Artificial Intelligence for Real-Time Prediction of the Histology of Colorectal Polyps by General Endoscopists.

BACKGROUND: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists. OBJECTIVE: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting. DESIGN: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615). SETTING: 6 centers across the United States. PARTICIPANTS: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features. INTERVENTION: Real-time use of CADx during routine colonoscopy. MEASUREMENTS: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided. RESULTS: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection. LIMITATION: Decision making based on CADx might differ outside a clinical trial. CONCLUSION: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal. PRIMARY FUNDING SOURCE: Olympus America Corporation served as the clinical study sponsor.

An Allee-based distributed algorithm for microbial whole-cell sensors.

Reliable detection of substances present at potentially low concentrations is a problem common to many biomedical applications. Complementary to well-established enzyme-, antibody-antigen-, and sequencing-based approaches, so-called microbial whole-cell sensors, i.e., synthetically engineered microbial cells that sense and report substances, have been proposed as alternatives. Typically these cells operate independently: a cell reports an analyte upon local detection.In this work, we analyze a distributed algorithm for microbial whole-cell sensors, where cells communicate to coordinate if an analyte has been detected. The algorithm, inspired by the Allee effect in biological populations, causes cells to alternate between a logical 0 and 1 state in response to reacting with the particle of interest. When the cells in the logical 1 state exceed a threshold, the algorithm converts the remaining cells to the logical 1 state, representing an easily-detectable output signal. We validate the algorithm through mathematical analysis and simulations, demonstrating that it works correctly even in noisy cellular environments.

Pyloric Functional Lumen Imaging Probe Measurements Are Dependent on Balloon Position.

Background/Aims: The functional lumen imaging probe (FLIP) device has been used to assess pyloric dysfunction in patients with gastroparesis. We aim to investigate whether varying FLIP catheter positions affect pyloric FLIP measurements. Methods: Patients undergoing endoscopy for chronic unexplained nausea and vomiting (CUNV) or gastroparesis were prospectively enrolled. FLIP balloon was adjusted for 3 positions within the pylorus: (1) proximal position, 75% of FLIP balloon in the duodenum and 25% in the antrum; (2) middle position, 50% in the duodenum and 50% in the antrum; and (3) distal position, 25% in the duodenum and 75% in the antrum. Pylorus cross-sectional area (CSA), intra-bag pressure (P), and distensibility indices (DI) were measured for 30, 40, and 50-mL balloon volumes. Fluoroscopic images were obtained to confirm FLIP balloon geometry. Data was analyzed separately using FLIP Analytic and customized MATLAB software. Results: Twenty-two patients with CUNV (n = 4) and gastroparesis (n = 18) were enrolled. Pressures were significantly higher in the proximal position compared to the middle and distal positions. CSA measurements were significantly higher at the proximal and middle positions for 30-mL and 40-mL volume compared to the distal position values. DI values were significantly lower at the proximal positions for 40-mL and 50-mL distensions when compared to the middle and distal positions. Fluoroscopic images confirmed increased balloon bending when placed mostly in the duodenum. Conclusions: FLIP balloon position within the pylorus directly affects balloon geometry which significantly affects P, CSA, and DI measurements. Standardized pyloric FLIP protocols and balloon design adjustments are needed for the continued application of this technology to the pylorus.

Effect of a One-Time Communication Training Session on Dental Students' Self-Efficacy Expectancy.

An implementation of training units that provide evidence for improving students' communication skills in the dental curriculum is now more than ever of utmost importance. This study aimed to investigate how students assess their skills after communication training and whether this training also increased students' self-efficacy expectancy. A total of 32 male and 71 female students with a mean age of 25.6 ± 3.9 years participated in the study. Self-assessment of communication skills and self-efficacy expectancies were collected at two time points using Likert scales. Our study shows that the communication training, consisting of a practical exercise with actors and an online theory module, significantly improved the students' self-assessment of their communication skills and also improved some aspects of self-efficacy expectancy. These results indicate that, in addition to the practical and technical-theoretical training of students, communication training is essential in the dental curriculum. In summary, this study showed that a one-time practical exercise with actors together with an online theory module could improve both the self-assessment of communication competence and some aspects of self-efficacy expectancy, which demonstrates the importance of training communication skills alongside practical and technical-theoretical training.

Assessing the discriminatory power of loss given default models.

