Effects of Helicobacter pylori therapy on gut microbiota: a systematic review and meta-analysis.

BACKGROUND: Although indications for evaluation and treatment of Helicobacter pylori (H. pylori) infection are broadening to include primary prevention for gastric adenocarcinoma, potential adverse effects on gut microbiota have been raised. We performed a systematic review and meta-analysis to evaluate the effects of H. pylori therapy on gut microbiota. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science (to 4/2021) were searched for studies quantitatively evaluating microbiota before and after H. pylori therapy. Meta-analysis was performed to assess early (<1 year) and long-term (≥1 year) effects on gut microbiota after H. pylori treatment. Subgroup analysis evaluating the effects of H. pylori therapy with addition of probiotics on gut microbiota was also performed. RESULTS: Thirty studies (N=1,218) met the criteria. Early after H. pylori therapy, intestinal microbial diversity was reduced in nearly all studies. At the genus level, reduction in the abundance of Enterococcus, while increase in Lactobacillus, Bifidobacterium, and Bacteroides counts were observed. However, Lactobacillus, Bifidobacterium, Bacteroides, and Enterococcus counts remained stable in patients who received probiotics with H. pylori therapy. At the phylum level, the relative abundance of Actinobacteria and Firmicutes increased after treatment. At ≥1 year, intestinal microbial diversity normalized in six of seven studies. No differences in the relative abundance of Actinobacteria, Firmicute, Bacteroidetes, and Proteobacteria were observed ≥1 year after therapy. CONCLUSION: The impact of H. pylori therapy on gut microbiota appears transient with early changes largely resolving after one year. Probiotics may reduce the early impact of H. pylori therapy on gut microbiota.

Body Orientation Affects the Perceived Size of Objects.

Here, we investigate how body orientation relative to gravity affects the perceived size of visual targets. When in virtual reality, participants judged the size of a visual target projected at simulated distances of between 2 and 10 m and compared it to a physical reference length held in their hands while they were standing or lying prone or supine. Participants needed to make the visual size of the target 5.4% larger when supine and 10.1% larger when prone, compared to when they were in an upright position to perceive that it matched the physical reference length. Needing to make the target larger when lying compared to when standing suggests some not mutually exclusive possibilities. It may be that while tilted participants perceived the targets as smaller than when they were upright. It may be that participants perceived the targets as being closer while tilted compared to when upright. It may also be that participants perceived the physical reference length as longer while tilted. Misperceiving objects as larger and/or closer when lying may provide a survival benefit while in such a vulnerable position.

Cost-effectiveness analysis of sofosbuvir and velpatasvir in chronic hepatitis C patients with decompensated cirrhosis.

BACKGROUND: Current literature indicates that direct-acting antivirals (DAAs) are cost-effective to treat compensated cirrhotic patients with hepatitis C. Although already funded by public payers, it is unknown whether it is economical to reimburse DAAs within the more advanced decompensated cirrhosis population. METHODS: A state-transition model was developed to conduct a cost-utility analysis of sofosbuvir-velpatasvir (SOF/VEL) plus ribavirin regimen for 12 weeks. The evaluated cohort had a mean age of 58 years and Child-Turcotte-Pugh (CTP) class B cirrhosis with decompensated symptoms. A scenario analysis was performed on CTP C patients. We used a payer perspective, a lifetime time horizon and a 1.5% annual discount rate. RESULTS: While SOF/VEL plus ribavirin treatment for 12 weeks increased costs by $156 676, it provided an extra 4.00 quality-adjusted life years (QALYs) compared to best supportive care (no DAA therapy). With an incremental cost-effectiveness ratio of $39 169 per QALY, SOF/VEL plus ribavirin was determined to be cost-effective at a willingness to pay of $50 000 per QALY. SOF/VEL reduced liver-related deaths and reduced progression to CTP C cirrhosis by 20.4% and 21.9%, respectively. On the contrary, SOF/VEL regimen resulted in increases in liver transplants and hepatocellular carcinoma (HCC) by 54.0% and 42.5%, respectively. Similar results were found for CTP C patients. CONCLUSION: This analysis informs payers that SOF/VEL should continue to be reimbursed in decompensated hepatitis C patients. It also supports the recommendations by the American Association for the Study of Liver Diseases to continue screening for HCC in decompensated cirrhotic patients who have achieved sustained virologic response.

Prophylactic clips to reduce delayed polypectomy bleeding after resection of large colorectal polyps: a systematic review and meta-analysis of randomized trials.

