A sub-10-nm, folic acid-conjugated gold nanoparticle as self-therapeutic treatment of tubulointerstitial fibrosis.

Nanomedicines for treating chronic kidney disease (CKD) are on the horizon, yet their delivery to renal tubules where tubulointerstitial fibrosis occurs remains inefficient. We report a folic acid-conjugated gold nanoparticle that can transport into renal tubules and treat tubulointerstitial fibrosis in mice with unilateral ureteral obstruction. The 3-nm gold core allows for the dissection of bio-nano interactions in the fibrotic kidney, ensures the overall nanoparticle (~7 nm) to be small enough for glomerular filtration, and naturally inhibits the p38α mitogen-activated protein kinase in the absence of chemical or biological drugs. The folic acids support binding to selected tubule cells with overexpression of folate receptors and promote retention in the fibrotic kidney. Upon intravenous injection, this nanoparticle can selectively accumulate in the fibrotic kidney over the nonfibrotic contralateral kidney at ~3.6% of the injected dose. Delivery to the fibrotic kidney depends on nanoparticle size and disease stage. Notably, a single injection of this self-therapeutic nanoparticle reduces tissue degeneration, inhibits genes related to the extracellular matrix, and treats fibrosis more effectively than standard Captopril therapy. Our data underscore the importance of constructing CKD nanomedicines based on renal pathophysiology.

Comparison of Over-the-Scope Clips to Standard Endoscopic Treatment as the Initial Treatment in Patients With Bleeding From a Nonvariceal Upper Gastrointestinal Cause : A Randomized Controlled Trial.

BACKGROUND: Current endoscopic methods in the control of acute nonvariceal bleeding have a small but clinically significant failure rate. The role of over-the-scope clips (OTSCs) as the first treatment has not been defined. OBJECTIVE: To compare OTSCs with standard endoscopic hemostatic treatments in the control of bleeding from nonvariceal upper gastrointestinal causes. DESIGN: A multicenter, randomized controlled trial. (ClinicalTrials.gov: NCT03216395). SETTING: University teaching hospitals in Hong Kong, China, and Australia. PATIENTS: 190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy. INTERVENTION: Standard hemostatic treatment (n = 97) or OTSC (n = 93). MEASUREMENTS: The primary outcome was 30-day probability of further bleeds. Other outcomes included failure to control bleeding after assigned endoscopic treatment, recurrent bleeding after initial hemostasis, further intervention, blood transfusion, and hospitalization. RESULTS: The 30-day probability of further bleeding in the standard treatment and OTSC groups was 14.6% (14 of 97) and 3.2% (3 of 93), respectively (risk difference, 11.4 percentage points [95% CI, 3.3 to 20.0 percentage points]; P = 0.006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 (risk difference, 5.1 percentage points [CI, 0.7 to 11.8 percentage points]), respectively, and 30-day recurrent bleeding was 8 versus 2 (risk difference, 6.6 percentage points [CI, -0.3 to 14.4 percentage points]), respectively. The need for further interventions was 8 versus 2, respectively. Thirty-day mortality was 4 versus 2, respectively. In a post hoc analysis with a composite end point of failure to successfully apply assigned treatment and further bleeds, the event rate was 15 of 97 (15.6%) and 6 of 93 (6.5%) in the standard and OTSC groups, respectively (risk difference, 9.1 percentage points [CI, 0.004 to 18.3 percentage points]). LIMITATION: Clinicians were not blinded to treatment and the option of crossover treatment. CONCLUSION: Over-the-scope clips, as an initial treatment, may be better than standard treatment in reducing the risk for further bleeding from nonvariceal upper gastrointestinal causes that are amenable to OTSC placement. PRIMARY FUNDING SOURCE: General Research Fund to the University Grant Committee, Hong Kong SAR Government.

Timing of Endoscopy for Acute Upper Gastrointestinal Bleeding.

