Effect of tobacco use on Zenker's diverticulotomy outcomes.

OBJECTIVE: To compare clinical outcomes in patients with and without history of tobacco use who underwent Zenker's diverticulotomy (ZD). STUDY DESIGN: Single institution retrospective review. SETTING: Tertiary care academic hospital. METHODS: A retrospective review of patients who underwent ZD via an open stapler, rigid endoscopic CO2 laser, stapler or harmonic scalpel, and flexible endoscopic technique from January 2006 to December 2020 was performed. Data were abstracted for patient demographics, diverticular features, and rates of adverse events and symptomatic recurrence. RESULTS: Out of 424 patients, 146 (34.4 %) had a history of tobacco use: 126 (29.7 %) were former smokers, and 20 (4.7 %) were active smokers. In univariable cross-sectional analyses, the likelihood of postoperative bleeding, perforation, emergency department visits, unplanned readmission, or recurrence did not demonstrate an association with tobacco use history even after adjustment for age, sex, and surgical approach. Similarly, in Cox Proportional Hazards regression, tobacco use was not associated with an increased risk of recurrence, even after correcting for age, sex, and type of surgery. The median time to recurrence observed in our cohort was 11.5 years amongst non-smokers, 8.7 years amongst former smokers, and 1.2 years amongst active smokers (p = 0.94). CONCLUSIONS: There were no significant differences in post-operative adverse events or frequency of recurrence of ZD between active, former, and non-smokers. Although underpowered and not statistically significant, median time to recurrence appears to be shorter in smokers when compared with former and non-smokers following surgery.

A novel blood-sensing capsule for rapid detection of upper GI bleeding: a prospective clinical trial.

BACKGROUND AND AIMS: Upper GI bleeding (UGIB) is a common medical emergency associated with high resource utilization, morbidity, and mortality. Timely EGD can be challenging from personnel, resource, and access perspectives. PillSense (EnteraSense Ltd, Galway, Ireland) is a novel swallowed bleeding sensor for the detection of UGIB, anticipated to aid in patient triage and guide clinical decision-making for individuals with suspected UGIB. METHODS: This prospective, open-label, single-arm comparative clinical trial of a novel bleeding sensor for patients with suspected UGIB was performed at a tertiary care center. The PillSense system consists of an optical sensor and an external receiver that processes and displays data from the capsule as "Blood Detected" or "No Blood Detected." Patients underwent EGD within 4 hours of capsule administration; participants were followed up for 21 days to confirm capsule passage. RESULTS: A total of 126 patients were accrued to the study (59.5% male; mean age, 62.4 ± 14.3 years). Sensitivity and specificity for detecting the presence of blood were 92.9% (P = .02) and 90.6% (P < .001), respectively. The capsule's positive and negative predictive values were 74.3% and 97.8%, and positive and negative likelihood ratios were 9.9 and .08. No adverse events or deaths occurred related to the PillSense system, and all capsules were excreted from patients on follow-up. CONCLUSIONS: The PillSense system is safe and effective for detecting the presence of blood in patients evaluated for UGIB before upper GI endoscopy. It is a rapidly deployed tool, with easy-to-interpret results that will affect the diagnosis and triage of patients with suspected UGIB. (Clinical trial registration number: NCT05385224.).

Lumen-apposing metal stents for the treatment of benign gastrointestinal tract strictures: a single-center experience and proposed treatment algorithm.

