DIAGNOSTIC IMAGING AND OROTRACHEAL INTUBATION IN CLINICALLY HEALTHY WILD SUNDA PANGOLINS (MANIS JAVANICA) IN SINGAPORE.

Pangolins are amongst the most overexploited species in the world and all eight species of pangolins are threatened with extinction. These animals are rare in zoological collections and often suffer high mortality rates in captivity. Maintaining healthy populations in captivity has become more important with the declining populations in the wild, but knowledge of veterinary care of these animals is limited. Interpreting radiography and ultrasonography images in a patient can be challenging without knowledge of normal findings. The Wildlife Healthcare and Research Center (WHRC) at Mandai Wildlife Reserve (MWR) admits an average of 25 Sunda pangolins (Manis javanica) annually, which is a Critically Endangered species native to Singapore. All the pangolins are triaged on admission and anesthetized for a health assessment before release into the wild. Endotracheal intubation using an otoscope and stylet is a novel technique in the species that has been developed and is commonly performed with these pangolins. A retrospective study was done on 20 clinically healthy wild pangolins to determine normal ultrasonography and radiography findings in the species. Notable findings include the presence of radio-opaque particles in the stomachs of all pangolins, the presence of free fluid cranial to the left kidney (13/20), a spleen with multifocal hypoechoic regions (6/20), and open epiphyseal plates of long bones even in large individuals weighing as heavy as 6.8 kg. Ultrasonographic images and measurements of kidney, spleen, and adrenal gland sizes as well as intestinal, gallbladder, and urinary bladder wall thickness were also described. These diagnostic imaging findings can advance the veterinary care of captive and wild pangolins.

ß-Galactosidase-activated nitroxyl (HNO) donors provide insights into redox cross-talk in senescent cells.

The cross-talk among reductive and oxidative species (redox cross-talk), especially those derived from sulfur, nitrogen and oxygen, influence several physiological processes including aging. One major hallmark of aging is cellular senescence, which is associated with chronic systemic inflammation. Here, we report a chemical tool that generates nitoxyl (HNO) upon activation by ß-galactosidase, an enzyme that is over-expressed in senescent cells. In a radiation-induced senescence model, the HNO donor suppressed reactive oxygen species (ROS) in a hydrogen sulfide (H2S)-dependent manner. Hence, the newly developed tool provides insights into redox cross-talk and establishes the foundation for new interventions that modulate levels of these species to mitigate oxidative stress and inflammation.

MANAGEMENT OF ENTAMOEBA INVADENS IN THE HERPETOLOGICAL COLLECTION AT THE SINGAPORE ZOO.

Amebiasis caused by Entamoeba invadens is an important disease in reptile collections, causing severe morbidity and mortality. Surveillance of the parasite at the Singapore Zoo was carried out over a 4-yr period by PCR testing on reptiles that presented with lethargy and enteritis for disease investigation. Asymptomatic reptiles sharing the same enclosures as positive individuals were also tested as part of outbreak investigation. Animals in the collection that tested positive for the parasite were treated with metronidazole at various doses, with the addition of paromomycin for two cases, until a negative PCR test result was obtained at the end of the treatment course. A total of 97 samples from 49 individuals across 19 species of reptiles were obtained, of which 24 samples (24.7%) from 19 animals were positive for E. invadens. Of these positive samples, 11 samples were for disease investigation, eight samples for outbreak surveillance, and five samples for treatment monitoring. Treatment was initiated for 10 animals, four of which were showing clinical signs of disease. The parasite was cleared in nine of these 10 animals (90%), with eight animals receiving metronidazole as a sole therapeutic agent. A total of nine animals died of the disease, four of which (44.4%) presented dead or died within 24 h of presentation. Necrotizing enteritis was a consistent postmortem finding resulting in gastrointestinal perforation in two cases, and coelomic adhesions and hepatic trophozoites were each seen in five animals. The results suggest that the management of Entamoeba epizootics in the collection requires prompt outbreak investigation. Diagnosis of the disease with advanced diagnostic tools like PCR, endoscopy, and ultrasonography and treatment with metronidazole in both symptomatic and asymptomatic animals may reduce mortalities during an outbreak.

Acetylcholine Structure-Based Small Activatable Fluorogenic Probe for Specific Detection of Acetylcholinesterase.

