person:boswob01 or changs05 or francf01 or latorm02 or axelrj01 or fayea02 or gq206 or shauka01 or suf03 or willir02 or popovv01 or pocham01 or gondat01 or goodma02 or grosss10 or haberg02 or hudesd01 or jacobi04 or khannl01 or liangp01 or maltel01 or northp02
9-Minute Withdrawal Time Improves Adenoma Detection Rate Compared With 6-Minute Withdrawal Time During Colonoscopy: A Meta-analysis of Randomized Controlled Trials
INTRODUCTION/BACKGROUND:Adenoma detection rate (ADR) is a quality metric that has been emphasized by multiple societies as improved ADR leads to reduced interval colorectal cancer (CRC). It is postulated that increased withdrawal time (WT) can lead to higher ADR. Multiple randomized controlled trials (RCTs) were undertaken to evaluate this. We performed a systematic review and meta-analysis of RCTs to analyze the impact of higher WT on ADR during colonoscopy. METHODS:The following databases were comprehensively searched through November 8, 2022: Embase, MEDLINE, Cochrane, Web of Science, and Google Scholar. Only RCTs were eligible for inclusion. We applied the random effects model using the DerSimonian Laird approach and calculated risk ratio (RR) for binary outcomes and mean difference (MD) for continuous outcomes. 95% CI and P values were generated. RESULTS:A total of 3 RCTs with 2159 patients were included of which 1136 patients were included in the 9-minute withdrawal group (9WT) and 1023 patients in the 6-minute withdrawal group (6WT). The mean age range was 53.6 to 56.8 years and the male gender was 50.7%. The overall ADR was significantly higher for 9WT (RR=1.23; 95% CI, 1.09-1.40; P<0.001). The overall adenoma per colonoscopy (APC) was also higher for the 9WT group (MD: 0.14; 95% CI, 0.04-0.25; P=0.008). CONCLUSION/CONCLUSIONS:The 9-minute withdrawal time improved ADR and APC compared with the 6-minute withdrawal. Given the high-quality evidence, we recommend that clinicians at least perform a 9-minute withdrawal to achieve higher quality metrics including ADR to reduce interval CRC.
Endoscopist-Level and Procedure-Level Factors Associated With Increased Adenoma Detection With the Use of a Computer-Aided Detection Device
INTRODUCTION/BACKGROUND:To investigate the impact of procedure-related and endoscopist-related factors on the effectiveness of a computer-aided detection (CADe) device in adenomas per colonoscopy (APC) detection. METHODS:The SKOUT clinical trial was conducted at 5 US sites. We present prespecified analyses of procedure-related and endoscopist-related factors, and association with APC across treatment and control cohorts. RESULTS:There were numeric increases in APC between SKOUT vs standard colonoscopy in community-based endoscopists, withdrawal time of ≥8 minutes, for endoscopists with >20 years of experience, and endoscopists with baseline adenoma detection rate <45%. DISCUSSION/CONCLUSIONS:The application of CADe devices in clinical practice should be carefully evaluated. Larger studies should explore differences in endoscopist-related factors for CADe.
Multimodal single-cell datasets characterize antigen-specific CD8+ T cells across SARS-CoV-2 vaccination and infection
The immune response to SARS-CoV-2 antigen after infection or vaccination is defined by the durable production of antibodies and T cells. Population-based monitoring typically focuses on antibody titer, but there is a need for improved characterization and quantification of T cell responses. Here, we used multimodal sequencing technologies to perform a longitudinal analysis of circulating human leukocytes collected before and after immunization with the mRNA vaccine BNT162b2. Our data indicated distinct subpopulations of CD8+ T cells, which reliably appeared 28 days after prime vaccination. Using a suite of cross-modality integration tools, we defined their transcriptome, accessible chromatin landscape and immunophenotype, and we identified unique biomarkers within each modality. We further showed that this vaccine-induced population was SARS-CoV-2 antigen-specific and capable of rapid clonal expansion. Moreover, we identified these CD8+ T cell populations in scRNA-seq datasets from COVID-19 patients and found that their relative frequency and differentiation outcomes were predictive of subsequent clinical outcomes.