BACKGROUND: Lumen-apposing metal stents (LAMS) are an alternative therapeutic option for benign gastrointestinal (GI) tract strictures. Our study aimed to evaluate the safety and efficacy of LAMS for the management of benign GI strictures. METHODS: Consecutive patients who underwent a LAMS placement for benign luminal GI strictures at a tertiary care center between January 2014 and July 2021 were reviewed. Primary outcomes included technical success, early clinical success, and adverse events (AEs). Other outcomes included rates of stent migration and re-intervention after LAMS removal. RESULTS: One hundred and nine patients who underwent 128 LAMS placements (67.9% female, mean age of 54.3 ± 14.2 years) were included, and 70.6% of the patients had failed prior endoscopic treatments. The majority of strictures (83.5%) were anastomotic, and the most common stricture site was the gastrojejunal anastomosis (65.9%). Technical success was achieved in 100% of procedures, while early clinical success was achieved in 98.4%. The overall stent-related AE rate was 25%. The migration rate was 27.3% (35/128). Of these, five stents were successfully repositioned endoscopically. The median stent dwell time was 119 days [interquartile range (IQR) 68-189 days], and the median follow-up duration was 668.5 days [IQR: 285.5-1441.5 days]. The re-intervention rate after LAMS removal was 58.3%. CONCLUSIONS: LAMS is an effective therapeutic option for benign GI strictures, offering high technical and early clinical success. However, the re-intervention rate after LAMS removal was high. In select cases, using LAMS placement as destination therapy with close surveillance is a reasonable option.

Flexible endoscopic Zenker's diverticulotomy - A retrospective review of outcomes in 75 patients.

OBJECTIVE: Flexible endoscopic Zenker's diverticulotomy (FEZD) is a procedure performed primarily by gastroenterologists for treatment of symptomatic Zenker's diverticulum (ZD). Given the lack of prior investigations with large sample sizes, we report on one of the largest series of patients who underwent FEZD. METHODS: A review of patients who underwent FEZD at our institution from 2006 to 2021 was performed. Data were abstracted for patient demographics, clinical features, procedural characteristics, adverse events, and outcomes. RESULTS: A total of 75 patients (37 women) with mean age of 77.9 (33-102) years and mean (range) follow-up of 1.1 (0-13.2) years were identified. 67.9 % of FEZD cases were performed under general anesthesia. The mean procedure time was 37.1 min. Same day discharge and resumption of oral intake was seen in 56.4 % and 57.1 % of cases, respectively. Adverse events included intraprocedural bleeding (15.7 %) controlled with endoscopic means, infection (4.8 %) exclusively managed with antibiotics in all but one case, subcutaneous emphysema (2.4 %), and perforation (10.7 %) conservatively managed in all but one case. 97.6 % of patients had sustained subjective improvement in symptoms following their procedure. Fifteen patients (20 %) experienced recurrence after undergoing initial FEZD-26.7 % percent of whom were sufficiently treated with repeat FEZDs. Younger age was associated with recurrence (p < 0.01). CONCLUSION: FEZD is an effective, safe procedure for the management of symptomatic ZD. It is a viable alternative for patients in whom otorhinolaryngological procedures via rigid endoscopy are not an option.

Initial multicenter experience using a novel endoscopic tack and suture system for challenging GI defect closure and stent fixation (with video).

BACKGROUND AND AIMS: Closure of endoscopic resection defects can be achieved with through-the-scope clips, over-the-scope clips, or endoscopic suturing. However, these devices are often limited by their inability to close large, irregular, and difficult-to-reach defects. Thus, we aimed to assess the feasibility and safety of a novel through-the-scope, suture-based closure system developed to overcome these limitations. METHODS: This was a retrospective multicenter study involving 8 centers in the United States. Primary outcomes were feasibility and safety of early use of the device. Secondary outcomes were assessment of need for additional closure devices, prolonged procedure time, and technical feasibility of performing the procedure with an alternative device(s). RESULTS: Ninety-three patients (48.4% women) with mean age 63.6 ± 13.1 years were included. Technical success was achieved in 83 patients (89.2%), and supplemental closure was required in 24.7% of patients (n = 23) with a mean defect size of 41.6 ± 19.4 mm. Closure with an alternative device was determined to be impossible in 24.7% of patients because of location, size, or shape of the defect. The use of the tack and suture device prolonged the procedure in 8.6% of cases but was considered acceptable. Adverse events occurred in 2 patients (2.2%) over a duration of follow-up of 34 days (interquartile range, 13-93.5) and were mild and moderate in severity. No serious adverse events or procedure-related deaths occurred. CONCLUSIONS: The novel endoscopic through-the-scope tack and suture system is safe, efficient, and permits closure of large and irregularly shaped defects that were not possible with established devices.