Early detection of Alzheimer's disease (AD) is important for taking proper measures against AD pathogenesis. Acetylcholinesterase (AChE) is widely reported to be associated with the pathogenicity of AD. Here, employing the "acetylcholine-mimic" approach, we designed and synthesized a new class of naphthalimide (Naph)-based fluorogenic probes for specific detection of AChE and avoiding interference of butyrylcholinesterase (BuChE), the pseudocholinesterase. We investigated the action of the probes on Electrophorus electricus AChE, and the native human brain AChE that we expressed in Escherichia coli and purified in the active form for the first time. The probe Naph-3 exhibited a substantial fluorescence enhancement with AChE and majorly avoided BuChE. Naph-3 successfully crossed the cell membrane of the Neuro-2a cells and fluoresced upon reaction with endogenous AChE. We further established that the probe could be effectively used for screening AChE inhibitors. Our study provides a new avenue for the specific detection of AChE, which can be extended to the diagnosis of AChE-related complications.

H2S contributed from CSE during cellular senescence suppresses inflammation and nitrosative stress.

Aging involves the time-dependent deterioration of physiological functions attributed to various intracellular and extracellular factors. Cellular senescence is akin to aging and involves alteration in redox homeostasis. This is primarily marked by increased reactive oxygen/nitrogen species (ROS/RNS), inflammatory gene expression, and senescence-associated beta-galactosidase activity, all hallmarks of aging. It is proposed that gasotransmitters which include hydrogen sulfide (H2S), carbon monoxide (CO), and nitric oxide (NO), may affect redox homeostasis during senescence. H2S has been independently shown to induce DNA damage and suppress oxidative stress. While an increase in NO levels during aging is well established, the role of H2S has remained controversial. To understand the role of H2S during aging, we evaluated H2S homeostasis in non-senescent and senescent cells, using a combination of direct measurements with a fluorescent reporter dye (WSP-5) and protein sulfhydration analysis. The free intracellular H2S and total protein sulfhydration levels are high during senescence, concomitant to cystathionine gamma-lyase (CSE) expression induction. Using lentiviral shRNA-mediated expression knockdown, we identified that H2S contributed by CSE alters global gene expression, which regulates key inflammatory processes during cellular senescence. We propose that H2S decreases inflammation during cellular senescence by reducing phosphorylation of IκBα and the p65 subunit of nuclear factor kappa B (NF-κB). H2S was also found to reduce NO levels, a significant source of nitrosative stress during cellular senescence. Overall, we establish H2S as a key gasotransmitter molecule that regulates inflammatory phenotype and nitrosative stress during cellular senescence.

Patient Education Materials Found via Google Search for Shoulder Arthroscopy Are Written at Too-High of a Reading Level.

Purpose: To evaluate the quality and correlation of readability on actionability and understandability of shoulder arthroscopy-related patient education materials (PEMs) found via a routine Google search. Methods: Two independent authors performed an online Google search with the term "shoulder arthroscopy." The first 5 pages of search results were then screened for PEMs. Journal articles, news articles, nontext materials, and unrelated websites were excluded. The readability of included resources was calculated using objective metrics: Flesch-Kincaid Grade Score, Simple Measure of Gobbledygook index, Coleman-Liau Index, and the Gunning Fog Index. Patient Education Material Assessment Tool for Printed Materials assessed for understandability and actionability. Associations between readability and actionability and understandability were determined using Spearman correlation and linear regression. Results: The searches returned 53 websites related to shoulder arthroscopy. A total of 34 (64%) met inclusion criteria. A high school reading level or greater was required to read the average PEM according to all scales used. The average PEM received a Patient Education Material Assessment Tool for Printed Materials score of 61.33 in understandability (range 18.75-89.47) and 55.59 points in actionability (range 16.67-83.33). An easily understood or actionable article would score at least 70 points. A moderate correlation was observed between readability and actionability on three of the scales used (r = 0.5, r = 0.59, r = 0.61). Conclusions: Most shoulder arthroscopy PEMs identified on Google are not written at a level that the average patient can read, understand, or act on (actionability). Clinical Relevance: Orthopaedic surgeons should be aware of the resources that patients use to obtain medical information. More accessible PEMs should be developed for patients undergoing shoulder arthroscopy to enhance comprehension of their condition and improve shared decision-making.

Positive Association Between Online Attention and the Bibliometric Impact of Shoulder Instability Publications.

