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Abstract Background Sickle cell disease (SCD) is the most common hemoglobinopathy caused by an autosomal recessive genetic disorder leading to increased morbidity and mortality rates. SCD is prevalent in the Tharu community in the lowland (Terai) region of Nepal. Prevalence of metabolic syndrome among adults with SCD is poorly studied. Methodology This prospective cross‐sectional study was conducted at Seti Provincial Hospital in Dhangadhi, Nepal, among 140 adolescents and adults with SCD, aged 15–60 years. Anthropometric and laboratory data were collected using an assisted questionnaire, and the SPSS software version 23 was used for data analysis. Descriptive and inferential statistics were used to summarize the presence of metabolic syndrome and were stratified in separate analyses by age and sex. National Cholesterol Education Program‐Adult Treatment Panel III criteria were used to define metabolic syndrome. Aim This cross‐sectional study aimed to assess the prevalence of metabolic syndrome among SCD patients with SCD registered at the Seti Provincial Hospital in Dhangadhi, Nepal. Results The prevalence of metabolic syndrome in the study participants was 7.8%. Our study revealed 5% of the patients overweight, and 1.4% obese. In this study, the mean triglyceride level was 118.5 mg/dL, and the mean high‐density lipoprotein (HDL) level was 36.2 mg/dL (men) and 36.7 mg/dL (women). This study found that the mean fasting blood glucose level was 88.6 gm/dL. Similarly, 3.5% of patients had increased systolic blood pressure, and 7.8% had raised diastolic blood pressure. Study shows that changes in triglyceride level (p = 0.013), waist circumference, and HDL level (p = 0.0001 and 0.0048, respectively) are significantly associated with smoking or alcohol consumption; however, change in blood pressure (p = 0.013) and fasting blood sugar level (p = 0.086) are not associated with smoking or alcohol consumption. Conclusion Study concluded that though a lower proportion of SCD patients met the criteria for metabolic syndrome than in studies conducted in developed countries, it is crucial to consider metabolic syndrome while managing patients with SCD. Nevertheless, the authors advocate a more comprehensive study to draw significant conclusions.

Abstract Purpose This study investigates three different calibration methods for the selection of background pixel intensity. Methods Film‐by‐Film (FBF) Method: Each film serves as its own control. Batch‐by‐Film (BBF) Method: A single film is used as a control for all calibration films. Generic (GEN) Method: A generic value (65535) is used as the background pixel value for all calibration films.Three calibration curves were established for the red, green, blue, and RGB channels, and the Radbard NIH (image) curve‐fitting model was used to predict the dose. Sensitivity at different dose levels was quantified by calculating the first derivative of each color channel. Results The GEN method exhibited a difference of up to 6% between the predicted and delivered doses below 2 Gy. The changes in optical density when using the GEN method differed significantly (p

Abstract Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder with a global prevalence and presentation that varies widely and is influenced by both intrinsic and extrinsic factors. While research into disease heterogeneity and burden has traditionally focused on biological and genetic differences (i.e., intrinsic factors), emerging evidence suggests that social determinants of health (SDOH) and structural determinants of health (StDOH) (i.e., extrinsic factors) play a pivotal role in the disparities observed in HS. This narrative review consolidates insights on the influence of SDOH and StDOH on HS incidence, severity, and health disparities. We highlight the importance of SDOH, including economic stability, education quality and access, healthcare quality and access, neighbourhood environment, and social/community context in shaping HS outcomes. Furthermore, we emphasize the overarching role of StDOH, including government processes, economic policies, social/public policies, and cultural and societal values in determining health outcomes. Addressing these determinants is crucial for devising effective interventions and enhancing patient outcomes. Future research should focus on a holistic understanding of HS, moving beyond a purely biological perspective to consider the intricate interplay of social and structural determinants.

Abstract Environmental parameters along elevational gradients affect the number of butterflies and the variety of species. However, which variables play significant roles and how they operate can be difficult to untangle. Here, we examine the relationships between observed butterfly richness (overall and subgroups) at different elevation gradients and remotely sensed environmental variables (vegetation productivity, surface temperature, landscape heterogeneity, and moisture stress) using generalized linear models. We surveyed butterflies with a fixed‐point count method in 19 elevation bands within 1600–5200 m above sea level in Manang district, trans‐Himalayan region, north‐central Nepal. The number of butterflies in each elevation band was studied and estimated, then interpolated across the lowest and highest elevation to estimate butterfly species richness. Then, the selection of models was performed on butterfly richness and elevations to test the best model support based on the lowest value of the Akaike information criterion and a multimodel averaging for other environmental variables. Altogether, 94 butterfly species, representing 20 subfamilies and six families, were recorded throughout the study periods. We obtained cubic model support for overall species richness, Papilionidae, and Hesperiidae, quadratic to Nymphalidae and Pieridae, and the linear model to Lycaenidae. In our study, vegetation productivity was found to have a significant positive impact on butterfly communities. Our study further suggests species richness of Papilionidae and Hesperiidae has a strong positive correlation with surface temperature and landscape heterogeneity and negative associations with moisture stress but other subgroups of butterfly communities including overall species richness showed insignificant relationships with these variables. This study provides significant information related to the responses of montane butterflies to environmental variables along elevational gradients from the Himalayas Nepal. However, further detailed studies on the functional behaviors of butterflies potentially offer more insights into their distribution patterns and ecological relationship in the montane environment.

Abstract Accurate arm circumference (AC) measurement is required for accurate blood pressure (BP) readings. Standards stipulate measuring arm circumference at the midpoint between the acromion process (AP) and the olecranon process. However, which part of the AP to use is not stipulated. Furthermore, BP is measured sitting but arm circumference is measured standing. We sought to understand how landmarking during AC measurement and body position affect cuff size selection. Two variations in measurement procedure were studied. First, AC was measured at the top of the acromion (TOA) and compared to the spine of the acromion (SOA). Second, standing versus seated measurements using each landmark were compared. AC was measured to the nearest 0.1 cm at the mid‐point of the upper arm by two independent observers, blinded from each other's measurements. In 51 participants, the mean (±SD) mid‐AC measurement using the anchoring landmarks TOA and SOA in the standing position were 32.4 cm (±6.18) and 32.1 cm (±6.07), respectively (mean difference of 0.3 cm). In the seated position, mean arm circumference was 32.2 (±6.10) using TOA and 31.1 (±6.03) using SOA (mean difference 1.1 cm). Kappa agreement for cuff selection in the standing position between TOA and SOA was 0.94 (p

Abstract Background Various cutoffs have been used to diagnose computed tomography (CT)‐defined low skeletal muscle mass; however, the impact of this variability on predicting physical functional limitations (PFL) remains unclear. In the present study we aimed to evaluate the diagnostic test metrics for predicting PFLs using a fixed cutoff value from previous reports and sought to create a prediction score that incorporated the skeletal muscle index (SMI) and other clinical factors. Methods In this cross‐sectional study including 237 patients with lung cancer, the SMI was assessed using CT‐determined skeletal muscle area at the third lumbar vertebra. Physical function was assessed using the short physical performance battery (SPPB) test, with PFL defined as an SPPB score ≤9. We analyzed the diagnostic metrics of the five previous cutoffs for CT‐defined low skeletal muscle mass in predicting PFL. Results The mean age of participants was 66.0 ± 10.4 years. Out of 237 patients, 158 (66.7%) had PFLs. A significant difference was observed in SMI between individuals with and without PFLs (35.7 cm2/m2 ± 7.8 vs. 39.5 cm2/m2 ± 8.4, p

ABSTRACT Submental intubation offers a valuable alternative for managing airway in patients with complex maxillofacial injuries, providing unobstructed access for surgical intervention and reducing complications associated with traditional intubation methods. It enhances both surgical visibility and patient safety.