BACKGROUND: It is recommended that patients with acute upper gastrointestinal bleeding undergo endoscopy within 24 hours after gastroenterologic consultation. The role of endoscopy performed within time frames shorter than 24 hours has not been adequately defined. METHODS: To evaluate whether urgent endoscopy improves outcomes in patients predicted to be at high risk for further bleeding or death, we randomly assigned patients with overt signs of acute upper gastrointestinal bleeding and a Glasgow-Blatchford score of 12 or higher (scores range from 0 to 23, with higher scores indicating a higher risk of further bleeding or death) to undergo endoscopy within 6 hours (urgent-endoscopy group) or between 6 and 24 hours (early-endoscopy group) after gastroenterologic consultation. The primary end point was death from any cause within 30 days after randomization. RESULTS: A total of 516 patients were enrolled. The 30-day mortality was 8.9% (23 of 258 patients) in the urgent-endoscopy group and 6.6% (17 of 258) in the early-endoscopy group (difference, 2.3 percentage points; 95% confidence interval [CI], -2.3 to 6.9). Further bleeding within 30 days occurred in 28 patients (10.9%) in the urgent-endoscopy group and in 20 (7.8%) in the early-endoscopy group (difference, 3.1 percentage points; 95% CI, -1.9 to 8.1). Ulcers with active bleeding or visible vessels were found on initial endoscopy in 105 of the 158 patients (66.4%) with peptic ulcers in the urgent-endoscopy group and in 76 of 159 (47.8%) in the early-endoscopy group. Endoscopic hemostatic treatment was administered at initial endoscopy for 155 patients (60.1%) in the urgent-endoscopy group and for 125 (48.4%) in the early-endoscopy group. CONCLUSIONS: In patients with acute upper gastrointestinal bleeding who were at high risk for further bleeding or death, endoscopy performed within 6 hours after gastroenterologic consultation was not associated with lower 30-day mortality than endoscopy performed between 6 and 24 hours after consultation. (Funded by the Health and Medical Fund of the Food and Health Bureau, Government of Hong Kong Special Administrative Region; ClinicalTrials.gov number, NCT01675856.).

Artificial Intelligence-Assisted Colonoscopy for Colorectal Cancer Screening: A Multicenter Randomized Controlled Trial.

BACKGROUND AND AIMS: Artificial intelligence (AI)-assisted colonoscopy improves polyp detection and characterization in colonoscopy. However, data from large-scale multicenter randomized controlled trials (RCT) in an asymptomatic population are lacking. METHODS: This multicenter RCT aimed to compare AI-assisted colonoscopy with conventional colonoscopy for adenoma detection in an asymptomatic population. Asymptomatic subjects 45-75 years of age undergoing colorectal cancer screening by direct colonoscopy or fecal immunochemical test were recruited in 6 referral centers in Hong Kong, Jilin, Inner Mongolia, Xiamen, and Beijing. In the AI-assisted colonoscopy, an AI polyp detection system (Eagle-Eye) with real-time notification on the same monitor of the endoscopy system was used. The primary outcome was overall adenoma detection rate (ADR). Secondary outcomes were mean number of adenomas per colonoscopy, ADR according to endoscopist's experience, and colonoscopy withdrawal time. This study received Institutional Review Board approval (CRE-2019.393). RESULTS: From November 2019 to August 2021, 3059 subjects were randomized to AI-assisted colonoscopy (n = 1519) and conventional colonoscopy (n = 1540). Baseline characteristics and bowel preparation quality between the 2 groups were similar. The overall ADR (39.9% vs 32.4%; P < .001), advanced ADR (6.6% vs 4.9%; P = .041), ADR of expert (42.3% vs 32.8%; P < .001) and nonexpert endoscopists (37.5% vs 32.1%; P = .023), and adenomas per colonoscopy (0.59 ± 0.97 vs 0.45 ± 0.81; P < .001) were all significantly higher in the AI-assisted colonoscopy. The median withdrawal time (8.3 minutes vs 7.8 minutes; P = .004) was slightly longer in the AI-assisted colonoscopy group. CONCLUSIONS: In this multicenter RCT in asymptomatic patients, AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists. (ClinicalTrials.gov, Number: NCT04422548).

Comparison of adenoma miss rate and adenoma detection rate between conventional colonoscopy and colonoscopy with second generation distal attachment cuff: a multicenter, randomized, back-to-back trial.

BACKGROUND AND AIMS: Endocuff VisionTM has been designed to enhance mucosal visualization thereby improving detection of (pre-)malignant colorectal lesions. This multicenter, international, back-to-back, randomized colonoscopy trial compared adenoma detection rate (ADR) and adenoma miss rate (AMR) between Endocuff Vision-assisted colonoscopy (EVC) and conventional colonoscopy (CC). METHODS: Patients aged 40-75 years referred for non-immunochemical fecal occult blood test-based screening, surveillance, or diagnostic colonoscopy were included at ten hospitals and randomized into four groups: Group 1; 2xCC, Group 2; CC followed by EVC, Group 3; EVC followed CC and Group 4; 2xEVC. Primary outcomes included ADR and AMR. RESULTS: A total of 717 patients were randomized of which 661 patients (92.2%) had one and 646 (90.1%) patients had two completed back-to-back colonoscopies. EVC did not significantly improve ADR compared to CC (41.1% [95%-CI;36.1-46.3] versus 35.5% [95%-CI;30.7-40.6], respectively, P=0.125), but EVC did reduced AMR by 11.7% (29.6% [95%-CI;23.6-36.5] versus 17.9% [95%-CI;12.5-23.5], respectively, P=0.049). AMR of 2xCC compared to 2xEVC was also not significantly different (25.9% [95%-CI;19.3-33.9] versus 18.8% [95%-CI;13.9-24.8], respectively, P=0.172). Only 3.7% of the polyps missed during the first procedures had advanced pathologic features. Factors affecting risk of missing adenomas were age (P=0.002), Boston Bowel Preparation Scale (P=0.008) and region where colonoscopy was performed (P<0.001). CONCLUSIONS: Our trial shows that EVC reduces the risk of missing adenomas but does not lead to a significant improved ADR. Remarkably, 25% of adenomas are still missed during conventional colonoscopies, which is not different from miss rates reported 25 years ago; reassuringly, advanced features were only found in 3.7% of these missed lesions. TRAIL REGISTRATION NUMBER: NCT03418948.

