Bleeding Risk of Cold Versus Hot Snare Polypectomy for Pedunculated Colorectal Polyps Measuring 10 mm or Less: Subgroup Analysis of a Large Randomized Controlled Trial.

INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm.

Longitudinal economic burden of incident complications among metabolic syndrome populations.

BACKGROUND: This study quantifies the longitudinal economic burden for a wide spectrum of incident complications, metabolic syndrome (MS)-related risk factors, and comorbidities in patients with MS. METHODS: This retrospective study utilized linked data from the 2013 National Health Interview Survey and the 2012-2021 National Health Insurance Research Database to identify MS individuals and their characteristics. The incidence rate of each complication was calculated as the number of complication events in the study period divided by the total person-years during follow-up. The healthcare costs of complications were analyzed using a generalized estimating equation model to determine the cost impact of complications after adjustment for patients' characteristics. Sensitivity analyses on variables with high missing rates (i.e., cause of death, body mass index) were performed. RESULTS: Among 837 identified MS individuals over 8.28 (± 1.35) years of follow-up, the most frequent complications were microvascular diseases (incidence rate for nephropathy/retinopathy/neuropathy: 6.49/2.64/2.08 events per 100 person-years), followed by cardiovascular diseases (2.47), peripheral vascular diseases (2.01), and cancers (1.53). Death was the costliest event (event-year cost per person: USD 16,429) and cancers were the most expensive complications (USD 9,127-11,083 for non-MS- and MS-related cancers). Developing non-MS/MS-related cancers, cardiovascular diseases, and obesity-related medical conditions increased annual costs by 273% (95% CI: 181-397%)/175% (105-269%), 159% (118-207%), and 140% (84-214%), respectively. Microvascular diseases had the lowest cost impact on annual costs (i.e., 27% [17-39%]/27% [11-46%]/24% [11-37%] increases for nephropathy/neuropathy/retinopathy, respectively). Having existing comorbidities increased annual costs by 20% (osteoarthritis) to 108% (depression). Having morbid obesity (i.e., body mass index ≥ 35 kg/m2) increased annual costs by 58% (30-91%). CONCLUSIONS: The economic burden from costly incident complications (i.e., cardiovascular diseases, peripheral vascular diseases, cancers), MS-related risk factors (i.e., morbid obesity), and comorbidities (i.e., depression) highlight the urgent need for early intervention to prevent MS and its progression. The comprehensive cost estimates reported in this study can facilitate the parameterization of economic analyses to identify cost-effective interventions for these patients.

Prognostic Evaluation of Conversion Therapy Following Hepatic Arterial Infusion Chemotherapy or Immunotherapy in Patients with Advanced or Transarterial Chemoembolization Unsuitable Intermediate-Stage Hepatocellular Carcinoma-A retrospective cohort study.

INTRODUCTION: Patients with advanced-stage or intermediate-stage hepatocellular carcinoma (HCC) unsuitable for transarterial chemoembolization (TACE) had poor prognoses. Recent advancements in hepatic arterial infusion chemotherapy (HAIC) and immune checkpoint inhibitors (ICIs) have demonstrated higher tumor response rates, which improved overall survival (OS). HAIC achieves an OS rate of approximately 14.5-15.3 months with a 39.1-42.5% tumor response rate. In comparison, ICIs have a 12-14 month OS rate with a 26-33% tumor response rate. Given these promising responses, this study evaluates the efficacy of conversion therapy with curative intent following HAIC or ICIs, focusing on survival outcomes. METHODS: We retrospectively analyzed 80 patients with advanced or TACE-unsuitable intermediate HCC. Patients completed two HAIC or four ICI cycles, followed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria imaging. Based on demographics, cirrhosis status, Barcelona Clinic Liver Cancer classification (BCLC) stage, treatment responses, and treatment modality, survival impacts were analyzed. OS was compared between HAIC and immunotherapy groups. The effect of conversion therapy with curative intent on survival outcomes was analyzed using a Cox regression model. RESULTS: Among the 80 patients, 26 achieved positive response (CR/PR) with HAIC or ICIs, and 9 of them subsequently underwent conversion therapy with curative intent. Key prognostic factors included Child-Pugh stage B vs. A (HR=2.21, p=0.041), BCLC stage C vs. B (HR=4.38, p=0.011), and elevated AFP levels (HR=5.02, p<0.001). Positive responders saw substantial survival benefits (HR=0.26, p=0.001). Patients undergoing conversion therapy exhibited significantly enhanced survival. Median OS was 13.58 months with standard therapy, while the curative intent surgery group did not reach the median OS (p=0.002). For CR/PR patients, 48-month survival was 75.0% for the curative surgery group versus 38.0% for standard treatment. CONCLUSION: Conversion therapy with curative intent following HAIC or ICIs might enhances survival in patients with advanced or TACE-unsuitable intermediate-stage HCC.

