Deep enteroscopy in children: techniques, applications, and future directions

Deep enteroscopy, encompassing push enteroscopy (PE) and balloon-assisted enteroscopy (BAE), has revolutionized the diagnosis and treatment of pediatric small bowel disorders. This review examines the evolving role of these techniques in managing conditions such as obscure gastrointestinal bleeding, Crohn's disease, polyposis syndromes, strictures, and small bowel tumors. While PE is effective for both diagnostic and therapeutic interventions in the proximal small bowel, its limited insertion depth has driven the adoption of BAE techniques. These include single-balloon enteroscopy (SBE) and double-balloon enteroscopy (DBE), which provide deeper and more comprehensive access. Both BAE modalities offer greater insertion depth and stability, enabling advanced therapeutic interventions such as polypectomy, stricture dilation, and hemostasis. Pediatric-specific data demonstrate high diagnostic yields for BAE, with comparable outcomes between SBE and DBE. These techniques have proven safe across diverse indications, though younger children may experience slightly higher complication rates due to anatomical considerations. Despite these advancements, challenges persist, including a limited evidence base in pediatrics, barriers to training, and the need for standardized protocols. Additionally, emerging innovations such as artificial intelligence offer opportunities to enhance diagnostic accuracy and procedural efficiency. Comparative analyses of PE, BAE, and capsule endoscopy are necessary to refine procedural selection and optimize outcomes in pediatric patients. Furthermore, structured pediatric training programs and simulation-based learning could address competency gaps, ensuring safe and effective application of these techniques. By addressing current research gaps, embracing technological advancements, and tailoring approaches to pediatric populations, deep enteroscopy can continue to transform the management of small bowel disorders in children

Host 3’ flap endonuclease Mus81 plays a critical role in trimming the terminal redundancy of hepatitis B virus relaxed circular DNA during covalently closed circular DNA formation

Hepatitis B virus (HBV) relaxed circular DNA (rcDNA) possesses an 8-9 nucleotide-long terminal redundancy (TR, or r) on the negative (-) strand DNA derived from the reverse transcription of viral pregenomic RNA (pgRNA). It remains unclear whether the TR forms a 5' or 3' flap structure on HBV rcDNA and which TR copy is removed during covalently closed circular DNA (cccDNA) formation. To address these questions, a mutant HBV cell line HepDES-C1822G was established with a C1822G mutation in the pgRNA coding sequence, altering the sequence of 3' TR of (-) strand DNA while the 5' TR remained wild type (wt). The production of HBV rcDNA and cccDNA in HepDES-C1822G cells was comparable to wt levels. Next-generation sequencing (NGS) analysis revealed that the positive (+) strand DNA of rcDNA and both strands of cccDNA predominantly carried the wt nt1822 residue, indicating that the 5' TR of (-) strand DNA serves as the template during rcDNA replication, forming a duplex with the (+) strand DNA, while the 3' TR forms a flap-like structure, which is subsequently removed during cccDNA formation. In a survey of known cellular flap endonucleases using a loss-of-function study, we found that the 3' flap endonuclease Mus81 plays a critical role in cccDNA formation in wild-type HBV replicating cells, alongside the 5' flap endonuclease FEN1. Additionally, we have mapped the potential Mus81 and FEN1 cleavage sites within the TR of nuclear DP-rcDNA by RACE-NGS analyses. The overlapping function between Mus81 and FEN1 in cccDNA formation indicates that the putative 5' and 3' flap formed by TR are dynamically interchangeable on rcDNA precursor. These findings shed light on HBV rcDNA structure and cccDNA formation mechanisms, contributing to our understanding of HBV replication cycle

Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial

Tirzepatide induces weight reduction but the underlying mechanisms are unknown. This 6-week phase 1 study investigated early effects of tirzepatide on energy intake. Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m2 were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide. The primary outcome was change from baseline to week 3 in energy intake during an ad libitum lunch with tirzepatide versus placebo. Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos. Tirzepatide reduced energy intake versus placebo at week 3 (estimated treatment difference -524.6 kcal (95% confidence interval -648.1 to -401.0), P < 0.0001). With regard to secondary outcomes versus placebo, tirzepatide decreased overall appetite, food cravings, tendency to overeat, perceived hunger and reactivity to foods in the environment but did not impact volitional restriction of dietary intake. At week 3 versus placebo, tirzepatide did not statistically significantly impact blood-oxygenation-level-dependent activation to highly palatable food photos (aggregated category of high-fat, high-sugar foods and high-fat, high-carbohydrate foods) but decreased activation to high-fat, high-sugar food photos in the medial frontal and cingulate gyri, orbitofrontal cortex and hippocampus. Our results suggest tirzepatide reduces food intake, potentially by impacting ingestive behavior

