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The method of rhodium‐catalyzed insertion reaction of perfluoroarenes between unprotected peptide cystine disulfides is developed. The method is applicable to peptides containing amino acids such as Ser, Asn, Asp, and Lys without affecting hydroxy, primary amine, carboxylic acid, and amide groups. The reaction does not require a base and proceeds under acidic, neutral, and basic conditions. No free thiols are detected, and the reaction is considered to proceed via rhodium thiolates. A crossover experiment shows minimal scrambling of organothio groups. [ABSTRACT FROM AUTHOR]

Background: Delayed bleeding (DB) rarely occurs after cold snare polypectomy (CSP) for colorectal polyps, but no large-scale studies have investigated this. The present study evaluated the rate, characteristics, and risk factors of DB of CSP. Methods: We conducted a multicenter retrospective study at 10 Japanese institutions. A total of 18,007 patients underwent CSP for colorectal polyps ≤ 10 mm in size from March 2015 to September 2019, and cases of DB (DB group) were analyzed for the rate, antithrombotic drugs, polyp size, morphology, location, and risk factors. As a control, 269 non-bleeding cases (non-DB group) with 606 polyps who underwent CSP at the same 10 facilities in the 2-week study period were extracted. Results: We analyzed 26 DB cases with 28 lesions, and the total DB rate was 0.14% (26/18,007). The DB group had significantly higher rates of using antiplatelets (42.3% vs. 13.0%, p < 0.001) and anticoagulants (19.2% vs. 2.6%, p = 0.002), and significantly higher rates of polyp size ≥ 5 mm (67.9% vs. 45.2%, p = 0.015), rectal lesion (25.0% vs. 6.6%, p = 0.003), and polypoid lesion (89.3% vs. 55.3%, p < 0.001) than the non-DB group. A multivariate analysis (odds ratio; 95% confidence interval) for patient characteristics showed antiplatelet use (4.521; 1.817–11.249, p = 0.001) and anticoagulant use (7.866; 20.63–29.988, p = 0.003) as independent risk factors for DB. Polyp size ≥ 5 mm (3.251; 1.417–7.463, p = 0.005), rectal lesion (3.674; 1.426–9.465, p = 0.007), and polypoid lesion (7.087; 20.81–24.132, p = 0.002) were also risk factors for lesion characteristics. Conclusions: The rate of DB was 0.14% and antithrombotic drug use, polyp size, location, and morphology were related to it. [ABSTRACT FROM AUTHOR]

A cross‐linked poly(acrylate) containing an ethynylhelicene (P)‐pentamer was synthesized by radical polymerization between two horizontally aligned films with a parallel arrangement in trifluoromethylbenzene. The resulting liquid crystal elastomer swollen in bromobenzene showed the Maltese cross, which indicated a cylindrical concentric monodomain structure of the millimeter‐order size as determined by polarized optical microscopy (POM) analysis. In toluene, a homogeneously bright POM image was obtained, which reversibly changed in intensity upon heating and cooling. Addition of an (M)‐tetramer to the liquid crystal elastomer in toluene produced a hetero‐double‐helix exhibiting the Maltese cross, whose intensity did not change upon heating and cooling. The three states can be switched by addition and removal of an (M)‐tetramer and solvents. [ABSTRACT FROM AUTHOR]

Background and Aim: High‐grade dysplasia (HGD) and T1 lesions are accidentally resected by cold snare polypectomy (CSP) and the characteristics, and follow‐up of them has not been reported. In this study, we analyzed the histopathological findings and recurrence of them. Methods: This was a multicenter retrospective‐cohort study. We collected HGD and T1 lesions of ≤ 10 mm resected by CSP among 15 520 patients receiving CSP from 2014 to 2019 at nine related institutions, and we extracted only cases receiving definite follow‐up colonoscopy after CSP of HGD and T1 lesions. We analyzed these tumor's characteristics and therapeutic results such as R0 resection and local recurrence and risk factors of recurrence. Results: We collected 103 patients (0.63%) and extracted 80 lesions in 74 patients receiving follow‐up colonoscopy for CSP scar. Mean age was 68.4 ± 12.0, and male rate was 68.9% (51/80). The mean tumor size (mm) was 6.6 ± 2.5, and the rate of polypoid morphology and rectum location was 77.5% and 25.0%. The rate of magnified observation was 53.8%. The rates of en bloc resection and R0 resection were 92.5% and 37.5%. The local recurrence rate was 6.3% (5/80, median follow‐up period: 24.0 months). The recurrence developed within 3 months after CSP for four out of five recurrent cases. Comparing five recurrent lesions to 75 non‐recurrent lesions, a positive horizontal margin was a significant risk factor (60.0% vs 10.7%, P < 0.001). Conclusions: High‐grade dysplasia and T1 resected by CSP were analyzed, and the local recurrence rate of them was substantially high. [ABSTRACT FROM AUTHOR]