BACKGROUND AND AIMS: Prophylactic clips to prevent delayed polypectomy bleeding (DPB) after endoscopic resection of large colorectal polyps remains controversial. We performed a systematic review and meta-analysis to evaluate the efficacy of prophylactic clips for preventing DPB by synthesizing the results of randomized trials. METHODS: PubMed, Cochrane Library, and EMBASE were searched to October 2019 to identify randomized controlled trials evaluating the efficacy of placing prophylactic clips to reduce DPB after resection of large (≥10 mm) colorectal polyps. The primary outcome was DPB defined by GI bleeding after the conclusion of the colonoscopy. RESULTS: Eight studies (n = 3415) met the study criteria, all with a low risk of bias. The overall pooled incidence of DPB was 3.9% (95% confidence interval [CI], 2.4%-5.4%) in patients receiving endoscopic resection of colorectal polyps ≥10 mm. Placing prophylactic clips reduced DPB in patients receiving prophylactic clips (relative risk [RR], 0.61; 95% CI, 0.43-0.85; I2 = 37.8%) compared with no clips with a number needed to treat (NNT) of 52 (95% CI, 31-163). In stratified analyses, placing clips was associated with reduced risks of DPB in patients with polyps ≥20 mm (RR, 0.54; 95% CI, 0.35-0.84; I2 = 0.0%; NNT, 30), nonpedunculated morphology (RR, 0.54; 95% CI, 0.36-0.81; I2 = 0.0%; NNT, 39), and located proximal to the hepatic flexure (RR, 0.49; 95% CI, 0.31-0.78; I2 = 54.8%; NNT, 25) compared with no clips. CONCLUSIONS: Prophylactic clips after endoscopic resection of colorectal polyps ≥10 mm demonstrated a modest reduction in the risk of DPB. Larger reductions were observed in patients with polyps ≥20 mm, nonpedunculated morphology, or located proximal to the hepatic flexure.

Lenvatinib Versus Sorafenib as First-Line Treatment of Unresectable Hepatocellular Carcinoma: A Cost-Utility Analysis.

BACKGROUND: In a global, phase III, open-label, noninferiority trial (REFLECT), lenvatinib demonstrated noninferiority to sorafenib in overall survival and a statistically significant increase in progression-free survival in patients with unresectable hepatocellular carcinoma (HCC). Recently, lenvatinib became the first agent in more than 10 years to receive approval as first-line therapy for unresectable HCC, along with the previously approved sorafenib. The objective of this study was to determine the comparative cost-effectiveness of lenvatinib and sorafenib as a first-line therapy of unresectable HCC. MATERIALS AND METHODS: A state-transition model of unresectable HCC was developed in the form of a cost-utility analysis. The model time horizon was 5 years; the efficacy of the model was informed by the REFLECT trial, and costs and utilities were obtained from published literature. Probabilistic sensitivity analyses and subgroup analyses were performed to test the robustness of the model. RESULTS: Lenvatinib dominated sorafenib in the base case analysis. A probabilistic sensitivity analysis indicated that lenvatinib remains a cost-saving measure in 64.87% of the simulations. However, if the cost of sorafenib was reduced by 57%, lenvatinib would no longer be the dominant strategy. CONCLUSION: Lenvatinib offered a similar clinical effectiveness at a lower cost than sorafenib, suggesting that lenvatinib would be a cost-saving alternative in treating unresectable HCC. However, lenvatinib may fail to remain cost-saving if a significantly cheaper generic sorafenib becomes available. IMPLICATIONS FOR PRACTICE: This analysis suggests an actionable clinical policy that will achieve cost saving. This cost-utility analysis showed that lenvatinib had a similar clinical effectiveness at a lower cost than sorafenib, indicating that lenvatinib may be a cost-saving measure in patients with unresectable HCC, in which $23,719 could be saved per patient. The introduction of a new therapeutic option for the first time in 10 years in Canada provides an important opportunity for clinicians, researchers, and health care decision-makers to explore potential modifications in recommendations and practice guidelines.

The effect of training on the perceived approach angle in visual vertical heading judgements in a virtual environment.