Performance and Predictors of Migration of Partially and Fully Covered Esophageal Self-Expanding Metal Stents for Malignant Dysphagia.

BACKGROUND & AIMS: Self-expanding metal stents (SEMS) are routinely used to palliate malignant dysphagia. However esophageal SEMS can migrate or obstruct due to epithelial hyperplasia. The aim of this study was to evaluate the rates and factors predicting migration and obstruction, and the nutritional outcomes in partially covered (pc) vs. fully covered (fc) SEMS vs. fcSEMS with antimigration fins (AF) placed for malignant dysphagia. METHODS: A retrospective review of consecutive patients undergoing SEMS placement for malignant dysphagia at three academic medical centers. RESULTS: Among 357 patients, there were 55 (15.4%) stent migrations, 45 (12.6%) obstructions from epithelial hyperplasia, and 20 (5.6%) food impactions. Median overall survival was 79 days (IQR 41,199). The percent weight change/change in albumin at 30 and 60 days after SEMS placement were -2.24%/-0.544 g/dL and -2.98%/-0.55 g/dL, respectively. Stent migration occurred significantly more often with fcSEMS than pcSEMS (25.3% vs 10.9%; P < .003), but there was no difference when either group was compared to fcSEMS-AF (19.3%). The overall rate of epithelial hyperplasia resulting in stent obstruction was low (12.6%) and not different between stent types. Factors associated with increased risk of SEMS migration on multivariable logistic regression included stricture traversability with a diagnostic endoscope (OR, 2.37; 95% CI, 1.29-4.35) and use of fcSEMS (OR, 2.56; 1.31-5.00) or fcSEMS-AF (OR, 2.30, 1.03-5.14). CONCLUSIONS: Traversability of a malignant esophageal stenosis predicts SEMS migration. In these patients with a limited overall survival, pcSEMS are associated with lower rates of stent migration and similar rates of obstruction compared to fcSEMS.

Efficacy of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasia in a Large Cohort in North America.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America. METHODS: We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death. RESULTS: Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD. CONCLUSIONS: ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions.

Outcomes of peroral endoscopic myotomy in patients with achalasia and prior bariatric surgery: A multicenter experience.

Peroral endoscopic myotomy (POEM) in patients with achalasia who are status post bariatric surgery may be technically challenging due to postsurgical scarring and altered anatomy. The aim of the study was to assess the efficacy and safety of POEM for achalasia in patients with prior bariatric surgery. A review of prospectively maintained databases at three tertiary referral centers from January 2015 to January 2021 was performed. The primary outcome of interest was clinical success, defined as a post-treatment Eckardt score ≤ 3 or improvement in Eckardt score by ≥ 1 when the baseline score was <3, and improvement of symptoms. Secondary outcomes were adverse event rates and symptom recurrence. Sixteen patients status post Roux-en-Y gastric bypass (n = 14) and sleeve gastrectomy (n = 2) met inclusion criteria. Indications for POEM were achalasia type I (n = 2), type II (n = 9), and type III (n = 5). POEM was performed either by anterior or posterior approach. The pre-POEM mean integrated relaxation pressure was 26.2 ± 7.6 mm Hg. The mean total myotomy length was 10.2 ± 2.7 cm. The mean length of hospitalization was 1.4 ± 0.7 days. Pre- and postprocedure Eckardt scores were 6.1 ± 2.1 and 1.7 ± 1.8, respectively. The overall clinical success rate was 93.8% (15/16) with mean follow-up duration of 15.5 months. One patient had esophageal leak on postprocedure esophagram and managed endoscopically. Dysphagia recurred in two patients, which was successfully managed with pneumatic dilation with or without botulinum toxin injection. POEM appears to be safe and effective in the management of patients with achalasia who have undergone prior bariatric surgery.