Characteristics of Esophageal Motility and Associated Symptom Profiles in Patients with Esophageal Diverticulum: A Study Based on High-Resolution Impedance Manometry.

BACKGROUND: Esophageal diverticulum (ED) is an uncommon structural disorder with heterogenous manifestations and elusive pathophysiology. Our aim was to investigate esophageal motility and associated symptom profiles in patients with ED based on high-resolution impedance manometry (HRIM). METHODS: Consecutive patients with ED referred to our motility laboratory between 2015 to 2022 were identified in our electronic database. All patients were evaluated based on an upper endoscopy, HRIM, and standardized symptom questionnaires. Patients with ED were further stratified into upper, middle, and lower (epiphrenic) cases. Esophageal motility was evaluated with HRIM and the updated Chicago Classification v4.0. RESULTS: Twenty-four patients with ED (9 upper, 4 middle, and 11 epiphrenic) were analyzed. Patients with ED were generally older (mean: 65 ± 13.3 years) and predominantly women (58.3%). Most ED cases were unilaterally located (95.8%) and left-side predominant (62.5%). Mean symptom duration was 20 months (range: 1-120) and the most common symptoms were dysphagia (70.8%) and regurgitation (37.5%). Erosive esophagitis was noted in 16 patients (69.6%), while barium stasis was noted in 5 patients (20.8%). Fourteen patients (58.3%) were diagnosed with esophageal motility disorders using HRIM, with achalasia being the most common diagnosis (n = 5, 20.8%). Patients with epiphrenic diverticulum had significantly higher symptom scores and achalasia prevalence. CONCLUSION: Patients with ED tended to be older and was associated with a high prevalence of EMD. A multi-disciplinary evaluation, including complete anatomical and motility surveys, may help clarify the underlying pathophysiology and tailor further treatment strategies.

Cold Versus Hot Snare Polypectomy for Small Colorectal Polyps : A Pragmatic Randomized Controlled Trial.

BACKGROUND: Although cold snare polypectomy (CSP) is considered effective in reducing delayed postpolypectomy bleeding risk, direct evidence supporting its safety in the general population remains lacking. OBJECTIVE: To clarify whether CSP would reduce delayed bleeding risk after polypectomy compared with hot snare polypectomy (HSP) in the general population. DESIGN: Multicenter randomized controlled study. (ClinicalTrials.gov: NCT03373136). SETTING: 6 sites in Taiwan, July 2018 through July 2020. PARTICIPANTS: Participants aged 40 years or older with polyps of 4 to 10 mm. INTERVENTION: CSP or HSP to remove polyps of 4 to 10 mm. MEASUREMENTS: The primary outcome was the delayed bleeding rate within 14 days after polypectomy. Severe bleeding was defined as a decrease in hemoglobin concentration of 20 g/L or more, requiring transfusion or hemostasis. Secondary outcomes included mean polypectomy time, successful tissue retrieval, en bloc resection, complete histologic resection, and emergency service visits. RESULTS: A total of 4270 participants were randomly assigned (2137 to CSP and 2133 to HSP). Eight patients (0.4%) in the CSP group and 31 (1.5%) in the HSP group had delayed bleeding (risk difference, -1.1% [95% CI, -1.7% to -0.5%]). Severe delayed bleeding was also lower in the CSP group (1 [0.05%] vs. 8 [0.4%] events; risk difference, -0.3% [CI, -0.6% to -0.05%]). Mean polypectomy time (119.0 vs. 162.9 seconds; difference in mean, -44.0 seconds [CI, -53.1 to -34.9 seconds]) was shorter in the CSP group, although successful tissue retrieval, en bloc resection, and complete histologic resection did not differ. The CSP group had fewer emergency service visits than the HSP group (4 [0.2%] vs. 13 [0.6%] visits; risk difference, -0.4% [CI, -0.8% to -0.04%]). LIMITATION: An open-label, single-blind trial. CONCLUSION: Compared with HSP, CSP for small colorectal polyps significantly reduces the risk for delayed postpolypectomy bleeding, including severe events. PRIMARY FUNDING SOURCE: Boston Scientific Corporation.