Past studies have found poorer performance on vertical heading judgement accuracy compared to horizontal heading judgement accuracy. In everyday life, precise vertical heading judgements are used less often than horizontal heading judgements as we cannot usually control our vertical direction. However, pilots judging a landing approach need to consistently discriminate vertical heading angles to land safely. This study addresses the impact of training on participants' ability to judge their touchdown point relative to a target in a virtual environment with a clearly defined ground plane and horizon. Thirty-one participants completed a touchdown point estimation task twice, using three angles of descent (3°, 6° and 9°). In between the two testing tasks, half of the participants completed a flight simulator landing training task which provided feedback on their vertical heading performance; while, the other half completed a two-dimensional puzzle game as a control. Overall, participants were more precise in their responses in the second testing compared to the first (from a SD of ± 0.91° to ± 0.67°), but only the experimental group showed improvement in accuracy (from a mean error of - 2.1° to - 0.6°). Our results suggest that with training, vertical heading judgments can be as accurate as horizontal heading judgments. This study is the first to show the effectiveness of training in vertical heading judgement in naïve individuals. The results are applicable in the field of aviation, informing possible strategies for pilot training.

Cardiac Pulsatility- and Respiratory-Induced Deformations of the Renal Arteries and Snorkel Stents After Snorkel Endovascular Aneurysm Sealing.

Purpose: To quantify deformations of renal arteries and snorkel stents after snorkel endovascular aneurysm sealing (Sn-EVAS) resulting from cardiac pulsatility and respiration and compare these deformations to patients with untreated abdominal aortic aneurysms (AAA) and snorkel endovascular aneurysm repair (Sn-EVAR). Materials and Methods: Ten Sn-EVAS patients (mean age 75±6 years; 8 men) were scanned with cardiac-gated, respiration-resolved computed tomography angiography. From 3-dimensional geometric models, changes in renal artery and stent angulation and curvature due to cardiac pulsatility and respiration were quantified. Respiration-induced motions were compared with those of 16 previously reported untreated AAA patients and 11 Sn-EVAR patients. Results: Renal artery bending at the stent end was greater for respiratory vs cardiac influences (6°±7° vs -1°±2°, p<0.025). Respiration caused a 3-fold greater deformation on the left renal artery as compared with the right side. Maximum curvature change was higher for respiratory vs cardiac influences (0.49±0.29 vs 0.24±0.17 cm-1, p<0.025), and snorkel renal stents experienced similar maximum curvature change due to cardiac pulsatility and respiration (0.14±0.10 vs 0.19±0.09 cm-1, p=0.142). When comparing the 3 patient cohorts for respiratory-induced deformation, there was significant renal branch angulation in untreated AAAs, but not in Sn-EVAR or Sn-EVAS, and there was significant bending at the stent end in Sn-EVAR and Sn-EVAS. Maximum curvature change due to respiration was ~10-fold greater in Sn-EVAR and Sn-EVAS compared to untreated AAAs. Conclusion: The findings suggest that cardiac and respiratory influences may challenge the mechanical durability of snorkel stents of Sn-EVAS; similarly, however, respiration may be the primary culprit for tissue irritation, increasing the risk for stent-end thrombosis, especially in the left renal artery. The bending stiffness of snorkel stents in both the Sn-EVAR and Sn-EVAS cohorts damped renal branch angulation while it intensified bending of the artery distal to the snorkel stent. Understanding these device-to-artery interactions is critical as they may affect mechanical durability of branch stents and quality and durability of treatment.

Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice.

BACKGROUND: The role of protease activated receptor-2 (PAR-2) in the pathogenesis of abdominal pain in irritable bowel syndrome (IBS) is not well defined. AIMS: To investigate the role of PAR-2-mediated visceral hypersensitivity in a post-infectious IBS (PI-IBS) mouse model. METHODS: T. spiralis-infected PI-IBS mouse model was used. Fecal serine protease activity and intestinal mast cells were evaluated. Intestinal permeability was assessed by urine lactulose/mannitol ratio, and colonic expressions of PAR-2 and tight junction (TJ) proteins were examined by Western blot. Intestinal immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was evaluated by abdominal withdrawal reflex in response to colorectal distention. RESULTS: Colonic PAR-2 expression as well as fecal serine protease activity and intestinal mast cell counts were elevated in PI-IBS compared to the control mice. Decreased colonic TJ proteins expression, increased lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and visceral hypersensitivity were observed in PI-IBS compared to the control mice. Administration of PAR-2 agonist in control mice demonstrated similar changes observed in PI-IBS mice, while PAR-2 antagonist normalized the increased intestinal permeability and reduced visceral hypersensitivity observed in PI-IBS mice. CONCLUSIONS: PAR-2 activation increases intestinal permeability leading to immune activation and visceral hypersensitivity in PI-IBS mouse model.