ABSTRACT This case report documents the first confirmed outbreak of African swine fever (ASF) in a wild boar (Sus scrofa) in Nepal. The case was identified in a wild boar carcass found in Shuklaphanta National Park in February 2023. Post‐mortem findings, including splenomegaly, haemorrhagic lymph nodes and congested organs, were suggestive of ASF, which was confirmed by real‐time PCR. Epidemiological evidence indicates potential transmission from nearby ASF‐infected domestic pigs. This case underscores the critical need for rigorous biosecurity protocols, comprehensive surveillance and targeted wildlife management strategies to prevent further transmission between domestic pig and wild boar populations.

Abstract The oxide surface structure plays a vital role in controlling and utilizing the emergent phenomena occurring at the interface of nanoarchitecture. A complete understanding of ternary oxide surfaces remains challenging due to complex surface reconstructions in various chemical and physical environments. Here a thermodynamic framework is developed to treat the stability of ternary oxide surfaces with finite temperature and chemical environments. Strontium titanate, as a representative ternary oxide, is used to establish the complete energy landscape of SrTiO3 (001) surface. The complete mapping yields a comprehensive understanding of various stable SrTiO3 surfaces with finite temperature and chemical potential or vapor pressure of the constituents, i.e., Sr (or Ti) metal and oxygen. This treatment also reveals a stable surface unknown yet with SrTi2O3 stoichiometry, which unveils the missing link between numerous previous experimental observations and the current understanding of SrTiO3 surface. Interestingly, the new surface shows an anisotropic surface‐localized metallic state originating from the characteristic surface structure. The findings would provide a viable way to understand ternary oxide surfaces and further utilize SrTiO3 surfaces for oxide nanoarchitectures.

ABSTRACT A balanced equilibrium between carnivores and their prey is crucial for maintaining ecosystem sustainability. In this study, we applied the predator–prey power law equation to assess the balance between the biomass densities of carnivores and their wild prey within Nepal's lowland protected areas during 2013, 2018, and 2022. The estimated value of the power law exponent k for predator–prey biomass was 0.71 (95% CI = 0.39–1.05), indicating an approximate threefold increase in predator biomass density for every fivefold increase in prey biomass density. Consequently, this creates a systematically bottom‐heavy predator–prey biomass pyramid. This finding, consistent with the k = 3/4 trophic biomass scaling across ecosystems, suggests that predator biomass is proportionally sustained by prey biomass, indicating a balance between top predators and their wild prey in Nepal's lowland protected areas. We further demonstrated it is possible to retain the overall power law exponent while jointly measuring intraguild competition between two predators with canonical correlation analysis. This understanding opens avenues for future research directed toward unraveling the factors that drive these consistent growth patterns in ecological communities.

Abstract Invasive alien plant species (IAPS) pose a serious threat to overall plant biodiversity across the globe. Nepal's national parks and protected areas are not devoid of the impact of IAPS. Unfortunately, there is a substantial gap in knowledge regarding the extent and impact of invasion in protected areas of Nepal. This study assessed the impact of invasive alien plant species on the resident plant species of the Koshi Tapu wildlife reserve. After a preliminary field observation, we selected five major IAPS in the area, Mesosphaerum suaveolens, Chromolaena odorata, Ipomoea carnea, Lantana camara, and Mikania micrantha for this study. Ten pairs of adjacent plots sized 4 m × 4 m were surveyed for each invasive species, comprising diverse vegetation types. Each pair consisted of one “invaded plot” where the invasive species was dominant with cover greater than 50%, and another “uninvaded plot” laid out in an adjacent area with similar site conditions but without the invasive species. We calculated the Sørensen Index of Similarity for each paired plot. Wilcoxon rank‐sum test was employed to compare ecological parameters between invaded and uninvaded plots for various plant species. Similarly, the difference in impact between each of the five invasive species was assessed using the Kruskal–Wallis test. Species richness varied significantly between invaded and uninvaded plots for C. odorata and I. carnea. The most significant impact on species composition of invaded communities (39.6%) was observed for C. odorata. The cover of the other dominant species varied significantly between invaded and uninvaded plots for all five species studied. The Kruskal–Wallis test showed no significant difference in the impact caused by the five studied invasive species on Species richness, Shannon–Wiener diversity index, species evenness, and height of dominant species. However, a significant difference was observed between the impacts of five studied invasive species and the cover of other dominant species. The crown cover of dominant species decreased much more in the invaded plots of L. camara and M. micrantha than in other species. Specialized management efforts are required to control highly invasive species, such as C. odorata and I. carnea, alongside proactive measures to prevent further spread in ecologically sensitive areas.

Abstract Background Treatment of keloids and hypertrophic scars is challenging. The current first‐line treatment is a steroid which has high resistance and recurrence rate along with unacceptable adverse effects. Different studies involving the combination of TAC and 5‐FU that have been done so far showed better treatment outcomes in terms of efficacy and safety. Objective The objective of this study was to compare the efficacy and safety of intralesional triamcinolone acetonide alone and its combination with 5‐fluorouracil in patients with keloids and hypertrophic scars at 12 weeks follow‐up. Methods In this randomized parallel group double‐blinded clinical trial, we enroled 66 cases of keloids and hypertrophic scars randomly allocated into two treatment groups. Patients received an intralesional injection of triamcinolone acetonide (20 mg/mL) in Group A and an intralesional injection of a combination of triamcinolone acetonide (20 mg/mL) and 5‐fluorouracil (25 mg/mL) in Group B for every 2 weeks until 10 weeks and the final evaluation was done at 12 weeks follow‐up. Results There was a reduction in all the parameters at every follow‐up visit in both groups. The ≥50% reduction in height, reduction in the VSS and POSAS scores, and good to excellent subjective improvement reported by both the patients and the observer were significantly greater in the combination group compared to TAC alone group. The response rate was faster and complications were lesser in the combination group as compared to TAC alone group. Limitation Single‐centred, no long‐term follow‐up, and recurrence could not be assessed. Conclusion TAC alone and its combination with the 5‐FU both were effective in keloids and hypertrophic scars. Yet, the TAC and 5‐FU combination treatment was more efficacious with a faster response rate and safer than the TAC alone treatment.

Key Clinical Message This case illustrates sarcoidosis as a potential complication of COVID‐19, highlighting the need for a comprehensive diagnostic approach, including histopathology and prolonged monitoring, to distinguish it from post‐COVID fibrosis. Further research is crucial to elucidate these associations and understand their underlying mechanisms. Abstract Severe Acute Respiratory Syndrome Coronavirus‐ 2 (SARS‐CoV‐2), a positive‐sense single‐stranded RNA virus, causes COVID‐19 and has been linked to autoimmune disorders. Sarcoidosis is a multi‐system disease that is frequently triggered by infections. It is characterized by non‐necrotizing granulomas in multiple organs. We present a case of sarcoidosis as rare sequelae of COVID‐19. A 26‐year‐old man presented with mild COVID‐19 symptoms, followed by prolonged fever and cough despite initial therapy, prompting a provisional diagnosis of post‐COVID fibrosis. A subsequent assessment at a tertiary hospital revealed dyspnea, weight loss, and abnormal chest imaging, all of which were consistent with pulmonary sarcoidosis with pulmonary tuberculosis as a differential diagnosis. A biopsy taken during bronchoscopy confirmed pulmonary sarcoidosis and treatment with inhalation steroids resulted in symptom relief, which was followed by remission with oral steroid therapy. Sarcoidosis is a systemic disease of unknown etiology, characterized by non‐necrotizing granulomas in multiple organs. It may be triggered by infections and involves an abnormal immune response. COVID‐19 can potentially initiate sarcoidosis, with both sharing common immune mechanisms. Diagnosis involves imaging and biopsy, and treatment typically includes glucocorticoids and regular monitoring. This case report emphasizes the potential link between COVID‐19 and autoimmune conditions like sarcoidosis, highlighting the need for a comprehensive diagnostic approach and long‐term observation to distinguish between sarcoidosis and post‐COVID fibrosis.

