Pharyngeal Residues Following Swallowing of Pureed Diets Thickened with a Gelling Agent or a Xanthan Gum-Based Thickener in Elderly Patients with Dysphagia.

The ideal texture of pureed diets to prevent aspiration pneumonia remains unclear. The aim of this study was to evaluate the effectiveness of a pureed diet with either a gelling agent or a xanthan gum-based thickener to prevent pharyngeal residues in patients with dysphagia. We retrospectively analyzed a randomized, crossover trial of pureed rice with either a gelling agent or a xanthan gum-based thickener in patients with dysphagia. The enrolled patients were classified into mild and moderate-to-severe dysphagia groups. The primary outcome measure was degree of need for cyclic ingestion using test jelly for pharyngeal residuals (cyclic ingestion score). The secondary outcome was the patient's sense of material remaining in the throat following swallowing. Sixty-two patients (58% men; mean age 83 ± 9 years) with dysphagia were included. They were classified into mild dysphagia (n = 26) and moderate-to-severe dysphagia (n = 36) groups. In the moderate-to-severe dysphagia group, pharyngeal residuals were significantly less likely with pureed diets using a gelling agent than with those using a xanthan gum-based thickener, with respective median cyclic ingestion scores (range) of 1 (0-4) vs. 2.5 (0-4) (p = 0.001). There was no significant difference in pharyngeal residuals between the pureed diets in the mild dysphagia group. The multivariate analysis identified gelling agent as an important factor significantly associated with less pharyngeal residual after swallowing of pureed diet in patients with moderate-to-severe dysphagia. Pureed diets thickened by a gelling agent decrease pharyngeal residues in patients with moderate-to-severe dysphagia and may reduce risk of aspiration pneumonia.

A 2-week intensive gastrointestinal endoscopy training program for pediatricians.

BACKGROUND: In Japan there are limited opportunities for pediatricians to learn gastrointestinal (GI) endoscopy. This study investigated whether a short-term intensive training for 2 weeks in an adult GI setting enabled pediatricians to acquire basic technical competence for pediatric GI endoscopic procedures. METHODS: This was a retrospective case series of pediatricians who underwent 2 weeks of intensive endoscopy training at an adult endoscopy unit in a community hospital. The numbers of esophagogastroduodenoscopy (EGD) and ileocolonoscopy procedures each pediatrician performed were evaluated. All enrolled pediatricians were asked to answer questionnaires regarding the 2 week intensive GI endoscopy training program. RESULTS: There were 17 enrolled pediatricians, of whom 13 were men; average age 32 years (range 27-54). The median (range) numbers of EGDs and ileocolonoscopies performed by each pediatrician during the 2-week training period were 102 (66-144) and 14 (1-48), respectively. Fifteen out of 17 pediatricians experienced more than 100 GI endoscopies during the 2 weeks. All pediatricians performed biopsies as part of some EGD procedures. All 17 pediatricians found this program satisfactory. All pediatricians became cable of performing pediatric EGD (i.e., for children ≤15 years) after this training program. Sixteen pediatricians have continued to perform pediatric GI endoscopy since this training program. CONCLUSIONS: A short-term intensive training program for 2 weeks in an adult GI setting enabled pediatricians to acquire basic technical competence for pediatric endoscopic procedures.

Managing bleeding risk after cold snare polypectomy in patients receiving direct-acting oral anticoagulants.