Purpose: For rectal neuroendocrine tumors (NETs) ≤ 10 mm, endoscopic resection is a standard treatment. However, there is no consensus whether additional surgery should be performed for patients at risk of lymph node metastasis (LNM) after endoscopic resection. The purpose of this study was to analyze the results of endoscopic resection and additional surgery of rectal NETs, thereby clarify the characteristics of cases with LNM. Methods: This study was a multicenter retrospective cohort study conducted at 12 Japanese institutions. A total of 132 NETs ≤ 10 mm were analyzed regarding various therapeutic results. A comparative analysis was performed by dividing the cases into two groups that underwent additional surgery or not. Furthermore, the relationship between tumor size and LNM was examined. Results: The endoscopic treatments were 12 endoscopic mucosal resections (EMR), 58 endoscopic submucosal resections with ligation (ESMR-L), 29 precutting EMRs, and 33 endoscopic submucosal dissections (ESD). The R0 resection rates of EMR were 41.7%, and compared to this rate, other three treatments were 86.2% (p < 0.001), 86.2% (p = 0.005), and 97.0% (p < 0.001), respectively. There were 41 non-curative cases (31.1%), and 13 had undergone additional surgery. Then, LNM was observed in 4 of the 13 patients, with an overall rate of LNM of 3.0% (4/132). The rate of positive lymphatic invasion and the rate of LNM by tumor size ≤ 6 mm and 7–10 mm were 9.7 vs. 15.4% (p = 0.375) and 0 vs. 10.3% (p = 0.007). Conclusions: A multicenter study revealed the priority of each endoscopic resection and the low rate of LNM for rectal NETs ≤ 6 mm. [ABSTRACT FROM AUTHOR]

Backgrounds and Aims. Sachets of polyethylene glycol plus electrolytes (PEG+E: Movicol: EA Pharma, Tokyo, Japan) are used for chronic constipation, and its efficacy is reported only for female and nonelderly people. Chronic constipation is one of the reasons of poor colonoscopic bowel preparation (BP). We analyzed its efficacy in improving chronic constipation and poor colonoscopic BP related to it, including male and elderly people. Materials and Methods. This multicenter retrospective study was conducted from September 2019 to September 2020 at 5 related institutions among patients ≥ 20 years old diagnosed with chronic constipation whose previous colonoscopic BP had had a fair or poor Aronchick score. Two or four sachets of PEG+E (13.7 or 27.4 g/day) were prescribed for 1 week before colonoscopy. We analyzed the rate of improvement in BP, effect-related factors, spontaneous bowel movements (SBMs), stool consistency, improvement of constipation symptoms, and adverse events. Results. We evaluated 106 cases (56 males) with an average age of 69.5 ± 9.4 years old (≤74 years old: 68 cases, ≥75 years old: 38 cases). The improvement rate of BP was 72.6%, and the insertion time and pain score also improved. A performance status of 1 or 2 was associated with poor BP. SBMs (times/week) increased from 4.0 ± 1.9 to 6.1 ± 2.6 (p < 0.001). The overall improvement rates of SBMs, stool consistency, symptoms of constipation, and rate of adverse events were 58.5%, 90.6%, 59.4%, and 6.6%, respectively, showing no significant differences with regard to age or gender. Conclusions. Short-duration PEG+E was effective for improving poor BP and chronic constipation. [ABSTRACT FROM AUTHOR]

