Impact of study design on adenoma detection in the evaluation of artificial intelligence-aided colonoscopy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Randomized controlled trials (RCTs) have reported that artificial intelligence (AI) improves endoscopic polyp detection. Different methodologies-namely, parallel and tandem designs-have been used to evaluate the efficacy of AI-assisted colonoscopy in RCTs. Systematic reviews and meta-analyses have reported a pooled effect that includes both study designs. However, it is unclear whether there are inconsistencies in the reported results of these 2 designs. Here, we aimed to determine whether study characteristics moderate between-trial differences in outcomes when evaluating the effectiveness of AI-assisted polyp detection. METHODS: A systematic search of Ovid MEDLINE, Embase, Cochrane Central, Web of Science, and IEEE Xplore was performed through March 1, 2023, for RCTs comparing AI-assisted colonoscopy with routine high-definition colonoscopy in polyp detection. The primary outcome of interest was the impact of study type on the adenoma detection rate (ADR). Secondary outcomes included the impact of the study type on adenomas per colonoscopy and withdrawal time, as well as the impact of geographic location, AI system, and endoscopist experience on ADR. Pooled event analysis was performed using a random-effects model. RESULTS: Twenty-four RCTs involving 17,413 colonoscopies (AI assisted: 8680; non-AI assisted: 8733) were included. AI-assisted colonoscopy improved overall ADR (risk ratio [RR], 1.24; 95% confidence interval [CI], 1.17-1.31; I2 = 53%; P < .001). Tandem studies collectively demonstrated improved ADR in AI-aided colonoscopies (RR, 1.18; 95% CI, 1.08-1.30; I2 = 0%; P < .001), as did parallel studies (RR, 1.26; 95% CI, 1.17-1.35; I2 = 62%; P < .001), with no statistical subgroup difference between study design. Both tandem and parallel study designs revealed improvement in adenomas per colonoscopy in AI-aided colonoscopies, but this improvement was more marked among tandem studies (P < .001). AI assistance significantly increased withdrawal times for parallel (P = .002), but not tandem, studies. ADR improvement was more marked among studies conducted in Asia compared to Europe and North America in a subgroup analysis (P = .007). Type of AI system used or endoscopist experience did not affect overall improvement in ADR. CONCLUSIONS: Either parallel or tandem study design can capture the improvement in ADR resulting from the use of AI-assisted polyp detection systems. Tandem studies powered to detect differences in endoscopic performance through paired comparison may be a resource-efficient method of evaluating new AI-assisted technologies.

The Role of Resilience in Irritable Bowel Syndrome, Other Chronic Gastrointestinal Conditions, and the General Population.

BACKGROUND & AIMS: Resilience is the ability to adapt positively to stress and adversity. It is a potential therapeutic target as it is reduced in irritable bowel syndrome (IBS) compared to healthy controls and associated with worse symptom severity and poorer quality of life. The aim of this study was to examine if these findings are generalizable by comparing resilience between IBS versus the general population and other chronic gastrointestinal (GI) conditions. METHODS: Participants in the general population completed an online survey containing questionnaires measuring demographics, diagnosis of IBS and other GI conditions, symptom severity, psychological symptoms, resilience, and early adverse life events (EALs). IBS was defined as having a physician diagnosis of IBS and/or meeting Rome criteria without co-morbid GI disease. All others were included in the general population group. The chronic GI conditions group included those with inflammatory bowel disease, celiac disease and/or microscopic colitis. RESULTS: Resilience was lower in IBS (n = 820) than the general population (n = 1026; p < 0.001) and associated with worse IBS symptom severity (p < 0.05). Global mental health affected resilience differently in IBS compared to the general population (all p's < 0.05). EALs were associated with decreased ability to bounce back from adversity in both IBS and the general population (p < 0.001). Resilience scores were similar in IBS and other chronic GI conditions that present with similar symptoms. CONCLUSIONS: Resilience is lower compared to the general U.S. population but does not appear to be specific to IBS as it is comparable to other chronic GI conditions. Low resilience negatively affects symptom severity and mental health and thus, may serve as a novel therapeutic target.

Efficacy of Biofeedback Therapy in Clinical Practice for the Management of Chronic Constipation and Fecal Incontinence.