BACKGROUND AND AIMS: The best strategy to manage direct-acting oral anticoagulants (DOACs) for patients undergoing cold snare polypectomy remains unclear. This study compared the effect of continuing versus stopping DOACs only on the day of the procedure on bleeding after cold snare polypectomy. METHODS: This prospective, observational, single-center cohort study enrolled consecutive patients receiving antithrombotic agents and undergoing cold snare polypectomy of colorectal polyps ≤10 mm in diameter. During period 1 (2017 and 2018) antithrombotic agents including DOACs were not discontinued (DOAC continued group). In period 2 (2019 and 2020) DOACs were withheld only on the day of the procedure (DOAC withheld group) and restarted the next day after the procedure. The primary outcome was delayed bleeding requiring endoscopic treatment occurring within 2 weeks after cold snare polypectomy. Secondary outcomes were immediate bleeding and the number of hemostatic clips used. RESULTS: For the 2 groups, 204 (DOAC continued group; 34% women; mean age, 75 years) and 264 (DOAC withheld group; 36% women; mean age, 74 years) patients were enrolled. Clinical features were similar between the 2 groups. Delayed bleeding after cold snare polypectomy occurred in 4 of 47 patients (8.5%) in the DOAC continued group versus 0 of 66 (0%) in the DOAC withheld group (P < .001). Immediate postpolypectomy bleeding occurred in 12 of 47 patients (25.5%) in the DOAC continued group versus 4 of 66 (6.1%) in the DOAC withheld group (P < .008). CONCLUSIONS: Cold snare polypectomy may be safely preformed if DOACs are withheld only on the day of the procedure. (Clinical trial registration number: NCT02594813.).

Effectiveness of Water Jelly Ingestion for Both Rehabilitation and Prevention of Aspiration Pneumonia in Elderly Patients With Moderate to Severe Dysphagia.

BACKGROUND AND AIMS: We evaluated the effectiveness of water jelly ingestion for both rehabilitation and the prevention of aspiration pneumonia in a retrospective analysis of elderly patients with moderate to severe dysphagia. PATIENTS AND METHODS: Study 1: consecutive patients with borderline ingestion in an endoscopic swallowing evaluation were enrolled (n=36, 18 men and 18 women: mean age 82±9 y) and categorized into a group with water jelly (50 to 100 mL) ingestion training 3×/day or an untrained control group. Their food intake levels were then compared using a Food Intake Level Scale. Study 2: consecutive patients who were hospitalized because of aspiration pneumonia were enrolled (n=64, 35 men and 29 women: mean age 81±9 y) and categorized into a group with cyclic ingestion of water jelly immediately after each meal or a control group. The incidence of aspiration pneumonia that was newly developed during hospitalization was compared between the groups. RESULTS: In study 1, 36 patients with a Hyodo-Komagane score of 8 were enrolled. Three of the 12 (25%) patients who underwent water jelly ingestion training were able to eat a pureed diet (level 5, 2 patients; level 6, 1 patient) while none of the 24 patients (0%) who did not undergo this training were able to eat any form of diet (levels 5 and 6, no patients) (P=0.011). In study 2, 64 patients were enrolled. No newly developed aspiration pneumonia was observed in the 34 patients (0%) who received cyclic water jelly ingestion, whereas 17% (5/30) of patients not receiving water jelly after meals newly developed aspiration pneumonia during hospitalization (P=0.031). CONCLUSIONS: Water jelly ingestion was effective for both rehabilitation and the prevention of aspiration pneumonia in elderly patients with moderate to severe dysphagia.

Short-term intensive gastrointestinal endoscopy training program.

BACKGROUND: In Japan there are limited opportunities for pediatric gastrointestinal (GI) trainees to learn GI endoscopy. This study investigated whether a short-term intensive training for 3 months in an adult GI unit enabled pediatric GI trainees to acquire the required number of cases and the technical competence to perform pediatric GI endoscopic procedures. METHODS: This was a retrospective case series of pediatric GI trainees who underwent 3 months of intensive endoscopy training, which also included direct observation and a questionnaire. The numbers of esophagogastroduodenoscopies (EGD), ileocolonoscopies, and snare polypectomies each trainee performed as well as cecal intubation rates were collected with the goal of meeting the standards of overseas educational guidelines. The trainees were also asked about continuing experience with pediatric endoscopic procedures after the intensive training. RESULTS: There were 10 enrolled trainees, 9 men, average age, 34 (range, 29-41). The average number (range) of EGD and ileocolonoscopies that the 10 trainees had done before this training period was 52 (0-200) and 15 (0-20), respectively. The average number (range) of EGD, ileocolonoscopies and snare polypectomies per each trainee was 651.7 (485-814), 159.2 (130-195) and 25.8 (10-55), respectively, over 3 months: all trainees thus fulfilled all of the criteria of the minimal training requirements. All trainees also reached the required threshold in the cecal intubation rate (>90%). In addition, all trainees were able to perform pediatric endoscopic procedures alone after the intensive training period. CONCLUSIONS: Short-term intensive training for 3 months in an adult GI setting enabled pediatric GI trainees to acquire technical competence for pediatric endoscopic procedures.