Global prospective case series of ERCPs using a single-use duodenoscope.

BACKGROUND: The first commercialized single-use duodenoscope was cleared by the US Food and Drug Administration in December 2019. Data regarding endoscopic retrograde cholangiopancreatography (ERCP) using a single-use duodenoscope are needed on a broader range of cases conducted by endoscopists with varying levels of experience in a wide range of geographic areas. METHODS: 61 endoscopists at 22 academic centers in 11 countries performed ERCP procedures in adult patients aged ≥ 18. Outcomes included ERCP completion for the intended indication, rate of crossover to a reusable endoscope, device performance ratings, and serious adverse events (SAEs). RESULTS: Among 551 patients, 236 (42.8 %) were aged > 65, 281 (51.0 %) were men, and 256 (46.5 %) had their procedure as an inpatient. ERCPs included 196 (35.6 %) with American Society for Gastrointestinal Endoscopy complexity of grades 3-4. A total of 529 ERCPs (96.0 %) were completed: 503 (91.3 %) using only the single-use duodenoscope, and 26 (4.7 %) with crossover to a reusable endoscope. There were 22 ERCPs (4.0 %) that were not completed, of which 11 (2.0 %) included a crossover and 11 (2.0 %) were aborted cases (no crossover). Median ERCP completion time was 24.0 minutes. Median overall satisfaction with the single-use duodenoscope was 8.0 (scale of 1 to 10 [best]). SAEs were reported in 43 patients (7.8 %), including 17 (3.1 %) who developed post-ERCP pancreatitis. CONCLUSIONS: In academic medical centers over a wide geographic distribution, endoscopists with varying levels of experience using the first marketed single-use duodenoscope had good ERCP procedural success and reported high performance ratings for this device.

Management of iron-deficiency anemia following acute gastrointestinal hemorrhage: A narrative analysis and review.

Many patients experiencing acute gastrointestinal bleeding (GIB) require iron supplementation to treat subsequent iron deficiency (ID) or iron-deficiency anemia (IDA). Guidelines regarding management of these patients are lacking. We aimed to identify areas of unmet need in patients with ID/IDA following acute GIB in terms of patient management and physician guidance. We formed an international working group of gastroenterologists to conduct a narrative review based on PubMed and EMBASE database searches (from January 2000 to February 2021), integrated with observations from our own clinical experience. Published data on this subject are limited and disparate, and those relating to post-discharge outcomes, such as persistent anemia and re-hospitalization, are particularly lacking. Often, there is no post-discharge follow-up of these patients by a gastroenterologist. Acute GIB-related ID/IDA, however, is a prevalent condition both at the time of hospital admission and at hospital discharge and is likely underdiagnosed and undertreated. Despite limited data, there appears to be notable variation in the prescribing of intravenous (IV)/oral iron regimens. There is also some evidence suggesting that, compared with oral iron, IV iron may restore iron levels faster following acute GIB, have a better tolerability profile, and be more beneficial in terms of quality of life. Gaps in patient care exist in the management of acute GIB-related ID/IDA, yet further data from large population-based studies are needed to confirm this. We advocate the formulation of evidence-based guidance on the use of iron therapies in these patients, aiding a more standardized best-practice approach to patient care.

The use of magnet-controlled capsule endoscopy as the initial diagnostic tool in patients with acute upper gastrointestinal bleeding.