Microparticle Delivery of Protein Markers for Single-Cell Western Blotting from Microwells.

Immunoblotting confers protein identification specificity beyond that of immunoassays by prepending protein electrophoresis (sizing) to immunoprobing. To accurately size protein targets, sample analysis includes concurrent analysis of protein markers with known molecular masses. To incorporate protein markers in single-cell western blotting, microwells are used to isolate individual cells and protein marker-coated microparticles. A magnetic field directs protein-coated microparticles to >75% of microwells, so as to 1) deliver a quantum of protein marker to each cell-laden microwell and 2) synchronize protein marker solubilization with cell lysis. Nickel-coated microparticles are designed, fabricated, and characterized, each conjugated with a mixture of histidine-tagged proteins (42.3-100 kDa). Imidazole in the cell lysis buffer solubilizes protein markers during a 30 s cell lysis step, with an observed protein marker release half-life of 4.46 s. Across hundreds of individual microwells and different microdevices, robust log-linear regression fits (R2 > 0.97) of protein molecular mass and electrophoretic mobility are observed. The protein marker and microparticle system is applied to determine the molecular masses of five endogenous proteins in breast cancer cells (GAPDH, ß-TUB, CK8, STAT3, ER-α), with <20% mass error. Microparticle-delivered protein standards underpin robust, reproducible electrophoretic cytometry that complements single-cell genomics and transcriptomics.

Impact of gluten consumption in patients with functional dyspepsia: A case-control study.

BACKGROUND AND AIM: Dietary factors and immune dysfunction may induce symptoms in patients with functional dyspepsia (FD). The aim of the study was to evaluate whether gluten consumption impacts symptom onset in patients with FD and to evaluate for possible histologic alterations in the duodenum of patients with FD. METHODS: We prospectively enrolled 101 patients newly diagnosed with FD and 31 asymptomatic controls. Specific FD symptoms and gluten consumption patterns were evaluated by self-reported questionnaires. Tight junction protein (claudin-1) expression and presence of intraepithelial lymphocyte (IEL) infiltration in the bulb (D1) and second portion (D2) of the duodenum were assessed by immunohistochemistry. RESULTS: Wheat bun consumption had higher frequency (P = 0.047) and increased average consumption (P = 0.01) scores in patients with FD compared with the control group. Of the 101 patients with FD, early satiety (P = 0.03) was associated with increased wheat bun consumption frequency score. On histologic evaluation, claudin-1 expression was decreased in D1 (0.003 ± 0.001 vs 0.012 ± 0.002, P = 0.003) and D2 (0.002 ± 0.0004 vs 0.012 ± 0.001, P < 0.001), while duodenal IEL counts were increased in D1 (15.5 ± 7.8 vs 3.1 ± 2.5, P < 0.001) and D2 (20.6 ± 7.7 vs 5.8 ± 3.4, P < 0.001) among patients with FD compared with the control group. Finally, Helicobacter pylori infection was associated with increased IELs in D1 (20.6 ± 7.0 vs 14.2 ± 7.4, P = 0.001) among patients with FD. CONCLUSIONS: Among patients with FD, gluten-rich food may lead to symptom onset, specifically early satiety. Intestinal epithelial barrier dysfunction characterized by decreased claudin-1 expression and mucosal immune activation demonstrated by IEL infiltration may contribute to the pathogenesis of FD.

Effect of selenomethionine on cell viability and heat shock protein 70 levels in rainbow trout intestinal epithelial cells at hypo-, normo-, and hyper-thermic temperatures.

As global warming and environmental pollution modify aquatic environments, the thermal biology of fish could be affected by interactions between temperature and pollutants, such as selenium (Se). Therefore, selenomethionine (SeMet) was studied for effects on cell viability and on heat shock protein 70 (HSP70) levels in the rainbow trout intestinal epithelial cell, RTgutGC, at hypothermic (4 °C), normothermic (14 and 18 °C) and hyperthermic (26 °C) temperatures. RTgutGC cultures remained viable for at least a week at all temperatures, although energy metabolism as measured with Alamar Blue (resazurin) was appreciably diminished at 4 °C. Over a 7-day incubation, HSP 70 levels in cultures remained steady at 4 °C, declined at 18 °C, and increased slightly at 26 °C. When 125 µM SeMet was present, cultures remained viable and HSP70 levels were neither increased nor decreased relative to control cultures, regardless of the temperature. With 500 and 1000 µM SeMet, cell viability was profoundly impaired after 7 days in cultures at 14, 18 and 26 °C but was unchanged at 4 °C. Overall the results suggest that only hypothermia modulated the response of rainbow trout cells to SeMet.