Colonic Mass After NSAID Use and Concerns for Malignancy
Blood Test Increases Colorectal Cancer Screening in Persons Who Declined Colonoscopy and Fecal Immunochemical Test: A Randomized Controlled Trial
BACKGROUND & AIMS/OBJECTIVE:The septin 9 blood test is indicated for colorectal cancer screening in individuals who decline first-line tests, but participation in this context is unclear. We conducted a randomized controlled trial to compare reoffering colonoscopy and fecal immunochemical test (FIT) alone versus also offering the blood test among individuals who declined colonoscopy and FIT. METHODS:Screen-eligible Veterans aged 50-75 years who declined colonoscopy and FIT within the previous 6 months were randomized to letter and telephone outreach to reoffer screening with colonoscopy/FIT only (control), or additionally offering the blood test as a second-line option (intervention). The primary outcome was completion of any screening test within 6 months. The secondary outcome was completion of a full screening strategy within 6 months, including colonoscopy for those with a positive noninvasive test. RESULTS:Of 359 participants who completed follow-up, 9.6% in the control group and 17.1% in the intervention group completed any screening (7.5% difference; P = .035). Uptake of colonoscopy and FIT was similar in the 2 groups. The full screening strategy was completed in 9.0% and 14.9% in the control and intervention groups, respectively (5.9% difference; P = .084). CONCLUSIONS:Among individuals who previously declined colonoscopy and FIT, offering a blood test as a secondary option increased screening by 7.5% without decreasing uptake of first-line screening options. However, completion of a full screening strategy did not increase. These findings indicate that a blood test is a promising method to improve colorectal cancer screening, but obtaining a timely colonoscopy after a positive noninvasive test remains a challenge (ClincialTrials.gov number, NCT03598166).
Blood-based colorectal cancer screening: are we ready for the next frontier?
Suboptimal Guideline Adherence and Biomarker Underutilization in Monitoring of Post-operative Crohn"™s Disease
Background: Crohn"™s disease recurrence after ileocecal resection is common. Guidelines suggest colonoscopy within 6"“12 months of surgery to assess for post-operative recurrence, but use of adjunctive monitoring is not protocolized. We aimed to describe the state of monitoring in post-operative Crohn"™s. Methods: We conducted a retrospective study of patients with Crohn"™s after ileocolic resection with â‰¥ 1-year follow-up. Patients were stratified into high and low risk based on guidelines. Post-operative biomarker (C-reactive protein, fecal calprotectin), cross-sectional imaging, and colonoscopy use were assessed. Biomarker, radiographic, and endoscopic post-operative recurrence were defined as elevated CRP/calprotectin, active inflammation on imaging, and Rutgeerts â‰¥ i2b, respectively. Data were stratified by surgery year to assess changes in practice patterns over time. P-values were calculated using Wilcoxon test and Fisher exact test. Results: Of 901 patients, 53% were female and 78% high risk. Median follow-up time was 60 m for LR and 50 m for high risk. Postoperatively, 18% low and 38% high risk had CRPs, 5% low and 10% high risk had calprotectins, and half of low and high risk had cross-sectional imaging. 29% low and 38% high risk had colonoscopy by 1 year. Compared to pre-2015, time to first radiography (584 days vs. 398 days) and colonoscopy (421 days vs. 296 days) were significantly shorter for high-risk post-2015 (P < 0.001). Probability of colonoscopy within 1 year increased over time (0.48, 2011 vs. 0.92, 2019). Conclusion: Post-operative colonoscopy completion by 1 year is low. The use of CRP and imaging are common, whereas calprotectin is infrequently utilized. Practice patterns are shifting toward earlier monitoring.