BACKGROUND: Chronic constipation (CC) and fecal incontinence (FI) are often secondary to pelvic floor neuromuscular sensory or motor dysfunction. Biofeedback therapy (BFT) uses visual and verbal feedback to improve anorectal coordination, strength and sensation. In clinical trials, BFT demonstrated response rates between 70% and 80%. The purpose of this study is to determine the effectiveness of BFT in clinical practice. METHODS: In this retrospective observational cohort study, the charts of all patients who completed BFT at our centre were reviewed. A positive response to BFT was defined as improvement in ARM profile from baseline or subjective symptom improvement or both. Descriptive statistics were used to analyze the data. RESULTS: One hundred thirty patients with an average age of 57.5 ± 16.4 years and 79.2% female were included. Of all patients, 43.1% were referred for CC, 37.7% for FI, 16.9% for alternating CC and FI, and 2.3% for rectal pain. The overall response rate to BFT was 76.2% (n=99). Of those that responded, 64.6% (n=64) demonstrated both ARM and symptom improvement, 27.3% (n=27) had ARM improvement but no symptom improvement, and 8.1% (n=8) had symptom improvement but no ARM improvement. In patients with FI, the overall response rate was 79.6% (n=39) with symptom improvement in 67.3% (n=33). In those with CC with dyssynergic defecation (n=53), the overall response rate was 69.8% (n=37); however, only 45.3% (n=24) had symptomatic improvement. CONCLUSION: In our clinical practice, although overall response rates to BFT are similar to published reports, patients with CC with dyssynergic defecation are less likely to have symptomatic response compared with those with FI.

Influence of video-based feedback on self-assessment accuracy of endoscopic skills: a randomized controlled trial.

Background and study aims Novice endoscopists are inaccurate in self-assessment of procedures. One means of improving self-assessment accuracy is through video-based feedback. We aimed to determine the comparative effectiveness of three video-based interventions on novice endoscopists' self-assessment accuracy of endoscopic competence. Materials and methods Novice endoscopists (performed < 20 previous procedures) were recruited. Participants completed a simulated esophagogastroduodenoscopy (EGD) on a virtual reality simulator. They were then randomized to one of three groups: self-video review (SVR), which involved watching a recorded video of their own performance; benchmark review (BVR), which involved watching a video of a simulated EGD completed by an expert; and self- and benchmark video (SBVR), which involved both videos. Participants then completed two additional simulated EGD cases. Self-assessments were conducted immediately after the first procedure, after the video intervention and after the additional two procedures. External assessments were conducted by two experienced endoscopists, who were blinded to participant identity and group assignment through video recordings. External and self-assessments were completed using the global rating scale component of the Gastrointestinal Endoscopy Competency Assessment Tool (GiECAT GRS). Results Fifty-one participants completed the study. The BVR group had significantly improved self-assessment accuracy in the short-term, compared to the SBVR group ( P  = .005). The SBVR group demonstrated significantly improved self-assessment accuracy over time ( P  = .016). There were no significant effects of group or of time for the SVR group. Conclusions Video-based interventions, particularly combined use of self- and benchmark video review, can improve accuracy of self-assessment of endoscopic competence among novices.

Negative Events During Adulthood Are Associated With Symptom Severity and Altered Stress Response in Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a stress-sensitive disorder associated with dysregulation of the hypothalamic-pituitary-adrenal axis. We studied the cumulative effect of events during adulthood on this pathway in patients with IBS. METHODS: We studied 129 patients with IBS, based on Rome III criteria (mean age 28.1 years, 66% women), and 108 healthy individuals (controls; mean age 29.8 years, 60% women) who completed the Life Experiences Survey from August 2013 to September 2017. Data were collected on the presence and effects of events since age 18, IBS severity scores, and IBS-related quality of life. For a subset of subjects, we measured serum cortisol and adrenocorticotropic hormone (ACTH) production in response to administration of corticotropin-releasing factor and ACTH. RESULTS: Compared with controls, patients with IBS perceived more adulthood life events as negative and had a significantly higher negative life event impact score (14.17 ± 12.04 vs 10.83 ± 9.98; P=.022). In patients with IBS, the presence of more-negatively perceived adulthood life events was associated with worse IBS symptom severity (ß = 1.53, 95% CI, 0.21-2.84; P = .025) and IBS-related quality of life (ß = -0.70; 95% CI, -1.02 to -0.38; P < .001). Negatively perceived adulthood life events were associated with reduced production of ACTH in response to corticotropin-releasing factor in patients with IBS compared with controls (P < .05). CONCLUSION: In a study of more than 200 subjects, we associated more-negatively perceived events during adulthood with an increased risk for IBS, worse symptom severity and quality of life, and a dysregulated stress response. Understanding the effects of events that cause stress in adults and their perceived effects on IBS may help guide disease management.

The Use of Standardized Questions in Identifying Patients with Dyssynergic Defecation.

BACKGROUND: Dyssynergic defecation (DD) is present in approximately 30% of patients with idiopathic chronic constipation (CC). Diagnostic criteria for DD require objective testing such as anorectal manometry (ARM); yet, ARM remains a limited resource in Canada. The aim of this study is to determine the predictability of DD in patients with CC using a standardized self-reported symptom questionnaire. METHOD: In this study, 166 consecutive English-speaking patients with CC who were referred for ARM completed a symptom questionnaire. DD was diagnosed if pelvic floor dyssynergy was demonstrated by ARM and balloon expulsion time was more than one minute. Likelihood ratios (LRs) were calculated for individual symptoms and prespecified symptom combinations. Likelihood ratios greater than five or less than 0.2 were considered significant. A recursive partitioning tree was used to find the symptoms best able to predict DD. RESULTS: No single constipation symptom was sufficient to predict a diagnosis of DD. Patients who reported sometimes feeling an urge to defecate and a prolonged straining duration of greater than five minutes were more likely to have DD (LR = 7.74). In patients who reported straining often or always and had a short straining duration of less than two minutes, the diagnosis of DD was less likely (LR = 0.04). The recursive partitioning tree analysis similarly identified a sense of urge with a prolonged straining duration as predictor for DD, as well as an incomplete evacuation as another potential predictor. CONCLUSION: Questions regarding need to strain, duration of straining, urge to defecate, and incomplete evacuation are useful to predict the presence of DD in patients with CC. These questions will enable clinicians to make a clinical diagnosis of DD to guide treatment.