Linked colour imaging versus white-light colonoscopy for the detection of flat colorectal lesions: A randomized controlled trial.

AIM: Linked colour imaging is an image-enhanced endoscopy system that emphasizes the red portion of the mucosa's colour. Our aim was to compare the effectiveness of linked colour imaging with white-light colonoscopy for the detection of flat-type colorectal polyps. METHOD: This was a single-centre, randomized controlled trial. Enrolled patients were those aged ≥50 years undergoing cap-assisted colonoscopy for colorectal cancer screening. They were randomized in a 1:1 ratio for observation using linked colour imaging or white-light colonoscopy. All colorectal polyps detected were removed or biopsied. The primary outcome was the number of flat-type polyps per patient in patients in whom flat polyps were detected. Secondary outcomes included adenoma and polyp detection rates. RESULTS: There were 302 subjects randomized: 152 to linked colour imaging and 150 to white-light colonoscopy. There were no differences in the clinical features between the two arms. The number of flat polyps detected per patient using linked colour imaging was approximately twice that with white light (2.9 ± 3.0 vs 1.2 ± 1.6, p = 0.045). Linked colour imaging also proved superior to white-light colonoscopy in terms of adenoma and polyp detection rates [adenomas 66% (101/152) vs 49% (73/150), p = 0.0024; polyps 69% (105/152) vs 55% (82/150), p = 0.013]. The ratio of polyps detected in the right colon compared with those detected in the left colon was significantly greater using linked colour than white-light imaging (168/64 vs 93/84; p < 0.001). CONCLUSION: Compared with white-light colonoscopy, linked colour imaging improved adenoma and polyp detection rates, including detection of flat-type colorectal polyps.

Risk of Gastrointestinal Endoscopic Procedure-Related Bleeding in Patients With or Without Continued Antithrombotic Therapy.

BACKGROUND: Prospective studies on bleeding risk during/after gastrointestinal endoscopic procedures are rare. AIM: We investigated the risk of endoscopic procedure-related bleeding in patients with biopsy and/or cold snare polypectomy (CSP) in relation to antithrombotic therapy. METHODS: This prospective, observational single-center cohort study (NCT02594813) enrolled consecutive patients who underwent diagnostic esophagogastroduodenoscopy (EGD) or colonoscopy. The primary outcome measure was delayed bleeding in patients with biopsy and/or CSP who required endoscopic treatment within 2 weeks post-procedure. The secondary outcomes were immediate bleeding and the number of hemostatic clips used during the procedure. RESULTS: From November 2015 to October 2018 at our institution, 3069 (mean age, 66 years) and 37,887 (57 years) patients underwent EGD with and without antithrombotic therapy, respectively. In addition, 1116 (72 years) and 11,901 (65 years) patients had colonoscopy with and without antithrombotic therapy, respectively. In the 3069 EGD patients receiving antithrombotic therapy, no delayed bleeding occurred, whereas immediate bleeding occurred in 9 of 141 patients (6.4%) with biopsy. Of the 1116 colonoscopy patients receiving antithrombotic therapy, delayed bleeding occurred in three of 228 (1.3%) following CSP. Immediate bleeding occurred in nine of 225 (4%) following biopsy and in 32 of 228 (14%) following CSP. Multivariate analysis following univariate analysis identified chronic kidney disease and CSP as factors significantly associated with procedure-related bleeding in patients taking antithrombotic agents. CONCLUSION: The risk of delayed bleeding in diagnostic EGD with biopsy or in colonoscopy with biopsy and/or CSP was low despite continuation of antithrombotic therapy.

Trends in gastroesophageal reflux disease in Japanese children and adolescents.