Key Clinical Message Congenital syphilis is a forgotten disease, and often misdiagnosed. It can present with a myriad of clinical features, mimicking various other conditions therefore posing difficulty in diagnosis. Patient may be born preterm with low birth weight, failure to thrive with hemolytic anemia, thrombocytopenia, and leukocytosis. It is a treatable condition, commonly treated with penicillin or ceftriaxone.

Abstract Power flow, planning, economics, dispatch, and stability analysis rely on accurate transmission line parameters (TLPE). Standard optimization methods are employed to develop such analyses and obtain TLPE. Additionally, these methods have limitations, including precision, accuracy, and time complexity. It is challenging to find improved solutions using standard optimization methods due to slow convergence and limitations in identifying local optima. Concerned with these challenges, the study suggest a new application for an effective hybrid optimization method capable of addressing such limitations. The hybrid algorithm, named the Salp Swarm Algorithm with Sine Cosine Algorithm (HSSASCA), that aims to tackle the issues of slow convergence and local optima. The Sine Cosine Algorithm (SCA) is employed after the Salp Swarm Algorithm (SSA), and Salp integration is utilized to successfully explore and analyze the search space. To enhance the performance of HSSASCA, the hybrid technique aims to provide expanded exploration capabilities, effective exploitation of the search space, and a better convergence rate. These key features position the HSSASCA algorithm as an effective solution to complex optimization problems. To assess the efficiency of the HSSASCA algorithm, six different test systems are employed. Initially, the evaluation of exploration, exploitation, and minimized local optima is conducted using the CEC 2019 benchmark functions. Secondly, efficiency monitoring and verification of HSSASCA across different scenarios occur by comparing it with established optimization algorithms such as SSA, SCA, firefly optimization algorithm (FFO), Grey Wolf Optimization (GWO), student psychology‐based optimization (SPBO), and Symbiotic Organisms Search (SOS). Finally, statistical analysis is performed, revealing that the HSSASCA outperforms SSA, SCA, FFO, GWO, SPBO, and SOS. In terms of statistical results and convergence curves, the HSSASCA demonstrates superior performance in searching efficiency, convergence accuracy, and local optimum avoidance ability.

Abstract Conventional Mobile Communication Systems (MCS) reliably transfer critical messages from authorised remote information sources like military bases and ground control stations in the war field. As tactical advancement grows rapidly, the challenges of transmitting tactical messages via conventional satellite methods increase the processing overhead related to cost, Line of Sight (LOS) communication, packet loss, delay, and retransmission requests. Modern mobile communication systems use Airborne Node Networks (ANN) between satellites and Mobile Ground Nodes (MGNs) as they provide many advantages in mobile communication systems. Hence airborne network reduces the burden of satellites as they are only used as relay stations. The mobility problem caused by ANN and MGNs is solved by proposing a novel constructive airborne‐ground matrix algorithm known as the Who‐To‐Whom (WTW) matrix. With the help of this matrix acting as a reference index, it determines which nodes relate to whom at every time interval T in the tactical environment. This WTW matrix holds precise status/information about connectivity among all stakeholders in the operating environment by carefully and effectively accounting for frequent location changes. The methodology of the proposed matrix is that it contains the physical parameters of the nodes and their behaviour in the tactical environment. The WTW matrix construction algorithm discusses how the reference matrix is constructed in every aerial node to monitor the mobile ground nodes by leading them to safety and providing aerial guidance as they move along the tactical environment. The performance metrics are measured with other existing schemes, and the merits and demerits of the proposed WTW matrix are identified and discussed in detail.

Abstract Objectives Rhinoscleroma is classically described as a chronic granulomatous disease caused by Klebsiella rhinoscleromatis which primarily affects the nose and nasopharynx. When present, tracheal manifestations will be seen late in the disease course rather than on initial presentation. We describe a rare case of nonendemic rhinoscleroma that presented with tracheal lesions as an initial manifestation of disease. Methods Case report and literature review. Results An 88‐year‐old male presented with longstanding dysphonia. Flexible laryngoscopy demonstrated a septal perforation and diffuse glottic lesions. CT neck demonstrated a nonobstructive polypoid tracheal lesion and mucosal thickening of the paranasal sinuses. Biopsy confirmed an atypical lympho‐histiocytic proliferation and microorganisms within macrophages on Grocott methenamine silver and Steiner stains consistent with rhinoscleroma. He was referred for rheumatology and pulmonology consultation. Conclusion Systemic diseases rarely affect the trachea, and even less frequently is a tracheal lesion identified as the initial manifestation of disease. The most common systemic diseases that affect the trachea include relapsing polychondritis, granulomatosis with polyangiitis, amyloidosis, and inflammatory bowel disease. The literature surrounding nasolaryngotracheal rhinoscleroma is limited, especially in nonendemic areas. It is necessary to include unusual etiologies of airway lesions in the differential diagnosis, which warrants comprehensive airway evaluation including biopsy. Level of Evidence 4.

Abstract Introduction Early studies exploring the physiological effects of space travel have indicated the body's capacity for reversible adaptation. However, the impact of long‐duration spaceflight, exceeding 6 months, presents more intricate challenges. Effects on the Cardiovascular (CV) System Extended exposure to microgravity and radiation profoundly affects the CV system. Notable phenomena include fluid shifts toward the head and modified arterial pressure. These changes disrupt blood pressure regulation and elevate cardiac output. Additionally, the loss of venous compression leads to a reduction in central venous pressure. Fluid and Plasma Volume Changes The displacement of fluid from the vascular system to the interstitium, driven by baroreceptor stimulation, results in a 10%–15% decline in plasma volume. Cardiac Muscle and Hematocrit Variations Intriguingly, despite potential increases in cardiac workload, cardiac muscle atrophy and perplexing variations in hematocrit levels have been observed. The mechanism underlying atrophy appears to involve a shift in protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin‐mediated mechanisms. Arrhythmias and QT Interval Prolongation Instances of arrhythmias have been recurrently documented, although generally nonlethal, in both Russian and American space missions. Long‐duration spaceflight has been associated with the prolongation of the QT interval, particularly in extended missions. Radiation Effects Exposure of the heart to the proton and heavy ion radiation pervasive in deep space contributes to coronary artery degeneration, augmented aortic stiffness, and carotid intima thickening through collagen‐mediated processes. Moreover, it accelerates the onset of atherosclerosis and triggers proinflammatory responses. Reentry and Postflight Challenges Upon reentry, astronauts frequently experience orthostatic intolerance and altered sympathetic responses, which bear potential hazards in scenarios requiring rapid mobilization or evacuation. Conclusion Consequently, careful monitoring of these cardiac risks is imperative for forthcoming missions. While early studies illuminate the adaptability of the body to space travel's challenges, the intricacies of long‐duration missions and their effects on the CV system necessitate continued investigation and vigilance to ensure astronaut health and mission success.