Linaclotide: a new option for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation in adults.

Chronic idiopathic constipation (CC) and irritable bowel syndrome with predominant constipation (IBS-C) are the 2 most common conditions among functional gastrointestinal disorders. Despite current multiple therapeutic options, treatment remains challenging and dissatisfactory to many patients. Linaclotide is a novel therapeutic agent, which is a guanylate cyclase receptor agonist that stimulates water secretion from the intestinal epithelium by promoting chloride and bicarbonate efflux into the lumen through activation of the cystic fibrosis transmembrane conductance regulator. Clinical trials have demonstrated that linaclotide is effective, safe and well tolerated in patients with CC and IBS-C. This review article highlights the mechanism of action of linaclotide, reviews published literature based on a search of databases, including MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), up to February 2013, and compares its utility with other currently available agents.

Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1.

BACKGROUND: The acute respiratory distress syndrome (ARDS), a clinical complication of severe acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. ALI is characterized by disruption of the lung alveolar-capillary membrane barrier and resultant pulmonary edema associated with a proteinaceous alveolar exudate. Current specific treatment strategies for ALI/ARDS are lacking. We hypothesized that mesenchymal stem cells (MSCs), with or without transfection with the vasculoprotective gene angiopoietin 1 (ANGPT1) would have beneficial effects in experimental ALI in mice. METHODS AND FINDINGS: Syngeneic MSCs with or without transfection with plasmid containing the human ANGPT1 gene (pANGPT1) were delivered through the right jugular vein of mice 30 min after intratracheal instillation of lipopolysaccharide (LPS) to induce lung injury. Administration of MSCs significantly reduced LPS-induced pulmonary inflammation, as reflected by reductions in total cell and neutrophil counts in bronchoalveolar lavage (BAL) fluid (53%, 95% confidence interval [CI] 7%-101%; and 60%, CI 4%-116%, respectively) as well as reducing levels of proinflammatory cytokines in both BAL fluid and lung parenchymal homogenates. Furthermore, administration of MSCs transfected with pANGPT1 resulted in nearly complete reversal of LPS-induced increases in lung permeability as assessed by reductions in IgM and albumin levels in BAL (96%, CI 6%-185%; and 74%, CI 23%-126%, respectively). Fluorescently tagged MSCs were detected in the lung tissues by confocal microscopy and flow cytometry in both naïve and LPS-injured animals up to 3 d. CONCLUSIONS: Treatment with MSCs alone significantly reduced LPS-induced acute pulmonary inflammation in mice, while administration of pANGPT1-transfected MSCs resulted in a further improvement in both alveolar inflammation and permeability. These results suggest a potential role for cell-based ANGPT1 gene therapy to treat clinical ALI/ARDS.

Cell-based angiopoietin-1 gene therapy for acute lung injury.

RATIONALE: The acute respiratory distress syndrome is a significant cause of morbidity and mortality in critically ill patients. Angiopoietin-1 (Ang-1), a ligand for the endothelial Tie2 receptor, is an endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte-endothelium interactions. OBJECTIVES: We hypothesized that Ang-1 counteracts vascular inflammation and pulmonary vascular leak in experimental acute lung injury. METHODS: We used cell-based gene therapy in a rat model of ALI. Transgenic mice overexpressing Ang-1 or deficient in the Tie2 receptor were also studied to better elucidate the mechanisms of protection. MEASUREMENTS AND MAIN RESULTS: The present report provides data that support a strong protective role for the Ang-1/Tie2 system in two experimental models of LPS-induced acute lung injury. In a rat model, cell-based Ang-1 gene transfer improved morphological, biochemical, and molecular indices of lung injury and inflammation. These findings were confirmed in a gain-of-function conditional, targeted transgenic mouse model, in which Ang-1 reduced endothelial cell activation and the expression of adhesion molecules, associated with a marked improvement in airspace inflammation and intraalveolar septal thickening. Moreover, heterozygous Tie2-deficient mice demonstrated enhanced evidence of lung injury and increased early mortality. CONCLUSIONS: These results support a critical role for the Ang-1/Tie2 axis in modulating the pulmonary vascular response to lung injury and suggest that Ang-1 therapy may represent a potential new strategy for the treatment and/or prevention of acute respiratory distress syndrome in critically ill patients.