Use of a Novel Artificial Intelligence System Leads to the Detection of Significantly Higher Number of Adenomas During Screening and Surveillance Colonoscopy: Results From a Large, Prospective, US Multicenter, Randomized Clinical Trial.

INTRODUCTION: Adenoma per colonoscopy (APC) has recently been proposed as a quality measure for colonoscopy. We evaluated the impact of a novel artificial intelligence (AI) system, compared with standard high-definition colonoscopy, for APC measurement. METHODS: This was a US-based, multicenter, prospective randomized trial examining a novel AI detection system (EW10-EC02) that enables a real-time colorectal polyp detection enabled with the colonoscope (CAD-EYE). Eligible average-risk subjects (45 years or older) undergoing screening or surveillance colonoscopy were randomized to undergo either CAD-EYE-assisted colonoscopy (CAC) or conventional colonoscopy (CC). Modified intention-to-treat analysis was performed for all patients who completed colonoscopy with the primary outcome of APC. Secondary outcomes included positive predictive value (total number of adenomas divided by total polyps removed) and adenoma detection rate. RESULTS: In modified intention-to-treat analysis, of 1,031 subjects (age: 59.1 ± 9.8 years; 49.9% male), 510 underwent CAC vs 523 underwent CC with no significant differences in age, gender, ethnicity, or colonoscopy indication between the 2 groups. CAC led to a significantly higher APC compared with CC: 0.99 ± 1.6 vs 0.85 ± 1.5, P = 0.02, incidence rate ratio 1.17 (1.03-1.33, P = 0.02) with no significant difference in the withdrawal time: 11.28 ± 4.59 minutes vs 10.8 ± 4.81 minutes; P = 0.11 between the 2 groups. Difference in positive predictive value of a polyp being an adenoma among CAC and CC was less than 10% threshold established: 48.6% vs 54%, 95% CI -9.56% to -1.48%. There were no significant differences in adenoma detection rate (46.9% vs 42.8%), advanced adenoma (6.5% vs 6.3%), sessile serrated lesion detection rate (12.9% vs 10.1%), and polyp detection rate (63.9% vs 59.3%) between the 2 groups. There was a higher polyp per colonoscopy with CAC compared with CC: 1.68 ± 2.1 vs 1.33 ± 1.8 (incidence rate ratio 1.27; 1.15-1.4; P < 0.01). DISCUSSION: Use of a novel AI detection system showed to a significantly higher number of adenomas per colonoscopy compared with conventional high-definition colonoscopy without any increase in colonoscopy withdrawal time, thus supporting the use of AI-assisted colonoscopy to improve colonoscopy quality ( ClinicalTrials.gov NCT04979962).

Nurse-Administered Propofol Continuous Infusion Sedation: A New Paradigm for Gastrointestinal Procedural Sedation.

INTRODUCTION: Nurse-Administered Propofol Continuous Infusion Sedation (NAPCIS) is a new nonanesthesia propofol delivery method for gastrointestinal endoscopy. NAPCIS is adopted from the computer-assisted propofol sedation (CAPS) protocol. We evaluated the effectiveness, efficiency, and safety of NAPCIS in low-risk subjects. METHODS: Between December 2016 and July 2017, patients who underwent esophagogastroduodenoscopy or colonoscopy with NAPCIS at our center were compared against 2 historical control groups of similar patients who had undergone procedures with CAPS or midazolam and fentanyl (MF) sedation. RESULTS: The mean age of the NAPCIS cohort (N = 3,331) was 55.2 years (45.8% male) for 945 esophagogastroduodenoscopies and 57.8 years (48.7% male) for 2,386 colonoscopies. The procedural success rates with NAPCIS were high (99.1%-99.2%) and similar to those seen in 3,603 CAPS (98.8%-99.0%) and 3,809 MF (99.0%-99.3%) controls. NAPCIS recovery times were shorter than both CAPS and MF (24.8 vs 31.7 and 52.4 minutes, respectively; P < 0.001). On arrival at the recovery unit, 86.6% of NAPCIS subjects were recorded as "Awake" compared with 82.8% of CAPS and 40.8% of MF controls (P < 0.001). Validated clinician and patient satisfaction scores were generally higher for NAPCIS compared with CAPS and MF subjects. For NAPCIS, there were only 4 cases of oxygen desaturation requiring transient mask ventilation and no serious sedation-related complications. These low complication rates were similar to those seen with CAPS (8 cases of mask ventilation) and MF (3 cases). DISCUSSION: NAPCIS seems to be a safe, effective, and efficient means of providing moderate sedation for upper endoscopy and colonoscopy in low-risk patients.