Positive and negative impact of anti-reflux mucosal intervention on gastroesophageal reflux disease.

BACKGROUND: Anti-reflux mucosal intervention (ARMI), including anti-reflux mucosectomy (ARMS) and anti-reflux mucosal ablation (ARMA), is a promising endoscopic treatment for gastroesophageal reflux disease (GERD). Few studies reported a detailed analysis of the objective reflux parameters. METHODS: Patients with chronic PPI-dependent GERD and receiving ARMI were prospectively enrolled. Comprehensive clinical symptom profiles, endoscopy results, and 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring were collected and analyzed before and 3 months after ARMI. RESULTS: Twenty-three patients undergoing ARMI (11 ARMS and 12 ARMA) were enrolled. The median (IQR) operative time and post-procedure stays were 50 (46-56) min and 2 (2-2) days without major complications. 73.9% of patients reported subjective global improvement. A significant decrease in the total reflux symptom index score was noted from 12 (5-19) to 8 (4-12) (P = 0.010). The esophageal acid exposure time (AET) significantly decreased from 4.6 (2.8-6.9) to 2.1 (1.1-5.6) (P = 0.013), and the number of acid refluxes and DeMeester score were significantly reduced. Three patients (13%) had increased AET (3.4% to 6.1%, 6.3% to 15.4%, and 3.2% to 5.6%); however, all reported global improvement and two patients could discontinue PPI subjectively. One patient (4.3%) had worsened erosive esophagitis and reflux symptoms. 56.5% of patients stopped PPI. CONCLUSIONS: ARMI is generally effective and safe in PPI-dependent patients. However, possible negative effects of ARMI exist in some patients; further application of MII-pH is necessitated to evaluate the treatment response after ARMI and avoid the detrimental effect of PPI discontinuation. Graph.

Novel Colorectal Endoscopic Submucosal Dissection With Double-Endoscope and Snare-Based Traction.

BACKGROUND: Colorectal endoscopic submucosal dissection is technically demanding, and the traction offered by gravity, cap, or clip-with-line during conventional endoscopic submucosal dissection remains unsatisfactory. Robotic systems are still under development and are expensive. We proposed double-scope endoscopic submucosal dissection with strong and adjustable traction offered by snaring the lesion with additional scope. OBJECTIVE: This study aimed to test the novel double-scope endoscopic submucosal dissection with snare-based traction. DESIGN: This was a retrospective study that reviewed double-scope endoscopic submucosal dissection compared with matched conventional endoscopic submucosal dissection, and size, location, morphology, and pathology between groups were compared. SETTINGS: This study was conducted in a referral endoscopy center in a local hospital. PATIENTS: This study included patients with colorectal lesions receiving double-scope endoscopic submucosal dissection and matched conventional endoscopic submucosal dissection. MAIN OUTCOME MEASURES: The pathological completeness, procedure time, and complications were analyzed. RESULTS: Fifteen double-scope endoscopic submucosal dissection procedures, with 11 lesions located in the proximal colon with a median size of 40 mm, were performed. The median procedure time of double-scope endoscopic submucosal dissection was 32.45 (interquartile range, 16.03-38.20) minutes. The time required for second scope insertion was 2.57 (interquartile range, 0.95-6.75) minutes; for snaring, 3.03 (interquartile range, 2.12-6.62) minutes; and for actual endoscopic submucosal dissection, 28.23 (interquartile range, 7.90-37.00) minutes. All lesions were resected completely. No major complication was encountered. The procedure time was significantly shorter than that of 14 matched conventional endoscopic submucosal dissections (54.61 [interquartile range, 33.11-97.25] min; p = 0.021). LIMITATIONS: This was a single-center, single-operator, retrospective case-controlled study with limited cases. CONCLUSIONS: This study confirmed the feasibility of double-scope endoscopic submucosal dissection with snare-based traction to shorten procedure time and to simplify endoscopic submucosal dissection. Additional trials are required.

Declining trends of prevalence of Helicobacter pylori infection and incidence of gastric cancer in Taiwan: An updated cross-sectional survey and meta-analysis.