For banks using the Advanced Internal Ratings-Based Approach in accordance with Basel III requirements, the amount of required regulatory capital relies on the banks' estimates of the probability of default, the loss given default and the conversion factor for their credit risk portfolio. Therefore, for both model development and validation, assessing the models' predictive and discriminatory abilities is of key importance in order to ensure an adequate quantification of risk. This paper compares different measures of discriminatory power suitable for multi-class target variables such as in loss given default (LGD) models, which are currently used among banks and supervisory authorities. This analysis highlights the disadvantages of using measures that solely rely on pairwise comparisons when applied in a multi-class setting. Thus, for multi-class classification problems, we suggest using a generalisation of the well-known area under the receiver operating characteristic (ROC) curve known as the volume under the ROC surface (VUS). Furthermore, we present the R-package VUROCS, which allows for a time-efficient computation of the VUS as well as associated (co)variance estimates and illustrate its usage based on real-world loss data and validation principles.

Relationships of Intestinal Lactase and the Small Intestinal Microbiome with Symptoms of Lactose Intolerance and Intake in Adults.

BACKGROUND: Approximately two-thirds of adults are genetically predisposed to decreased lactase activity after weaning, putting them at risk of lactose intolerance. However, symptoms are a poor marker of lactose maldigestion. AIMS: We assessed association between self-reported lactose intolerance and intestinal lactase, lactose intake, and the small intestinal microbiome. METHODS: Patients 18-75 years presenting for upper endoscopy were recruited prospectively. Observational study participants completed a lactose intolerance symptom questionnaire and reported lactose intake. Post-bulbar biopsies were obtained to measure lactase activity and assess the small intestinal mucosal microbiome. We compared intestinal lactase between patients with and without lactose intolerance. We assessed associations between lactose intolerance symptoms and lactase and lactose intake. We examined associations of small bowel microbial composition with self-reported lactose intolerance and symptoms. RESULTS: Among 34 patients, 23 (68%) reported lactose intolerance. Those with lactose intolerance had higher total symptom scores, more frequent bowel urgency, and more bowel movements after consuming dairy. The proportion of individuals with abnormal lactase activity did not differ by lactose intolerance status. Median lactase levels were correlated with total lactose intolerance symptom scores (p = 0.038) and frequency of bowel urgency (p = 0.012). Daily lactose intake did not differ between groups. In 19 patients, we observed significant associations of small intestinal microbiome beta diversity with stool consistency after consuming dairy (p = 0.03). CONCLUSIONS: Intestinal lactase is associated with lactose intolerance symptoms and bowel urgency in adults but does not distinguish the clinical phenotype entirely. Studying other contributing factors (microbiota, diet) may further clarify the pathophysiology of lactose intolerance.

Evaluation of timed barium esophagram after per-oral endoscopic myotomy to predict clinical response.

Background and study aims The aim of this study was to evaluate whether timed barium esophagram within 24 hours post-per-oral endoscopic myotomy (POEM) (TBE-PP) could predict clinical outcomes. Patients and methods This was a single-center retrospective study of prospectively collected data on consecutive patients with ≥ 6-month follow-up who underwent POEM followed by TBE-PP. Esophageal contrast retention 2 minutes after TBE-PP was assessed as Grade 1 (< 10 %), 2 (10 %-49 %), 3 (50 %-89 %) or 4 (> 90 %). Eckardt score, esophagogastroduodenoscopy (EGD), high-resolution manometry (HRM) and function lumen imaging probe (FLIP) of the esophagogastric junction (EGJ) were obtained at baseline. These tests along with pH testing of antisecretory therapy were repeated 6 and 24 months after POEM. Clinical response by Eckardt score ≤ 3, EGJ-distensibility index (EGJ-DI) > 2.8 mm 2 /mm Hg, and integrated relaxation pressure (IRP) < 15 mm Hg and incidence of gastroesophageal reflux disease (GERD) were compared by transit time. Results Of 181 patients (58 % male, mean 53 ±â€Š17 yr), TBE-PP was classified as Grade 1 in 122 (67.4 %), Grade 2 in 41 (22.7 %), Grade 3 in 14 (7.7 %) and Grade 4 in 4 (2.2 %). At 6 months, overall clinical response by ES (91.7 %), IRP (86.6 %), EGJ-DI (95.7 %) and the diagnosis of GERD (68.6 %) was similar between Grade 1 and Grade 2-4 TBE-PP. At 24 months, Grade 1 had a higher frequency of a normal IRP compared to Grades 2-4 (95.7 % vs. 60 %, P  = 0.021) but overall response by ES (91.2 %), EGJ-DI (92.3 %) and the diagnosis of GERD (74.3 %) were similar. Conclusions Contrast emptying rate by esophagram after POEM has limited utility to predict clinical response or risk of post-procedure GERD.