Purpose: To obtain a quantifiable measure of the frequency with which a shoulder instability article is discussed online and the association with its corresponding bibliometric impact, based on the Scopus Cite Score (SCS) or Web of Science Impact Factor (WSIF). Methods: The top 100 most-mentioned articles on shoulder instability based on Altmetric Attention Score (AAS) were extracted from the Altmetric Database. Mentions within blogs, news articles and outlets, public policy, and social media platforms, such as Twitter and Facebook, were included. Study impact was assessed using SCS or WSIF. The degree of association between AAS and impact was determined using Spearman correlation, logarithmic regression, and multivariate regression. Results: The most common study designs were "Clinical Trial," with 52 articles (49.5%), "Systematic Review" with 16 articles (15.2%), and "Review" with 10 articles (9.5%). Twitter provided more online mentions than other platforms, with the average article being discussed 27.7 times (range 0-220 times). A significant positive effect (estimate = 2.616, P = .0075) was observed between the AAS and WSIF, based on the logarithmic regression. Multivariate regression revealed that blogs help raise both WSIF and SCS (estimate = 7.272, P < .05). Conclusions: Social media and other online platforms are a strong way to disseminate information to patients. A positive association was observed between overall online attention and the bibliometric impact of an article related to shoulder instability. Clinical trials related to shoulder instability that receive online mentions, especially discussion in blogs, are more likely to be cited in the future than their counterparts. Clinical Relevance: The results of our study can guide authors as they aim to disseminate their articles. Twitter may be used as a tool to reach patients who may not venture into academic journals with current peer-reviewed articles. Further, blogs may be used to reach academic audiences and raise bibliometric impact broadly.

Challenges of developing and executing a multi-site registry for a novel device with evolving indications for use.

BACKGROUND: The introduction of new technologies in endoscopy has been met with uncertainty, skepticism, and lack of standardization or training parameters, particularly when disruptive devices or techniques are involved. The widespread availability of a novel endoscopic suturing device (OverStitch™) for tissue apposition has enabled the development of applications of endoscopic suturing. METHODS: The American Gastroenterological Association partnered with Apollo Endosurgery to develop a registry to capture in a pragmatic non-randomized study the safety, effectiveness, and durability of endoscopic suturing in approximating tissue in the setting of bariatric revision and fixation of endoprosthetic devices. RESULTS: We highlight the challenges of the adoption of novel techniques by examining the process of developing and executing this multicenter registry to assess real-world use of this endoscopic suturing device. We also present our preliminary data on the safety and effectiveness of the novel device as it is applied in the treatment of obesity. CONCLUSIONS: The Prospective Registry for Trans-Orifice Endoscopic Suturing Applications (ES Registry) was an effective Phase 4, postmarketing registry aimed at capturing pragmatic, real-world use of a novel device. These findings serve to solidify the role of endoscopic suturing in clinical practice.

The Durability of EUS-Guided Chemoablation of Mucinous Pancreatic Cysts: A Long-Term Follow-Up of the CHARM trial.

Pancreatic cancer has known precursor lesions with potential to develop into malignancy over time. At least 20% of pancreatic cancer evolves from mucinous cystic neoplasms and intraductal papillary mucinous neoplasms, which are often discovered incidentally.1,2 Current guidelines for the management of mucinous cystic neoplasms and intraductal papillary mucinous neoplasms include long-term surveillance, which is expensive and nontherapeutic, or surgical resection, which is associated with major risk and may not be an option for patients with significant concomitant illness.3.

Treatments and outcomes of severe hemorrhagic enteritis in three eastern bongos (Tragelpahus eurycerus isaacii) at the Singapore Zoo.

Three eastern bongos (Tragelaphus eurycerus isaaci) presented acutely with hemorrhagic diarrhea at the Singapore Zoo, thought to be caused by a mouldy batch of hay. Repeated fecal tests were negative of parasites and common gastrointestinal bacteria including salmonella and campylobacter. The diarrhea resolved for all individuals after a week of leaf-only diet. However, 2 individuals developed signs of colic. Both animals were anesthetized for examination including blood tests and imaging studies. The findings were consistent of gastrointestinal ileus and a possible impaction. With intensive treatment involving repeated sedations for fluid therapy administration and treatments for gastrointestinal impaction, one individual eventually made a full recovery, but the other individual died due to septic peritonitis secondary to a rupture in the spiral colon. Persistent supportive therapy may be vital in treating severe gastrointestinal disease in this species.