Key Clinical Message This case emphasizes the need for early recognition and accurate diagnosis of achalasia in young adults to avoid exacerbation of the condition and misdiagnosis as GERD. Patient outcomes and quality of life are greatly enhanced by suitable diagnostic techniques, appropriate therapy, interdisciplinary care, and comprehensive patient education along with frequent follow‐ups. Abstract Achalasia results from the degeneration of inhibitory ganglion cells within the esophageal myenteric plexus and the lower esophageal sphincter (LES), leading to a loss of inhibitory neurons and resulting in the absence of peristalsis with failure of LES relaxation. Its origins are multifactorial, potentially involving infections, autoimmune responses, and genetics, with equal incidence in males and females. The hallmark symptoms include progressive dysphagia for solids and liquids, along with regurgitation, heartburn, and non‐cardiac chest pain. A 22‐year‐old female patient initially diagnosed with gastroesophageal reflux disease (GERD) received proton pump inhibitors and antacid gel for persistent dysphagia and regurgitation. Subsequent tests including barium esophagogram and manometry indicated Type II Achalasia Cardia. The patient showed clinical improvement with relief of dysphagia, regurgitation, and heartburn symptoms after pneumatic balloon dilatation (PBD). She was advised to follow up after 6 months with upper gastrointestinal (UGI) endoscopy and manometry in the outpatient clinic for regular endoscopic surveillance as there is a risk of transformation to esophageal carcinoma. Diagnosing achalasia in young adults poses challenges due to its diverse presentation and resemblance to other esophageal disorders like GERD. Diagnosis relies on clinical symptoms and imaging studies such as barium esophagogram revealing a bird's beak appearance and esophageal manometry showing absent peristalsis. UGI endoscopy is needed to rule out malignancy. Treatment options include non‐surgical approaches like medication and Botox injections, as well as surgical methods such as pneumatic balloon dilation, laparoscopic Heller myotomy, and per‐oral endoscopic myotomy (POEM). The treatment options depend upon the patient's condition at presentation and their individual choices. This case report emphasizes that it is crucial to consider achalasia as a potential differential diagnosis in young adults with dysphagia, especially if conventional treatments for acid peptic disorder do not alleviate symptoms. Prompt diagnosis and appropriate management can lead to significant clinical improvement and better patient outcomes.

Abstract Background Patients with atopic dermatitis (AD) exhibit heterogeneous clinical phenotypes, reflecting different combinations of itch and lesional severity. AD with severe itch but clear‐moderate lesions, also known as itch‐dominant AD, is a common clinical phenotype. Objectives To evaluate abrocitinib efficacy in patients with moderate‐to‐severe AD who have itch‐dominant AD. Methods This post hoc analysis includes pooled data from clinical trials of patients with moderate‐to‐severe AD receiving abrocitinib (100 or 200 mg) as monotherapy (phase 2b; phase 3 JADE MONO‐1 and JADE MONO‐2) or in combination with topical therapy (phase 3 JADE COMPARE). Data from the ongoing long‐term JADE EXTEND trial (data cutoff April 2020) were also evaluated. Itch‐dominant AD was defined as baseline Peak Pruritus Numerical Rating Scale (PP‐NRS) score of 7−10 and Investigator's Global Assessment of 0−3 or Eczema Area and Severity Index of 0‒21. Assessments included a ≥4‐point improvement in PP‐NRS (PP‐NRS4), PP‐NRS score of 0 (no itch) or 1 (little itch) in patients with PP‐NRS score ≥2 at baseline, ≥4‐point improvement from baseline in Patient‐Oriented Eczema Measure (POEM‐4), Patient Global Assessment (PtGA) of clear or almost clear, and Dermatology Life Quality Index (DLQI) score of 0 or 1 (no impact or little impact of AD on quality of life [QoL]). Results In the pooled monotherapy trials, 37% of patients had itch‐dominant AD at baseline. As early as Week 2, more patients with itch‐dominant AD achieved PP‐NRS4 with abrocitinib 100 mg (35%) and abrocitinib 200 mg (57%) versus placebo (7%); 6% and 22% versus 0%, respectively, achieved PP‐NRS 0/1. More patients achieved a PtGA of clear/almost clear at Week 12 with abrocitinib 100 mg (28%) and abrocitinib 200 mg (45%) than placebo (9%). Additionally, abrocitinib led to clinically meaningful improvements in POEM and DLQI. Most patients with itch‐dominant AD experienced itch improvement over time with abrocitinib monotherapy or with concomitant topical therapy; 86%–87% and 62%–67% of patients had no itch‐moderate itch and clear‐moderate lesions by weeks 24 and 48, respectively. Conclusions Abrocitinib is highly efficacious in patients with itch‐dominant AD, demonstrating rapid, deep, and sustained improvements in itch and clinically meaningful improvements in patients' QoL. Trial Registration Numbers NCT02780167; NCT03349060; NCT03575871; NCT03720470; NCT03422822.

Abstract Objective To use pharyngeal pressure recordings to distinguish different upper airway collapse patterns in obstructive sleep apnea (OSA) patients, and to assess whether these pressure recordings correlate with candidacy assessment for hypoglossal nerve stimulator (HGNS) implantation. Study Design Prospective case series. Setting Single tertiary‐quaternary care academic center. Methods Subjects with OSA prospectively underwent simultaneous drug‐induced sleep endoscopy (DISE) and transnasal pharyngeal pressure recording with a pressure‐transducing catheter. Pressure was recorded in the nasopharynx and oropharynx, and endoscopic collapse patterns were classified based on site, extent, and direction of collapse. Pressure recordings were classified categorically by waveform shape as well as numerically by inspiratory and expiratory amplitudes and slopes. Waveform shape, amplitude, and slope were then compared with the endoscopic findings. Results Twenty‐five subjects with OSA were included. Nasopharyngeal waveform shape was associated with the extent of collapse at the level of the palate (P = .001). Oropharyngeal waveform shape was associated with anatomical site of collapse (P

Abstract The EFSA Panel on Animal Health and Welfare (AHAW) was asked to deliver a scientific opinion on the use of high‐expansion foam for stunning and killing pigs and poultry. A dossier was provided by the applicant as the basis for an assessment of the extent to which the method is able to provide a level of animal welfare at least equivalent to that ensured by the currently allowed methods for pigs and poultry. According to legislation, to be approved in the EU, new stunning methods must ensure (1) the absence of pain, distress or suffering until the onset of unconsciousness, and (2) that the animal remains unconscious until death. An ad hoc Working Group set up by EFSA performed the assessment as follows: (1) The data provided were checked against the criteria laid down in the EFSA Guidance (EFSA, 2018), and was found to partially fulfil those criteria; (2) extensive literature search; (3) data extraction for quantitative assessment; (4) qualitative exercise based on non‐formal expert elicitation. The assessment led to conclude that it is more likely than not (certainty > 50%–100%) that high‐expansion foam for stunning and killing pigs and poultry, named NEFS in container (Nitrogen Expansion Foam Stunning in container), provides a level of welfare at least equivalent to one or more of the currently allowed methods listed in Annex I of Council Regulation (EC) No 1099/2009. The overall assessment of EFSA is valid only under the technical conditions described in this Opinion for laying hens, broiler chickens of all age and pigs weighing 15–41 kg in situations other than slaughter. The overall assessment of EFSA is that NEFS can be suitable for depopulation using containers for pig and poultry farms respecting the technical conditions and the categories and types of animals defined in this Scientific Opinion.