Nurse-Administered Propofol Continuous Infusion Sedation for Gastrointestinal Endoscopy in Patients Who Are Difficult to Sedate.

BACKGROUND & AIMS: Patients who chronically use alcohol, marijuana, or opioids, or suffer from post-traumatic stress disorder (PTSD), can be difficult to sedate with midazolam and fentanyl, and often are referred for monitored anesthesia care during endoscopy. Nurse-administered propofol continuous infusion sedation (NAPCIS), which confers the benefit of propofol-based sedation without the added expense of anesthesia, is effective and safe for sedation of healthy patients. We investigated whether NAPCIS also is effective for patients who are difficult to sedate. METHODS: We performed a retrospective study of patients who underwent upper endoscopy or colonoscopy with NAPCIS at a single center from January 2018 through April 2018. We reviewed records from patients who were heavy users of alcohol (n = 105), daily users of marijuana (n = 267) or opioids (n = 178), had a diagnosis of PTSD (n = 91), or were none of these (controls, n = 786). We compared mean fentanyl and propofol doses (adjusted for body weight), procedure and recovery times, procedure success rates, and adverse events. RESULTS: Compared with the controls, the marijuana group required higher mean adjusted sedative doses for colonoscopies (0.6 vs 0.4 mcg/kg fentanyl and 5.0 vs 4.7 mg/kg propofol; P ≤ .025 for both) and upper endoscopies (0.8 vs 0.3 mcg/kg fentanyl and 3.7 vs 3.2 mg/kg propofol; P ≤ .021 for both), the PTSD group required a higher dose of fentanyl for colonoscopies (0.6 vs 0.4 mcg/kg; P = .009), and the alcohol group required a higher dose of fentanyl for upper endoscopies (0.7 vs 0.3 mcg/kg; P < .001). Procedure success rates were high (95.1%-100%) and did not differ significantly between the difficult-to-sedate groups and controls; mean procedure times (7.0-9.0 minutes for upper endoscopies, 21.1-22.9 minutes for colonoscopies) and recovery times (22.5-29.6 minutes) also were similar among groups. Upper endoscopies were associated with lower sedative doses and shorter procedure and recovery times than colonoscopies. Sedation-related adverse events were rare in all groups (only 26 cases total), and there were no serious complications or deaths. CONCLUSIONS: NAPCIS seems to be a safe and effective means of providing sedation for endoscopy to patients who may be difficult to sedate owing to alcohol, marijuana, or opioid use, or PTSD.

Computer-Assisted Propofol Sedation for Esophagogastroduodenoscopy Is Effective, Efficient, and Safe.

BACKGROUND AND AIMS: Computer-assisted propofol sedation (CAPS) allows non-anesthesiologists to administer propofol for gastrointestinal procedures in relatively healthy patients. As the first US medical center to adopt CAPS technology for routine clinical use, we report our 1-year experience with CAPS for esophagogastroduodenoscopy (EGD). METHODS: Between September 2014 and August 2015, 926 outpatients underwent elective EGDs with CAPS at our center. All EGDs were performed by 1 of 17 gastroenterologists certified in the use of CAPS. Procedural success rates, procedure times, and recovery times were compared against corresponding historical controls done with midazolam and fentanyl sedation from September 2013 to August 2014. Adverse events in CAPS patients were recorded. RESULTS: The mean age of the CAPS cohort was 56.7 years (45% male); 16.2% of the EGDs were for variceal screening or Barrett's surveillance and 83.8% for symptoms. The procedural success rates were similar to that of historical controls (99.0% vs. 99.3%; p = 0.532); procedure times were also similar (6.6 vs. 7.4 min; p = 0.280), but recovery time was markedly shorter (31.7 vs. 52.4 min; p < 0.001). There were 11 (1.2%) cases of mild transient oxygen desaturation (< 90%), 15 (1.6%) cases of marked agitation due to undersedation, and 1 case of asymptomatic hypotension. In addition, there were six (0.6%) patients with more pronounced desaturation episodes that required brief (< 1 min) mask ventilation. There were no other serious adverse events. CONCLUSIONS: CAPS appears to be a safe, effective, and efficient means of providing sedation for EGD in healthy patients. Recovery times were much shorter than historical controls.