Randomized trial of 1-week versus 2-week intervals for endoscopic ligation in the treatment of patients with esophageal variceal bleeding.

UNLABELLED: The appropriate interval between ligation sessions for treatment of esophageal variceal bleeding is uncertain. The optimal interval would provide variceal eradication as rapidly as possible to lessen early rebleeding while minimizing ligation-induced adverse events. We randomly assigned patients hospitalized with acute esophageal variceal bleeding who had successful ligation at presentation to repeat ligation at 1-week or 2-week intervals. Beta-blocker therapy was also prescribed. Ligation was performed at the assigned interval until varices were eradicated and then at 3 and 9 months after eradication. The primary endpoint was the proportion of patients with variceal eradication at 4 weeks. Four-week variceal eradication occurred more often in the 1-week than in the 2-week group: 37/45 (82%) versus 23/45 (51%); difference = 31%, 95% confidence interval 12%-48%. Eradication occurred more rapidly in the 1-week group (18.1 versus 30.8 days, difference = -12.7 days, 95% confidence interval -20.0 to -5.4 days). The mean number of endoscopies to achieve eradication or to the last endoscopy in those not achieving eradication was comparable in the 1-week and 2-week groups (2.3 versus 2.1), with the mean number of postponed ligation sessions 0.3 versus 0.1 (difference = 0.2, 95% confidence interval -0.02 to 0.4). Rebleeding at 4 weeks (4% versus 4%) and 8 weeks (11% versus 9%), dysphagia/odynophagia/chest pain (9% versus 2%), strictures (0% versus 0%), and mortality (7% versus 7%) were similar with 1-week and 2-week intervals. CONCLUSION: One-week ligation intervals led to more rapid eradication than 2-week intervals without an increase in complications or number of endoscopies and without a reduction in rebleeding or other clinical outcomes; the decision regarding ligation intervals may be individualized based on patient and physician preferences and local logistics and resources. (Hepatology 2016;64:549-555).

Accuracy of ASGE high-risk criteria in evaluation of patients with suspected common bile duct stones.

BACKGROUND AND AIMS: ERCP is recommended for patients considered high risk for choledocholithiasis after biochemical testing and abdominal US. Our aim was to determine whether the American Society for Gastrointestinal Endoscopy (ASGE) guidelines accurately select patients for whom the risk of ERCP is justified. METHODS: Consecutive patients hospitalized with suspected choledocholithiasis at Sir Run Run Shaw Hospital who received biochemical testing, abdominal US, and definitive testing for choledocholithiasis (MRCP, EUS, ERCP, intraoperative cholangiogram, and/or common bile duct [CBD] exploration) were identified. Patients with choledocholithiasis on abdominal US, with bilirubin levels >4 mg/dL (normal values <1.2 mg/dL), bilirubin levels ≥1.8 mg/dL plus a dilated CBD and/or clinical cholangitis were considered high risk per ASGE guidelines. RESULTS: Of 2724 patients with suspected choledocholithiasis, 1171 (43%) met high-risk criteria. Definitive testing (MRCP in 2442 [90%], EUS in 67 [2%], ERCP in 659 [24%], intraoperative cholangiogram in 229 [8%], and CBD exploration in 447 [16%]) revealed choledocholithiasis in 1076 [40%] patients. The specificity of the ASGE high-risk criteria was 74% (95% confidence interval [CI], 72%-77%) and positive predictive value was 64% (95% CI, 61%-67%). Using a more restrictive criteria (choledocholithiasis on abdominal US, bilirubin >4 mg/dL plus dilated CBD) improved the specificity to 94% (95% CI, 93%-95%) and positive predictive value to 85% (95% CI, 82%-88%). Doubling or more of bilirubin to >4 mg/dL and ≥1.8 mg/dL at second testing had specificities of 98% (95% CI, 96%-99%) and 95% (95% CI, 93%-96%), with positive predictive values of 62% (95% CI, 48%-76%) and 54% (95% CI, 44%-65%), respectively. CONCLUSIONS: Although ASGE high-risk criteria demonstrated >50% probability of the patient having choledocholithiasis, more than a third of the patients would receive diagnostic ERCPs. Criteria with choledocholithiasis on abdominal US and/or bilirubin levels >4 mg/dL plus a dilated CBD showed higher specificity and positive predictive value.