Abstract Human–wildlife conflict studies of high‐altitude areas are rare due to budget constraints and the challenging nature of research in these remote environments. This study investigates the prevalence and increasing trend of human–wildlife conflict (HWC) in the mountainous Gaurishankar Conservation Area (GCA) of Nepal, with a specific focus on leopard (Panthera pardus) and Himalayan black bear (Ursus thibetanus laniger). The study analyzes a decade of HWC reports and identifies goats as the livestock most targeted by leopards. The Dolakha district of GCA received the highest number of reports, highlighting the need for mitigation measures in the area. In GCA, livestock attacks accounted for 85% of compensation, with the remaining 15% for human injuries. We estimate that the number of reported wildlife attacks grew on average by 33% per year, with an additional increase of 57 reports per year following the implementation of a new compensation policy during BS 2076 (2019 AD). While bear attacks showed no significant change post‐rule alteration, leopard attack reports surged from 1 to 60 annually, indicating improved compensation may have resulted in increased leopard‐attack reporting rates. The findings emphasize the economic impact of HWC on local communities and suggest strategies such as increasing prey populations, promoting community education and awareness, enhancing alternative livelihood options, developing community‐based insurance programs, and implementing secure enclosures (corrals) to minimize conflicts and foster harmonious coexistence. This research addresses a knowledge gap in HWC in high‐altitude conservation areas like the GCA, providing valuable insights for conservation stakeholders and contributing to biodiversity conservation and the well‐being of humans and wildlife.

Key Clinical Message Lateral medullary syndrome, resulting from cerebellar/brainstem infarction, can occur due to cardioembolic stroke from atrial fibrillation caused by rheumatic heart disease. This rare association highlights the importance of strict arrhythmia management, prophylactic anticoagulation, and timely diagnosis to prevent debilitating neurological outcomes.

Key Clinical Message Chronic ketamine use can lead to sphincter of oddi dysfunction (SOD), causing various hepatobiliary complications. Recognizing substance abuse history is vital for early detection. Timely intervention can prevent irreversible liver and pancreas damage. Abstract Ketamine is commonly abused as a recreational drug worldwide due to its ability to induce euphoria‐like effects. Ketamine abuse is associated with many hepatobiliary side effects ranging from cholestasis to biliary sepsis and death. Here we present a case of a young 29‐year female with upper abdominal pain due to SOD resulting from chronic use of ketamine. SOD can result in obstruction or dysfunction of the bile and pancreatic ducts. Ketamine induces SOD by activation of the muscarinic receptors in the sphincter of oddi. Detail history of substance abuse is crucial for early identification of ketamine‐induced SOD. Early identification and treatment of this rare condition can prevent permanent injury to the liver and pancreas.

Key Clinical Message Immune checkpoint inhibitors can rarely lead to occurrence of myositis, myocarditis, and myasthenia gravis (MG). Early recognition and multidisciplinary management are crucial for optimal outcomes. Vigilance for overlapping toxicities is essential in patients receiving combination immunotherapy. Abstract The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, but it is associated with immune‐related adverse events (IRAEs) affecting various organ systems. The simultaneous occurrence of MG, myocarditis, and myositis highlights the complex nature of IRAEs. Early recognition and comprehensive multidisciplinary management are crucial for optimal patient outcomes. We present a unique case report of a 76‐year‐old male patient with advanced melanoma who developed concurrent myositis, myocarditis, and MG while receiving combination immunotherapy with Nivolumab and Ipilimumab. This case underscores the significance of recognizing and addressing the “Terrible Triad” of IRAEs in patients receiving ICIs. Healthcare providers should maintain a high index of suspicion for overlapping toxicities and promptly initiate appropriate interventions.

Key Clinical Message In babies presenting with an omphalocele, other components of the prune belly syndrome should be scrutinized for early diagnosis and timely intervention. Abstract A male baby on his 13th day of life presented with an omphalocele. On evaluation, he had congenital absence of left kidney and bilateral cryptorchidism. Therefore, he was diagnosed with prune belly syndrome. He responded well to abdminoplasty, and wait and watch policy was applied for his cryptorchidism.

Abstract Sheep and goats of different ages may have to be killed on‐farm for purposes other than slaughter (where slaughter is defined as killing for human consumption) either individually (i.e. on‐farm killing of unproductive, injured or terminally ill animals) or on a large scale (i.e. depopulation for disease control purposes and for other situations, such as environmental contamination and disaster management) outside the slaughterhouses. The purpose of this opinion was to assess the hazards and welfare consequences associated with the on‐farm killing of sheep and goats. The whole killing procedure was divided into Phase 1 (pre‐killing) – that included the processes (i) handling and moving the animals to the killing place and (ii) restraint of the animals before application of the killing methods and Phase 2 – that included stunning and killing of the animals. The killing methods for sheep and goats were grouped into three categories: (1) mechanical, (2) electrical and (3) lethal injection. Welfare consequences that sheep and goats may experience during each process were identified (e.g. handling stress, restriction of movements and tissue lesions during restraint) and animal‐based measures (ABMs) to assess them were proposed. During application of the killing method, sheep and goats will experience pain and fear if they are ineffectively stunned or if they recover consciousness. ABMs related to the state of consciousness can be used to indirectly assess pain and fear. Flowcharts including ABMs for consciousness specific to each killing method were included in the opinion. Possible welfare hazards were identified for each process, together with their origin and related preventive and corrective measures. Outcome tables linking hazards, welfare consequences, ABMs, origins, preventive and corrective measures were developed for each process. Mitigation measures to minimise welfare consequences were proposed.

Abstract Background and Aim The model for end‐stage liver disease (MELD) was updated to MELDNa and recently to MELD3.0 to predict survival of cirrhotic patients. We validated the prognostic performance of MELD3.0 and compared with MELDNa and MELD amongst cirrhotic inpatients. Methods Demographical, clinical, biochemical, and survival data of cirrhotic inpatients in Singapore General Hospital (SGH) from 01 January 2018 to 31 December 2018, were studied retrospectively. Patients were followed up from first admission in 2018 until death or until 01 April 2023. Area under the receiver operating characteristic curves (AUROC) were computed for the discriminative effects of MELD3.0, MELDNa, and MELD to predict 30‐, 90‐, and 365‐day mortalities. AUROC was compared with DeLong's test. The cutoff MELD3.0 score for patients at high risk of 30‐day mortality was determined using Youden's Index. Survival curves of patients with MELD3.0 score above and below the cutoff were estimated with Kaplan–Meier method and compared with log‐rank analysis. Results Totally 862 patients were included (median age 71.0 years [interquartile range, IQR: 64.0–79.0], 65.4% males, 75.8% Chinese). Proportion of patients with Child‐Turcotte‐Pugh classes A/B/C were 55.5%/35.5%/9.0%. Median MELD3.0/MELDNa/MELD scores were 12.2 (IQR: 8.7–18.3)/11.0 (IQR: 8.0–17.5)/10.3 (IQR: 7.8–15.0). Median time of follow‐up was 51.9 months (IQR: 8.5–59.6). The proportion of 30‐/90‐/365‐day mortalities was 5.7%/13.2%/26.9%. AUROC of MELD3.0/MELDNa/MELD in predicting 30‐, 90‐, and 365‐day mortalities, respectively, were 0.823/0.793/0.783, 0.754/0.724/0.707, 0.682/0.654/0.644 (P 19 (sensitivity = 67.4%, specificity = 82.4%). Patients with MELD3.0 > 19, compared with patients with MELD3.0 ≤ 19, had shorter median time to death (98.0 days [IQR: 28.8–398.0] vs 390.0 days [IQR: 134.3–927.5]), and higher proportion of 30‐day mortality (68.8% vs 43.0%) (P 19 predicts higher 30‐day mortality.