Delayed Gastric Emptying Is Not Associated with a Microbiological Diagnosis of Small Intestinal Bacterial Overgrowth.

BACKGROUND: Clinical symptoms of patients with small intestinal bacterial overgrowth (SIBO) may overlap with symptoms of gastroparesis. Prior studies suggest delayed small intestinal transit is associated with SIBO, but have not shown an association between delayed gastric emptying and SIBO. However, these studies have generally relied on the indirect method of breath testing to diagnose SIBO. AIMS: The aim of this study was to examine the association between a microbiological diagnosis of SIBO and delayed gastric emptying by scintigraphy. METHODS: In a single-center retrospective study of previous research participants who presented for small bowel enteroscopy for diagnostic evaluation of SIBO, we identified 73 participants who underwent gastric emptying study by scintigraphy. A microbiological diagnosis of SIBO was made in patients based on culture results of jejunal aspirates. Clinical symptoms were assessed using the total gastroparesis cardinal symptom index (GCSI) score. We compared delayed gastric emptying, 2- and 4-h gastric retention, and gastroparesis symptoms between patients with and without a microbiological diagnosis of SIBO. KEY RESULTS: Among 29 participants with SIBO and 44 without SIBO, 33 (45%) had evidence of delayed gastric emptying. There was no significant association between a microbiological diagnosis of SIBO and delayed gastric emptying by scintigraphy. Percent retained at 2 and 4 h, and total GCSI scores did not differ significantly between those with and without SIBO. CONCLUSIONS: Although delayed gastric emptying is common in patients with suspected SIBO, gastric emptying is not associated with a microbiological diagnosis of SIBO.

Impact of the isoelectric point of model parvoviruses on viral retention in anion-exchange chromatography.

Anion-exchange chromatography (AEX) is used in the downstream purification of monoclonal antibodies to remove impurities and potential viral contamination based on electrostatic interactions. Although the isoelectric point (pI) of viruses is considered a key factor predicting the virus adsorption to the resin, the precise molecular mechanisms involved remain unclear. To address this question, we compared structurally homologous parvoviruses that only differ in their surface charge distribution. A single charged amino acid substitution on the capsid surface of minute virus of mice (MVM) provoked an increased apparent pI (pIapp ) 6.2 compared to wild-type MVM (pIapp = 4.5), as determined by chromatofocusing. Despite their radically different pIapp , both viruses displayed the same interaction profile in Mono Q AEX at different pH conditions. In contrast, the closely related canine parvovirus (pIapp = 5.3) displayed a significantly different interaction at pH 5. The detailed structural analysis of the intricate three-dimensional structure of the capsids suggests that the charge distribution is critical, and more relevant than the pI, in controlling the interaction of a virus with the chromatographic resin. This study contributes to a better understanding of the molecular mechanisms governing virus clearance by AEX, which is crucial to enable robust process design and maximize safety.

Gastric peroral endoscopic myotomy for the treatment of refractory gastroparesis: a prospective single-center experience with mid-term follow-up (with video).