One year experience with computer-assisted propofol sedation for colonoscopy.

AIM: To report our one-year experience with computer assisted propofol sedation (CAPS) for colonoscopy as the first United States Medical Center to adopt CAPS technology for routine clinical use. METHODS: Between September 2014 and August 2015, 2677 patients underwent elective outpatient colonoscopy with CAPS at our center. All colonoscopies were performed by 1 of 17 gastroenterologists certified in the use of the CAPS system, with the assistance of a specially trained nurse. Procedural success rates, polyp detection rates, procedure times and recovery times were recorded and compared against corresponding historical measures from 2286 colonoscopies done with midazolam and fentanyl from September 2013 to August 2014. Adverse events in the CAPS group were recorded. RESULTS: The mean age of the CAPS cohort was 59.9 years (48.7% male); 31.3% were ASA I, 67.3% ASA II and 1.4% ASA III. 45.1% of the colonoscopies were for screening, 31.5% for surveillance, and 23.4% for symptoms. The mean propofol dose administered was 250.7 mg (range 16-1470 mg), with a mean fentanyl dose of 34.1 mcg (0-100 mcg). The colonoscopy completion and polyp detection rates were similar to that of historical measures. Recovery times were markedly shorter (31 min vs 45.6 min, P < 0.001). In CAPS patients, there were 20 (0.7%) cases of mild desaturation (< 90%) treated with a chin lift and reduction or temporary discontinuation of the propofol infusion, 21 (0.8%) cases of asymptomatic hypotension (< 90 systolic blood pressure) treated with a reduction in the propofol rate, 4 (0.1%) cases of marked agitation or discomfort due to undersedation, and 2 cases of pronounced transient desaturation requiring brief (< 1 min) mask ventilation. There were no sedation-related serious adverse events such as emergent intubation, unanticipated hospitalization or permanent injury. CONCLUSION: CAPS appears to be a safe, effective and efficient means of providing moderate sedation for colonoscopy in relatively healthy patients. Recovery times were much shorter than historical measures. There were few adverse events, and no serious adverse events, related to CAPS.

Incidence and outcomes of Clostridium difficile-associated disease in hematopoietic cell transplant recipients.

Hematopoietic stem cell transplant (HSCT) recipients are at a high risk of Clostridium difficile-associated disease (CDAD) given frequent hospitalizations, prolonged antibiotic usage and altered integrity of intestinal mucosa. The prevalence and trends of CDAD in HSCT patients have not been extensively studied. In this study, the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes were used to identify CDAD in HSCT patients using a nationwide inpatient sample in the United States from 2000 to 2009. The prevalence of CDAD and in-hospital mortality in HSCT were investigated and compared to those without any transplants. Multivariate analysis was performed to identify if BMT and graft versus host disease (GVHD) were independently associated with mortality in CDAD patients. Of the 344,507 HSCT discharges, 4.7 % had CDAD. This was about 5 times higher when compared to non-transplant discharges. During engraftment admission, rates of CDAD were higher in allogenic group (8.4 vs. 5.7 %, p < 0.001). In subsequent admissions, those with GVHD had higher rates of CDAD (5.7 vs. 3.2 %, p < 0.001). On adjusted analysis in patients with CDAD, during engraftment admission, allogenic group had significantly higher mortality when compared with non-transplants (OR 3.7). Notably, there was no significant difference in mortality between patients with and without CDAD during the engraftment period for the allogeneic group. In subsequent admissions, there was higher mortality in those with GVHD (OR 4.8). Though the prevalence of CDAD in non-transplant population doubled (from 0.44 % in 2000 to 0.99 % in 2008), it has remained stable in HSCT patients (from 4.8 % in 2000 to 5.6 % in 2008). HSCT and GVHD are independently associated with CDAD though its presence does not affect mortality.

Dickkopf-1, the Wnt antagonist, is induced by acidic pH and mediates epithelial cellular senescence in human reflux esophagitis.