BACKGROUND: We aimed to assess the latest prevalence and secular trend of Helicobacter pylori infection and its association with the incidence and mortality of gastric cancer in Taiwan. MATERIALS AND METHODS: Adults naive to H. pylori eradication received 13 C-urea breath test (13 C-UBT), H. pylori stool antigen test, and serology test during 2019-2020 in this prospective screening program. Children and adolescent aged between 7 and 19 years received 13 C-UBT for H. pylori screening. We also conducted a systematic review and meta-analysis to assess the secular trend of prevalence of H. pylori from 1990 to 2020 in Taiwan. The secular trends of age-standardized incidence and mortality of gastric cancer were obtained from the Taiwan Cancer Registry. RESULTS: A total of 1494 participants were enrolled, including 294 children or adolescents and 1200 adults. The overall prevalence of active H. pylori infection by 13 C-UBT was 26.6% (397/1494), which was 30.8% in adults and 9.5% in adolescents/children. The age-standardized prevalence of active H. pylori infection was 32.3% in adults after adjustment of the population structure in Taiwan. Of the 29 studies including 38,597 subjects eligible for the meta-analysis, the pooled prevalence of H. pylori infection decreased from 63.8% (95% CI: 55.9%-71%) in 1990-2000 to 28.2% (95% CI:21.8%-35.6%) in 2016-2020. The age-standardized incidence and mortality of gastric cancer have also declined from 15.2 to 10.75 per 100,000, respectively, in 1999 to 9.29 and 5.4 per 100,000, respectively, in 2019. CONCLUSIONS: The prevalence of H. pylori infection has declined in Taiwan, which correlates with the declining trends of age-standardized incidence and mortality of gastric cancer in Taiwan.

Clinical efficacy and safety of peroral endoscopic myotomy for esophageal achalasia: A multicenter study in Taiwan.

BACKGROUND/OBJECTIVE: Peroral endoscopic myotomy (POEM), a novel minimally invasive treatment for esophageal achalasia, is becoming more popular globally because of its efficacy and safety. We aimed to clarify the technical concerns, efficacy, and safety of POEM for treating esophageal achalasia in Taiwan. METHODS: We conducted a retrospective study on consecutive patients with achalasia who underwent POEM between October 2016 and May 2021 at three medical centers in Taiwan. All patients underwent a comprehensive work-up before POEM, including symptom questionnaires, esophagogastroduodenoscopy, timed barium esophagogram (TBE), and high-resolution impedance manometry (HRIM), and were re-evaluated three months after POEM. We compared procedure variables, adverse events, and clinical responses, including Eckardt score ≤3 and TBE and HRIM findings. RESULTS: We analyzed 92 patients in total (54 men; mean age 49.5 years [range: 20-87]; type I/II/III/unclassified: 24/51/1/16). The mean POEM procedure duration was 89.5 ± 38.2 min, though it was significantly longer in patients with prior treatment or sigmoid-type achalasia. In total, 91 patients (98.9%) showed immediate technical success, and the overall clinical success rate at three months after POEM was 95.7%. Nearly 60% of patients experienced adverse events during POEM, but most of these were mild and none required further endoscopic or surgical intervention. During a follow-up period of up to five years (median 25 months), only four patients (4.3%) showed symptomatic recurrence, but none required further treatment. CONCLUSION: POEM is a very effective and safe treatment for Taiwanese patients with achalasia, irrespective of their achalasia subtype or prior treatment failure.

Mitochondrial Dysfunction as an Underlying Cause of Skeletal Muscle Disorders.

Mitochondria are an important energy source in skeletal muscle. A main function of mitochondria is the generation of ATP for energy through oxidative phosphorylation (OXPHOS). Mitochondrial defects or abnormalities can lead to muscle disease or multisystem disease. Mitochondrial dysfunction can be caused by defective mitochondrial OXPHOS, mtDNA mutations, Ca2+ imbalances, mitochondrial-related proteins, mitochondrial chaperone proteins, and ultrastructural defects. In addition, an imbalance between mitochondrial fusion and fission, lysosomal dysfunction due to insufficient biosynthesis, and/or defects in mitophagy can result in mitochondrial damage. In this review, we explore the association between impaired mitochondrial function and skeletal muscle disorders. Furthermore, we emphasize the need for more research to determine the specific clinical benefits of mitochondrial therapy in the treatment of skeletal muscle disorders.

Factors Associated with the Refusal of Direct-Acting Antiviral Agents for the Treatment of Hepatitis C in Taiwan.