BACKGROUND: Although the prevalence of gastroesophageal reflux disease (GERD) has been increasing in Japan, little is known about the prevalence and severity of GERD in pediatric patients. This study compared the prevalence and severity of endoscopically proven GERD in pediatric patients seen at an endoscopy center in Japan over a 15-year period. METHODS: This was a retrospective chart review of Japanese children aged 5-18 years undergoing esophagogastroduodenoscopy for upper gastrointestinal symptoms or anemia between 2005 and 2019. The prevalence and severity of reflux esophagitis and endoscopic Barrett's esophagus were compared between the periods 2005-2012 and 2013-2019. RESULTS: A total of 564 patients were evaluated: 315 from 2005 to 2012 (mean ± SD) age 13.8 ± 3.0 (range, 5-18 years; 147 boys; and 249 from 2013 to 2019 (mean ± SD) 14.7 ± 2.8 (range, 5-18) years; 108 boys. Demographics and clinical features were similar between the two groups. The proportion with erosive esophagitis or endoscopic Barrett's esophagus increased significantly between the two periods (9.8% to 18.1% for GERD, P = 0.0045 and 2.5% to 9.6% for Barrett's esophagus, P = 0.0003). The proportion of GERD patients with endoscopic Barrett's esophagus also significantly increased between the two periods (24/45 [53.3%]) vs (8/31 [25.8%]), P = 0.017]. CONCLUSION: The prevalence and severity of endoscopically proven GERDs has significantly increased over the past 15 years at an endoscopy center in Japan. Detailed population-based studies are needed to assess whether this is occurring throughout Japan.

Synergistic biofilm formation by Parvimonas micra and Fusobacterium nucleatum.

Parvimonas micra is frequently isolated from lesions of apical periodontitis and is a major disease-related pathogen. One of the main causes of apical periodontitis is extraradicular biofilm. In this study, we investigated polymicrobial biofilm formation by P. micra and species associated with apical periodontitis. The coaggregation activity of P. micra with partner strains was investigated by visual assays. Synergistic biofilm formation was evaluated by cocultures of P. micra and partner strains. Growth of planktonic cells was measured by evaluating the absorbance at OD660, and biofilm formation was examined by staining with crystal violet. The effects of soluble components on synergistic biofilm formation and planktonic cell growth were examined after coculture of P. micra and other strains separated with a 0.4-µm pore-size porous membrane. P. micra coaggregated with Fusobacterium nucleatum, Porphyromonas gingivalis, or Capnoctyophaga ochracea. P. micra showed no coaggregation with Staphylococcus aureus, S. epidermidis, or Prevotella intermedia. In mixed cultures, biofilm formation by P. micra and F. nucleatum was greater than that by P. micra and P. gingivalis or C. ochracea. In separated cocultures, planktonic cell growth of P. micra was enhanced by each of the three species. Biofilm formation by P. micra was enhanced by F. nucleatum or C. ochracea; however, no significant enhancement was observed with P. gingivalis. These data indicated that P. micra and F. nucleatum had synergistic effects in biofilm formation and that these effects may be important for colonization by these two species in apical periodontitis lesions.

Safety and Effectiveness of Nurse-Administered Propofol Sedation in Outpatients Undergoing Gastrointestinal Endoscopy.

BACKGROUND & AIMS: Esophagogastroduodenoscopy (EGD) and colonoscopy are common outpatient gastrointestinal endoscopic procedures that frequently use sedation. We aimed to identify a protocol that combines safety with cost effectiveness. METHODS: We collected data from consecutive outpatients (age, 20-98 y) who underwent diagnostic EGD (n = 117,661) or colonoscopy (n = 32,550) with propofol sedation from January 2006 through December 2016. Propofol was administered by a nurse via bolus injection using an age-adjusted standard protocol, up to a total of 200 mg. The primary outcome measure was occurrence of adverse events within 24 hours. Secondary outcome measures included rates of procedure success, respiratory depression, and other procedure-related adverse events. RESULTS: The median dose of propofol administered for EGD was 77 mg (range, 20-160 mg) and for colonoscopy was 99 mg (range, 40-200 mg). Among patients undergoing EGD, those younger than 41 years required 1.5-fold more propofol than patients 61-80 years old. The only adverse event was the transient need for supplemental oxygen supply, required by 1950 patients (1.3%): 1689 undergoing EGD (1.4%) and 261 undergoing colonoscopy (0.8%). Patients were discharged after 60 minutes and at least 66,250 patients (44%) drove themselves from the hospital. None experienced a traffic accident within 24 hours after receiving propofol sedation. CONCLUSIONS: Nurse-administered propofol monosedation using an age-adjusted standard protocol up to a maximal of 200 mg is safe and practical for outpatient gastrointestinal endoscopy.