Squamous esophageal epithelium adapts to acid reflux-mediated injury by proliferation and differentiation via signal transduction pathways. Induction of the Wnt antagonist Dickkopf-1 (Dkk1) is involved in tissue repair during inflammation and cellular injury. In this study, we aimed to identify the biological role of Dkk1 in human reflux esophagitis with respect to cell growth and regulation of Wnt signaling. Esophageal biopsies from reflux-esophagitis patients (n = 15) and healthy individuals (n = 10) were characterized in terms of Dkk1 expression. The role of Dkk1 in response to acid-mediated epithelial injury was analyzed by cellular assays in vitro utilizing squamous esophageal epithelial cell lines (EPC1-hTERT, EPC2-hTERT, and HEEC). Dkk1 was significantly overexpressed in human reflux-esophagitis tissue compared with healthy esophageal mucosa at transcriptional and translational levels. After acute and chronic acid (pH 4) exposure, esophageal squamous epithelial cell lines expressed and secreted high levels of Dkk1 in response to stress-associated DNA injury. High extracellular levels of human recombinant Dkk1 inhibited epithelial cell growth and induced cellular senescence in vitro, as demonstrated by reduced cell proliferation, G0/G1 cell cycle arrest, elevated senescence-associated ß-galactosidase activity, and upregulation of p16. Acid pulsing induced Dkk1-mediated senescence, which was directly linked to the ability of Dkk1 to antagonize the canonical Wnt/ß-catenin signaling. In healthy esophageal mucosa, Dkk1 expression was associated with low expression of transcriptionally active ß-catenin, while in reflux-esophagitis tissue, Dkk1 overexpression correlated with increased senescence-associated ß-galactosidase activity and p16 upregulation. The data indicate that, in human reflux esophagitis, Dkk1 functions as a secreted growth inhibitor by suppressing Wnt/ß-catenin signaling and promoting cellular senescence. These findings suggest a significant role for Dkk1 and cellular senescence in esophageal tissue homeostasis during reflux esophagitis.

Surgical outcomes in the elderly with inflammatory bowel disease are similar to those in the younger population.

BACKGROUND: Inflammatory bowel disease (IBD) has a bimodal distribution with approximately 15 % of patients manifesting after age 65. Previous reports suggest an increased risk of surgical complications in the elderly. AIM: To compare surgical outcomes in elderly IBD patients (≥ 65 years at the time of surgery) to matched younger IBD cohorts. METHODS: This was a retrospective cohort study at a single academic center of patients who underwent surgery for IBD. Forty-two elderly patients (≥ 65 years) were matched at least 1:1 (median 1:5) to patients in each of three control groups [18-35 years (n = 71); 36-49 years (n = 62); 50-64 years (n = 58)] according to gender, disease type/location, and type of surgery. Postoperative complications were compared. Patient characteristics were used in multivariate risk models. Analysis was performed using ordinary logistic regression. RESULTS: Twenty ileal or ileocolonic resections, 12 partial or total colectomies, four stricturoplasties, and six laparoscopic partial or total colectomies were performed in the elderly group. The post-operative complication rate was not statistically different between the elderly and younger cohorts (38 % vs. 39 % vs. 40 % vs. 48 % in the 18-35, 36-49, 50-64, and ≥ 65 years groups, respectively, p = 0.26). The only significant risk factors for complication were Charlson comorbidity index (p = 0.0002), preoperative hemoglobin (p = 0.0065), total parenteral nutrition use (p = 0.024), and failed medical therapy (as the indication for surgery) (p = <0.0001). CONCLUSIONS: The surgical complication rate among elderly and younger IBD patients was similar. Advanced age by itself should not be considered a risk factor for adverse operative outcome.

Gene signature distinguishes patients with chronic ulcerative colitis harboring remote neoplastic lesions.