Suboptimal Guideline Adherence and Biomarker Underutilization in Monitoring of Post-operative Crohn's Disease
BACKGROUND:Crohn's disease recurrence after ileocecal resection is common. Guidelines suggest colonoscopy within 6-12 months of surgery to assess for post-operative recurrence, but use of adjunctive monitoring is not protocolized. We aimed to describe the state of monitoring in post-operative Crohn's. METHODS:We conducted a retrospective study of patients with Crohn's after ileocolic resection with ≥ 1-year follow-up. Patients were stratified into high and low risk based on guidelines. Post-operative biomarker (C-reactive protein, fecal calprotectin), cross-sectional imaging, and colonoscopy use were assessed. Biomarker, radiographic, and endoscopic post-operative recurrence were defined as elevated CRP/calprotectin, active inflammation on imaging, and Rutgeerts ≥ i2b, respectively. Data were stratified by surgery year to assess changes in practice patterns over time. P-values were calculated using Wilcoxon test and Fisher exact test. RESULTS:Of 901 patients, 53% were female and 78% high risk. Median follow-up time was 60 m for LR and 50 m for high risk. Postoperatively, 18% low and 38% high risk had CRPs, 5% low and 10% high risk had calprotectins, and half of low and high risk had cross-sectional imaging. 29% low and 38% high risk had colonoscopy by 1 year. Compared to pre-2015, time to first radiography (584 days vs. 398 days) and colonoscopy (421 days vs. 296 days) were significantly shorter for high-risk post-2015 (P < 0.001). Probability of colonoscopy within 1 year increased over time (0.48, 2011 vs. 0.92, 2019). CONCLUSION:Post-operative colonoscopy completion by 1 year is low. The use of CRP and imaging are common, whereas calprotectin is infrequently utilized. Practice patterns are shifting toward earlier monitoring.
Through-the-scope suture closure of nonampullary duodenal endoscopic mucosal resection defects: a retrospective multicenter cohort study
BACKGROUND: Delayed bleeding is among the most common adverse events associated with endoscopic mucosal resection (EMR) of nonampullary duodenal polyps. We evaluated the rate of delayed bleeding and complete defect closure using a novel through-the-scope (TTS) suturing system for the closure of duodenal EMR defects. METHODS: We reviewed the electronic medical records of patients who underwent EMR for nonampullary duodenal polyps of ≥ 10 mm and prophylactic defect closure with TTS suturing between March 2021 and May 2022 at centers in the USA. We evaluated the rates of delayed bleeding and complete defect closure. RESULTS: 36 nonconsecutive patients (61 % women; mean [SD] age, 65  years) underwent EMR of ≥ 10-mm duodenal polyps followed by attempted defect closure with TTS suturing. The mean (SD) lesion size was 29 (19) mm, defect size was 37 (25) mm; eight polyps (22 %) involved > 50 % of the lumen circumference. Complete closure was achieved in all cases (78 % with TTS suturing alone), using a median of one TTS suturing kit. There were no cases of delayed bleeding and no adverse events attributed to application of the TTS suturing device. CONCLUSION/CONCLUSIONS: Prophylactic closure of nonampullary duodenal EMR defects using TTS suturing resulted in a high rate of complete closure and no delayed bleeding events.