Gastric Emptying of Elemental Liquid Diets Versus Semisolid Diets in Bedridden Gastrostomy-fed Patients.

BACKGROUND: Aspiration is a common problem in bedridden gastrostomy-fed patients. We compared gastric emptying of an elemental liquid diet and a commercial semisolid diet in bedridden gastrostomy-fed patients. METHODS: Study 1: from January 2013 to December 2016, consecutive bedridden patients receiving percutaneous endoscopic gastrostomy (PEG) semisolid feeding hospitalized due to aspiration pneumonia were switched to elemental liquid diet feedings. The frequency of defecation, tube feed contents aspirated from the trachea, and aspiration pneumonia during hospitalization were retrospectively reviewed. Study 2 was a randomized, crossover trial comparing C sodium acetate gastric emptying of a commercial elemental liquid or a commercial semisolid diet in bedridden PEG patients and controls. RESULTS: Study 1: 18 patients were enrolled. Elemental liquid diet was aspirated from the trachea in 1 (5.6%) (once in 24 observations); neither aspiration pneumonia nor diarrhea developed during elemental liquid diet feeding over 2 weeks observation. Study 2: 8 PEG patients and 8 healthy subjects were separately randomized to assess gastric emptying of the commercial elemental and semisolid diets. The elemental liquid diet was associated with a significant decrease of the 10%, 30%, or 50% emptying (excretion) time (P<0.05) and an increased the area under the curve (% dose/h) compared with the commercial semisolid diet (P<0.05). In healthy subjects there was no significant difference in gastric empting between the 2 diets. CONCLUSIONS: Elemental liquid diets emptied more rapidly from the stomach than semisolid diets in bedridden PEG patients. They may prevent or reduce aspiration pneumonia compared with semisolid diets.

Cold snare polypectomy: Indications, devices, techniques, outcomes and future.

Colonoscopy has been shown to reduce the risk of colon cancer by enabling the removal of precancerous lesions. Although cold snare and hot snare polypectomy have similar retrieval rates and complete resection rates, rates of delayed bleeding tend to be lower with cold snare polypectomy than with hot snare polypectomy, especially for patients taking antithrombotic agents. However, among cold snares there may be differences in terms of the completeness of polyp excision, as complete removal appears more likely with thin-wire dedicated cold snares compared to the traditional, thick-wire cold snares. Cold snare polypectomy may be especially well suited for use in patients taking antithrombotic agents, due to its minimal risk of delayed bleeding. Histological analyses suggest that cold snare polypectomy causes less damage to blood vessels in the submucosal layers, which results in a reduced incidence of hemorrhage compared to hot snare polypectomy. However, cold snare removal of small polyps may result in fragmentation of small specimens during collection and concerns as to whether the resection is complete. An endoscopy biomarker of effective cold snare polypectomy technique is needed to ensure complete removal of non-pedunculated colorectal polyps ≤10 mm. Future uses of cold snare polypectomy may include piecemeal removal of sessile serrated adenoma/polyp lesions >10 mm. Currently, cold snare polypectomy should be considered a primary method for colorectal polyps of less than 10 mm, especially those in the 4- to 10-mm range.

Delayed Bleeding Following Cold Snare Polypectomy for Small Colorectal Polyps in Patients Taking Antithrombotic Agents.