BACKGROUND: Individuals with ulcerative colitis (UC) are at increased risk for colorectal cancer. The standard method of surveillance for neoplasia in UC by colonoscopy is invasive and can miss flat lesions. We sought to identify a gene expression signature in nondysplastic mucosa without active inflammation that could serve as a marker for remote neoplastic lesions. METHODS: Gene expression was analyzed by complementary DNA microarray in 5 normal controls, 4 UC patients without dysplasia, and 11 UC patients harboring remote neoplasia. Common gene ontology pathways of significantly differentially expressed genes were identified. Expression of genes which were progressively and significantly upregulated from controls to UC without neoplasia, to UC with remote neoplasia were evaluated by real-time polymerase chain reaction. Several gene products were also examined by immunohistochemistry. RESULTS: Four hundred and sixty-eight genes were significantly upregulated, and 541 genes were significantly downregulated in UC patients with neoplasia compared with UC patients without neoplasia. Nine genes (ACSL1, BIRC3, CLC, CREM, ELTD1, FGG, S100A9, THBD, and TPD52L1) were progressively and significantly upregulated from controls to nondysplastic UC to UC with neoplasia. Immunostaining of proteins revealed increased expression of S100A9 and REG1α in UC-associated cancer and in nondysplastic tissue from UC patients harboring remote neoplasia compared with UC patients without neoplasia and controls. CONCLUSIONS: Gene expression changes occurring as a field effect in the distal colon of patients with chronic UC identify patients harboring remote neoplastic lesions. These markers may lead to a more accurate and less invasive method of detection of neoplasia in patients with inflammatory bowel disease.

Multiple progressive focal nodular hyperplasia lesions of liver in a patient with hemosiderosis.

Focal nodular hyperplasia (FNH) is the second most common benign lesion of the liver. It is a solitary lesion and usually does not enlarge. We present the magnetic resonance imaging findings of multiple progressive FNH lesions in a patient with hemosiderosis using Gadolinium-EOB-DTPA (Eovist) as a hepatobiliary contrast agent. The possible mechanisms underlying the occurrence and progression of FNH lesions and the potential value of Eovist in characterizing the lesions were discussed.

Multiple abdominal vascular anomalies in a patient with Alagille syndrome.

Alagille syndrome affects multiple organ systems. The most common vascular manifestation of Alagille syndrome is peripheral pulmonary artery stenosis. A few cases of abdominal vasculature involvement have been reported, particularly in the pediatric age group. Herein, the authors describe an adult patient with Alagille syndrome who presented with multiple visceral vascular abnormalities, including a high-grade stenosis of the celiac artery, superior mesenteric artery (SMA), aneurysms of the distal common hepatic artery, and distal SMA detected with computed tomographic angiography.

Ca2+-dependent calmodulin binding to FcRn affects immunoglobulin G transport in the transcytotic pathway.

The Fcgamma receptor FcRn transports immunoglobulin G (IgG) so as to avoid lysosomal degradation and to carry it bidirectionally across epithelial barriers to affect mucosal immunity. Here, we identify a calmodulin-binding site within the FcRn cytoplasmic tail that affects FcRn trafficking. Calmodulin binding to the FcRn tail is direct, calcium-dependent, reversible, and specific to residues comprising a putative short amphipathic alpha-helix immediately adjacent to the membrane. FcRn mutants with single residue substitutions in this motif, or FcRn mutants lacking the cytoplasmic tail completely, exhibit a shorter half-life and attenuated transcytosis. Chemical inhibitors of calmodulin phenocopy the mutant FcRn defect in transcytosis. These results suggest a novel mechanism for regulation of IgG transport by calmodulin-dependent sorting of FcRn and its cargo away from a degradative pathway and into a bidirectional transcytotic route.

Bidirectional transepithelial IgG transport by a strongly polarized basolateral membrane Fcgamma-receptor.

The human MHC class I-related neonatal Fc receptor, hFcRn, mediates bidirectional transport of IgG across mucosal barriers. Here, we find that at steady state hFcRn distributes predominantly to an apical intracellular compartment and almost exclusively to the basolateral cell surface of polarized epithelial cells. It moves only transiently to the apical membrane. Ligand binding does not redistribute the steady state location of the receptor. Removal of the cytoplasmic tail that contains di-leucine and tryptophan-based endocytosis motifs or incubation at low temperature (18 degrees C) redistributes the receptor apically. The rates of endocytosis of the full-length hFcRn from the apical or basolateral membrane domains, however, are equal. Thus, the strong cell surface polarity displayed by hFcRn results from dominant basolateral sorting by motifs in the cytoplasmic tail that nonetheless allows for a cycle of bidirectional transcytosis.