Abstract Objectives With the legalization of cannabis in New Jersey on April 21, 2022, including the licensing of cannabis dispensaries, concerns have arisen about potential adverse events related to cannabis use. Here, we explore temporal trends and risk factors for cannabis‐related harm in both adult and pediatric cannabis‐related visits at a tertiary care academic institution. Methods We performed a retrospective chart review and temporal trend analysis via the electronic health record from May 1, 2019 to October 31, 2022, covering 2 years before, and 6 months after, cannabis legalization in New Jersey. The pediatric charts identified were analyzed for root causes of adverse events, and changes in the frequency of specific unsafe practices since cannabis legalization were tracked. Results We found that adult cannabis ED‐related visits significantly increased during the COVID‐19 pandemic and remained higher than pre‐pandemic levels for the remainder of the study periods, without a significant change upon legalization. Pediatric rates of cannabis‐related ED visits did not vary significantly during the study period. The vast majority of visits for children aged 0–12 years were related to accidental cannabis exposures—often a household member's edibles—whereas most visits for older children stemmed from intentional cannabis use. Conclusion This project highlights the unintended consequences of wider cannabis access in New Jersey. Notably, cannabis use increased even before its legalization, presumably in response to the COVID‐19 pandemic and its attendant mental health effects. Rates of cannabis use disorder and its highlight of other concurrent psychiatric disorders are important topics for both clinicians and lawmakers to consider.

Aldehyde dehydrogenase 1A3 (ALDH1A3) is a cancer stem cell marker that promotes metastasis. Triple‐negative breast cancer (TNBC) progression has been linked to ALDH1A3‐induced gene expression changes. To investigate the mechanism of ALDH1A3‐mediated breast cancer metastasis, we assessed the effect of ALDH1A3 on the expression of proteases and the regulators of proteases that degrade the extracellular matrix, a process that is essential for invasion and metastasis. This revealed that ALDH1A3 regulates the plasminogen activation pathway; it increased the levels and activity of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA). This resulted in a corresponding increase in the activity of serine protease plasmin, the enzymatic product of tPA and uPA. The ALDH1A3 product all‐trans‐retinoic acid similarly increased tPA and plasmin activity. The increased invasion of TNBC cells by ALDH1A3 was plasminogen‐dependent. In patient tumours, ALDH1A3 and tPA are co‐expressed and their combined expression correlated with the TNBC subtype, high tumour grade and recurrent metastatic disease. Knockdown of tPA in TNBC cells inhibited plasmin generation and lymph node metastasis. These results identify the ALDH1A3–tPA–plasmin axis as a key contributor to breast cancer progression.

Abstract Background Primary breast diffuse large B‐cell lymphoma (PB‐DLBCL) is a rare subtype of extranodal DLBCL, and the standard treatment remains controversial. In this study, we aimed to define the optimal treatment management in the rituximab era. Methods A total of 5089 newly diagnosed DLBCL patients treated with rituximab‐containing immunochemotherapy between 2008 and 2019 from the Chinese Southwest Oncology Group‐affiliated institutes were identified, of whom 135 diagnosed with PB‐DLBCL were eligible for this analysis. Results PB‐DLBCL accounted for 2.7% of all DLBCLs. With a median follow‐up of 4.2 years, the 5‐year overall survival and progression‐free survival rates were 84.8% and 71.6%, respectively. Breast and central nervous system (CNS) relapses were the main cause of treatment failure. We observed that consolidative breast radiotherapy (RT) significantly decreased breast relapse risk (5‐year risk, 2.9% vs. 20.1%, p = 0.007). The CNS relapse risk was lower for patients who received high‐dose methotrexate (HD‐MTX) than for patients who did not (5‐year risk, 0% vs. 15.2%, p = 0.015). We further screened the genetic mutation profile of 20 patients from two institutes, and found that MYD88 (25%) and CD79B mutations (25%) frequently occur in PB‐DLBCL. In addition, four patients with MYD88 and/or CD79B mutations experienced CNS relapse, while three patients with MYD88 and/or CD79B mutations who received HD‐MTX did not experience CNS relapse. Conclusion Collectively, our results indicate combined modality therapy including rituximab‐containing immunochemotherapy and consolidative breast RT is a promising approach for PB‐DLBCL, while HD‐MTX is useful for preventing CNS relapse.

Abstract Diagnosing extrapulmonary tuberculosis (EPTB) is challenging. Immunohistochemistry or immunocytochemistry has been used to diagnose tuberculosis (TB) by detection of MPT64 antigen from various extrapulmonary specimens and has shown good diagnostic performance in our previous studies. The test can distinguish between disease caused by Mycobacterium tuberculosis (Mtb) complex and nontuberculous mycobacteria and can be applied on formalin‐fixed paraffin‐embedded tissue. As the antibodies previously used were in limited supply, a new batch of polyclonal antibodies was developed for scale‐up and evaluated for the first time in this study. Our aim was to assess the diagnostic accuracy of the MPT64 test with reproduced antibodies in the high burden settings of Pakistan and India. Patients were enrolled prospectively. Samples from suspected sites of infection were collected and subjected to histopathologic and/or cytologic evaluation, routine TB diagnostics, GeneXpert MTB/RIF (Xpert), and the MPT64 antigen detection test. Patients were followed until the end of treatment. Based on a composite reference standard (CRS), 556 patients were categorized as TB cases and 175 as non‐TB cases. The MPT64 test performed well on biopsies with a sensitivity and specificity of 94% and 75%, respectively, against a CRS. For cytology samples, the sensitivity was low (36%), whereas the specificity was 81%. Overall, the MPT64 test showed higher sensitivity (73%) than Xpert (38%) and Mtb culture (33%). The test performed equally well in adults and children. We found an additive diagnostic value of the MPT64 test in conjunction with histology and molecular tests, increasing the yield for EPTB. In conclusion, immunochemical staining with MPT64 antibodies improves the diagnosis of EPTB in high burden settings and could be a valuable addition to routine diagnostics.