BACKGROUND: The latest magnet-controlled capsule endoscopy (MCCE) system can examine the water-distended stomach, duodenum, and the small bowel. We assessed the use of MCCE as the first diagnostic tool in patients with acute upper gastrointestinal bleeding (AUGIB). METHODS: This was a prospective cohort study that enrolled patients admitted with AUGIB from two teaching hospitals. Patients underwent MCCE as the initial diagnostic modality. Our primary endpoint was the diagnostic yield of MCCE. The subsequent care of these patients was guided by MCCE findings. RESULTS: Of 100 enrolled patients, 99 (mean age 54 years, 70.7% men) with a median Glasgow-Blatchford score of 6 (IQR 3-9) underwent MCCE. In three patients, MCCE found active bleeding (two duodenal ulcers and Dieulafoy's lesion). The overall diagnostic yield of MCCE was 95.8% (92 lesions in 96 patients); five in the esophagus (Mallory Weiss tears 2, varices 1, and esophagitis 2), 51 in the stomach (gastric erosions 26, gastric ulcers 14, cancer 3, GIST 3, gastric polyps 3, antral vascular ectasia 1,angiodysplasia 1), 32 in the duodenum (ulcers 28, erosions 3, polyp 1), and four in the small bowel (ulcers 2, an erosion with a nonbleeding vessel 1, Meckel's diverticulum 1). Fifty-two (52.5%) patients were discharged without endoscopy. Forty-five (45.5%) patients underwent inpatient esophagogastroduodenoscopy (EGD), which found an antral ulcer and six duodenal ulcers in addition. CONCLUSIONS: In stable patients with AUGIB, MCCE can be used as a diagnostic tool. EGD should follow in patients with an inadequate view of the duodenum.

Comparison of a Hemostatic Powder and Standard Treatment in the Control of Active Bleeding From Upper Nonvariceal Lesions : A Multicenter, Noninferiority, Randomized Trial.

BACKGROUND: The effectiveness of the hemostatic powder TC-325 as a single endoscopic treatment for acute nonvariceal upper gastrointestinal bleeding is uncertain. OBJECTIVE: To compare TC-325 with standard endoscopic hemostatic treatments in the control of active bleeding from nonvariceal upper gastrointestinal causes. DESIGN: One-sided, noninferiority, randomized, controlled trial. (ClinicalTrials.gov: NCT02534571). SETTING: University teaching hospitals in the Asia-Pacific region. PATIENTS: 224 adult patients with acute bleeding from a nonvariceal cause on upper gastrointestinal endoscopy. INTERVENTION: TC-325 (n = 111) or standard hemostatic treatment (n = 113). MEASUREMENTS: The primary outcome was control of bleeding within 30 days. Other outcomes included failure to control bleeding during index endoscopy, recurrent bleeding after initial hemostasis, further interventions, blood transfusion, hospitalization, and death. RESULTS: 224 patients were enrolled (136 with gastroduodenal ulcers [60.7%], 33 with tumors [14.7%], and 55 with other causes of bleeding [24.6%]). Bleeding was controlled within 30 days in 100 of 111 patients (90.1%) in the TC-325 group and 92 of 113 (81.4%) in the standard treatment group (risk difference, 8.7 percentage points [1-sided 95% CI, 0.95 percentage point]). There were fewer failures of hemostasis during index endoscopy with TC-325 (3 [2.7%] vs. 11 [9.7%]; odds ratio, 0.26 [CI, 0.07 to 0.95]). Recurrent bleeding within 30 days did not differ between groups (9 [8.1%] vs. 10 [8.8%]). The need for further interventions also did not differ between groups (further endoscopic treatment: 8 [7.2%] vs. 10 [8.8%]; angiography: 2 [1.8%] vs. 4 [3.5%]; surgery: 1 [0.9%] vs. 0). There were 14 deaths in each group (12.6% vs. 12.4%). LIMITATION: Clinicians were not blinded to treatment. CONCLUSION: TC-325 is not inferior to standard treatment in the endoscopic control of bleeding from nonvariceal upper gastrointestinal causes. PRIMARY FUNDING SOURCE: General Research Fund to the University Grants Committee, Hong Kong SAR Government.

Timing of endoscopy for acute upper gastrointestinal bleeding: a territory-wide cohort study.

OBJECTIVE: While it is recommended that patients presenting with acute upper gastrointestinal bleeding (AUGIB) should receive endoscopic intervention within 24 hours, the optimal timing is still uncertain. We aimed to assess whether endoscopy timing postadmission would affect outcomes. DESIGN: We conducted a retrospective, territory-wide, cohort study with healthcare data from all public hospitals in Hong Kong. Adult patients (age ≥18) that presented with AUGIB between 2013 and 2019 and received therapeutic endoscopy within 48 hours (n=6474) were recruited. Patients were classified based on endoscopic timing postadmission: urgent (t≤6), early (6

Evidence-based Guidelines on the Use of Virtual Surgical Education Pertaining to the Domains of Cognition and Curriculum, Psychomotor Skills Training, and Faculty Development and Mentorship.