MFAP9: Characterization of an extracellular thermostable antibacterial peptide from marine fungus with biofilm eradication potential.

An extracellular thermostable antibacterial peptide designated as MFAP9 was purified from marine Aspergillus fumigatus BTMF9 by ammonium sulfate precipitation followed by ion exchange chromatography on a DEAE-sepharose column. The molecular weight of MFAP9 was found to be∼3 kDa in SDS-PAGE gel corresponding a single intensity peak in MALDI-TOF. The distinct peak with a retention time of 32.5 min appeared in high performance liquid chromatography (HPLC), further confirming the purity. Isoelectric focusing, two-dimensional gel electrophoresis and peptide mass fingerprinting were performed for the characterization of MFAP9. Functional analysis of purified MFAP9 exhibited strong antibacterial activity against Bacillus circulans (NCIM 2107) with MIC and MBC values of 0.525 µg/mL and 4.2 µg/mL, respectively. The in vitro antibiofilm effect of MFAP9 was analyzed against bacteria which have strong biofilm forming potential. The antibiofilm effect of MFAP9 treatment on Bacillus pumilus was examined using scanning electron microscopy. MFAP9 was found to be active at high temperatures and a wide range of pH (28). In addition, it showed varied sensitivity towards proteolytic enzymes. The peptide was nontoxic to human RBCs at higher concentrations. These results indicate that MFAP9 is an antibacterial peptide, suitable for the development of novel anti-infective agent with strong antibiofilm potential.

Factors associated with complete clip closure after endoscopic mucosal resection of large colorectal polyps.

BACKGROUND AND STUDY AIM : Delayed bleeding is a common adverse event following endoscopic mucosal resection (EMR) of large colorectal polyps. Prophylactic clip closure of the mucosal defect after EMR of nonpedunculated polyps larger than 20 mm reduces the incidence of severe delayed bleeding, especially in proximal polyps. This study aimed to evaluate factors associated with complete prophylactic clip closure of the mucosal defect after EMR of large polyps. METHODS : This is a post hoc analysis of the CLIP study (NCT01936948). All patients randomized to the clip group were included. Main outcome was complete clip closure of the mucosal resection defect. The defect was considered completely closed when no remaining mucosal defect was visible and clips were less than 1 cm apart. Factors associated with complete closure were evaluated in multivariable analysis. RESULTS : In total, 458 patients (age 65, 58 % men) with 494 large polyps were included. Complete clip closure of the resection defect was achieved for 338 polyps (68.4 %); closure was not complete for 156 (31.6 %). Factors associated with complete closure in adjusted analysis were smaller polyp size (odds ratio 1.06 for every millimeter decrease [95 % confidence interval 1.02-1.08]), good access (OR 3.58 [1.94-9.59]), complete submucosal lifting (OR 2.28 [1.36-3.90]), en bloc resection (OR 5.75 [1.48-22.39]), and serrated histology (OR 2.74 [1.35-5.56]). CONCLUSIONS : Complete clip closure was not achieved for almost one in three resected large nonpedunculated polyps. While stable access and en bloc resection facilitate clip closure, most factors associated with clip closure are not modifiable. This highlights the need for alternative closure options and measures to prevent bleeding.

Practice patterns, techniques, and outcomes of flexible endoscopic myotomy for Zenker's diverticulum: a retrospective multicenter study.

BACKGROUND: Flexible endoscopic myotomy has been increasingly performed for Zenker's diverticulum using various endoscopic techniques and devices. The main aims of this study were to assess practice patterns and compare outcomes of endoscopic myotomy for Zenker's diverticulum. METHODS: Procedures performed at 12 tertiary endoscopy centers from 1/2012 to 12/2018 were reviewed. Patients (≥ 18 years) with Zenker's diverticulum who had dysphagia and/or regurgitation and underwent endoscopic myotomy were included. Outcomes assessed included technical success, clinical success, and adverse events. RESULTS: 161 patients were included. Traditional endoscopic septotomy was performed most frequently (137/161, 85.1 %) followed by submucosal dissection of the septum and myotomy (24/161, 14.9 %). The hook knife (43/161, 26.7 %) and needle-knife (33/161, 20.5 %) were used most frequently. Overall, technical and clinical success rates were 98.1 % (158/161) and 78.1 % (96/123), respectively. Adverse events were noted in 13 patients (8.1 %). There was no significant difference in technical and clinical success between traditional septotomy and submucosal dissection groups (97.1 % vs. 95.8 %, P = 0.56 and 75.2 % vs. 90.9 %, P  = 0.16, respectively). Clinical success was higher with the hook knife (96.7 %) compared with the needle-knife (76.6 %) and insulated tip knife (47.1 %). Outcomes were similar between centers performing > 20, 11 - 20, and ≤ 10 procedures. CONCLUSIONS: Flexible endoscopic myotomy is an effective therapy for Zenker's diverticulum, with a low rate of adverse events. There was no significant difference in outcomes between traditional septotomy and a submucosal dissection approach, or with centers with higher volume, though clinical success was higher with the hook knife.