Abstract Background Previously, we discovered that human solid tumours, but not normal human tissues, preferentially overexpress interleukin‐13Receptor alpha2, a high binding receptor for IL‐13. To develop novel anti‐cancer approaches, we constructed a chimeric antigen receptor construct using a high binding and codon optimised scFv‐IL‐13Rα2 fragment fused with CD3ζ and co‐stimulatory cytoplasmic domains of CD28 and 4‐1BB. Methods We developed a scFv clone, designated 14‐1, by biopanning the bound scFv phages using huIL‐13Rα2Fc chimeric protein and compared its binding with our previously published clone 4‐1. We performed bioinformatic analyses for complementary determining regions (CDR) framework and residue analyses of the light and heavy chains. This construct was packaged with helper plasmids to produce CAR‐lentivirus and transduced human Jurkat T or activated T cells from peripheral blood mononuclear cells (PBMCs) to produce CAR‐T cells and tested for their quality attributes in vitro and in vivo. Serum enzymes including body weight from non‐tumour bearing mice were tested for assessing general toxicity of CAR‐T cells. Results The binding of 14‐1 clone is to IL‐13Rα2Fc‐chimeric protein is ∼5 times higher than our previous clone 4‐1. The 14‐1‐CAR‐T cells grew exponentially in the presence of cytokines and maintained phenotype and biological attributes such as cell viability, potency, migration and T cell activation. Clone 14‐1 migrated to IL‐13Rα2Fc and cell free supernatants only from IL‐13Rα2+ve confluent glioma tumour cells in a chemotaxis assay. scFv‐IL‐13Rα2‐CAR‐T cells specifically killed IL‐13Rα2+ve but not IL‐13Rα2‐ve tumour cells in vitro and selectively caused significant release of IFN‐γ only from IL‐13Rα2+ve co‐cultures. These CAR‐T cells regressed IL‐13Rα2+ve glioma xenografts in vivo without any general toxicity. In contrast, the IL‐13Rα2 gene knocked‐down U251 and U87 xenografts failed to respond to the CAR‐T therapy. Conclusion Taken together, we conclude that the novel scFv‐IL‐13Rα2 CAR‐T cell therapy may offer an effective therapeutic option after designing a careful pre‐clinical and clinical study.

Abstract Ferroptosis and apoptosis are key cell‐death pathways implicated in several human diseases including cancer. Ferroptosis is driven by iron‐dependent lipid peroxidation and currently has no characteristic biomarkers or gene signatures. Here a continuous phenotypic gradient between ferroptosis and apoptosis coupled to transcriptomic and metabolomic landscapes is established. The gradual ferroptosis‐to‐apoptosis transcriptomic landscape is used to generate a unique, unbiased transcriptomic predictor, the Gradient Gene Set (GGS), which classified ferroptosis and apoptosis with high accuracy. Further GGS optimization using multiple ferroptotic and apoptotic datasets revealed highly specific ferroptosis biomarkers, which are robustly validated in vitro and in vivo. A subset of the GGS is associated with poor prognosis in breast cancer patients and PDXs and contains different ferroptosis repressors. Depletion of one representative, PDGFA‐assaociated protein 1(PDAP1), is found to suppress basal‐like breast tumor growth in a mouse model. Omics and mechanistic studies revealed that ferroptosis is associated with enhanced lysosomal function, glutaminolysis, and the tricarboxylic acid (TCA) cycle, while its transition into apoptosis is attributed to enhanced endoplasmic reticulum(ER)‐stress and phosphatidylethanolamine (PE)‐to‐phosphatidylcholine (PC) metabolic shift. Collectively, this study highlights molecular mechanisms underlying ferroptosis execution, identified a highly predictive ferroptosis gene signature with prognostic value, ferroptosis versus apoptosis biomarkers, and ferroptosis repressors for breast cancer therapy.

Background We evaluated the potential benefits of renin‐angiotensin‐aldosterone system inhibitors (RAASi) in patients with left ventricular assist device support. Methods and Results A total of 165 consecutive patients undergoing left ventricular assist device implant and alive at 6‐month on support were studied. RAASi status after 6‐month visit along with clinical reasons for nonprescription/uptitration were retrospectively assessed. The primary outcome was a composite of heart failure hospitalization or cardiovascular death between 6 and 24 months after left ventricular assist device implant. Remodeling and hemodynamic outcomes were explored by studying the association of RAASi new prescription/uptitration versus unmodified therapy at 6‐month visit with the change in echocardiographic parameters and hemodynamics between 6 and 18 months. After the 6‐month visit, 76% of patients were on RAASi. Patients' characteristics among those receiving and not receiving RAASi were mostly similar. Of 85 (52%) patients without RAASi new prescription/uptitration at 6‐month visit, 62% had no apparent clinical reason. RAASi were independently associated with the primary outcome (adjusted hazard ratio, 0.31 [95% CI, 0.16–0.69]). The baseline rates of optimal echocardiographic profile (neutral interventricular septum, mitral regurgitation less than mild, and aortic valve opening) and hemodynamic profile (cardiac index ≥2.2 L/min per m2, wedge pressure

Background Lower extremity endovascular revascularization for peripheral artery disease carries nonnegligible perioperative risks; however, outcome prediction tools remain limited. Using machine learning, we developed automated algorithms that predict 30‐day outcomes following lower extremity endovascular revascularization. Methods and Results The National Surgical Quality Improvement Program targeted vascular database was used to identify patients who underwent lower extremity endovascular revascularization (angioplasty, stent, or atherectomy) for peripheral artery disease between 2011 and 2021. Input features included 38 preoperative demographic/clinical variables. The primary outcome was 30‐day postprocedural major adverse limb event (composite of major reintervention, untreated loss of patency, or major amputation) or death. Data were split into training (70%) and test (30%) sets. Using 10‐fold cross‐validation, 6 machine learning models were trained using preoperative features. The primary model evaluation metric was area under the receiver operating characteristic curve. Overall, 21 886 patients were included, and 30‐day major adverse limb event/death occurred in 1964 (9.0%) individuals. The best performing model for predicting 30‐day major adverse limb event/death was extreme gradient boosting, achieving an area under the receiver operating characteristic curve of 0.93 (95% CI, 0.92–0.94). In comparison, logistic regression had an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.70–0.74). The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.09. The top 3 predictive features in our algorithm were (1) chronic limb‐threatening ischemia, (2) tibial intervention, and (3) congestive heart failure. Conclusions Our machine learning models accurately predict 30‐day outcomes following lower extremity endovascular revascularization using preoperative data with good discrimination and calibration. Prospective validation is warranted to assess for generalizability and external validity.

Background The purpose of this study is to compare the prevalence of self‐reported cardiovascular conditions among individuals with moderate to severe traumatic brain injury (TBI) to a propensity‐matched control cohort. Methods and Results A cross‐sectional study described self‐reported cardiovascular conditions (hypertension, congestive heart failure [CHF], myocardial infarction [MI], and stroke) from participants who completed interviews between January 2015 and March 2020 in 2 harmonized large cohort studies, the TBI Model Systems and the National Health and Nutrition Examination Survey. Mixed‐effect logistic regression models were used to compare the prevalence of cardiovascular conditions after 1:1 propensity‐score matching based on age, sex, race, ethnicity, body mass index, education level, and smoking status. The final sample was 4690 matched pairs. Individuals with TBI were more likely to report hypertension (odds ratio [OR], 1.18 [95% CI, 1.08–1.28]) and stroke (OR, 1.70 [95% CI, 1.56–1.98]) but less likely to report CHF (OR, 0.81 [95% CI, 0.67–0.99]) or MI (OR, 0.66 [95% CI, 0.55–0.79]). There was no difference in rate of CHF or MI for those ≤50 years old; however, rates of CHF and MI were lower in the TBI group for individuals >50 years old. Over 65% of individuals who died before the first follow‐up interview at 1 year post‐TBI were >50 years old, and those >50 years old were more likely to die of heart disease than those ≤50 years old (17.6% versus 8.6%). Conclusions Individuals with moderate to severe TBI had an increased rate of self‐reported hypertension and stroke but lower rate of MI and CHF than uninjured adults, which may be due to survival bias.

