخياطة العابرة وضع الغرز الأساسية على سطح الطعم، وقطب أخرى عابر بين مركز الطعم والسرير المستقبل معاً، لزيادة الثباتية والالتصاق على الأرضية وبالتالي تكييفه جيدًا مع السرير المتلقي. الهدف: هدفنا في هذه الدراسة إلى تقييم فعالية الضماد الضاغط مقارنة بالقطب الجلدية العابرة في تثبيت الطعوم الجلدية كاملة السماكة من حيث زمن الشفاء التام ونسبة حدوث المضاعفات. مواد وطرائق البحث: بـعـد موافقة المرضى على الدخول في عينة الدراسة، أجري تنضير جيد لسرير الجرح وبعدها أجري طعم كامل السماكة للجرح وتم تطبيق الضماد. تم توزيع المرضى عشوائياً الى مجموعتين، في المجموعة الأولى: المرضى الذين أجري لهم طعم جلدي كامل السماكة مع تطبيق ضماد ضاغط. وفي المجموعة الثانية: المرضى الذين أجري لهم طعم جلدي كامل السماكة مع تثبيت عبر القطب الجلدية العابرة. عدد القطب المستخدمة ونوع الخيط كان مختلفاً بحسب موقع وحجم كل ضياع مادي. بعد تطبيق الضماد تمت متابعة المرضى في اليوم الخامس من العمل الجراحي وكشف الضماد والتأكد من حيوية الطعم، ثم توبع المرضى بعد شهر للتأكد من النجاح الكامل للطعم والتحقق من وجود أي اختلاط. النتائج: شملت الدراسة 36 مريضاً، تراوحت أعمار المرضى في العينة بين 19-63 سنة، كان عدد المرضى الذكور في العينة 21 مريضاً (58.3%)، أما الإناث 15 مريضةً (41.7%). كانت الضياعات المادية الناجمة عن العمليات الجراحية هي السبب الأشيع (16 مريضاً)، وكان أشيع مكان لتوضع الإصابات كان في الوجه والعنق عند 19 مريضاً، تراوح متوسط مساحة الضياع المادي لدى مرضى العينة 6.8 ± 0.5 سم2، وبلغت مدة الإجراء بين (40-60) دقيقة، حدث تموت في الطعم بعد 5 أيام، كان 6 مرضى منهم من المجموعة الأولى، ومريضين فقط من المجموعة الثانية، أما بعد شهر من المتابعة وجد تموت في الطعم عند 3 مرضى من المجموعة الأولى، واثنان من المجموعة الثانية، كان متوسط زمن الشفاء عند المرضى 17.2 ± 2.8 يوماً، تراوح متوسط مدة الاستشفاء لدى مرضى المجموعة الأولى 5.9 يوماً ± 1.2، وعند أولئك في المجموعة الثانية 5.1 يوماً ± 0.9. أما عدد مرات الضماد فقد كانت في المجموعة الأولى 15.2 يوماً ± 2.7، وفي المجموعة الثانية كان 9.7 يوماً ± 3.2. بلغ عدد المرضى الذين حدثت لديهم اختلاطات أثناء فترة المتابعة 19 مريضاً (52.8%). الاستنتاجات: قللت القطب العابرة من مدة العمل الجراحي، واختلاطات ما بعد العمل الجراحي، كما قللت من عدد مرات الضماد ومدة الاستشفاء عند المرضى، ما أدى إلى تقليل التكاليف وتحقيق الراحة للطبيب والمريض على حد سواء، ولذلك فإننا نفضل استخدام القطب العابرة في تثبيت الطعوم.