Digital Phenotyping and Patient-Generated Health Data for Outcome Measurement in Surgical Care: A Scoping Review.

Digital phenotyping-the moment-by-moment quantification of human phenotypes in situ using data related to activity, behavior, and communications, from personal digital devices, such as smart phones and wearables-has been gaining interest. Personalized health information captured within free-living settings using such technologies may better enable the application of patient-generated health data (PGHD) to provide patient-centered care. The primary objective of this scoping review is to characterize the application of digital phenotyping and digitally captured active and passive PGHD for outcome measurement in surgical care. Secondarily, we synthesize the body of evidence to define specific areas for further work. We performed a systematic search of four bibliographic databases using terms related to "digital phenotyping and PGHD," "outcome measurement," and "surgical care" with no date limits. We registered the study (Open Science Framework), followed strict inclusion/exclusion criteria, performed screening, extraction, and synthesis of results in line with the PRISMA Extension for Scoping Reviews. A total of 224 studies were included. Published studies have accelerated in the last 5 years, originating in 29 countries (mostly from the USA, n = 74, 33%), featuring original prospective work (n = 149, 66%). Studies spanned 14 specialties, most commonly orthopedic surgery (n = 129, 58%), and had a postoperative focus (n = 210, 94%). Most of the work involved research-grade wearables (n = 130, 58%), prioritizing the capture of activity (n = 165, 74%) and biometric data (n = 100, 45%), with a view to providing a tracking/monitoring function (n = 115, 51%) for the management of surgical patients. Opportunities exist for further work across surgical specialties involving smartphones, communications data, comparison with patient-reported outcome measures (PROMs), applications focusing on prediction of outcomes, monitoring, risk profiling, shared decision making, and surgical optimization. The rapidly evolving state of the art in digital phenotyping and capture of PGHD offers exciting prospects for outcome measurement in surgical care pending further work and consideration related to clinical care, technology, and implementation.

Effects of Blended (Yellow) vs Forced Coagulation (Blue) Currents on Adverse Events, Complete Resection, or Polyp Recurrence After Polypectomy in a Large Randomized Trial.

BACKGROUND & AIMS: There is debate over the type of electrosurgical setting that should be used for polyp resection. Some endoscopists use a type of blended current (yellow), whereas others prefer coagulation (blue). We performed a single-blinded, randomized trial to determine whether type of electrosurgical setting affects risk of adverse events or recurrence. METHODS: Patients undergoing endoscopic mucosal resection of nonpedunculated colorectal polyps 20 mm or larger (n = 928) were randomly assigned, in a 2 × 2 design, to groups that received clip closure or no clip closure of the resection defect (primary intervention) and then to either a blended current (Endocut Q) or coagulation current (forced coagulation) (Erbe Inc) (secondary intervention and focus of the study). The study was performed at multiple centers, from April 2013 through October 2017. Patients were evaluated 30 days after the procedure (n = 919), and 675 patients underwent a surveillance colonoscopy at a median of 6 months after the procedure. The primary outcome was any severe adverse event in a per patient analysis. Secondary outcomes were complete resection and recurrence at first surveillance colonoscopy in a per polyp analysis. RESULTS: Serious adverse events occurred in 7.2% of patients in the Endocut group and 7.9% of patients in the forced coagulation group, with no significant differences in the occurrence of types of events. There were no significant differences between groups in proportions of polyps that were completely removed (96% in the Endocut group vs 95% in the forced coagulation group) or the proportion of polyps found to have recurred at surveillance colonoscopy (17% and 17%, respectively). Procedural characteristics were comparable, except that 17% of patients in the Endocut group had immediate bleeding that required an intervention, compared with 11% in the forced coagulation group (P = .006). CONCLUSIONS: In a randomized trial to compare 2 commonly used electrosurgical settings for the resection of large colorectal polyps (Endocut vs forced coagulation), we found no difference in risk of serious adverse events, complete resection rate, or polyp recurrence. Electrosurgical settings can therefore be selected based on endoscopist expertise and preference. Clinicaltrials.gov ID NCT01936948.