OBJECTIVE: To identify, categorize, and evaluate the quality of literature, and to provide evidence-based guidelines on virtual surgical education within the cognitive and curricula, psychomotor, and faculty development and mentorship domains. SUMMARY OF BACKGROUND DATA: During the coronavirus disease 2019 pandemic, utilizing virtual learning modalities is expanding rapidly. Although the innovative methods must be considered to bridge the surgical education gap, a framework is needed to avoid expansion of virtual education without proper supporting evidence in some areas. METHODS: The Association for Surgical Education formed an ad-hoc research group to evaluate the quality and methodology of the current literature on virtual education and to build evidence-based guidelines by utilizing the SiGN methodology. We identified patient/problem-intervention-comparison-outcome-style questions, conducted systematic literature reviews using PubMed, EMBASE, and Education Resources information Center databases. Then we formulated evidence-based recommendations, assessed the quality of evidence using Grading of Recommendations, Assessment, Development, and Evaluation, Newcastle-Ottawa Scale for Education, and Kirkpatrick ratings, and conducted Delphi consensus to validate the recommendations. RESULTS: Eleven patient/problem-intervention-comparison-outcome-style questions were designed by the expert committees. After screening 4723 articles by the review committee, 241 articles met inclusion criteria for full article reviews, and 166 studies were included and categorized into 3 domains: cognition and curricula (n = 92), psychomotor, (n = 119), and faculty development and mentorship (n = 119). Sixteen evidence-based recommendations were formulated and validated by an external expert panel. CONCLUSION: The evidence-based guidelines developed using SiGN methodology, provide a set of recommendations for surgical training societies, training programs, and educators on utilizing virtual surgical education and highlights the area of needs for further investigation.

Two vs One Forward View Examination of Right Colon on Adenoma Detection: An International Multicenter Randomized Trial.

BACKGROUND & AIMS: Second forward view (SFV) examination of the right colon (RC) in colonoscopy was suggested to improve the adenoma detection rate (ADR), but multicenter data to inform its routine use remain limited. We performed an international multicenter randomized trial comparing SFV vs a standard single forward view examination of the RC on adenoma detection. METHODS: Asymptomatic individuals undergoing screening or surveillance colonoscopies from 6 Asia Pacific regions were invited for study. A forward view examination of the RC was first performed in all patients, followed by randomization at the hepatic flexure to either SFV examination of the RC and standard withdrawal examination from the hepatic flexure to rectum, or a standard withdrawal colonoscopy (SWC) examination from the hepatic flexure to rectum. The primary outcome was RC ADR. RESULTS: Between 2016 and 2019, there were 1011 patients randomized (SFV group, 502 patients; SWC group, 509 patients). Forty-five endoscopists performed the colonoscopies. The RC ADR was significantly higher in the SFV group than in the SWC group (27.1% vs 21.6%; P = .042). The whole-colon ADR was high in both groups (49.0% vs 45.0%; P =.201). The SFV examination identified 58 additional adenomas in 49 patients (9.8%), leading to a change in surveillance recommendations in 15 patients (3.0%). The median overall withdrawal time was 1.5 minutes longer in the SFV group (12.0 vs 10.5 min; P < .001). Older age, male sex, ever smoking, and longer RC withdrawal time were independent predictors of right-sided adenoma detection. CONCLUSIONS: In this multicenter trial, SFV examination significantly increased the RC ADR in screening and surveillance colonoscopies. Routine RC SFV examination should be considered. ClinicalTrials.gov ID: NCT03121495.

Fully Covered Self-Expanding Metal Stent vs Multiple Plastic Stents to Treat Benign Biliary Strictures Secondary to Chronic Pancreatitis: A Multicenter Randomized Trial.

BACKGROUND & AIMS: Benign biliary strictures (BBS) are complications of chronic pancreatitis (CP). Endotherapy using multiple plastic stents (MPS) or a fully covered self-expanding metal stent (FCSEMS) are acceptable treatment options for biliary obstructive symptoms in these patients. METHODS: Patients with symptomatic CP-associated BBS enrolled in a multicenter randomized noninferiority trial comparing 12-month treatment with MPS vs FCSEMS. Primary outcome was stricture resolution status at 24 months, defined as absence of restenting and 24-month serum alkaline phosphatase not exceeding twice the level at stenting completion. Secondary outcomes included crossover rate, numbers of endoscopic retrograde cholangiopancreatography (ERCPs) and stents, and stent- or procedure-related serious adverse events. RESULTS: Eighty-four patients were randomized to MPS and 80 to FCSEMS. Baseline technical success was 97.6% for MPS and 98.6% for FCSEMS. Eleven patients crossed over from MPS to FCSEMS, and 10 from FCSEMS to MPS. For MPS vs FCSEMS, respectively, stricture resolution status at 24 months was 77.1% (54/70) vs 75.8% (47/62) (P = .008 for noninferiority intention-to-treat analysis), mean number of ERCPs was 3.9 ± 1.3 vs 2.6 ± 1.3 (P < .001, intention-to-treat), and mean number of stents placed was 7.0 ± 4.4 vs 1.3 ± .6 (P < .001, as-treated). Serious adverse events occurred in 16 (19.0%) MPS and 19 (23.8%) FCSEMS patients (P = .568), including cholangitis/fever/jaundice (9 vs 7 patients respectively), abdominal pain (5 vs 5), cholecystitis (1 vs 3) and post-ERCP pancreatitis (0 vs 2). No stent- or procedure-related deaths occurred. CONCLUSIONS: Endotherapy of CP-associated BBS has similar efficacy and safety for 12-month treatment using MPS compared with a single FCSEMS, with FCSEMS requiring fewer ERCPs over 2 years. (ClinicalTrials.gov, Number: NCT01543256.).