Reduced interstitial cells of Cajal and increased intraepithelial lymphocytes are associated with development of small intestinal bacterial overgrowth in post-infectious IBS mouse model.

OBJECTIVE: Intestinal dysmotility and immune activation are likely involved in the pathogenesis of small intestinal bacteria overgrowth (SIBO) in irritable bowel syndrome (IBS). We aimed at investigating the role of interstitial cells of Cajal (ICC) and intestinal inflammation in the development of SIBO using a post-infectious IBS (PI-IBS) mouse model. MATERIALS AND METHODS: NIH mice were randomly infected with Trichinella spiralis. Visceral sensitivity and stool pattern were assessed at 8-weeks post-infection (PI). Intestinal bacteria counts from jejunum and ileum were measured by quantitative real-time PCR to evaluate the presence of SIBO. ICC density, intraepithelial lymphocytes (IELs) counts, and intestinal cytokine levels (IL1-ß, IL-6, toll-like receptor-4 (TLR-4), IL-10) in the ileum were examined. RESULTS: PI-IBS mice demonstrated increased visceral sensitivity compared with the control group. One-third of the PI-IBS mice developed SIBO (SIBO+/PI-IBS) and was more likely to have abnormal stool form compared with SIBO negative PI-IBS (SIBO-/PI-IBS) mice but without difference in visceral sensitivity. SIBO+/PI-IBS mice had decreased ICC density and increased IELs counts in the ileum compared with SIBO-/PI-IBS mice. No difference in inflammatory cytokine expression levels were detected among the groups except for increased TLR-4 in PI-IBS mice compared with the control group. CONCLUSIONS: Development of SIBO in PI-IBS mice was associated with reduced ICC density and increased IELs counts in the ileum. Our findings support the role of intestinal dysmotility and inflammation in the pathogenesis of SIBO in IBS and may provide potential therapeutic targets.

Predictors and outcomes of delayed plastic biliary stent removal following endoscopic retrograde cholangiopancreatography.

OBJECTIVE: Plastic biliary stents are commonly placed during endoscopic retrograde cholangiopancreatography (ERCP) and should be removed or replaced within 3 months to reduce the risk of stent obstruction. The aim of the study was to identify predictors and outcomes of patients who had delayed plastic biliary stent removal following ERCP. MATERIALS AND METHODS: Consecutive patients who received ERCP with plastic biliary stent placement at Loma Linda University Medical Center (10/2004-6/2013) were identified. Delayed removal was defined as presence of stent >3 months after index ERCP. Multivariable regression analysis to identify baseline characteristics associated with delayed removal was performed. Clinical outcomes of stent obstruction (e.g., cholangitis, hospitalization, intensive care) were also collected for those with delayed removal. RESULTS: Among 374 patients undergoing ERCP with plastic biliary stent, 71 (19%) had delayed stent removal. Patients who had anesthesia assistance (AOR = 3.8, 95%CI 1.2-11.4), non-English primary language (AOR = 3.0, 95%CI 1.5-6.2), and outpatient ERCP (AOR = 2.0, 95%CI 1.1-3.4) had increased while choledocholithiasis (AOR = 0.5, 95%CI 0.3-0.99) had lower odds of delayed stent removal. Among those with delayed removal, 13 (18%) were hospitalized for stent obstruction (5 (7%) had cholangitis, 8 (11%) were hospitalized for more than a week, and 3 (4%) required intensive care). CONCLUSIONS: Almost one-fifth of patients who underwent ERCP with plastic biliary stent placement had delayed removal with nearly one-fifth of these patients requiring hospitalization for stent obstruction. Targeting patients at risk by improving communication and ease of scheduling an ERCP may reduce preventable adverse events associated with delayed biliary stent removal.

Dynamic Geometric Analysis of the Renal Arteries and Aorta following Complex Endovascular Aneurysm Repair.

