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Objectives Despite substantial morbidity and mortality associated with acute pancreatitis (AP), only one small randomized controlled drug trial (RCT) is available in the past few decades from the United States. Hence, we conducted a single-center, double-blind, placebo-controlled RCT of pentoxifylline in AP. Methods A total of 9 doses of oral pentoxifylline 400 mg or placebo tablet, three times daily, was administered within 72 h of diagnosis, using randomization blocks by pharmacy. Primary outcome was a composite outcome including any of the following: death, peripancreatic and/or pancreatic necrosis, infected pancreatic necrosis, persistent organ failure, persistent systemic inflammatory response syndrome, hospital stay longer than 4 days, need for intensive care, and need for intervention for necrosis. Results Between July 7, 2015, and April 4, 2017, we identified 685 patients with AP, 233 met eligibility criteria and 176 were approached for the study. Of these, 91 (51.7%) declined and finally 45 in pentoxifylline group and 38 in placebo group (83 total) were compared. There were no significant differences in primary outcome (27 [60.0%] vs 15 [39.5%]; P = .06). Pentoxifylline group was not associated with any benefit, but withlonger stay (42% vs. 21%; P = .04) and higher readmission rates (16 %vs 3%; P = .047). Conclusions We could not demonstrate superiority of pentoxifylline over placebo. Smaller sample size and inclusion of all types of severity might be the reasons for lack of efficacy. The challenges observed in the present study indicate that, in order to conduct a successful drug trial in AP, a multi center collaboration is essential.

Background and study aims The preferred management of bleeding esophageal varices includes endoscopic band ligation. Endoscopic ligation devices (ELDs) are expensive and designed for single use, limiting their uptake in developing countries. We aimed to assess the efficacy of reprocessing ELDs using terminal microbial cultures and adenosine triphosphate (ATP) testing. Materials and methods ELDs were recovered after clinical use and their components (cap, handle, and cord) were subjected to reprocessing. This included manual cleaning, automated high-level disinfection (HLD), and drying with forced air. Using sterile technique, ELD components were sampled for ATP at three stages: before manual cleaning, after manual cleaning, and after HLD. Components were sent to an external laboratory for culturing. Cultures were interpreted as positive upon identification of Gram-negative bacilli. Results A total of 14 clinically used ELDs were studied, and 189 ATP tests and 41 cultures were evaluated. Overall, 95 % (39/41) of components and 86 % (12/14) of ELDs were culture-negative or did not yield Gram-negative bacilli. Two components (5 %; one handle and one cord) harbored Gram-negative bacilli in quantities of 1 CFU per component. There was no apparent correlation between ATP at any juncture of reprocessing and terminal cultures. Conclusions Reprocessing of ELDs is effective, resulting in infrequent and minimal microbial contamination. Microbial culturing can be used to ensure adequacy of ELD reprocessing if pursued. Until reusable ELDs are commercially available, continued efforts to better define the adequacy and long-term effects of reprocessing ELDs are needed.

Infected (peri)pancreatic necrosis (IPN) in acute pancreatitis (AP) is associated with organ failure (OF) and high mortality. There are no established early markers of primary IPN. This study aimed to assess the association of simple parameters with primary IPN in AP.We retrospectively studied 281 patients with AP admitted to Mayo Clinic hospitals and identified those with microbiologically confirmed infections in (peri)pancreatic necrosis and collections. We defined primary IPN as infection of (peri)pancreatic necrotic tissue that developed before interventions. We recorded admission hematocrit, BMI, BUN, serum creatinine, SIRS score and development of persistent organ failure within 48 h of admission; and performed serial SIRS and BUN calculations for at least 48 h. We used univariate and multivariable analysis to assess associations and expressed results as odds ratio (OR)[95% CI].27 (9.6%) patients developed IPN, of which 21 (77.7%) had primary IPN. 38.1% had Gram positive, 9.5% Gram negative and 52.3% mixed bacterial infections. Five (23.8%) of the patients with IPN had fungal infection. On univariate analysis, SIRS ≥ 2 at admission, rise in BUN by 5 mg/dL within 48 h of admission, persistence of SIRS for 48 h and development of persistent OF within 48 h of disease had significant association with development of primary IPN with OR (95% CI) of 4.12 (1.53-11.15), 10.25 (3.95-26.61), 1.19 (1.69-10.39) and 7.62 (2.58-21.25) [2-tailed p = 0.004,0.0001, 0.002 and0.0001] respectively. On multivariable analysis, only rise in BUN by 5 mg/dL within 48 h of admission was associated with primary IPN (p = 0.007).Rising BUN within 48 h of admission can be used to predict development of primary IPN in AP.

In acute pancreatitis (AP) tumor necrosis factor-α mediates multi-organ failure; in animal models its blockade with pentoxifylline ameliorates AP. The efficacy of pentoxifylline in predicted severe AP (pSAP) was tested in a double-blinded, randomized, control trial. Twenty-eight patients with pSAP were randomized within 72 hours of diagnosis to pentoxifylline or placebo. Baseline characteristics were similar in both groups. The pentoxifylline group had fewer intensive care unit admissions and shorter intensive care unit and hospital stays of longer than 4 days (all P.05). Patients receiving pentoxifylline had no adverse effects. Pentoxifylline within 72 hours of pSAP is safe; a larger study of pentoxifylline in AP is needed to confirm efficacy. ClinicalTrials.gov number: NCT01292005.