Endoscopic Management of Large Peripancreatic Fluid Collections in Two Pediatric Patients by Endoscopic Ultrasound-guided Transmural Drainage.

The incidence of acute pancreatitis (AP) has increased in the pediatric population over the past few decades and it stands to follow that the complications of severe AP, including symptomatic pancreatic fluid collections (PFCs) will increase as well. In adults, the therapeutic options for this situation have undergone a dramatic evolution from mainly surgical approaches to less invasive endoscopic approaches, mainly endoscopic ultrasound-guided transmural drainage (EUS-TD) followed be direct endoscopic necrosectomy if needed. This has proven safe and effective in adults; however, this approach has not been well studied or reported in pediatric populations. Here we demonstrate that EUS-TD seems to offer a safe, efficacious and minimally invasive approach to the management of large PFCs in pediatric patients by reviewing two representative cases at our institution.

Percutaneous debridement and washout of walled-off abdominal abscess and necrosis by the use of flexible endoscopy: an attractive clinical option when transluminal approaches are unsafe or not possible.

BACKGROUND AND AIMS: Walled-off pancreatic necrosis is a well-known serious adverse event of severe acute pancreatitis. EUS-guided transluminal access followed by direct endoscopic necrosectomy is increasingly used to remove necrosis, with good efficacy and a superior safety profile when compared with surgery. However, a percentage of patients is too critically ill to undergo this procedure or lack an appropriate transluminal window for access. Here we describe the use of percutaneous flexible endoscopic necrosectomy (PEN) with use of standard-sized upper endoscopes and accessories in a retrospective single-institution experience with a video demonstration of 1 patient in the series. METHODS: The authors present a 23-patient retrospective case series of PEN with standard-sized endoscopes. The series includes 12 patients from a previously published analysis in 2016 and 11 additional patients from 2013 to 2018. A representative case illustrates the described technique in a patient with severe acute pancreatitis complicated by multisystem organ failure who required immediate drainage of a pancreatic fluid collection and placement of a percutaneous drain into the collection for decompression. The drain was serially upsized to 28F, and its tract was used for PEN. RESULTS: A total of 23 patients have undergone PEN at our institution. On average, the size of the pancreatic fluid collection was 11.6 cm in cross-sectional diameter. Of those 23 patients, 11 presented with symptoms of severe disease. The median time from onset of symptoms to PEN was 84 days. The median number of procedures per patient was 2.1. The median time to complete resolution of symptoms and fluid collections was 67 days. In total, resolution was reached in 22 of 23 patients. Two patients died of unrelated causes. CONCLUSION: PEN is a minimally invasive and effective treatment approach to walled-off pancreatic necrosis in patients who are not amenable to transluminal drainage and in whom percutaneous drains have been successfully placed. This case series demonstrates the efficacy and safety of this approach. A randomized prospective trial would be warranted to validate these results.

Successful treatment of large cavity esophageal disruptions with transluminal washout and endoscopic vacuum therapy: a report of two cases.

Acute, high-grade esophageal perforation and postoperative leak after esophagogastrostomy are associated with high morbidity and mortality due to the development of mediastinitis and thoracic contamination. Endoscopic vacuum therapy has proven to be a feasible, safe therapy for management of esophageal wall defects, but with limited success. We describe a retrospective single-center analysis of two patients who underwent endoscopic vacuum therapy for significant esophageal disruptions with a median cross-sectional diameter of 10.7 cm. The technique involved the use of a standard upper video endoscope, nasogastric tube, and vacuum-assisted closure dressing kit, with endoscopic placement of a polyurethane sponge and nasogastric tube assembly into the mediastinal or thoracic cavity. Serial washout and debridement were performed prior to each sponge insertion. Data were collected on indication, size of the cavities, time to intervention, number of procedures, time to resolution, outcomes, and adverse events. Two patients underwent therapy with a mean age of 69.5. The median size of the collections via longest cross-sectional diameter was 10.7 cm. The average number of endoscopic vacuum therapy performed was six and average duration of therapy was 49 days. Complete resolution was achieved in both patients. One patient died 6 weeks later due to severe sepsis from aspiration pneumonia. Endoscopic washout and debridement followed by endoscopic vacuum therapy can be effective for large, even multiple, thoracic and mediastinal contaminations following esophageal perforation and gastroesopagheal anastomotic dehiscence and leaks in appropriately selected patients.