BACKGROUND AND AIMS: Gastroparesis (GP) is a multifactorial disease associated with a large burden on the health care systems. Pyloric-directed therapies including gastric peroral endoscopic myotomy (G-POEM) can be effective in improving patient quality of life and symptom severity. We report on the safety and efficacy of G-POEM and its impact on the quality of life of patients managed at a large referral center. METHODS: Consecutive patients with confirmed GP referred for G-POEM due to failure of medical therapy were included. All patients were assessed at baseline and then at 1, 3, 6, and 12 and 24 months after G-POEM using validated symptom and quality of life instruments, including the Gastroparesis Cardinal Symptom Index (GCSI), Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM), and 36-Item Short Form Survey (SF-36). Patients were evaluated before and 6 months after the procedure with EGD, 4-hour scintigraphy, and pyloric EndoFLIP. Technical success was defined as the ability to perform full-thickness pyloromyotomy. Clinical response was defined as an improvement of ≥1 point on GCSI. RESULTS: Fifty-two patients (median age, 48 years; range, 25-80 years, 88% female) underwent G-POEM between February 2018 and September 2020 for the following phenotypes: vomiting-predominant (n=30), dyspepsia-predominant (n=16), and regurgitation-predominant (n=6) GP. The technical success rate was 100%. Adverse events were noted in 3 of 52 patients (5.77%), and were all managed successfully endoscopically. Clinical response was achieved in 68%, 58%, and 48% of patients at 1-month, 6-month, and 12-month follow-up (P < .001, P < .001, and P < .01, respectively). When classified by the cause of GP, the clinical response rates were diabetic GP 64% (11 of 17), postsurgical GP 67% (6 of 9), and idiopathic GP 72% (13 of 18). A statistically significant improvement in PAGI-SYM scores was observed at 1, 3, 6, 12, and 24 months, in addition to significant improvement in several domains of SF-36. Mean 4-hour gastric emptying was reduced 6 months after G-POEM (10.2%) compared with baseline (36.5%, P < .001). We report a significant reduction in the number of emergency department visits and days spent in the hospital up to 24 months after G-POEM. CONCLUSIONS: G-POEM appears to be a safe and feasible treatment alternative for refractory GP with significant short-term and mid-term improvements in overall symptoms, quality of life scores, and health care utilization.

An emerging method to noninvasively measure and identify vagal response markers to enable bioelectronic control of gastroparesis symptoms with gastric electrical stimulation.

BACKGROUND: Gastric electrical stimulation (GES) can be a life-changing, device-based treatment option for drug-resistant nausea and vomiting associated with diabetic or idiopathic gastroparesis (GP). Despite over two decades of clinical use, the mechanism of action remains unclear. We hypothesize a vagal mechanism. NEW METHOD: Here, we describe a noninvasive method to investigate vagal nerve involvement in GES therapy in 66 human subjects through the compound nerve action potential (CNAP). RESULTS: Of the 66 subjects, 28 had diabetic GP, 35 had idiopathic GP, and 3 had postsurgical GP. Stimulus charge per pulse did not predict treatment efficacy, but did predict a significant increase in total symptom score in type 1 diabetics as GES stimulus charge per pulse increased (p < 0.01), representing a notable side effect and providing a method to identify it. In contrast, the number of significant left and right vagal fiber responses that were recorded directly related to patient symptom improvement. Increased vagal responses correlated with significant decreases in total symptom score (p < 0.05). COMPARISON WITH EXISTING METHOD(S): We have developed transcutaneous recording of cervical vagal activity that is synchronized with GES in conscious human subjects, along with methods of discriminating the activity of different nerve fiber groups with respect to conduction speed and treatment response. CONCLUSIONS: Cutaneous vagal CNAP analysis is a useful technique to unmask relationships among GES parameters, vagal recruitment, efficacy and side-effect management. Our results suggest that CNAP-guided GES optimization will provide the most benefit to patients with idiopathic and type 1 diabetic gastroparesis.

Choice of parvovirus model for validation studies influences the interpretation of the effectiveness of a virus filtration step.

Different parvoviruses are used interchangeably as models in validation studies to demonstrate effective clearance of small viruses by filtration in the manufacturing of biotherapeutics. The aim of these experiments was to determine if filtration of different parvoviruses (canine parvovirus [CPV], minute virus of mice [MVM], and porcine parvovirus [PPV]) results in similar virus retention. While filtration with a Planova™ 20 N filter (mean pore size: 19 ±â€¯2 nm) completely removed PPV and MVM from the filtrate (mean log reduction factors [LRFs] ≥5.8 to ≥7.3 log10), CPV was only partly retained (3.6 log10) in a series of single and co-spike experiments. Additional co-spike experiments in 2 different feedstreams using 10 commercially available small pore filters confirmed these results; the LRF for CPV was around 2 log10 lower than for MVM and PPV. A sizing study using filters with mean pore sizes between 16.5 and 19 nm resulted in complete removal of CPV only with smaller pore sizes (17 and 16.5 nm). CPV behaves differently to MVM and PPV in viral filtration due to its apparent smaller size, suggesting CPV represents a worst-case model for other parvoviruses. Interpretation of efficacy and robustness of virus filtration thus depends on the choice of model virus.

Implementation and evaluation of high-dose methotrexate administration guidelines.