Objective We described the entity moderately severe acute pancreatitis (MSAP), characterized by local complications (LCs) without organ failure (OF). The aim of this study was to validate MSAP. Methods We classified a prospectively collected cohort of 137 acute pancreatitis patients admitted to Mayo Clinic Hospitals into (a) severe acute pancreatitis (SAP; n = 15), presence of OF with/without LCs; (b) MSAP (n = 27), presence of LCs without OF; and (c) mild acute pancreatitis (MAP; n = 95), no OF and LCs. Primary outcomes were need for intensive care unit (ICU) care, total ICU days, total hospital stay, need for interventions, and death. Results Scores in the Acute Physiology and Chronic Health Evaluation II during admission were significantly different among the 3 groups (MAP vs MSAP, P = 0.02; MSAP vs SAP, P = 0.001); scores in the systemic inflammatory response syndrome during admission were similar between MAP and MSAP. Compared with patients with MAP, patients with MSAP had a significantly longer hospital stay (4 [3.0-7.0] vs 6 [4.0-18.0] days). Compared with those with SAP, a significantly smaller proportion of patients with MSAP required ICU care (12% vs 80%); total hospital stay and need for interventions were similar (6 [4.0-18.0] vs 21 [11.8-27] days and 44% vs 33%, respectively). None of the MSAP patients died compared with 40% from the SAP group. Conclusions We have validated MSAP as an exclusive entity.

Introduction Electronic-noses (e-noses) have the ability of converting smells to digital signatures. By interacting with volatile organic compounds (VOC's) emitted by metabolic end-products of disease, e-noses create distinct patterns of aggregate VOC's to generate unique signatures that can be used to identify disease. The detection of Clostridium difficile (C. diff) by VOC's is prototypic as it has been successfully identified by scent using canines. We seek to pilot a novel portable e-nose device to profile fecal headspace to diagnose C. diff infection. Methods We are prospectively enrolling patients undergoing stool testing by C. diff PCR for infectious diarrhea for fecal headspace analysis using the Aetholab e-nose (eNose Company, Zutphen, NL). Stool specimens were obtained from the clinical microbiology lab of our institution within 7 days of ambient collection and aliquots of 10-ml of homogenized stool were transferred to disposable analysis bottles. The e-nose circulates fecal headspace gas within each analysis bottle to allow interaction with its respective sensor array. Each sensor array comprises of three metal-oxide sensors that undergo reversible redox reactions with VOC's at an electrochemical interface. Electrical resistance changes are measured by applying a 32-point thermal cycle to the sensor array generating a digital signature (Figure 1). This process has been shown to interact with a wide range of VOC's. Combined data from the 3 sensors in 7 combinations (A, B, C, AB, AC, AC, ABC) is permuted across 3 scaling factors generating a total of 21 data sets per analysis. These are then compressed through a multi-way analysis to reduce the large amount of data to avoid spurious associations. Finally each sample's compressed dataset is introduced into an artificial neural network (ANN) using a supervised approach. The 5 best models generated using a leave-one-out approach are used to obtain the reported results. Results Separation was observed using all 20 C. diff-PCR positive and 53 C. diff-PCR negative stools. The ROC curve for this model is shown in Figure 2 with an AUC = 0.85. This demonstrated 80% sensitivity, 85% specificity with 84% accuracy. The positive predictive value was 0.67 and the negative predictive value 0.92. Matthews correlation coefficient was 0.64. Conclusion Through the use of a pattern-recognition e-nose device it is possible to distinguish C. diffinfected stools. This is the first time that this type of device has been used for this diagnosis, and also the first time this e-nose has been applied for fecal headspace analysis of infectious disease. This indicates that C. diff testing can translate into a point-of-care evaluation.

Background: Screening for Barrett's esophagus and esophageal adenocarcinoma is not currently advocated due to lack of data supporting its efficacy and concerns regarding expense. The cost of a screening program is primarily related to sedation and physician expertise. Performance of unsedated procedures by physician extenders (PEs) in the primary care setting could lead to an increased uptake of screening and decreased costs. Objective: Determine feasibility andmeasure learning curve while training PEs to independently perform transnasal endoscopy (TNE) screening for Barrett's esophagus. Methods: Two PEs underwent a one week structured didactic training program, which reviewed basic esophageal anatomy and pathology. This was followed by observation of nasopharyngoscopy procedures in ENT clinic to familiarize trainees with nasopharyngeal anatomy. To learn TNE, patients were then recruited with research consent among veterans undergoing sedated EGD in the Louis Stokes Veteran Affairs Medical Center in Cleveland, OH. Supervised TNE training procedures were assessed by two attendings who measured learning of individual technical and cognitive components of TNE and overall performance on a 9 point structured scale. Scores of 7 or more defined procedural competence. TNEs performed by two PEs were analyzed by method of cumulative summation (CUSUM) to construct individual learning curves. Results: Only 1 of 55 procedures could not be completed in the training phase. PE 1 and 2 could both identify anatomic landmarks including GE junction, diaphragm and gastric folds after 16 consecutive procedures and needed to complete 19 and 22 procedures, respectively to satisfactorily learn the technique of nasal intubation. Esophageal intubation was satisfactorily learned by PE 1 after 22 procedures whereas PE 2 is approaching but has not yet achieved a satisfactory score after 25 procedures. Figure 1 illustrates gradual improvement in overall performance based on number of completed procedures. Conclusion: A program to train PEs in the performance of TNE has been developed. PEs require a moderate number of supervised procedures to train in TNE. Esophageal intubation is the most challenging aspect of TNE.