BACKGROUND: This study compared the incidence of delayed bleeding following 2 methods of cold snare polypectomy for colorectal polyps in patients taking antithrombotic agents. METHODS: Patients undergoing cold snare polypectomy for colorectal polyps ≤10 mm without discontinuation of antithrombotic agents were enrolled. This was a retrospective study of a prospectively collected cohort based on a historical comparison of 2 time periods. A traditional cold snare was used between January 2012 and December 2013 and a dedicated cold snare was used between January 2014 and December 2015. Patients' and polyps' characteristics, antithrombotic agents used, the snare used, the number of clips used, and adverse events were documented from a hospital online database. Delayed bleeding was defined as bleeding that required endoscopic treatment within 2 weeks after polypectomy. The submucosal layer of the resected polyps (6 to 10 mm) was histologically examined for the presence of injured arteries. RESULTS: A total of 172 patients having 370 eligible polyps were enrolled; traditional cold snare group, N=100 (212 polyps) and dedicated cold snare group, N=72 (158 polyps). The patients' and polyps' characteristics were similar between the 2 groups. Hemostatic clips were used more often with the traditional than dedicated cold snares [33/100 (33%) vs. 13/72 (18%), P=0.044]. Delayed bleeding following cold snare polypectomy occurred in 1.2% (2/172); 0% (0/72) with dedicated snare versus 2% (2/100) with the traditional snare (P=0.63). The presence of histologically demonstrated injured submucosal arteries with the dedicated cold snare was significantly less than with the traditional cold snare [4.1% (4/98) vs. 16% (17/105), P=0.009]. CONCLUSIONS: Colorectal polyps ≤10 mm can be removed without an increase in delayed bleeding using dedicated cold snare polypectomy in patients taking antithrombotic agents.

Miglitol attenuates non-alcoholic steatohepatitis in diabetic patients.

AIM: Postprandial hyperglycemia is frequently accompanied by non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). Although α-glucosidase inhibitors (αGIs) can slow glucose absorption from the intestine and suppress the surge of circulating glucose concentration after meals, it remains unclear whether αGIs are also beneficial for NASH. The aim of this prospective study was to examine the efficacy and safety of miglitol, a typical αGI, for NASH. METHODS: Seventeen patients with histologically confirmed NASH and hemoglobin A1c (HbA1c) >6.5% were treated with miglitol (150 mg/day) for 12 months. The changes in clinical parameters and liver histology were analyzed. RESULTS: All patients completed the 12-month miglitol treatment course with no severe adverse events. The treatment significantly decreased body mass index, serum alanine aminotransferase levels, and HbA1c (all P < 0.001). Post-treatment liver biopsy of 11 patients revealed significant improvements in steatosis (from 2.2 ± 0.6 to 1.5 ± 0.7, P = 0.001), lobular inflammation (from 1.8 ± 0.8 to 1.3 ± 0.5, P = 0.014), portal inflammation scores (from 0.6 ± 0.5 to 0.1 ± 0.3, P = 0.025), and NAFLD activity score (from 5.5 ± 1.5 to 3.9 ± 1.4, P = 0.012). Fibrosis and hepatocyte ballooning scores were unchanged. CONCLUSIONS: Miglitol appears to safely ameliorate NASH activity by attenuation of steatosis and lobular/portal inflammation. Appropriately powered controlled trials are warranted to validate our results.

Clinicopathological characteristics of non-B non-C hepatocellular carcinoma without past hepatitis B virus infection.

AIM: Past hepatitis B virus (HBV) infection is considered a risk factor for hepatocarcinogenesis, but the clinicopathological characteristics of non-B non-C hepatocellular carcinoma (NBNC-HCC) excluding past HBV infection have not been investigated. This study aimed to clarify the clinicopathological features of strictly defined NBNC-HCC. METHODS: Among HCC patients who underwent surgical resection at our affiliated hospitals in Nagano prefecture, Japan, between 1996 and 2012, 77 were negative for serum anti-HBV core/surface antibodies in addition to HBV surface antigen and anti-hepatitis C virus antibody without signs of autoimmune liver disease, Wilson disease, or hemochromatosis. These patients were divided into the alcohol intake-positive group (ethanol intake >20 g/day, n = 31), non-alcoholic fatty liver group (steatosis >5% and ethanol intake <20 g/day, n = 30), and cryptogenic group (no ethanol intake or steatosis, n = 16). Preoperative clinical parameters, tumor and background liver pathology, and prognosis were analyzed. RESULTS: Advanced fibrosis and steatosis were detected in 64% and 60% of all patients, respectively. Approximately 85% of the alcohol intake-positive patients had advanced fibrosis. Non-alcoholic fatty liver HCC subjects had the highest body mass index and prevalence of diabetes, but 30-40% had none to mild fibrosis. The cryptogenic group of HCC patients had the lowest incidence of accompanying hepatic inflammation/fibrosis but the largest tumor size. Recurrence/survival rates were comparable among the groups. CONCLUSIONS: Liver fibrosis and steatosis are risk factors of HCC regardless of past HBV infection and ethanol consumption. The present results also indicate the possibility of hepatocarcinogenesis independent of hepatic steatosis, inflammation and fibrosis, ethanol intake, and past HBV infection.