Safety and histologic outcomes of endoscopic submucosal dissection with a novel articulating knife for esophageal neoplasia.

BACKGROUND AND AIMS: Treatment of large esophageal neoplasia is gradually evolving from piecemeal to en bloc resections. Endoscopic submucosal dissection (ESD) is known to achieve more complete resections than piecemeal EMR for large lesions, yet it remains underused in the West because of technical and safety concerns with traditional electrosurgical knives. We aimed to evaluate a novel endoscopic articulating knife used with ESD (ESD-AR) to determine its safety and efficacy for large esophageal neoplasms in comparison with EMR. METHODS: We retrospectively studied clinically indicated cases of ESD-AR and EMR for esophageal lesions that were 15 mm or greater. All EMR cases had at least 3 simultaneous EMRs to adequately compare resection area. Rates of perforation, GI bleeding, technical performance, and pre- and postendoscopic resection diagnoses were evaluated. RESULTS: Seventy-two ESD-AR and 72 widespread EMR cases were evaluated for Barrett's esophagus (56%), adenocarcinoma (36%), squamous nodularity (2%), and squamous cell carcinoma (6%). There were no statistical differences in age, sex, Barrett's esophagus length, and lesion or resection size between the 2 groups. No perforations occurred. Two adverse events were recorded with ESD-AR and none with EMR (3% vs 0%, P = .50); these were associated with anticoagulation use (P = .04) and greater resection area (P = .02). There were more upgraded diagnoses post-ESD versus EMR (27% vs 12%, P = .05). CONCLUSIONS: ESD-AR by an experienced endoscopist has a comparable safety profile with widespread EMR for large esophageal neoplasia and may have advantages for diagnostic staging.

Sensitivity to major versus minor musical modes is bimodally distributed in young infants.

The difference between major and minor scales plays a central role in Western music. However, recent research using random tone sequences ("tone-scrambles") has revealed a dramatically bimodal distribution in sensitivity to this difference: 30% of listeners are near perfect in classifying major versus minor tone-scrambles; the other 70% perform near chance. Here, whether or not infants show this same pattern is investigated. The anticipatory eye-movements of thirty 6-month-old infants were monitored during trials in which the infants heard a tone-scramble whose quality (major versus minor) signalled the location (right versus left) where a subsequent visual stimulus (the target) would appear. For 33% of infants, these anticipatory eye-movements predicted target location with near perfect accuracy; for the other 67%, the anticipatory eye-movements were unrelated to the target location. In conclusion, six-month-old infants show the same distribution as adults in sensitivity to the difference between major versus minor tone-scrambles.

Endoscopic Full Thickness Resection.

Recent advances in minimally invasive endoscopic approaches have pushed the boundaries of well-established resection techniques for therapeutic and diagnostic applications. Endoscopic full thickness resection techniques are a key development in the management of challenging epithelial and subepithelial lesions that are not amenable to conventional endoscopic resection methods and previously required a surgical approach. Endoscopic full thickness biopsy represents a paradigm shift in tissue acquisition and will enhance our understanding of the pathophysiology, and guide therapy, of gastrointestinal neuromuscular diseases, as well as other inflammatory and neoplastic conditions. This review highlights current tools and techniques available for endoscopic full thickness resection and biopsy, as well as outcomes from such interventions.

A phase III, multicenter, prospective, single-blinded, noninferiority, randomized controlled trial on the performance of a novel esophageal stent with an antireflux valve (with video).