BACKGROUND: High-dose methotrexate is used to treat a variety of malignancies. Methotrexate-associated supportive care and the threshold methotrexate level for the discontinuation of supportive care are not consistent among studies. We evaluated the implementation of high-dose methotrexate administration guidelines, which raised the standard threshold methotrexate level for the discontinuation of supportive care from <0.05 to <0.1 µmol. METHODS: A single-center, observational analysis of patients receiving high-dose methotrexate from 1 January 2015 to 31 May 2017 was conducted. The primary endpoint was time from the start of the methotrexate infusion until the discontinuation of the sodium bicarbonate infusion, before and after guideline implementation. RESULTS: Fifty-two patients met the inclusion criteria, which comprised of a total of 136 individual methotrexate doses and were included in the retrospective analysis. Twenty-four patients were included in the prospective analysis, which comprised a total of 46 individual methotrexate doses. The primary endpoint, time until discontinuation of the sodium bicarbonate infusion, was a median of 97.7 h in the retrospective group versus 73.2 h in the prospective group (p = 0.098). Secondary endpoints also favored patients in the prospective group, including hours of hospitalization, number of methotrexate levels checked, weight gained during admission, and adherence to the guideline. CONCLUSION: Among patients who received high-dose methotrexate, implementation of a guideline using a methotrexate threshold of <0.1 µmol was able to significantly decrease the time to discontinuation of supportive care and subsequently may lead to early hospital discharge given that we did not show a statistical significance.

Effective inactivation of a wide range of viruses by pasteurization.

BACKGROUND: Careful selection and testing of plasma reduces the risk of blood-borne viruses in the starting material for plasma-derived products. Furthermore, effective measures such as pasteurization at 60°C for 10 hours have been implemented in the manufacturing process of therapeutic plasma proteins such as human albumin, coagulation factors, immunoglobulins, and enzyme inhibitors to inactivate blood-borne viruses of concern. A comprehensive compilation of the virus reduction capacity of pasteurization is presented including the effect of stabilizers used to protect the therapeutic protein from modifications during heat treatment. STUDY DESIGN AND METHODS: The virus inactivation kinetics of pasteurization for a broad range of viruses were evaluated in the relevant intermediates from more than 15 different plasma manufacturing processes. Studies were carried out under the routine manufacturing target variables, such as temperature and product-specific stabilizer composition. Additional studies were also performed under robustness conditions, that is, outside production specifications. RESULTS: The data demonstrate that pasteurization inactivates a wide range of enveloped and nonenveloped viruses of diverse physicochemical characteristics. After a maximum of 6 hours' incubation, no residual infectivity could be detected for the majority of enveloped viruses. Effective inactivation of a range of nonenveloped viruses, with the exception of nonhuman parvoviruses, was documented. CONCLUSION: Pasteurization is a very robust and reliable virus inactivation method with a broad effectiveness against known blood-borne pathogens and emerging or potentially emerging viruses. Pasteurization has proven itself to be a highly effective step, in combination with other complementary safety measures, toward assuring the virus safety of final product.

Pathogen safety and characterisation of a highly purified human alpha1-proteinase inhibitor preparation.

Alpha1-proteinase inhibitor (A1PI) deficiency is a genetic condition predisposing to emphysema. Respreeza/Zemaira, a therapeutic preparation of A1PI, is prepared from human plasma. This article describes the purity and stability of Respreeza/Zemaira and the capacity of virus and prion reduction steps incorporated into its manufacturing process. Purity and stability of Respreeza/Zemaira were analysed using established methods. To test pathogen clearance capacity, high levels of test viruses/prions were spiked into aliquots of production intermediates and clearance studies were performed for selected manufacturing steps, under production and robustness conditions, using validated scale-down models. Respreeza/Zemaira had a purity of 99% A1PI and consisted of 96% monomers. It remained stable after storage for 3 years at 25 °C. Specific activity was 0.895 mg active A1PI/mg protein. Pasteurisation inactivated enveloped viruses and the non-enveloped hepatitis A virus. 20 N/20 N virus filtration was highly effective and robust at removing all tested viruses, including parvoviruses, to below the limit of detection. Cold ethanol fractionation provided substantial reduction of prions. The manufacturing process of Respreeza/Zemaira ensures the production of a stable and pure product. Taking into consideration the donor selection process, the testing of donations, and the highly effective virus and prion reduction, Respreeza/Zemaira has a high safety margin.

Pathogen safety of a pasteurized four-factor human prothrombin complex concentrate preparation using serial 20N virus filtration.