Background and Objectives: Direct-acting antiviral agents (DAA) are a safe and highly effective treatment for hepatitis C virus (HCV) infection. However, the uptake of DAA treatment remains a challenge. This study aims to examine the reasons for DAA refusal among HCV patients covered by the Taiwan National Health Insurance system. Materials and Methods: This retrospective observational study covered the period from January 2009 to December 2019 and was conducted at a single hepatitis treatment center in Taiwan. This study involved chart reviews and phone-based surveys to confirm treatment status and refusal causes. To confirm treatment status, subjects with HCV without treatment records were phone-contacted to confirm treatment status. Patients who did not receive treatment were invited back for treatment. If the patient refused, the reason for refusal was discussed. Results: A total of 3566 patients were confirmed with DAA treatment; 418 patients (179 patients who were lost to contact or refused the survey and 239 patients who completed the survey of DAA refusal) were included in the no-DAA-therapy group. Factors associated with receiving DAAs were hemoglobin levels, hepatitis B virus co-infection, and regular gastroenterology visits. Meanwhile, male sex, platelet levels, and primary care physician visits were associated with DAA refusal. The leading causes of treatment refusal were multiple comorbidities, low health literacy, restricted access to hospitals, nursing home residence, and old age. The rate of DAA refusal remains high (10%). Conclusions: The reasons for treatment refusal are multifactorial, and addressing them requires complex interventions.

Complete Response in Metastatic Hepatocellular Carcinoma with Cardiac and Lung Involvement via Multimodality Treatment.

Background: Until recently, advanced HCC patients with major vessel and cardiac involvement have had an extremely poor prognosis without satisfactory treatment. Case presentation: A 63-year-old Taiwanese male presented with metastatic HCC with RA and IVC thrombi, as well as pulmonary metastases that were successfully treated by multimodal management, encompassed by surgical thrombectomy, concurrent systemic sorafenib and locoregional therapies, and immunotherapy. The patient has achieved a complete response over the past 33 months. Conclusions: Through this case report, which shows a successful outcome via multimodal management, a more aggressive approach should be considered when a patient is expected to tolerate the risks and side effects of various treatments.

Hepatic Arterial Infusion Chemotherapy Followed by Lipiodol Infusion for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Single-Center Experience.

Background and Objectives: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) followed by lipiodol infusion in advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Materials and Methods: Thirty-two patients with advanced HCC and PVTT who received HAIC with regimens of cisplatin, mitomycin-C, and 5-fluorouracil followed by lipiodol infusion were enrolled. The primary efficacy endpoint was tumor response rate. The modified Response Evaluation Criteria in Solid Tumors (mRECIST) was used for assessment of treatment response. The secondary endpoints were overall survival (OS) and progression free survival (PFS). Prognostic factors for survival also were evaluated. Results: The median OS and PFS were 11.9 and 9.5 months, respectively. Seventeen patients (53.1%) achieved objective response, and 23 patients (71.9%) achieved disease control. The length of survival in the responder and disease control groups was longer than in the non-responder and progressive disease groups after two cycles of HAIC (responder vs. non-responder: 16.5 vs. 7.9 months, p = 0.001; disease control vs. progressive disease: 12.3 vs. 5.6 months, p < 0.001) and after completing HAIC (responder vs. non-responder: 15.7 vs. 6.9 months, p = 0.001; disease control vs. progressive disease: 13.6 vs. 6.9 months, p < 0.001). Better survival was associated with Child-Pugh A liver function (p = 0.013), with early response to two HAIC cycles (p = 0.009), and with response (p = 0.02) and disease control (p = 0.001) after completing HAIC treatment. Conclusion: HAIC followed by lipiodol infusion is a safe and feasible treatment for advanced HCC with PVTT. Patients with early response could continue HAIC treatment with expected prolonged survival.

Serum Pepsinogen as a Predictor for Gastric Cancer Death: A 16-Year Community-based Cohort Study.