BACKGROUND: Aneurysm regression and target vessel patency during early and mid-term follow-up may be related to the effect of stent-graft configuration on the anatomy. We quantified geometry and remodeling of the renal arteries and aneurysm following fenestrated (F-) or snorkel/chimney (Sn-) endovascular aneurysm repair (EVAR). METHODS: Twenty-nine patients (mean age, 76.8 ± 7.8 years) treated with F- or Sn-EVAR underwent computed tomography angiography at preop, postop, and follow-up. Three-dimensional geometric models of the aorta and renal arteries were constructed. Renal branch angle was defined relative to the plane orthogonal to the aorta. End-stent angle was defined as the angulation between the stent and native distal artery. Aortic volumes were computed for the whole aorta, lumen, and their difference (excluded lumen). Renal patency, reintervention, early mortality, postoperative renal impairment, and endoleak were reviewed. RESULTS: From preop to postop, F-renal branches angled upward, Sn-renal branches angled downward (P < 0.05), and Sn-renals exhibited increased end-stent angulation (12 ± 15°, P < 0.05). From postop to follow-up, branch angles did not change for either F- or Sn-renals, whereas F-renals exhibited increased end-stent angulation (5 ± 10°, P < 0.05). From preop to postop, whole aortic and excluded lumen volumes increased by 5 ± 14% and 74 ± 81%, whereas lumen volume decreased (39 ± 27%, P < 0.05). From postop to follow-up, whole aortic and excluded lumen volumes decreased similarly (P < 0.05), leaving the lumen volume unchanged. At median follow-up of 764 days (range, 7-1,653), primary renal stent patency was 94.1% and renal impairment occurred in 2 patients (6.7%). CONCLUSIONS: Although F- and Sn-EVAR resulted in significant, and opposite, changes to renal branch angle, only Sn-EVAR resulted in significant end-stent angulation increase. Longitudinal geometric analysis suggests that these anatomic alterations are primarily generated early as a consequence of the procedure itself and, although persistent, they show no evidence of continued significant change during the subsequent postoperative follow-up period.

Lower yield of endoscopic ultrasound-guided fine-needle aspiration in patients with pancreatic head mass with a biliary stent.

BACKGROUND: In jaundiced patients with suspected pancreatic cancer, endoscopic retrograde cholangiopancreatography (ERCP) with biliary stent is frequently performed prior to histologic diagnosis by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). AIMS: To compare the accuracy of jaundiced patients undergoing EUS-FNA for a pancreatic mass with or without a biliary stent. METHODS: Consecutive patients with a pancreatic mass and jaundice who underwent EUS-FNA between 4/2005 and 4/2013 were identified. Final diagnosis was based on histologic or radiologic evaluation with >6-month follow-up if the index EUS-FNA was negative for malignancy. Primary endpoint was histologic accuracy of EUS-FNA. RESULTS: Mean age of the 180 patients was 65 ± 12 years; 83 (46 %) had ERCP prior to EUS-FNA and 75 (42 %) received a biliary stent. Onsite cytopathologist was present for 81 (45 %) procedures. Final diagnosis revealed malignancy in 172 (96 %) patients, with adenocarcinoma in 159 (88 %). Patients with biliary stents had lower accuracy of EUS-FNA for malignancy than those without a biliary stent: 77 % (95 % CI 67-85 %) versus 89 % (95 % CI 81-93 %). On multivariate analysis, having a biliary stent (OR = 0.37, 95 % CI 0.15-0.90), onsite cytopathologist (OR = 9.24, 95 % CI 2.64-32.37), and receiving a core biopsy (OR = 2.60, 95 % CI 1.07-6.29) were associated with accuracy of EUS-FNA. CONCLUSIONS: Presence of a biliary stent was associated with a significant decrease in the accuracy of EUS-FNA for histologic diagnosis of pancreatic cancer, while accuracy was increased when a cytopathologist was onsite. EUS-FNA should be performed prior to ERCP in jaundiced patients with suspected pancreatic cancer.

Cancer/testis antigen PAGE4, a regulator of c-Jun transactivation, is phosphorylated by homeodomain-interacting protein kinase 1, a component of the stress-response pathway.

Prostate-associated gene 4 (PAGE4) is a cancer/testis antigen that is typically restricted to the testicular germ cells but is aberrantly expressed in cancer. Furthermore, PAGE4 is developmentally regulated with dynamic expression patterns in the developing prostate and is also a stress-response protein that is upregulated in response to cellular stress. PAGE4 interacts with c-Jun, which is activated by the stress-response kinase JNK1, and plays an important role in the development and pathology of the prostate gland. Here, we have identified homeodomain-interacting protein kinase 1 (HIPK1), also a component of the stress-response pathway, as a kinase that phosphorylates PAGE4 at T51. We show that phosphorylation of PAGE4 is critical for its transcriptional activity since mutating this T residue abolishes its ability to potentiate c-Jun transactivation. In vitro single molecule FRET indicates phosphorylation results in compaction of (still) intrinsically disordered PAGE4. Interestingly, however, while our previous observations indicated that the wild-type nonphosphorylated PAGE4 protein interacted with c-Jun [Rajagopalan , K. et al. ( 2014 ) Biochim, Biophys. Acta 1842 , 154 -163], here we show that phosphorylation of PAGE4 weakens its interaction with c-Jun in vitro. These data suggest that phosphorylation induces conformational changes in natively disordered PAGE4 resulting in its decreased affinity for c-Jun to promote interaction of c-Jun with another, unidentified, partner. Alternatively, phosphorylated PAGE4 may induce transcription of a novel partner, which then potentiates c-Jun transactivation. Regardless, the present results clearly implicate PAGE4 as a component of the stress-response pathway and uncover a novel link between components of this pathway and prostatic development and disease.

