Long-term impact of artificial intelligence on colorectal adenoma detection in high-risk colonoscopy.

BACKGROUND: Improved adenoma detection rate (ADR) has been demonstrated with artificial intelligence (AI)-assisted colonoscopy. However, data on the real-world application of AI and its effect on colorectal cancer (CRC) screening outcomes is limited. AIM: To analyze the long-term impact of AI on a diverse at-risk patient population undergoing diagnostic colonoscopy for positive CRC screening tests or symptoms. METHODS: AI software (GI Genius, Medtronic) was implemented into the standard procedure protocol in November 2022. Data was collected on patient demographics, procedure indication, polyp size, location, and pathology. CRC screening outcomes were evaluated before and at different intervals after AI introduction with one year of follow-up. RESULTS: We evaluated 1008 colonoscopies (278 pre-AI, 255 early post-AI, 285 established post-AI, and 190 late post-AI). The ADR was 38.1% pre-AI, 42.0% early post-AI (P = 0.77), 40.0% established post-AI (P = 0.44), and 39.5% late post-AI (P = 0.77). There were no significant differences in polyp detection rate (PDR, baseline 59.7%), advanced ADR (baseline 16.2%), and non-neoplastic PDR (baseline 30.0%) before and after AI introduction. CONCLUSION: In patients with an increased pre-test probability of having an abnormal colonoscopy, the current generation of AI did not yield enhanced CRC screening metrics over high-quality colonoscopy. Although the potential of AI in colonoscopy is undisputed, current AI technology may not universally elevate screening metrics across all situations and patient populations. Future studies that analyze different AI systems across various patient populations are needed to determine the most effective role of AI in optimizing CRC screening in clinical practice.

Autonomic nervous system and endocrine system response to upper or lower cervical spine mobilization in males with persistent post-concussion symptoms: a proof-of-concept trial.

INTRODUCTION: The peripheral stress response, consisting of the autonomic nervous system (ANS) and hypothalamic pituitary adrenal-axis (HPA-axis), functions to maintain homeostasis in response to stressors. Cervical spine manual therapy has been shown to differentially modulate the stress response in healthy populations. No study has investigated whether cervical spine mobilizations can differentially modulate the stress response in individuals with persistent post-concussion symptoms (PPCS), a population characterized by a dysfunctional stress response. METHODS: A randomized, controlled, parallel design trial was performed to investigate whether upper or lower cervical spine mobilization can differentially modulate components of the stress response in individuals with PPCS. The outcomes were salivary cortisol (sCOR) concentration (primary) and the HRV metric, rMSSD, measured with a smartphone application (secondary). Nineteen males diagnosed with PPCS, aged 19-35, were included. Participants were randomly assigned into either intervention group, upper (n = 10) or lower (n = 9) cervical spine mobilization. Each outcome was collected at different time points, pre- and post-intervention. Statistical analyses were performed using the Friedman's Two-Way ANOVA, Mann-Whitney U test, and Wilcoxon Signed Rank Test. RESULTS: There was a statistically significant within-group reduction in sCOR concentration 30 minutes following lower cervical spine mobilizations and statistically significant within-group increase in rMSSD 30 minutes following upper cervical spine mobilizations. CONCLUSION: The results of this trial provide preliminary evidence for cervical spine mobilizations to differentially modulate components of the stress response at specific time points. Understanding the mechanisms of the effect of cervical spine mobilizations on the stress response provides a novel rationale for selecting cervical spine mobilizations to rehabilitate individuals with PPCS.

The molecular immune modulator adenosine deaminase-1 enhances HIV specific humoral and cellular responses to a native-like HIV envelope trimer DNA vaccine.

There is currently no prophylactic vaccine available for human immunodeficiency virus (HIV). Research efforts have resulted in improved immunogens that mimic the native envelope (Env) glycoprotein structure. Recently, a novel triple tandem trimer (TTT) platform has been used to generate a plasmid encoding Env immunogen (pBG505-TTT) that expresses only as trimers, making it more suitable for nucleic acid vaccines. We have previously demonstrated that adenosine deaminase-1 (ADA-1) is critical to the T follicular helper (TFH) function and improves vaccine immune responses in vivo. In this study, we demonstrate that co-delivery of plasmid-encoded adenosine deaminase 1 (pADA) with pBG505-TTT enhances the magnitude, durability, isotype switching and functionality of HIV-specific antibodies in a dose-sparing manner. Co-delivery of the molecular immune modulator ADA-1 also enhances HIV-specific T cell polyfunctionality, activation, and degranulation as well as memory B cell responses. These data demonstrate that pADA enhances HIV-specific cellular and humoral immunity, making ADA-1 a promising immune modulator for HIV-targeting vaccines.