BACKGROUND: Beriplex P/N/Kcentra/Coaplex/Confidex is a four-factor human prothrombin complex concentrate (PCC). Here, we describe the pathogen safety profile and biochemical characteristics of an improved manufacturing process that further enhances the virus safety of Beriplex P/N. STUDY DESIGN AND METHODS: Samples of product intermediates were spiked with test viruses, and prions were evaluated under routine production and robustness conditions of the scale-down version of the commercial manufacturing process for their capacity to inactivate or remove pathogens. The PCC was characterized by determining the activity of Factor (F)II, FVII, FIX, FX, protein C, and protein S and the concentration of heparin and antithrombin III in nine product lots. RESULTS: The manufacturing process had a very high virus reduction capacity for a broad variety of virus challenges (overall reduction factors ≥15.5 to ≥18.4 log for enveloped viruses and 11.5 to ≥11.9 log for nonenveloped viruses). The high virus clearance capacity was provided by two dedicated virus reduction steps (pasteurization and serial 20N virus filtration) that provided effective inactivation and removal of viruses and a purification step (ammonium sulfate precipitation and adsorption to calcium phosphate) that contributed to the overall virus removal capacity. The diethylaminoethyl (DEAE) chromatography and ammonium sulfate precipitation steps removed prions to below the limit of detection. The levels of different clotting factors in the final product were well balanced. CONCLUSION: The improved manufacturing process of Beriplex P/N further enhances the margin of pathogen safety based on its capacity to remove and inactivate a wide range of virus challenges.

Gastric Electrical Stimulation for Gastroparesis and Chronic Unexplained Nausea and Vomiting.

OPINION STATEMENT: Gastroparesis is a heterogeneous clinical syndrome. Some patients have debilitating vomiting, weight loss, and dehydration, while others have effortless regurgitation of undigested foods or postprandial distress suggestive of functional dyspepsia. Gastric electrical stimulation (GES) has been proposed as an effective treatment option for patients with gastroparesis refractory to medical therapy. Evidence suggests that the clinically available device, a low-energy high-frequency GES, activates the vagal afferent pathways to influence the central control mechanisms for nausea and vomiting. Myoelectrical effects of the stomach are also involved. The results of randomized controlled trials (RCTs) for adults with diabetic and idiopathic gastroparesis are conflicting. There are no RCTs in adults with chronic unexplained nausea and vomiting (CUNV) with normal gastric emptying or in children with gastroparesis. However, there is increasing evidence from large unblinded studies showing the long-term efficacy in selected adults with gastroparesis. Selection criteria should be based on three categories: (a) underlying etiology, (b) clinical presentation and predominant symptoms, and (c) potential risk for complication. Significant abdominal pain, daily opiate use, and idiopathic gastroparesis are identified as negative predictors of success. Temporary GES has been utilized to identify patients who may benefit from surgical GES, but this strategy has yet to be proven in controlled studies. Objectives for this review are to highlight the mechanisms of action for GES, to look at the evidence for clinical efficacy, and to select patients who are likely to benefit.

Retrograde ascending Stanford B aortic dissection complicating a routine infrarenal endovascular aortic reconstruction.

Retrograde ascending aortic dissections usually complicate endovascular reconstructions of Stanford B dissections. Although rare, with an incidence of 1.3% to 6.8%, they are catastrophic, with a high mortality rate of up to 42%. The exact mechanism is not known, but all indications point to a mechanical interaction between the tips of the proximal bare stent and a fragile aortic wall. Practically all reported cases involve dissections of the thoracic aorta. We report a patient with an asymptomatic retrograde ascending aortic dissection that originated at the level of a damaged suprarenal stent during capture tip retrieval during a routine endovascular aneurysm repair to treat an infrarenal aortic aneurysm.

On the performance of a retransmission-based synchronizer.

Designing algorithms for distributed systems that provide a round abstraction is often simpler than designing for those that do not provide such an abstraction. Further, distributed systems need to tolerate various kinds of failures. The concept of a synchronizer deals with both: It constructs rounds and allows masking of transmission failures. One simple way of dealing with transmission failures is to retransmit a message until it is known that the message was successfully received. We calculate the exact value of the average rate of a retransmission-based synchronizer in environments with probabilistic message loss, within which the synchronizer shows nontrivial timing behavior. We show how to make this calculation efficient, and present analytical results on the convergence speed. The theoretic results, based on Markov theory, are backed up with Monte Carlo simulations.