BACKGROUND AND AIMS: Self-expanding metal stents (SEMSs) when deployed across the gastroesophageal junction (GEJ) can lead to reflux with risks of aspiration. A SEMS with a tricuspid antireflux valve (SEMS-V) was designed to address this issue. The aim of this study was to evaluate the efficacy and safety of this stent. METHODS: A phase III, multicenter, prospective, noninferiority, randomized controlled trial was conducted on patients with malignant dysphagia requiring SEMSs to be placed across the GEJ. Patients were randomized to receive SEMSs with no valve (SEMS-NV) or SEMS-V. Postdeployment dysphagia score at 2 weeks and Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) questionnaire score at 4 weeks were measured. Patients were followed for 24 weeks. RESULTS: Sixty patients were randomized (SEMS-NV: 30 patients, mean age 67 ± 13 years; SEMS-V: 30 patients, mean age 65 ± 12 years). Baseline dysphagia scores (SEMS-NV, 2.5 ± .8; SEMS-V, 2.5 ± .8) and GERD-HRQL scores (SEMS-NV, 11.1 ± 8.2; SEMS-V, 12.8 ± 8.3) were similar. All SEMSs were successfully deployed. A similar proportion of patients in both arms improved from advanced dysphagia to moderate to no dysphagia (SEMS-NV, 71%; SEMS-V, 74%; 95% confidence interval, 1.93 [-17.8 to 21.7]). The dysphagia scores were also similar across all follow-up time points. Mean GERD-HRQL scores improved by 7.4 ± 10.2 points in the SEMS-V arm and by 5.2 ± 8.3 in the SEMS-NV group (P = .96). The GERD-HRQL scores were similar across all follow-up time points. Aspiration pneumonia occurred in 3.3% in the SEMS-NV arm and 6.9% in the SEMS-V arm (P = .61). Migration rates were similar (SEMS-NV, 33%; SEMS-V, 48%; P = .29). Two SEMS-V spontaneously fractured. There was no perforation, food impaction, or stent-related death in either group. CONCLUSIONS: The SEMS-V was equally effective in relieving dysphagia as compared with the SEMS-NV. Presence of the valve did not increase the risks of adverse events. GERD symptom scores were similar between the 2 stents, implying either that the valve was not effective or that all patients on proton pump inhibitors could have masked the symptoms of GERD. Studies with objective evaluations such as fluoroscopy and/or pH/impedance are recommended. (Clinical trial registration number: NCT02159898.).

Efficacy and safety of an internal magnet traction device for endoscopic submucosal dissection: ex vivo study in a porcine model (with video).

BACKGROUND: Appropriate traction allows for safer and easier endoscopic submucosal dissection (ESD). The aim of this study was to evaluate the efficacy and safety of an internal magnet traction device (MTD) for ESD in an ex vivo porcine model. METHODS: The MTD consisted of a small neodymium magnet and a suture attached to a through-the-scope clip. A circumferential mucosal incision was completed around a 30-mm diameter template that served as the target lesion. The first MTD was deployed at the proximal edge of the lesion. A second MTD was deployed on the wall opposite the lesion. With both magnets connected, this created traction or lifting of the target lesion towards the opposing wall during submucosal dissection. Primary endpoint was comparison of submucosal dissection times between conventional ESD (C-ESD) and MTD-assisted ESD (MTD-ESD). RESULTS: Twenty lesions along the anterior wall, posterior wall and greater curvature were resected using either C-ESD or MTD-ESD. The submucosal dissection time in MTD-ESD was significantly shorter than C-ESD (median: 6.4 [interquartile range {IQR} 4.6-8.7] min vs. 14.4 min [IQR 11.8-18.0], p < 0.05). There was a significant difference between MTD-ESD and C-ESD in total procedure times for lesions on the posterior gastric wall and greater curvature (median: 23.0 min [IQR 21.1-24.5] vs. 29.2 min [IQR 24.8-33.2], p < 0.05) with no difference for lesions on the anterior gastric wall (median: 18.8 min [IQR 15.5-20.5] vs. 17.1 min [IQR 13.1-20.0], p = 0.5). The number of muscularis propria injuries per lesion was significantly lower in MTD-ESD than C-ESD (median: 0 [IQR 0-0] vs. 1 [IQR 0-2], p < 0.05). CONCLUSIONS: MTD for ESD is effective and safe when compared to C-ESD. This approach significantly reduced submucosal dissection times with less injury to the muscularis propria. Furthermore, MTD-ESD was particularly beneficial for more challenging gastric lesions located on the posterior wall and greater curvature.