Retraction notice to "Non-neuronal cholinergic system delays cardiac remodelling in type 1 diabetes" [Heliyon 9 (2023) e17434].

[This retracts the article DOI: 10.1016/j.heliyon.2023.e17434.].

Characteristics of Drug Poisonings Seen in the Emergency Department of an Urban Hospital.

Background: Drug poisoning, either intentional or non-intentional, is a frequent diagnosis in the emergency department (ED), necessitating patient management from multiple services. Objective: To describe the drug poisonings seen in the ED of a large academic urban hospital. Methods: This retrospective descriptive study used 3 years of data (2018-2020) abstracted from the hospital's electronic medical record system and linked to validated, coded extracts from the Canadian Institute for Health Information Discharge Abstract Database. Patients with a diagnosis of acute drug poisoning who presented to the ED were identified on the basis of International Statistical Classification of Diseases and Related Health Problems, 10th revision, Canada (ICD-10-CA) codes, and data were collected for demographic characteristics, the drugs involved, in-hospital management, and inpatient outcomes. Patients with diagnosis of an acute drug reaction, inebriation, or nondrug or in-hospital poisoning were excluded. Data were stratified and analyzed in relation to the intent of drug poisoning. Results: A total of 2983 visits for drug poisoning, involving 2211 unique patients (mean age 38.3 [standard deviation 16.2] years, 54.7% female), were included, yielding an overall incidence rate of 15.7 drug poisonings per 1000 ED visits (8.1 intentional, 6.4 non-intentional, and 1.3 unknown intent). Among the 1505 intentional drug poisonings, the most prevalent drug sources were antidepressants (n = 405, 26.9%), benzodiazepines (n = 375, 24.9%), and acetaminophen (n = 329, 21.9%); in contrast, opioids (n = 594, 48.1%) were most prevalent for the 1236 non-intentional poisonings. For 716 (24.0%) of the poisoning visits, the patient was admitted to acute care services, and the in-hospital mortality rate was 1.0% (n = 31). In addition, 111 patients (9.0%) with non-intentional drug poisoning left against medical advice. Finally, for 772 (25.9%) of the poisoning visits, the patient returned to the ED after discharge with a subsequent drug poisoning. Conclusions: Drug poisonings are a common cause of visits to urban EDs. They are rarely fatal but are associated with substantial utilization of hospital resources and considerable recidivism.

Contexte: L'intoxication médicamenteuse, intentionnelle ou non, est un diagnostic fréquent dans le service des urgences (SU); elle nécessite la prise en charge des patients par plusieurs services. Objectif: Décrire les intoxications médicamenteuses observées dans le SU d'un grand hôpital universitaire urbain. Méthodologie: Pour cette étude rétrospective et descriptive, des données contenues dans le système de dossiers médicaux électroniques de l'hôpital et liées à des extraits validés et codés de la base de données sur les congés des patients de l'Institut canadien d'information sur la santé pendant 3 ans (2018­2020) ont été utilisées. Les patients ayant reçu un diagnostic d'intoxication médicamenteuse aiguë qui se sont présentés à l'urgence ont été identifiés sur la base des codes de la Classification statistique internationale des maladies et des problèmes de santé connexes, 10e version, Canada (CIM-10-CA), et des données ont été recueillies pour les caractéristiques démographiques, les médicaments impliqués, la prise en charge à l'hôpital et les résultats pour les patients hospitalisés. Les patients présentant un diagnostic de réaction médicamenteuse aiguë, d'ébriété ou d'intoxication non médicamenteuse ou à l'hôpital ont été exclus. Les données ont été stratifiées et analysées en fonction de l'intention de l'empoisonnement médicamenteux. Résultats: Au total, 2983 cas mettant en cause 2211 patients (âge moyen 38,3 [écart type 16,2] ans, dont 54,7 % de femmes) ont été inclus; les résultats ont donné un taux d'incidence global de 15,7 intoxications médicamenteuses pour 1000 visites au SU (8,1 intentionnelles; 6,4 non intentionnelles; et 1,3 intention inconnue). Parmi les 1505 intoxications médicamenteuses intentionnelles, les médicaments les plus répandues étaient les antidépresseurs (n = 405, 26,9 %), les benzodiazépines (n = 375, 24,9 %) et l'acétaminophène (n = 329, 21,9 %); les opioïdes (n = 594, 48,1 %) étaient les plus répandus parmi les 1236 intoxications non intentionnelles. Dans 716 des cas (24,0 %), le patient a été admis dans les services de soins aigus. Le taux de mortalité hospitalière était de 1,0 % (n = 31). Par ailleurs, 111 patients (9,0 %) présentant une intoxication médicamenteuse non intentionnelle ont quitté l'hôpital contre avis médical. Enfin, dans 772 des cas d'intoxication (25,9 %), le patient est retourné à l'urgence après sa sortie à cause d'une intoxication médicamenteuse ultérieure. Conclusions: Les intoxications médicamenteuses sont une cause fréquente de visites dans les SU urbains. Ils sont rarement mortels, mais sont associés à une utilisation importante des ressources hospitalières et à une récidive considérable.

DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma.

Fibrolamellar carcinoma (FLC) is a liver tumor with a high mortality burden and few treatment options. A promising therapeutic vulnerability in FLC is its driver mutation, a conserved DNAJB1-PRKACA gene fusion that could be an ideal target neoantigen for immunotherapy. In this study, we aim to define endogenous CD8 T cell responses to this fusion in FLC patients and evaluate fusion-specific T cell receptors (TCRs) for use in cellular immunotherapies. We observe that fusion-specific CD8 T cells are rare and that FLC patient TCR repertoires lack large clusters of related TCR sequences characteristic of potent antigen-specific responses, potentially explaining why endogenous immune responses are insufficient to clear FLC tumors. Nevertheless, we define two functional fusion-specific TCRs, one of which has strong anti-tumor activity in vivo. Together, our results provide insights into the fragmented nature of neoantigen-specific repertoires in humans and indicate routes for clinical development of successful immunotherapies for FLC.

A Rare Case of Esophageal Carcinoma Cuniculatum Palliated by Esophageal and Endobronchial Stenting.

Carcinoma cuniculatum is a rare variant of well-differentiated squamous cell carcinoma. To date, there are less than 30 cases of esophageal carcinoma cuniculatum reported. It is frequently a diagnostic challenge: A definitive diagnosis typically cannot be made before esophagectomy. We present a uniquely aggressive case of esophageal carcinoma cuniculatum complicated by a bronchoesophageal fistula and successfully palliated with dual esophageal and endobronchial stenting.

Population Based Time Trends in the Epidemiology and Mortality of Gastroesophageal Junction and Esophageal Adenocarcinoma.

BACKGROUND: Limited data are available on the epidemiology of gastroesophageal junction adenocarcinoma (GEJAC), particularly in comparison to esophageal adenocarcinoma (EAC). With the advent of molecular non-endoscopic Barrett's esophagus (BE) detection tests which sample the esophagus and gastroesophageal junction, early detection of EAC and GEJAC has become a possibility and their epidemiology has gained importance. AIMS: We sought to evaluate time trends in the epidemiology and survival of patients with EAC and GEJAC in a population-based cohort. METHODS: EAC and GEJAC patients from 1976 to 2019 were identified using ICD 9 and 10 diagnostic codes from the Rochester Epidemiology Project (REP). Clinical data and survival status were abstracted. Poisson regression was used to calculate incidence rate ratios (IRR). Survival analysis and Cox proportional models were used to assess predictors of survival. RESULTS: We included 443 patients (287 EAC,156 GEJAC). The incidence of EAC and GEJAC during 1976-2019 was 1.40 (CI 1.1-1.74) and 0.83 (CI 0.61-1.11) per 100,000 people, respectively. There was an increase in the incidence of EAC (IRR = 2.45, p = 0.011) and GEJAC (IRR = 3.17, p = 0.08) from 2000 to 2004 compared to 1995-1999, plateauing in later time periods. Most patients had associated BE and presented at advanced stages, leading to high 5-year mortality rates (66% in EAC and 59% in GEJAC). Age and stage at diagnosis were predictors of mortality. CONCLUSION: The rising incidence of EAC/GEJAC appears to have plateaued somewhat in the last decade. However, both cancers present at advanced stages with persistently poor survival, underscoring the need for early detection.