Metabolic signatures suggest o-phosphocholine to UDP-N-acetylglucosamine ratio as a potential biomarker for high-glucose and/or palmitate exposure in pancreatic ß-cells.

INTRODUCTION: Chronic exposure to high-glucose and free fatty acids (FFA) alone/or in combination; and the resulting gluco-, lipo- and glucolipo-toxic conditions, respectively, have been known to induce dysfunction and apoptosis of ß-cells in Diabetes. The molecular mechanisms and the development of biomarkers that can be used to predict similarities and differences behind these conditions would help in easier and earlier diagnosis of Diabetes. OBJECTIVES: This study aims to use metabolomics to gain insight into the mechanisms by which ß-cells respond to excess-nutrient stress and identify associated biomarkers. METHODS: INS-1E cells were cultured in high-glucose, palmitate alone/or in combination for 24 h to mimic gluco-, lipo- and glucolipo-toxic conditions, respectively. Biochemical and cellular experiments were performed to confirm the establishment of these conditions. To gain molecular insights, abundant metabolites were identified and quantified using 1H-NMR. RESULTS: No loss of cellular viability was observed in high-glucose while exposure to FFA alone/in combination with high-glucose was associated with increased ROS levels, membrane damage, lipid accumulation, and DNA double-strand breaks. Forty-nine abundant metabolites were identified and quantified using 1H-NMR. Chemometric pair-wise analysis in glucotoxic and lipotoxic conditions, when compared with glucolipotoxic conditions, revealed partial overlap in the dysregulated metabolites; however, the dysregulation was more significant under glucolipotoxic conditions. CONCLUSION: The current study compared gluco-, lipo- and glucolipotoxic conditions in parallel and elucidated differences in metabolic pathways that play major roles in Diabetes. o-phosphocholine and UDP-N-acetylglucosamine were identified as common dysregulated metabolites and their ratio was proposed as a potential biomarker for these conditions.

Clip Closure Prevents Bleeding After Endoscopic Resection of Large Colon Polyps in a Randomized Trial.

BACKGROUND & AIMS: Bleeding is the most common severe complication after endoscopic mucosal resection of large colon polyps and is associated with significant morbidity and cost. We examined whether prophylactic closure of the mucosal defect with hemoclips after polyp resection reduces the risk of bleeding. METHODS: We performed a multicenter, randomized trial of patients with a large nonpedunculated colon polyp (≥20 mm) at 18 medical centers in North America and Spain from April 2013 through October 2017. Patients were randomly assigned to groups that underwent endoscopic closure with a clip (clip group) or no closure (control group) and followed. The primary outcome, postprocedure bleeding, was defined as a severe bleeding event that required hospitalization, a blood transfusion, colonoscopy, surgery, or another invasive intervention within 30 days after completion of the colonoscopy. Subgroup analyses included postprocedure bleeding with polyp location, polyp size, or use of periprocedural antithrombotic medications. We also examined the risk of any serious adverse event. RESULTS: A total of 919 patients were randomly assigned to groups and completed follow-up. Postprocedure bleeding occurred in 3.5% of patients in the clip group and 7.1% in the control group (absolute risk difference [ARD] 3.6%; 95% confidence interval [CI] 0.7%-6.5%). Among 615 patients (66.9%) with a proximal large polyp, the risk of bleeding in the clip group was 3.3% and in the control group was 9.6% (ARD 6.3%; 95% CI 2.5%-10.1%); among patients with a distal large polyp, the risks were 4.0% in the clip group and 1.4% in the control group (ARD -2.6%; 95% CI -6.3% to -1.1%). The effect of clip closure was independent of antithrombotic medications or polyp size. Serious adverse events occurred in 4.8% of patients in the clip group and 9.5% of patients in the control group (ARD 4.6%; 95% CI 1.3%-8.0%). CONCLUSIONS: In a randomized trial, we found that endoscopic clip closure of the mucosal defect following resection of large colon polyps reduces risk of postprocedure bleeding. The protective effect appeared to be restricted to large polyps located in the proximal colon. ClinicalTrials.gov no: NCT01936948.