Steatogenesis in adult-onset type II citrullinemia is associated with down-regulation of PPARα.

SLC25A13 (citrin or aspartate-glutamate carrier 2) is located in the mitochondrial membrane in the liver and its genetic deficiency causes adult-onset type II citrullinemia (CTLN2). CTLN2 is one of the urea cycle disorders characterized by sudden-onset hyperammonemia due to reduced argininosuccinate synthase activity. This disorder is frequently accompanied with hepatosteatosis in the absence of obesity and ethanol consumption. However, the precise mechanism of steatogenesis remains unclear. The expression of genes associated with fatty acid (FA) and triglyceride (TG) metabolism was examined using liver samples obtained from 16 CTLN2 patients and compared with 7 healthy individuals. Although expression of hepatic genes associated with lipogenesis and TG hydrolysis was not changed, the mRNAs encoding enzymes/proteins involved in FA oxidation (carnitine palmitoyl-CoA transferase 1α, medium- and very-long-chain acyl-CoA dehydrogenases, and acyl-CoA oxidase 1), very-low-density lipoprotein secretion (microsomal TG transfer protein), and FA transport (CD36 and FA-binding protein 1), were markedly suppressed in CTLN2 patients. Serum concentrations of ketone bodies were also decreased in these patients, suggesting reduced mitochondrial ß-oxidation activity. Consistent with these findings, the expression of peroxisome proliferator-activated receptor α (PPARα), a master regulator of hepatic lipid metabolism, was significantly down-regulated. Hepatic PPARα expression was inversely correlated with severity of steatosis and circulating ammonia and citrulline levels. Additionally, phosphorylation of c-Jun-N-terminal kinase was enhanced in CTLN2 livers, which was likely associated with lower hepatic PPARα. Collectively, down-regulation of PPARα is associated with steatogenesis in CTLN2 patients. These findings provide a novel link between urea cycle disorder, lipid metabolism, and PPARα.

Comparison between endoscopic mucosal resection and hot snare resection of large nonpedunculated colorectal polyps: a randomized trial.

BACKGROUND AND STUDY AIMS: It is unclear whether endoscopic mucosal resection (EMR) or hot snare resection is better for resecting large nonpedunculated polyps. The aim of this study was to determine a cutoff size of nonpedunculated neoplastic colorectal polyps at which the risk of incomplete resection differed between EMR and hot snare resection. PATIENTS AND METHODS: Patients with nonpedunculated neoplastic polyps (10 - 25 mm in diameter) were randomly assigned to undergo endoscopic resection using EMR (52 patients with 63 polyps) or hot snare resection (52 patients with 62 polyps). EMR included submucosal injection of saline before resection. The primary outcome measure was the proportion with complete polyp resection determined by histopathology. The secondary outcome was total procedure time. RESULTS: Patient characteristics were similar between groups. EMR achieved complete resection more frequently than hot snare resection (89 % vs. 73 %; P = 0.02), particularly for polyps ≥ 20 mm (75 % [9 /12] vs. 18 % [2 /11]; P = 0.006). A complete resection rate of > 90 % was achieved for polyps of size < 19 mm with EMR, and for polyps of size ≤ 14 mm with hot snare resection. In multivariate analysis, incomplete resection was associated with hot snare resection (odds ratio [OR] 2.8, 95 % confidence interval (95 %CI) 1.0 - 8.3; P = 0.04) and polyp size ≥ 15 mm (OR 4.0, 95 %CI 1.3 - 14; P = 0.01). Total procedure time was shorter with hot snare resection than with EMR (mean 14.8 min vs. 17.2 min; P < 0.001). CONCLUSIONS: EMR and hot snare resection appear to achieve similar complete resection rates for polyps up to 14 mm; however, EMR may be superior for larger polyps, particularly for those ≥ 20 mm.Registered at Clinicaltrials.gov: NCT 01950117.