An internal magnet traction device reduces procedure time for endoscopic submucosal dissection by expert and non-expert endoscopists: ex vivo study in a porcine colorectal model (with video).

BACKGROUND: Efficacy of an internal magnet traction device (MTD) for gastric endoscopic submucosal dissection (ESD) by an expert endoscopist has been reported. We hypothesized that use of the MTD would enhance the performance of colorectal ESD in a non-expert endoscopist in ESD compared to the conventional technique. Primary aim of this study was to compare procedure times between conventional ESD (C-ESD) and MTD-assisted ESD (MTD-ESD) by expert and non-expert endoscopists in ESD. Secondary aims included rate of en bloc resection, iatrogenic injury, visualization score of the submucosal layer, and endoscopist satisfaction score. METHODS: A total of 56 lesions were created in an ex vivo porcine colorectum. Two endoscopists completed C-ESD (n = 28) and MTD-ESD (n = 28). Lesions measured 3 cm in diameter and were located on either the anterior or posterior colorectal wall. The MTD consisted of a small neodymium magnet and nylon monofilament attached to a through-the-scope clip. The first MTD was deployed on the opposing colorectal wall of the target lesion and a second MTD was then deployed directly onto the distal margin of the lesion. RESULTS: Total procedure time for MTD-ESD was significantly shorter than C-ESD for both expert (median: 15.8 vs. 19.3 min, p < 0.05) and non-expert (median: 21.3 vs. 33.9 min, p < 0.001) endoscopists. All lesions were resected en bloc. There was no iatrogenic muscularis propria injury in the MTD-ESD group. For both the expert and non-expert, scores for MTD-ESD were significantly higher for submucosal layer visualization (p < 0.05) and endoscopist satisfaction (p < 0.001) compared to C-ESD. CONCLUSIONS: Use of the MTD significantly reduced procedure time for both expert and non-expert endoscopists performing ESD. Improving the efficiency, safety, and satisfaction of ESD with such a device particularly for non-expert endoscopists is appealing and could potentially minimize the complexity and duration of the procedure allowing for more widespread use of the technique.

Development of spatial suppression surrounding the focus of visual attention.

In adulthood, research has demonstrated that surrounding the spatial location of attentional focus is a suppressive field, resulting from top-down attention promoting the processing of relevant stimuli and inhibiting surrounding distractors (e.g., Hopf et al., 2006). It is not fully known, however, how this phenomenon manifests during development. This is an important question since attention processes are likely even more critical in development because of their potential impact on learning and day-to-day activities. The current study examined whether spatial suppression surrounding the focus of visual attention, a predicted by-product of top-down attentional modulation, is observed in development. A wide age range separated in six incremental age levels was included, allowing for a detailed examination of potential differences in the effect of attention on visual processing across development. Participants between 12 and 27 years of age exhibited spatial suppression surrounding their focus of visual attention. Their accuracy increased as a function of the separation distance between a spatially cued (and attended) target and a second target, suggesting that a ring of suppression surrounded the attended target. Attentional surround suppression was not observed in 8- to 11-years-olds, even with a longer spatial cue presentation time, demonstrating that the lack of the effect at these ages is not due to slowed attentional feedback processes. Our findings demonstrate that top-down attentional processes exhibit functional maturity beginning around 12 years of age with continuing maturation of their expression until 17, which likely impacts education and the diagnosis of visual and cognitive clinical pathologies.

The spacing effect stands up to big data.