Backgrounds and Aims. Elobixibat is a bile acid transporter inhibitor indicated for constipation. Previous studies were performed mainly for the nonelderly and were biased to female. We analyzed the efficacy of elobixibat also for the elderly and male. Materials and Methods. This was a multicenter retrospective cohort study. The subjects were patients aged ≥20 years treated for chronic constipation from May 2018 to November 2019 at 12 related institutions. Patients were divided into ≤74 years and ≥75 years old. Elobixibat at 10 mg/day was prescribed for two weeks. We then analyzed the discontinuation due to ineffectiveness, change of spontaneous bowel movements (SBM), stool consistency, the time until the first SBM, adverse events, and effect-related factors. Results. There were 140 cases (61 males) evaluated, with an average age of 72.1 ± 13.6 years (≤74 years: 71 cases; ≥75 years: 69 cases). The discontinuation rate was 7.9%. The SBM (times/week) increased from 2.86 to 6.08 (p < 0.001). The overall SBM improvement rate was 74.0% (≤74 years: 78.2% vs. ≥75 years: 68.9%, p = 0.31 ; male: 75.0% vs. female: 73.3%, p = 0.78). The overall improvement rate of stool consistency was 59.6% (≤74 years: 62.9%, ≥75 years: 56.1%, p = 0.42). The time until the first SBM (hours) for those ≤74 years and ≥75 years was 17.2 ± 14.3 and 11.2 ± 8.4 (p = 0.04). Adverse event rates for those ≤74 years and ≥75 years were 28.2% and 10.1% (p < 0.01). There were no significant effect-related factors for gender, age, and use of laxatives. Conclusions. Short-period elobixibat is shown to be effective also for the elderly and male. [ABSTRACT FROM AUTHOR]

Background: Clinical data regarding Helicobacter pylori ( H. pylori) infection in nonalcoholic fatty liver disease (NAFLD) are limited. The aim was to evaluate H. pylori infection in patients with NAFLD and its association with disease severity. Methods: One hundred and thirty patients with biopsy-proven NAFLD [43 with nonalcoholic fatty liver (NAFL) and 87 with nonalcoholic steatohepatitis (NASH)] were recruited for blood samples for anti- H. pylori immunoglobulin G (IgG) and standard biochemical tests were obtained after overnight fasting. Glucose tolerance was evaluated by 75-g oral glucose tolerance test. Liver biopsies were scored for NAFLD activity score (NAS), fibrosis and iron deposits. Results: H. pylori IgG seropositivity was found in 40 % of patients overall. The prevalence of NASH was significantly higher in the patients with H. pylori IgG seropositivity (81 %) than in those without (58 %, p = 0.008). Glucose intolerance was similar between the two groups. The total NAS and the grade of hepatocyte ballooning were higher in the patients with H. pylori IgG seropositivity than in those without, while the hepatic iron grade was lower in the patients with H. pylori IgG seropositivity than in those without. H. pylori infection ( p = 0.030), female gender ( p = 0.029), and NAFIC score ≥ 2 points ( p < 0.001) could independently predict NASH in logistic regression analysis, independent of age, obesity and glucose tolerance. Conclusion: The association of H. pylori seropositivity with hepatocyte ballooning suggests that H. pylori infection may represent another contributing factor in the progression from NAFL to NASH. Eradicating H. pylori infection may have therapeutic prospects in NASH treatment. [ABSTRACT FROM AUTHOR]