Proto‐Oncogene HRAS Transcript Level and Overall Survival in Stages II and III Colorectal Cancer

Background: Mutational landscape is prognostic in colorectal cancer (CRC). Rat sarcoma (RAS) oncogenes, such as KRAS and NRAS, with driver mutations, portend poor survival outcomes, whereas pathologic mutations in HRAS are extremely rare, and their prognostic value remains uncertain. Methods: This retrospective study analyzed the Oncology Research Information Exchange Network (ORIEN) alliance tumor RNA‐Seq data in Stages II and III CRC to investigate the association between RAS gene expression and survival outcomes. Results: High transcript levels of HRAS were associated with superior overall survival (OS). The high HRAS‐associated OS benefit was most pronounced in patients with right‐sided primary expressing low KRAS transcript levels in the absence of pathologic KRAS mutations. Conclusions: Contrary to the notion that RAS family genes are proto‐oncogenic, this study demonstrates that high HRAS transcript levels are associated with superior OS in Stages II and III CRC. The potential of HRAS as a prognostic biomarker should be explored further

Novel set of plasma proteins classifies Alzheimer's dementia in African American individuals with high accuracy

Introduction: African American (AA) individuals are underrepresented in biomarker studies for Alzheimer's disease (AD). Biomarkers that reflect the heterogeneity of AD and achieve the greatest accuracy across populations are sorely needed. Methods: Untargeted proteome measurements were obtained using the SomaScan 7k platform to identify novel plasma biomarkers for AD in AA participants with clinical diagnoses of AD dementia (n = 181) and cognitively unimpaired (CU, n = 142). Machine learning was used to identify a set of plasma proteins that yielded the best classification accuracy. Results: A set of 36 proteins achieved an area under the curve (AUC) of 0.94 to classify AD dementia versus CU, a 16% improvement over age, sex, and apolipoprotein E (APOE). This finding was replicated in multiple plasma and brain datasets (AUCs 0.73-0.97). Our findings underscore the importance of matrisome and cerebrovascular dysfunction in AD pathophysiology. Discussion: This study demonstrates the potential of biomarker discovery through untargeted plasma proteomics and machine learning. Highlights: Conducted large-scale plasma proteomics in Alzheimer's disease (AD) versus cognitively unimpaired controls. Machine learning biomarker discovery was replicated in an independent cohort. Novel set of proteins distinguishes AD versus controls with high accuracy (area under the curve [AUC] = 0.94). Achieved reproducibility across multiple replication cohorts (AUC = 0.73-0.97). Network analyses implicates matrisome biology and cerebrovascular dysfunction

Long‐Term (5‐Years) Outcomes of Current Drug‐Eluting Stents in Percutaneous Coronary Intervention: A Network Meta‐Analysis of Randomized Controlled Trials

Background: Various drug-eluting stents (DES) are currently used for percutaneous coronary intervention (PCI). However, long-term trials reveal inconsistent results in head-to-head comparisons. Aims: To conduct a network meta-analysis of relevant trials to assess the performance of different DES currently used in PCI. Methods: We systematically searched major databases for randomized controlled trials (RCTs) reporting 5-year outcomes of currently used DES and conducted a network meta-analysis using a frequentist random-effects model with odds ratios (ORs) as effect measures. DES were ranked by P-scores across several outcomes, with definite/probable stent thrombosis as the primary outcome. Statistical analyses were conducted in R software (v4.4.1), with significance set at p < 0.05. Results: Twenty-nine RCTs involving 46,502 patients were included in the analysis. Six currently used DES-Orsiro, Xience, Resolute, Nobori/BioMatrix, Synergy, and Promus-were analyzed. All comparisons showed nonsignificant results for outcomes at 5-year follow-up. Synergy ranked highest for definite/probable stent thrombosis (p = 0.85), all-cause mortality (p = 0.76), cardiac death (p = 0.87), and target vessel revascularization (p = 0.91). Promus ranked best for any myocardial infarction (MI) (p = 0.86), target lesion revascularization (p = 0.93), and target vessel-related MI (p = 0.73). Nobori/BioMatrix ranked highest for target lesion failure (p = 0.80). The newer generation Biofreedom stent also showed nonsignificant results but was excluded from the main analysis due to the availability of 5-year outcomes from only one study. Global and local inconsistencies were nonsignificant for all outcomes and comparisons. Conclusion: The analysis revealed no significant differences in 5-year outcomes among the various DES. However, Synergy and Promus performed best for key outcomes such as stent thrombosis, mortality, and MI, suggesting their potential for favorable performance in clinical practice

Glenoid morphology in patients undergoing reverse total shoulder arthroplasty due to fracture