Many studies have shown that repetition of study material with temporal gaps between the repetitions (i.e., spaced in time) is more effective for long-term retention than are repetitions in immediate succession (i.e., massed; Greene, 1989). Although this spacing effect has proven to be robust in the laboratory (Cepeda, Pashler, Vul, Wixted, & Rohrer, 2006), its status in the real world is relatively understudied. Other research has demonstrated the benefit of memory retrieval on subsequent retrieval of the same information (Bjork, 1975, 1988; Roediger & Karpicke, 2006), referred to as the testing effect. However, it is not clear how spacing and retrieval can be optimally combined in order to enhance knowledge retention in a real-world setting. To investigate this question, we analyzed longitudinal data from 10,514 individuals, collected in the context of naturally occurring workplace training. To determine the impact of spaced retrieval on knowledge retention, these data were analyzed using a generalized linear mixed model with the following fixed factors: (1) spacing interval between repetitions of content training (retrieval practice), (2) retention interval, and (3) question format. Random factors included the specific content on which employees were trained, which was clustered by employee and, in turn, by company, resulting in a three-level hierarchy. The results showed a significant interaction between spacing interval and retention interval: the optimal amount of spacing between repeated retrieval events increased as the retention interval increased. These findings are in line with the results of laboratory studies, demonstrating the relevance and transferability of laboratory-based research to real-world contexts.

Efficacy of Over-the-Scope Clips in Management of High-Risk Gastrointestinal Bleeding.

BACKGROUND & AIMS: Standard endoscopic therapies do not control bleeding or produce complications in as many as 20% of patients with nonvariceal gastrointestinal bleeding. Most bleeding comes from ulcers with characteristics such as high-risk vascular territories and/or large vessels. We evaluated the efficacy of using over-the-scope clips (OTSCs) as primary or rescue therapy for patients with bleeding from lesions that have a high risk for adverse outcomes. METHODS: We performed a retrospective analysis of data from 67 patients with gastrointestinal bleeding from high-risk lesions who were treated with OTSCs as primary (n = 49) or rescue therapy (n = 18) at a quaternary center, from December 2011 through February 2015. The definition of high-risk lesions was lesions that were situated in the area of a major artery and larger than 2 mm in diameter and/or a deep penetrating, excavated, fibrotic ulcer with high-risk stigmata, in which a perforation could not be ruled out or thermal therapy would cause perforation, or lesions that could not be treated by standard endoscopy. Clinical severity was determined based on the Rockall score and a modified Blatchford score. Our primary outcome was the incidence of rebleeding within 30 days after OTSC placement. We assessed risk factors for rebleeding using univariate hazard models followed by multivariable analysis. RESULTS: Of the 67 patients, 47 (70.1%) remained free of rebleeding at 30 days after OTSC placement. We found no difference in the proportion of patients with rebleeding who received primary or rescue therapy (hazard ratio, 0.639; 95% confidence interval, 0.084-4.860; P = .6653). Only 9 rebleeding events were linked clearly to OTSCs and required intervention, indicating an OTSC success rate of 81.3%. We found no significant associations between rebleeding and clinical scores. However, on multivariable analysis, patients with coronary artery disease had a higher risk of rebleeding after OTSC independent of international normalized ratio and antiplatelet use (hazard ratio, 7.30; P = .0002). CONCLUSIONS: In a retrospective analysis of 67 patients with bleeding from high-risk gastrointestinal lesions, we found OTSCs to prevent rebleeding in more than 80% of cases. In the past, these lesions were treated with surgical or radiologic interventions. Patients with coronary artery disease have an increased risk of rebleeding after OTSCs, suggesting the need for escalated therapies.

Changes in multimodality functional imaging parameters early during chemoradiation predict treatment response in patients with locally advanced head and neck cancer.