Aim No pharmacological therapies have been established for non-alcoholic steatohepatitis ( NASH), which can lead to liver-related mortality. Human placental extract ( HPE), which has anti-inflammatory effects, has been expected to be a promising treatment for chronic liver disease. This pilot study was conducted to evaluate the efficacy of HPE for biopsy-diagnosed NASH. Methods After a lifestyle intervention for 12 weeks, 10 subjects with abnormal alanine aminotransferase (≥30 IU/L) and biopsy-proven NASH (Non-Alcoholic Fatty Liver Disease Activity Score [ NAS], ≥4) received i.m. injections of HPE (Laennec) at a dose of 4 mL/day twice per week for 24 weeks, and seven of them underwent a second liver biopsy after the treatment. Liver biopsies were scored for NAS and fibrosis. Histological response was defined as a decrease of 2 points or more in NAS and no increase in fibrosis. Results Serum transaminase activities were significantly lower at 8 weeks compared with pretreatment levels in nine patients who continued treatment for 24 weeks. One patient refused to continue the treatment soon after starting therapies. In seven patients undergoing post-treatment biopsies, NAS (mean [standard deviation]) mildly decreased from 5.29 (0.95) to 4.00 (1.83) without reaching statistical significance ( P = 0.078). Histological response was observed in all three obese patients and in only one of four non-obese ones. No significant changes were observed in body mass index, lipid profiles and diabetic control/insulin resistance. Conclusion In NASH patients who received HPE treatment, significant reductions in serum liver enzymes were obtained after 8 weeks. Histological efficacy may be better in obese patients than in non-obese ones. [ABSTRACT FROM AUTHOR]

Background and Aim The pathogenesis of non-steroidal anti-inflammatory drugs ( NSAIDs)-induced small intestinal lesions remains unclear, although it is considered to be quite different from that of upper gastrointestinal tract ulcers due to the absence of acid and the presence of bacteria and bile in the small intestine. The aim of this study was to characterize specific gene expression profiles of intestinal mucosa in indomethacin-induced small intestinal injury, and to investigate the effects of rebamipide on the expression of these genes. Methods Intestinal injury was induced in male Wistar rats by subcutaneous administration of indomethacin. Total RNA of the intestinal mucosa was extracted 24 h after indomethacin administration, gene expression was investigated using microarray analysis, and the identified genes were confirmed by real-time polymerase chain reaction ( PCR). In addition, we investigated whether the treatment with rebamipide altered the expression of these identified genes. Results The administration of indomethacin induced small intestine injuries, and these lesions were significantly inhibited by the treatment with rebamipide. Microarray analysis showed that the genes for several matrix metalloproteinases ( MMPs) and several chemokine-related genes were significantly upregulated, and metallothionein 1a ( MT1a) was downregulated in the intestinal mucosa after administration of indomethacin. The expressions of these genes were reversed by the treatment with rebamipide. Conclusion These data suggest that MMPs, chemokines, and MT1a may play an important role in the intestinal mucosal injury induced by indomethacin. In particular, the inhibition of MMP genes and chemokine-related genes by rebamipide may be important for the therapeutic effect against NSAIDs-induced small intestinal injury. [ABSTRACT FROM AUTHOR]

Background and Aim: During catheter exchange for percutaneous endoscopic gastrostomy (PEG), endoscopic or radiological observation is widely used to confirm that the catheter is placed correctly. However, to carry out these procedures in all patients at every catheter exchange costs time and money. It is therefore important to develop a reliable and safe method, which can also be used outside the clinic, to check the exchanged catheter. We examined the usefulness and safety of intragastric observation using a small-diameter rigid telescope, which can be inserted through the catheter lumen of a PEG tube. Methods: Before and after catheter exchange, observation was carried out using the rigid telescope E02700 (external diameter: 2.7 mm; Nisco Co., Tokyo, Japan). After air insufflation by the novel air-supplying adaptor, the rigid telescope was inserted through the button catheter for observation of the fistula and gastric lumen with guidewire introduction. Next, the old gastrostomy catheter was replaced by a new one, using the guidewire technique. Subsequently, the telescope was re-inserted to check the fistula and gastric lumen. Results: With this technique, observation inside the stomach as well as inside the fistula was achieved without any complication during all 80 exchange trials in the 55 patients studied. A homemade adaptor was used effectively to convey air and water into the stomach during the observation. Conclusion: It is suggested that observation inside the stomach using a small-diameter rigid telescope at the time of gastrostomy exchange is useful and safe for checking the location of the newly fixed catheter. [ABSTRACT FROM AUTHOR]