Use of topical mineral powder as monotherapy for treatment of active peptic ulcer bleeding.

BACKGROUND AND AIMS: The aim of this study was to evaluate the safety and effectiveness of Hemospray (Cook Medical, Winston-Salem, NC, USA), a hemostatic powder, as monotherapy for active peptic ulcer bleeding. METHODS: In this prospective, multicenter, single-arm study, patients with Forrest Ia or Ib peptic ulcers underwent endoscopic application of Hemospray as treatment of first intent. Effectiveness endpoints were successful hemostasis at the end of the index endoscopy, recurrent bleeding within 72 hours and from 72 hours to 30 days, adverse events requiring reintervention or resulting in morbidity or mortality, and 30-day mortality. RESULTS: Hemospray was successfully administered in 98.5% of patients (66/67). Hemostasis was achieved at the index endoscopy in 90.9% of patients (60/66) with Hemospray alone and in an additional 4 patients treated with additional modalities, yielding an overall hemostasis rate of 97.0% (64/66). Rebleeding occurred in 13.3% of patients (8/60), 5 within 72 hours and 3 between 72 hours and 30 days. Two cases of perforation and 2 patient deaths occurred during the study, but none of these cases or any other adverse events were attributed to the use of Hemospray. The rate of early rebleeding was significantly higher in patients with Forrest Ia ulcers compared with patients with Forrest Ib ulcers. Higher rates of early bleeding in patients with Forrest Ia ulcers is consistent with results from studies where Hemospray was used as rescue after failure of conventional methods. CONCLUSIONS: Hemospray is an effective initial treatment for patients with active peptic ulcer bleeding, but care should be taken to monitor for recurrent bleeding. (Clinical trial registration number: NCT01306864.).

Scheduled second look endoscopy after endoscopic hemostasis to patients with high risk bleeding peptic ulcers: a Randomized Controlled Trial.

BACKGROUND: The recommendation of second look endoscopy (SLOGD) in selected patients at high risk for rebleeding has been inconclusive. This study aimed to evaluate the benefit of SLOGD in selected patients predicted at high risk of recurrent bleeding. METHODS: From a cohort of 939 patients with bleeding peptic ulcers who underwent endoscopic hemostasis, we derived a 9-point risk score (age > 60, Male, ulcer ≥ 2 cm in size, posterior bulbar or lesser curve gastric ulcer, Forrest I bleeding, haemoglobin < 8 g/dl) to predict recurrent bleeding. We then validated the score in another cohort of 1334 patients (AUROC 0.77). To test the hypothesis that SLOGD in high-risk patients would improve outcomes, we did a randomized controlled trial to compare scheduled SLOGD with observation alone in those predicted at high risk of rebleeding (a score of ≥ 5). The primary outcome was clinical bleeding within 30 days of the index bleed. RESULTS: Of 314 required, we enrolled 157 (50%) patients (SLOGD n = 78, observation n = 79). Nine (11.8%) in SLOGD group and 14 (18.2%) in observation group reached primary outcome (absolute difference 6.4%, 95% CI - 5.0% to 17.8%). Twenty-one of 69 (30.4%) patients who underwent SLOGD needed further endoscopic treatment. No surgery for bleeding control was needed. There were 6 vs. 3 of 30-day deaths in either group (p = 0.285, log rank). No difference was observed regarding blood transfusion and hospitalization. CONCLUSIONS: In this aborted trial that enrolled patients with bleeding peptic ulcers at high-risk of recurrent bleeding, scheduled SLOGD did not significantly improve outcomes. CLINICALTRIALS: gov:NCT02352155.

Management of acute upper gastrointestinal bleeding: Urgent versus early endoscopy.