OBJECTIVE: To assess the optimal timing and predictive value of early intra-treatment changes in multimodality functional and molecular imaging (FMI) parameters as biomarkers for clinical remission in patients receiving chemoradiation for head and neck squamous cell carcinoma (HNSCC). METHODS: Thirty-five patients with stage III-IVb (AJCC 7th edition) HNSCC prospectively underwent 18F-FDG-PET/CT, and diffusion-weighted (DW), dynamic contrast-enhanced (DCE) and susceptibility-weighted MRI at baseline, week 1 and week 2 of chemoradiation. Patients with evidence of persistent or recurrent disease during follow-up were classed as non-responders. Changes in FMI parameters at week 1 and week 2 were compared between responders and non-responders with the Mann-Whitney U test. The significance threshold was set at a p value of <0.05. RESULTS: There were 27 responders and 8 non-responders. Responders showed a greater reduction in PET-derived tumor total lesion glycolysis (TLG40%; p = 0.007) and maximum standardized uptake value (SUVmax; p = 0.034) after week 1 than non-responders but these differences were absent by week 2. In contrast, it was not until week 2 that MRI-derived parameters were able to discriminate between the two groups: larger fractional increases in primary tumor apparent diffusion coefficient (ADC; p < 0.001), volume transfer constant (Ktrans; p = 0.012) and interstitial space volume fraction (Ve; p = 0.047) were observed in responders versus non-responders. ADC was the most powerful predictor (∆ >17%, AUC 0.937). CONCLUSION: Early intra-treatment changes in FDG-PET, DW and DCE MRI-derived parameters are predictive of ultimate response to chemoradiation in HNSCC. However, the optimal timing for assessment with FDG-PET parameters (week 1) differed from MRI parameters (week 2). This highlighted the importance of scanning time points for the design of FMI risk-stratified interventional studies.

Endoscopic muscle biopsy sampling of the duodenum and rectum: a pilot survival study in a porcine model to detect myenteric neurons.

BACKGROUND AND AIMS: Small bowel and colorectal muscle biopsy sampling requires a surgical approach. Advancing our understanding of the pathophysiology of motility disorders, such as functional bowel disorders, intestinal pseudo-obstruction, and slow-transit constipation, is hindered by our inability to noninvasively obtain muscularis propria (MP) for evaluation of multiple cell types, including myenteric neurons. The aims of this study were to determine (1) technical feasibility, reproducibility, and safety of performing duodenal endoscopic muscle biopsy sampling (dEMB) and rectal endoscopic muscle biopsy sampling (rEMB) using a clip-assist technique and (2) the presence of myenteric neurons in tissue samples. METHODS: Five 40-kg pigs were studied. Each animal underwent a dEMB and rEMB procedure. dEMB was performed using a single resection clip-assist technique. An over-the-scope clip was advanced to the duodenum. Tissue was suctioned into the cap and the clip deployed. The pseudopolyp of the duodenal wall created was then resected using snare electrocautery. rEMB was performed using a double resection clip-assist technique. EMR was initially performed to uncover the underlying MP using a band ligation technique. An over-the-scope clip was then advanced to the exposed MP. The MP was retracted and suctioned into the cap and the clip deployed. The pseudopolyp of the MP was resected using snare electrocautery. An antibody to protein gene product 9.5 was used to determine the presence of myenteric neurons in the samples. Animals were kept alive for 2 weeks, at which time an upper endoscopy and necropsy were performed. RESULTS: dEMB and rEMB were successfully performed in all animals with no procedural adverse events using this "no hole" (close then cut) approach. Mean procedure times for dEMB and rEMB were 23.7 ± 2.5 minutes and 13.25 ± 2.8 minutes, respectively. Mean length of resected full-thickness duodenal wall was 13.25 ± 4.3 mm and rectal MP was 12.5 ± 1.7 mm. Hematoxylin and eosin stain and antibody to protein gene product 9.5 confirmed the presence of MP with inner circular, outer longitudinal, and intermuscular layers, including myenteric neurons, in all samples. Clinical course was uneventful in all animals. Repeat upper endoscopy at 2 weeks showed well-healed dEMB sites. Necropsy in all animals showed no perforation, fluid collection, or abscess at the dEMB and rEMB sites. CONCLUSIONS: Based on this preclinical study, dEMB and rEMB appear to be technically feasible, reproducible, and safe. Sufficient MP tissue was obtained to identify myenteric neurons. These promising results are a step toward successful and safe implementation of these techniques into clinical practice for tissue diagnosis of muscle-based pathologies.