BTB and CNC homologue 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1). This study hypothesized that Bach1 plays an important role in the indomethacin-induced apoptosis in the case of small-intestinal mucosal injury. Eight-week-old male C57BL/6 (wild-type) and homozygous Bach1-deficient C57BL/6 mice were included in this study. Mucosal injuries induced by subcutaneously administering indomethacin were evaluated macroscopically, histologically and biochemically. Indomethacin-induced injuries were improved in Bach1-deficient mice. Immunohistochemistry showed an increase in the number of HO-1-positive cells, which were mainly F4/80 positive macrophages, in Bach1-deficient mice. Indomethacin administration increased the expression of HO-1 mRNA and protein in the small intestine in Bach1-deficient mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining showed that the extent of apoptosis was suppressed in Bach1-deficent mice. In conclusion, deficiency of the Bach1 gene inhibited apoptosis and thus suppressed mucosal injury, indicating that Bach1 is a novel therapeutic target for indomethacin-induced intestinal injury. [ABSTRACT FROM AUTHOR]

The pathogenesis of enteropathy induced by non-steroidal anti-inflammatory drugs (NSAIDs) is still unclear, and there are no established treatments. Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has been associated with the development of chronic inflammatory diseases, including autoimmune diseases. To define the role of IL-17A in small intestinal injury and inflammation, we studied the effects of indomethacin administration in mice with targeted deletions of the IL-17A gene. Male C57BL/6 (wild-type) and homozygous IL-17A C57BL/6 mice were subjected to this study. Indomethacin (10 mg/kg) was subcutaneously administered to induce small-intestinal damage. Indomethacin-induced lesions in the small intestine were evaluated by measuring the injured area and by histopathology. Also assessed were myeloperoxidase (MPO) activity, as an index of neutrophil accumulation, and intestinal mRNA expression for inflammatory cytokines. The area of macroscopic ulcerative lesions, the MPO activity and the mRNA expression of inflammatory-associated chemokines, such as keratinocyte chemoattractant (KC), monocyte chemotactic protein-1 (MCP-1), and granulocyte-colony stimulating factor (G-CSF), were significantly increased in indomethacin-treated groups compared with the sham groups. The development of intestinal lesions by indomethacin was inhibited in IL-17A mice compared with wild-type mice, together with significant suppression of the increased levels of MPO activities and KC, MCP-1, and G-CSF levels. These findings demonstrate that IL-17A contributes to the development of indomethacin-induced small intestinal injury through upregulation of G-CSF, KC, and MCP-1. IL-17A might be a promising new therapeutic target to treat NSAID-induced enteritis. [ABSTRACT FROM AUTHOR]

A 75-year-old man with general malaise and appetite loss was transferred to our hospital for assessment and treatment of liver failure. Laboratory findings on admission showed anemia, and gastroduodenoscopy (GDS) revealed linear esophageal varices and tensive duodenal varices (DV) in the second portion of the duodenum. Systemic examinations did not reveal any significant lesion capable of explaining his anemia, except for DV. Balloon-occluded retrograde transvenous obliteration was carried out to prevent DV bleeding. Good pooling of sclerosant was observed using two balloon catheters. However, contrast-enhanced computed tomography after the procedure revealed no thrombosis in DV, and the patient complained of tarry stools before additional therapy. Emergent GDS revealed ruptured DV with fresh blood and erosions on the surface. Emergent endoscopic obliteration using the tissue adhesive N-butyl-2-cyanoacrylate was carried out and complete hemostasis was achieved. Although no rebleeding episodes were observed after emergent obliteration, the patient died of sepsis following spontaneous bacterial peritonitis 53 days after admission. Autopsy revealed that DV dropped out, and the deep vein was replaced by granulation tissue. No signs of thrombi were detected, except varices. This autopsy case revealed the difficulty in DV management. [ABSTRACT FROM AUTHOR]

A 68-year-old man with hemophilia A and liver cirrhosis caused by hepatitis C virus was referred to our hospital to receive prophylactic endoscopic treatment for gastroesophageal varices (GOV). He had large, tense, and winding esophageal varices (EV) with cherry red spots extending down to lesser curve, predicting the likelihood of bleeding. Esophageal endoscopic injection sclerotherapy (EIS) was performed with a total 15mL of 5% ethanolamine oleate with iopamidol (EOI). Radiographic imaging during EIS demonstrated that 5% EOI reached the afferent vein of the varices. He was administered sufficient factor VIII concentrate before and after EIS to prevent massive bleeding from the varices. Seven days after EIS, upper gastrointestinal endoscopy (UGIE) showed that the varices were eradicated almost completely. Eighteen months after EIS, the varices continued to diminish.We report a successful case of safe and effective EIS for GOV in a high-risk cirrhotic patient with hemophilia A. [ABSTRACT FROM AUTHOR]