For decades, timing of endoscopy has been a controversy in the management of patients who present with upper gastrointestinal bleeding (GIB). The advent of endoscopic hemostatic therapy led to reduced further bleeding, surgery and mortality. Observational studies suggest that in patients at low risk of further bleeding, early endoscopy establishes diagnosis and allows their prompt hospital discharge. In the high-risk patients, early endoscopy with hemostatic treatment can stop bleeding and improve outcomes. Sample size in early randomized controlled trials (RCTs) was small. They included low-risk patients or patients with poorly defined risks. We designed a RCT to test the hypothesis that in high-risk patients (defined by those with an admission Glasgow Blatchford Score of 12 or greater), endoscopy within 6 h of gastrointestinal consultation, when compared to the standard of care i.e. endoscopy within 24 h, would improve outcomes. The primary outcomes, all-cause mortality at 30 days did not differ between groups; 23 of 258 (8.9%) in the urgent-endoscopy group and 17 of 258 (6.6%) in the early-endoscopy group died (difference 2.3%, 95% confidence interval -2.3 to 6.9%). Further bleeding was similar (10.9% vs. 7.8%) between groups. A higher rate in endoscopic hemostatic treatment was observed in the urgent-endoscopy group (60.1% vs. 48.4%). In patients with peptic ulcers, active bleeding or visible vessels were found on initial endoscopy in 105 of the 158 patients (66.4%) and in 76 of 159 (47.8%) in the respective group. In the majority of patients with GIB, endoscopy earlier than 24 h is not indicated.

Consensus guidelines on the role of cholangioscopy to diagnose indeterminate biliary stricture.

BACKGROUND: Indeterminate strictures pose a therapeutic dilemma. In recent years, cholangioscopy has evolved and the availability of cholangioscopy has increased. However, the position of cholangioscopy in the diagnostic algorithm to diagnose malignancy have not been well established. We aim to develop a consensus statement regarding the clinical role of cholangioscopy in the diagnosis of indeterminate biliary strictures. METHODS: The international experts reviewed the evidence and modified the statements using a three-step modified Delphi method. Each statement achieves consensus when it has at least 80% agreement. RESULTS: Nine final statements were formulated. An indeterminate biliary stricture is defined as that of uncertain etiology under imaging or tissue diagnosis. When available, cholangioscopic assessment and guided biopsy during the first round of ERCP may reduce the need to perform multiple procedures. Cholangioscopy are helpful in diagnosing malignant biliary strictures by both direct visualization and targeted biopsy. The absence of disease progression for at least 6 months is supportive of non-malignant etiology. Direct per-oral cholangioscopy provides the largest accessory channel, better image definition, with image enhancement but is technically demanding. Image enhancement during cholangioscopy may increase the diagnostic sensitivity of visual impression of malignant biliary strictures. Cholangioscopic imaging characteristics including tumor vessels, papillary projection, nodular or polypoid mass, and infiltrative lesions are highly suggestive for neoplastic/malignant biliary disease. The risk of cholangioscopy related cholangitis is higher than in standard ERCP, necessitating prophylactic antibiotics and ensuring adequate biliary drainage. Per-oral cholangioscopy may not be the modality of choice in the evaluation of distal biliary strictures due to inherent technical difficulties. CONCLUSION: Evidence supports that cholangioscopy has an adjunct role to abdominal imaging and ERCP tissue acquisition in order to evaluate and diagnose indeterminate biliary strictures.

Super-resolution imaging reveals extrastriatal synaptic dysfunction in presymptomatic Huntington disease mice.

Synaptic structure and function are compromised prior to cell death and symptom onset in a variety of neurodegenerative diseases. In Huntington disease (HD), a CAG repeat expansion in the gene encoding the huntingtin protein results in a presymptomatic stage that typically spans multiple decades and is followed by striking degeneration of striatal tissue and the progression of debilitating motor symptoms. Many lines of evidence demonstrate that the HD presymptomatic window is associated with injurious effects to striatal synapses, many of which appear to be prerequisites to subsequent cell death. While the striatum is the most vulnerable region in the HD brain, it is widely recognized that HD is a brain-wide disease, affecting numerous extrastriatal regions that contribute to debilitating non-motor symptoms including cognitive dysfunction. Currently, we have a poor understanding of the synaptic integrity, or lack thereof, in extrastriatal regions in the presymptomatic HD brain. If early therapeutic intervention seeks to maintain healthy synaptic function, it is important to understand early HD-associated synaptopathy at a brain-wide, rather than striatal-exclusive, level. Here, we focused on the hippocampus as this structure is generally thought to be affected only in manifest HD despite the subtle cognitive deficits known to emerge in prodromal HD. We used super-resolution microscopy and multi-electrode array electrophysiology as sensitive measures of excitatory synapse structure and function, respectively, in the hippocampus of presymptomatic heterozygous HD mice (Q175FDN model). We found clear evidence for enhanced AMPA receptor subunit clustering and hyperexcitability well before the onset of a detectable HD-like behavioral phenotype. In addition, activity-dependent re-organization of synaptic protein nanostructure, and functional measures of synaptic plasticity were impaired in presymptomatic HD mice. These data demonstrate that synaptic abnormalities in the presymptomatic HD brain are not exclusive to the striatum, and highlight the need to better understand the region-dependent complexities of early synaptopathy in the HD brain.

Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2021.

1: ESGE recommends in patients with acute upper gastrointestinal hemorrhage (UGIH) the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Patients with GBS ≤ 1 are at very low risk of rebleeding, mortality within 30 days, or needing hospital-based intervention and can be safely managed as outpatients with outpatient endoscopy.Strong recommendation, moderate quality evidence. 2: ESGE recommends that in patients with acute UGIH who are taking low-dose aspirin as monotherapy for secondary cardiovascular prophylaxis, aspirin should not be interrupted. If for any reason it is interrupted, aspirin should be re-started as soon as possible, preferably within 3-5 days.Strong recommendation, moderate quality evidence. 3: ESGE recommends that following hemodynamic resuscitation, early (≤ 24 hours) upper gastrointestinal (GI) endoscopy should be performed. Strong recommendation, high quality evidence. 4: ESGE does not recommend urgent (≤ 12 hours) upper GI endoscopy since as compared to early endoscopy, patient outcomes are not improved. Strong recommendation, high quality evidence. 5: ESGE recommends for patients with actively bleeding ulcers (FIa, FIb), combination therapy using epinephrine injection plus a second hemostasis modality (contact thermal or mechanical therapy). Strong recommendation, high quality evidence. 6: ESGE recommends for patients with an ulcer with a nonbleeding visible vessel (FIIa), contact or noncontact thermal therapy, mechanical therapy, or injection of a sclerosing agent, each as monotherapy or in combination with epinephrine injection. Strong recommendation, high quality evidence. 7 : ESGE suggests that in patients with persistent bleeding refractory to standard hemostasis modalities, the use of a topical hemostatic spray/powder or cap-mounted clip should be considered. Weak recommendation, low quality evidence. 8: ESGE recommends that for patients with clinical evidence of recurrent peptic ulcer hemorrhage, use of a cap-mounted clip should be considered. In the case of failure of this second attempt at endoscopic hemostasis, transcatheter angiographic embolization (TAE) should be considered. Surgery is indicated when TAE is not locally available or after failed TAE. Strong recommendation, moderate quality evidence. 9: ESGE recommends high dose proton pump inhibitor (PPI) therapy for patients who receive endoscopic hemostasis and for patients with FIIb ulcer stigmata (adherent clot) not treated endoscopically. (A): PPI therapy should be administered as an intravenous bolus followed by continuous infusion (e. g., 80 mg then 8 mg/hour) for 72 hours post endoscopy. (B): High dose PPI therapies given as intravenous bolus dosing (twice-daily) or in oral formulation (twice-daily) can be considered as alternative regimens.Strong recommendation, high quality evidence. 10: ESGE recommends that in patients who require ongoing anticoagulation therapy following acute NVUGIH (e. g., peptic ulcer hemorrhage), anticoagulation should be resumed as soon as the bleeding has been controlled, preferably within or soon after 7 days of the bleeding event, based on thromboembolic risk. The rapid onset of action of direct oral anticoagulants (DOACS), as compared to vitamin K antagonists (VKAs), must be considered in this context.Strong recommendation, low quality evidence.

Operating Room In Situ Interprofessional Simulation for Improving Communication and Teamwork.

BACKGROUND: Effective teamwork and communication are correlated with improved patient care quality and outcomes. The belief that each team member contributes to excellent patient care in the operating room (OR) leads to a more productive work environment. However, poor teamwork and communication lead to poorer OR outcomes. We qualitatively and quantitatively explored perspectives of three OR professions (nursing, anesthesiology, and surgery) on teamwork and communication in the OR preinterprofessional and postinterprofessional in situ OR simulation. MATERIALS AND METHODS: One-on-one semi-structured interviews were conducted; 14 pre-in situ simulations during July-October 2017 (three surgery, four anesthesiology, and six nursing staff), and 10 post-in situ simulations during August-November 2017 (five surgery, four anesthesiology, and one nursing staff). Themes were identified inductively to create a codebook. The codebook was used to consensus code all interviews. This analysis informed the development of a quantitative survey distributed to all contactable interviewees (22). RESULTS: Presimulation and postsimulation interview participants concurred on teamwork and communication importance, believed communication to be key to effective teamwork, and identified barriers to communication: lack of cordiality, lack of engagement from other staff, distractions, role hierarchies, and lack of familiarity with other staff. The large majority of survey participants-all having participated in simulations-believed they could use effective communication in their workplace. CONCLUSIONS: Establishing methods for improving and maintaining the ability of OR professionals to communicate with each other is imperative for patient safety. Effective team communication leads to safe and successful outcomes, as well as a productive and supportive OR work environment.