Impact of aging and comorbidity on the efficacy of low-intensity shock wave therapy for erectile dysfunction.

OBJECTIVES: To evaluate the efficacy of low-intensity shock wave therapy and to identify the predictive factors of its efficacy in Japanese patients with erectile dysfunction. METHODS: The present study included 57 patients with erectile dysfunction who satisfied all the following conditions: more than 6-months history of erectile dysfunction, sexual health inventory for men score of ≤ 12 without phosphodiesterase type-5 inhibitor, erection hardness score grade 1 or 2, mean penile circumferential change by erectometer assessing sleep related erection of < 25 mm and non-neurological pathology. Patients were treated by a low-energy shock waves generator (ED1000; Medispec, Gaithersburg, MD, USA). A total of 12 shock wave treatments were applied. Sexual health inventory for men score, erection hardness score with or without phosphodiesterase type-5 inhibitor, and mean penile circumferential change were assessed at baseline, 1, 3 and 6 months after the termination of low-intensity shock wave therapy. RESULTS: Of 57 patients who were assigned for the low-intensity shock wave therapy trial, 56 patients were analyzed. Patients had a median age of 64 years. The sexual health inventory for men and erection hardness score (with and without phosphodiesterase type-5 inhibitor) were significantly increased (P < 0.001) at each time-point. The mean penile circumferential change was also increased from 13.1 to 20.2 mm after low-intensity shock wave therapy (P < 0.001). In the multivariate analysis, age and the number of concomitant comorbidities were statistically significant predictors for the efficacy. CONCLUSIONS: Low-intensity shock wave therapy seems to be an effective physical therapy for erectile dysfunction. Age and comorbidities are negative predictive factors of therapeutic response.

Prospective, randomized comparison of 2 methods of cold snare polypectomy for small colorectal polyps.

BACKGROUND: Both cold-only snare and hot polypectomy snare are used for the removal of small colorectal polyps. OBJECTIVE: To compare the outcome of cold snare polypectomy of small colorectal polyps with a snare exclusively designed as a cold snare versus cold snare polypectomy by using a traditional polypectomy snare. DESIGN: Prospective, randomized, controlled study. SETTING: Municipal hospital in Japan. INTERVENTIONS: Patients with colorectal polyps 10 mm or smaller in diameter were randomized to dedicated cold snare (dedicated cold snare group) or traditional cold snare (traditional cold snare group). The primary outcome measure was complete resection rates by cold snaring based on pathological examination. Secondary outcomes included bleeding within 2 weeks after polypectomy and identification of submucosal arteries and injured arteries in the resected specimens. RESULTS: Seventy-six patients having 210 eligible polyps were randomized: dedicated cold snare group, N = 37 (98 polyps) and traditional cold snare group, N = 39 (112 polyps). Patient demographic characteristics including the number, size, and shape of the polyps removed were similar in the 2 groups. The complete resection rate was significantly greater with the dedicated cold than with the traditional cold snare (91% [89/98] vs 79% [88/112], P = .015), with a marked difference with 8- to 10-mm polyps, both flat and pedunculated. Immediate bleeding and hematochezia rates were similar (19% vs 21%, P = .86; 5.4% vs 7.7%, P = .69). No delayed bleeding occurred. Histology demonstrated a similar prevalence of arteries and injured arteries in the submucosa (33% [32/96] vs 30% [31/104], P = .59; 3.1% [3/96] vs 6.7% [7/104], P = .24). LIMITATIONS: Small sample size, single-center study. CONCLUSION: Polypectomy by using a dedicated cold snare resulted in complete polyp removal more often than did cold snaring with a traditional snare, especially polyps 8 to 10 mm in diameter, whether flat or pedunculated. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT02036047.)