Background/Aim: Insulin resistance and hepatic iron overload are frequently demonstrated in hepatitis C virus (HCV)-related liver diseases. We investigated the relationship between insulin resistance and hepatic iron deposition in patients with chronic HCV infection. Methods: Insulin resistance was evaluated using the homeostasis model assessments for insulin resistance (HOMA-IR) in 56 non-diabetic non-obese patients with biopsy proven chronic hepatitis C. The relationship between insulin resistance and serum ferritin levels or the grade of hepatic iron deposition was assessed. Results: The levels of plasma immunoreactive insulin (IRI) and HOMA-IR were significantly correlated with serum ferritin levels and the grade of hepatic iron deposition ( P = 0.003).Although IRI and HOMA-IR increased in parallel with the development of hepatic fibrosis, insulin resistance (HOMA-IR > 2) was observed in 11 (26.2%) of 42 patients even without severe fibrosis (F0–2). Among patients without severe fibrosis, IRI and HOMA-IR were significantly higher in patients with iron deposits than in those without iron deposits. Conclusion: Hepatic iron overload may be associated with insulin resistance in patients with chronic hepatitis C, especially in patients with mild to moderate fibrosis. [ABSTRACT FROM AUTHOR]

Aims: The present study was aimed at determining the predictors of hepatic steatosis and fibrosis in Japanese patients with chronic hepatitis C. Methods: The relationship between the degrees of hepatic steatosis or fibrosis and several clinical parameters was evaluated using univariate and multivariate analyses. Results: Steatosis was observed in 117 out of 184 patients (64%), including 45 patients (25%) with grade 1 (<10% of hepatocytes affected), 56 patients (30%) with grade 2 (10–30%), 12 patients (7%) with grade 3 (30–50%), and four patients (2%) with grade 4 (>50%). In the multivariate analysis, body mass index (BMI) ( P = 0.0038) and serum ferritin ( P < 0.0001) were selected as independent predictors of hepatic steatosis. Six of the 184 patients (3%) had stage 0 fibrosis (no fibrosis), 87 patients (47%) had stage 1, 55 patients (30%) had stage 2 and 36 patients (20%) had stage 3. In the multivariate analysis, platelet count ( P = 0.0012), aspartate aminotransferase (AST) ( P = 0.0219), hyaluronic acid ( P < 0.0001) and the grade of steatosis ( P = 0.0008) were selected as independent predictors of hepatic fibrosis. Conclusion: Obesity and iron storage, as evaluated by BMI and serum ferritin level, respectively, have important roles in the pathogenesis of hepatic steatosis, which is a factor responsible for the development of hepatic fibrosis in Japanese patients with chronic hepatitis C. [ABSTRACT FROM AUTHOR]

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Abstract: Increased hepatic iron deposition may play a role in the pathogenesis of nonalcoholic steatohepatitis (NASH). This study aimed to test whether iron removal by phlebotomy improves serum transaminase activities in patients with NASH. Eleven patients (six males and five females) with biopsy-proven NASH underwent phlebotomy biweekly until they reached near-iron deficiency (NID) (serum ferritin concentration lower than or equal to 30ng/ml). Nine patients completed this study. Serum ferritin levels in these patients fell from 563±322 to 18±9ng/ml (p =0.001). The treatment reduced mean serum alanine aminotransferase (ALT) activity from 126±47 to 56±17IU/l (p =0.002). Their weight did not change significantly throughout the study period. Although two patients withdrew from the study, none was affected by any side effects of repeated phlebotomy that required discontinuing the treatment. In conclusion, this pilot study suggests that iron reduction therapy by phlebotomy will be one of the promising therapies for NASH. [Copyright &y& Elsevier]