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)

Abstract Background and Aim Obesity affects nearly 650 million adults worldwide, and the prevalence is steadily rising. This condition has significant adverse effects on cardiovascular health, increasing the risk of hypertension, coronary artery disease, heart failure, and atrial fibrillation (AF). While anticoagulation for obese patients with AF is a well‐established therapy for the prevention of thromboembolism, the safety and efficacy of different anticoagulants in this specific population are not well explored. This meta‐analysis aimed to compare direct oral anticoagulants (DOAC) to vitamin K antagonists in obese populations with AF. Methods The PRISMA guidelines were followed for this meta‐analysis, registered in PROSPERO (CRD42023392711). PubMed, PubMed Central, Embase, Cochrane Library, and Scopus databases were searched for relevant articles from inception through January 2023. Two independent authors screened titles and abstracts, followed by a full‐text review in Covidence. Data were extracted in Microsoft Excel and analyzed using RevMan v5.4 using odds ratio as an effect measure. Results Two thousand two hundred fifty‐nine studies were identified from the database search, and 18 were included in the analysis. There were statistically significant reductions in the odds of ischemic and hemorrhagic stroke in the DOAC group compared with the VKA group (OR 0.70, CI 0.66–0.75) and (OR 0.47, CI 0.35–0.62), respectively. In addition, the DOAC group exhibited lower odds of systemic embolism (OR 0.67, CI 0.54–0.83), major bleeding (OR 0.62, CI 0.54–0.72), and composite outcome (OR 0.72, CI 0.63–0.81). Conclusion Based on the findings from this meta‐analysis, DOACs demonstrate superior safety and efficacy in obese patients with AF compared with VKAs. These results may have significant implications for guiding anticoagulation strategies in this patient population.

Key Clinical Message Nitrobenzene poisoning is a rare yet life‐threatening contention. The ensuing acute methemoglobinemia has a high fatality rate, hence early prompt intervention is required. Methylene blue (intravenous or oral) and ascorbic acid are the cornerstones of management. They must be administered to suspected patients without tardiness. Abstract An aromatic organic chemical used in paints and the printing industry is nitrobenzene. Its poisoning causes potentially fatal methemoglobinemia. One aspect of its management involves reducing the iron moiety from its ferric to ferrous form by administering intravenous methylene blue. A 23‐year‐old man who had deliberately consumed nitrobenzene presented to us with a history of headache and vomiting. He was diagnosed to have methemoglobinemia on the basis of clinical grounds and was managed successfully with intravenous methylene blue and vitamin C.

Abstract Objective(s) Hematologic malignancy involving the trachea is rare. It is even less common for tracheal involvement to be the initial manifestation of this disease. We present a case report highlighting an unusual diagnosis of acute myeloid leukemia (AML) that first presented with prominent tracheal manifestations. There have been only three other published case reports of extramedullary AML with involvement of the trachea. Methods We discuss direct laryngoscopy and bronchoscopy findings, including pinkish‐white irregular lesions, which were similar to findings described in the available literature for tracheal AML. Results Laboratory findings from our case are reported, including peripheral smear demonstrating 57% blasts and bone marrow biopsy confirming the diagnosis of AML, and the relevance of these findings is discussed. Conclusion In patients with unusual airway lesions, laboratory testing and a comprehensive airway evaluation including biopsy are necessary to narrow the differential diagnosis. Level of Evidence 5.

Abstract Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate (HR) response upon standing and symptoms indicative of inadequate cerebral perfusion. We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular function measured using magnetic resonance (MR) imaging. Eleven patients with POTS and 10 healthy controls were studied at rest and during 20 min of −25 mmHg LBNP. Biventricular volumes, stroke volume (SV), cardiac output (Qc), and HR were determined by cardiac MR. Cerebral oxygen uptake (VO2) in the superior sagittal sinus was calculated from cerebral blood flow (CBF; MR phase contrast), venous O2 saturation (SvO2; susceptometry‐based oximetry), and arterial O2 saturation (pulse oximeter). Regional cerebral perfusion was determined using arterial spin labelling. HR increased in response to LBNP (p

Abstract Background The presence of intestinal parasites influences the growth and well‐being of canids. Additionally, infected dogs and their faeces with considerably higher eggs/oocysts released per gram (epg/opg) of zoonotic parasites contribute to parasitic spillover to humans, domestic animals and sympatric wildlife. Objectives The current study aimed to reveal the prevalence of intestinal parasites (protozoa and helminths) and to list the zoonotically significant parasites in free‐roaming street dogs in Lalitpur Metropolitan City, Nepal. Methods Fresh faecal samples (n = 332) were collected from feral dogs of varying ages and sexes and transported to the research laboratory. The copro microscopic examination was carried out via direct wet mount, formalin ethyl acetate sedimentation, saturated salt flotation, acid‐fast staining and sporulation techniques. Results Coproscopy revealed an overall 95.7% (318/332) prevalence rate with 23 diverse species of intestinal parasites (10 protozoa and 13 helminths). Among them, 5 protozoa and 11 helminths possessed zoonotic potential, and their overall prevalence was 92.5%. Helminth's overall prevalence was double that of the protozoa (87.7% vs. 43%). Polyparasitism was dominant over mono parasitism (79.5% vs. 16.3%), and co‐infection of up to seven species of parasites at a time was recorded. Conclusions Urban street dogs harboured a higher prevalence of intestinal parasites that varied with age and sex. Since most of the reported parasites are zoonotic, dog density and parasitic richness indicate a greater spillover risk to humans and domestic animals. Furthermore, this study also provides appropriate ‘baseline’ data for assessing effective control measures against parasitic infestations among street dogs and controlling their transmission to humans.

Abstract Cardiac allograft vasculopathy (CAV) remains a common long‐term complication of cardiac transplantation. While invasive coronary angiography is considered the gold standard, it is also invasive and lacks sensitivity to detect early, distal CAV. Although vasodilator stress myocardial contrast echocardiography perfusion imaging (MCE) is used in the detection of microvascular disease in non‐transplant patients, there is little data guiding its use in transplant recipients. Herein is a case series of four heart transplant recipients that had vasodilator stress MCE performed in addition to invasive coronary angiography for CAV surveillance. MCE at rest and after regadenason was performed using a continuous infusion of lipid‐shelled microbubbles. We describe a case of normal microvascular function, diffuse microvascular dysfunction, patchy sub‐endocardial perfusion defects and a focal sub‐endocardial perfusion defect. Cardiac allograft vasculopathy can be heralded by several different perfusion patterns on MCE in patients after orthotopic heart transplant. The varying prognoses and potential interventions for these different patterns require further investigation.

Abstract Background Mutations in kinases are the most frequent genetic alterations in cancer; however, experimental evidence establishing their cancerous nature is available only for a small fraction of these mutants. Aims Predicition analysis of kinome mutations is the primary aim of this study. Further objective is to compare the performance of various softwares in pathogenicity prediction of kinase mutations. Materials and methods We employed a set of computational tools to predict the pathogenicity of over forty‐two thousand mutations and deposited the kinase‐wise data in Mendeley database (Estimated Pathogenicity of Kinase Mutants [EPKiMu]). Results Mutations are more likely to be drivers when being present in the kinase domain (vs. non‐kinase domain) and belonging to hotspot residues (vs. non‐hotspot residues). We identified that, while predictive tools have low specificity in general, PolyPhen‐2 had the best accuracy. Further efforts to combine all four tools by consensus, voting, or other simple methods did not significantly improve accuracy. Discussion The study provides a large dataset of kinase mutations along with their predicted pathogenicity that can be used as a training set for future studies. Furthermore, a comparative sensitivity and selectivity of commonly used computational tools is presented. Conclusion Primary‐structure‐based in silico tools identified more cancerous/deleterious mutations in the kinase domains and at the hot spot residues while having higher sensitivity than specificity in detecting deleterious mutations.