Efficacy and safety of the siRNA JNJ-73763989 and the capsid assembly modulator JNJ-56136379 (bersacapavir) with nucleos(t)ide analogues for the treatment of chronic hepatitis B virus infection (REEF-1): a multicentre, double-blind, active-controlled, randomised, phase 2b trial
BACKGROUND:JNJ-73763989 (JNJ-3989), a small interfering RNA, targets all hepatitis B virus (HBV) RNAs, reducing all HBV proteins. JNJ-56136379 (JNJ-6379; also known as bersacapavir), a capsid assembly modulator, inhibits HBV replication. We aimed to evaluate the efficacy (ie, antiviral activity) and safety of these therapeutics in combination with nucleos(t)ide analogues in patients with chronic hepatitis B. METHODS:The REEF-1 multicentre, double-blind, active-controlled, randomised, phase 2b study was done at 108 hospitals or outpatient centres across 19 countries in Asia, Europe, and North and South America. We included patients aged 18-65 years with chronic hepatitis B (defined as HBsAg positivity at screening and at least 6 months before screening or alternative markers of chronicity [eg, HBV DNA]), including those not currently treated, virologically suppressed, HBeAg positive, and HBeAg negative. Patients were randomly assigned (1:1:2:2:2:2) via permuted block randomisation according to a computer-generated schedule to receive oral nucleos(t)ide analogues once per day plus placebo (control group); oral JNJ-6379 250 mg daily plus nucleos(t)ide analogues (JNJ-6379 dual group); nucleos(t)ide analogues plus subcutaneously injected JNJ-3989 at doses of 40 mg (JNJ-3989 dual 40 mg group), 100 mg (JNJ-3989 dual 100 mg group), or 200 mg (JNJ-3989 dual 200 mg group) every 4 weeks; or JNJ-6379 250 mg plus JNJ-3989 100 mg every 4 weeks plus nucleos(t)ide analogues (triple group) for 48 weeks followed by a follow-up phase. An interactive web response system provided concealed treatment allocation, and investigators remained masked to the intervention groups until the primary analysis at week 48. The primary endpoint was the proportion of patients meeting predefined nucleos(t)ide analogue-stopping criteria (alanine aminotransferase <3 × upper limit of normal, HBV DNA below the lower limit of quantitation, HBeAg negative, and HBsAg <10 IU/mL) at week 48. All patients who received at least one dose of study drug were included in the analysis population used for primary efficacy assessment, excluding those who withdrew because of COVID-19-related reasons, withdrew before week 44, or had no efficacy data (ie, the modified intention-to-treat population). Safety was assessed in all participants who received at least one dose of study drugs. This trial is registered with ClinicalTrials.gov, NCT03982186. The study has been completed. FINDINGS/RESULTS:Between Aug 1, 2019, and April 26, 2022, 470 patients (310 [66%] male and 244 [52%] White) were randomly assigned: 45 to the control group, 48 to the JNJ-6379 dual group, 93 to the JNJ-3989 dual 40 mg group, 93 to the JNJ-3989 dual 100 mg group, 96 to the JNJ-3989 dual 200 mg group, and 95 to the triple group. At week 48, five (5%; 90% CI 2-11) of 91 patients in the JNJ-3989 dual 40 mg group, 15 (16%; 10-24) of 92 in the JNJ-3989 dual 100 mg group, 18 (19%; 13-27) of 94 in the JNJ-3989 dual 200 mg group, eight (9%; 4-15) of 94 in the triple group, and one (2%; 0-10) of 45 in the control group met nucleos(t)ide analogue stopping criteria. No patients in the JNJ-6379 dual group met stopping criteria. 38 (81%) patients who met nucleos(t)ide analogue-stopping criteria at week 48 were virologically suppressed and HBeAg negative at baseline. Ten (2%) of 470 patients had serious adverse events during the treatment phase, and two patients (one each from the JNJ-3989 dual 200 mg group [exercise-related rhabdomyolysis] and the triple group [increase in ALT or AST]) had serious adverse events related to study treatment. During follow-up, 12 (3%) of 460 patients had a serious adverse event; one (<1%), a gastric ulcer, was considered to be related to nucleos(t)ide analogues and occurred in a patient from the JNJ-3989 dual 200 mg group. 29 (6%) of 460 patients in the treatment phase and in ten (2%) of 460 patients in the follow-up phase had grade 3 or 4 adverse events. Five (1%) of 470 patients discontinued treatment due to adverse events, and there were no deaths. INTERPRETATION/CONCLUSIONS:Although treatment with JNJ-3989 led to a dose-dependent response for meeting nucleos(t)ide analogue-stopping criteria, it rarely led to HBsAg seroclearance. However, most patients treated with JNJ-3989 had clinically meaningful reductions in HBsAg that might contribute to a liver environment conducive to better immune control and, in turn, might improve the response to immune-modulating therapies. FUNDING/BACKGROUND:Janssen Research and Development.