GOALS: The purpose of this article is to validate the long-term association between initial serum pepsinogen (PG) measurements and subsequent gastric cancer-specific deaths from a long-term longitudinal cohort. BACKGROUND: Endoscopic surveillance can be effective and efficient in reducing gastric cancer mortality if a biomarker such as serum PG is available to identify high-risk individuals and if the biomarker also is specific to gastric cancer risk. STUDY: Between 1995 and 1998, a gastric cancer-screening program was conducted in a high-risk population: The first stage involved PG testing, and the second stage involved upper endoscopy. The outcome was gastric cancer death, which was monitored until December 31, 2010; results were expressed as the hazard ratio (HR) and corresponding 95% confidence interval (CI) using the Cox proportional hazards regression model. Other causes of death were used as comparators. RESULTS: Among participants (n=3514) aged ≥30 years, 1682 (47.9%) were screened to determine serum PG levels. After 16 years of follow-up, 14 deaths from gastric cancer were documented. Multivariate analyses adjusted for age, sex, and Helicobacter pylori serological positivity showed that PG-I <30 µg/L and PG-I <30 µg/L or PG-I/II ratio <3 were significantly associated with the risk of gastric cancer death (HR, 3.27; 95% CI, 1.11-9.61 and HR, 3.45; 95% CI, 1.18-10.12, respectively). In contrast, there were no significant associations between PG and other causes of death, including neoplastic and non-neoplastic diseases. CONCLUSION: This long-term cohort study shows the usefulness of PG measurement as a biomarker that is specific to the risk of gastric cancer death.

14 day sequential therapy versus 10 day bismuth quadruple therapy containing high-dose esomeprazole in the first-line and second-line treatment of Helicobacter pylori: a multicentre, non-inferiority, randomized trial.

Background: Whether extending the treatment length and the use of high-dose esomeprazole may optimize the efficacy of Helicobacter pylori eradication remains unknown. Objectives: To compare the efficacy and tolerability of optimized 14 day sequential therapy and 10 day bismuth quadruple therapy containing high-dose esomeprazole in first-line therapy. Methods: We recruited 620 adult patients (≥20 years of age) with H. pylori infection naive to treatment in this multicentre, open-label, randomized trial. Patients were randomly assigned to receive 14 day sequential therapy or 10 day bismuth quadruple therapy, both containing esomeprazole 40 mg twice daily. Those who failed after 14 day sequential therapy received rescue therapy with 10 day bismuth quadruple therapy and vice versa. Our primary outcome was the eradication rate in the first-line therapy. Antibiotic susceptibility was determined. ClinicalTrials.gov: NCT03156855. Results: The eradication rates of 14 day sequential therapy and 10 day bismuth quadruple therapy were 91.3% (283 of 310, 95% CI 87.4%-94.1%) and 91.6% (284 of 310, 95% CI 87.8%-94.3%) in the ITT analysis, respectively (difference -0.3%, 95% CI -4.7% to 4.4%, P = 0.886). However, the frequencies of adverse effects were significantly higher in patients treated with 10 day bismuth quadruple therapy than those treated with 14 day sequential therapy (74.4% versus 36.7% P < 0.0001). The eradication rate of 14 day sequential therapy in strains with and without 23S ribosomal RNA mutation was 80% (24 of 30) and 99% (193 of 195), respectively (P < 0.0001). Conclusions: Optimized 14 day sequential therapy was non-inferior to, but better tolerated than 10 day bismuth quadruple therapy and both may be used in first-line treatment in populations with low to intermediate clarithromycin resistance.

Elevated levels of liver methylglyoxal and d-lactate in early-stage hepatitis in rats.

Methylglyoxal (MGO) is highly cytotoxic and its levels are elevated in diabetes, nephropathy and atherosclerosis. However, it has never been studied in liver disease. For this reason, we aimed to assess the levels of MGO and its metabolite d-lactate in an early hepatitis model. Wistar rats were administered CCl4 (0.75 mL/kg, i.p.) to induce hepatitis. In either CCl4 -treated or untreated rats, alanine transaminase and aspartate transaminase levels did not change over the course of the study, indicating that significant liver damage did not occur following CCl4 treatment. However, the levels of MGO and d-lactate were higher in the livers of CCl4 -treated animals than in untreated animals (MGO: 128.2 ± 18.8 and 248.1 ± 64.9 µg/g protein, p < 0.01; d-lactate: 0.860 ± 0.040 and 1.293 ± 0.078 µmol/g protein, respectively p < 0.01). Furthermore, in untreated and treated animals, serum d-lactate levels were 57.65 ± 2.59 and 92.16 ± 16.69 µm and urine d-lactate levels were 1.060 ± 0.007 and 1.555 ± 0.366 µmol/mg UCr, respectively (p < 0.01). These data show that in this model of early-stage liver damage, the levels of MGO and its metabolite d-lactate are elevated and that d-lactate could be useful as a reference marker for the early stage of hepatitis.