Delayed paracentesis is associated with increased in-hospital mortality in patients with spontaneous bacterial peritonitis.

OBJECTIVES: Spontaneous bacterial peritonitis (SBP) is associated with high mortality. Early paracentesis (EP) is essential for rapid diagnosis and optimal treatment. The aim of the study is to compare the outcomes of patients with SBP who received EP vs. delayed paracentesis (DP). METHODS: Consecutive patients who were diagnosed with SBP (ascites neutrophil count ≥250 cells/mm(3) and clinical evidence of cirrhosis) <72 h from the first physician encounter at two centers were identified. EP was defined by receiving paracentesis <12 h and DP 12-72 h from hospitalization. Primary outcome was in-hospital mortality. RESULTS: The mean age of 239 patients with SBP was 53±10 years; mean Model for End-Stage Liver Disease (MELD) score was 22±9. In all, 98 (41%) patients who received DP had a higher in-hospital mortality (27% vs. 13%, P=0.007) compared with 141 (59%) who received EP. Furthermore, DP group had longer intensive care days (4.0±9.5 vs. 1.3±4.1, P=0.008), hospital days (13.0±14.7 vs. 8.4±7.4, P=0.005), and higher 3-month mortality (28/76, 37% vs. 21/98, 21%; P=0.03) compared with the EP group. Adjusting for MELD score ≥22 (adjusted odds ratio (AOR)=5.7, 95% confidence interval (CI)=1.8-18.5) and creatinine levels ≥1.5 mg/dl (AOR=3.2, 95% CI=1.4-7.2), DP was associated with increased in-hospital mortality (AOR=2.7, 95% CI=1.3-4.8). Each hour delay in paracentesis was associated with a 3.3% (95% CI=1.3-5.4%) increase in in-hospital mortality after adjusting for MELD score and creatinine levels. CONCLUSIONS: Hospitalized patients with SBP who received DP had a 2.7-fold increased risk of mortality adjusting for MELD score and renal dysfunction. Diagnostic paracentesis performed <12 h from hospitalization in patients with cirrhosis and ascites may improve short-term survival.

Low adherence to Helicobacter pylori testing in hospitalized patients with bleeding peptic ulcer disease.

BACKGROUND: Helicobacter pylori (H. pylori) testing in patients with bleeding ulcers is recommended by society guidelines and considered a quality indicator. The aim of the study is to examine the proportion of patients with bleeding ulcers who had H. pylori testing and identify predictors associated with H. pylori testing. MATERIALS AND METHODS: Consecutive hospitalized patients with bleeding ulcers documented endoscopically at a single center from 10/2004-5/2011 were identified retrospectively from an endoscopy database. The proportion of patients undergoing direct H. pylori testing (histology, rapid urease test, breath test or stool antigen) and any H. pylori testing (direct or serologic) were determined. RESULTS: Among 330 patients with bleeding ulcers, 105 (32%, 95% CI 27-37%) underwent direct testing and another 52 (16%, 95% CI 12-20%) had serologic testing during a median follow-up of 9 months (range, 0-86). H. pylori testing occurred at the index hospitalization in 146 (93%) of the 157 patients tested. Among the 105 patients who had direct H. pylori testing, 90 (86%) had biopsy-based testing during the initial endoscopy. On multivariate analysis, undergoing biopsy of a gastric ulcer was strongly associated with having direct H. pylori testing performed (OR = 5.1, 95% CI 2.3-11.5; p < .0001). CONCLUSIONS: Among patients hospitalized with bleeding ulcers, less than half received H. pylori testing and less than a third received the more accurate direct testing. Most of the direct H. pylori testing was biopsy-based with very few being tested after the index hospitalization. Efforts to increase H. pylori testing in patients with bleeding ulcers are needed to improve outcomes.