Introduction: Glenoid morphology in patients undergoing reverse total shoulder arthroplasty (rTSA) due to arthritis has been previously studied; however, it has not been as thoroughly evaluated in fracture populations. The purpose of this study is to utilize pre-operative computed tomography (CT) scans to better understand the glenoid anatomy of those patients undergoing rTSA due to fracture. Materials and methods: Patients over the age of 18 who underwent rTSA for proximal humerus fractures from January 1, 2015 to October 31, 2023 at two university health system affiliated hospitals were included if they had a CT scan available for review and image reconstruction. Patients were excluded if a pathologic fracture was identified, surgery was performed greater than 6 weeks after the initial injury, surgery was a conversion or revision surgery, or if a glenoid fracture was present. Glenoid version and reverse shoulder arthroplasty (RSA) angles were measured by a musculoskeletal fellowship-trained radiologist and a shoulder and elbow fellowship-trained orthopaedic surgeon and averaged for final values. Glenoid morphologies were determined using the Walch and Favard classifications. Results: A total of 53 patients with a mean age of 70.4 years (range 36.6-91.2) were included in this study, 84.9% of which were female. Walch A1 glenoid morphology was noted in 92.5% of patients, and Favard E0 morphology was present in 98.1% of patients. Median glenoid version was 3° of retroversion. Median RSA angle was 19°. Of note, 37.7% of patients had a RSA angle of ≥ 20°. Conclusions: Patients undergoing rTSA for fracture may not have significant glenoid deformity from arthritic wear. However, surgeons should be aware of variations in glenoid version and RSA angle. In this study population, over one-third of patients had a RSA angle of ≥ 20°. Thus, surgeons should take these findings into account when performing rTSA for fracture

An Unusual Case of Cutaneous Langerhans Cell Sarcoma Lacking S100 Expression: A Case Report and Review of the Literature

Langerhans cell sarcoma (LCS) is a rare neoplastic proliferation of Langerhans cell with aggressive clinical behavior and involves multiple organ systems, including the skin. LCS is characterized by marked cytologic atypia, frequent mitoses including atypical ones, and expression of CD1a, S100, and langerin (CD207). CD1a and Langerin-positive but S100- negative LCS is extremely rare in clinical practice. We present a case of a 71-year-old female with a history of melanoma and atypical fibroxanthoma who presented with an erythematous plaque on her left knee. Histopathologic examination revealed a dermal infiltrate comprised of large pleomorphic cells with irregular nuclear contours, prominent longitudinal grooves, and vesicular chromatin, and a high mitotic rate. Notably, there were epidermotropism and a distinctive immunohistochemical profile: S100-, CD1a+, Langerin+, and focal CD68+. Next-generation sequencing identified copy number loss of CDKN2A, CDKN2B, and FOXA1, mutations in TP53, POT1, SH2B3, and SMARCA4, and a high tumor mutational burden. Herein, we discuss the clinical and pathologic features of 38 cases of LCS with cutaneous involvement reported in the literature, including recent advances in understanding molecular characteristics of this disease. This exceptional case may contribute to our understanding of the etiology of this rare neoplasm

2023 Indiana Registered Nurse (RNs Only) Workforce Snapshot

This report presents a snapshot of Indiana’s actively practicing registered nurse (RN) workforce as of the 2023 renewal period. It outlines key demographic and professional characteristics, including primary practice settings, specialties, populations served, and geographic distribution. It excludes advanced practice registered nurses (APRNs) and focuses solely on RNs, offering insights into educational backgrounds and service areas across various healthcare environments. The data serves as a resource for workforce planning, policy development, and healthcare system evaluation

Ketamine’s Therapeutic Role in Substance Use Disorders: A Narrative Review

Interest in ketamine as a novel treatment for substance use disorders (SUDs) has been increasing due to its N-methyl-D-aspartate (NMDA) glutamate receptor antagonism and mounting evidence that glutamate neurotransmission is involved in the pathogenesis of both depression and addictions. This narrative review provides an outline of clinical evidence reported in the literature from the 1970s to 2025 that examines the efficacy of ketamine for the treatment of SUDs, focusing primarily on randomized blinded controlled trials (RBCTs). Key cohort studies, retrospective studies, secondary analyses, case reports, and relevant basic neuroscience studies are reviewed to complement the more rigorous human controlled trial data. Thus far, ketamine has been tested in nine RBCTs targeting cocaine (three studies), alcohol (three studies), opioid use disorder (two studies), and nicotine (one study), suggesting efficacy for addiction in combination with psychotherapies, and often when doses produce subjectively reported mystical or psychedelic experiences. This review highlights promising preliminary evidence, and the need for more rigorous studies to elucidate the scope of drug addictions ketamine may target, its optimal dosing or route of administration, the importance of concurrent psychotherapies, professional supervision and safety monitoring, and which psychiatric comorbidities or contexts may contraindicate its use for SUDs