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INTRODUCTION: Fluid resuscitation reduces mortality and morbidity in acute pancreatitis (AP); however, whether glucose-containing fluids negatively impact AP remains uncertain. We aimed to examine the association between glucose-containing fluids and AP outcomes. METHODS: This multicenter retrospective cohort study included patients diagnosed with AP between January 2015 and December 2018. Glucose density was defined as total glucose content divided by total fluid volume (g/dl) on day 1, and was considered high if the level exceeded the median. Endpoints were early organ failure (OF), including cardiovascular, renal, or respiratory system failure within 7 days; 30-day OF; ICU admission; and AP-related 90-day mortality. Logistic regression models, restricted cubic spline curves, and Cox proportional hazards models were used for statistical analysis. RESULTS: From the database, 1,146 patients with AP were included. Early OF occurred in 8.8% of patients within 7 days. The high glucose-density group (>5 g/dl) had increased risk of early OF (9.7% vs. 8.2%; adjusted odds ratio [aOR], 1.69; 95% confidence interval [CI], 1.03-2.80; P = 0.039), respiratory failure (8.0% vs. 6.2%; aOR, 1.88; 95% CI, 1.09-3.24; P = 0.024), cardiovascular failure (3.4% vs. 2.4%; aOR, 3.59; 95% CI, 1.28-10.0; P = 0.015), and ICU admission (6.8% vs. 5.8%; aOR, 2.06; 95% CI, 1.08-3.94; P = 0.029), with a dose-response effect observed for cardiovascular failure and ICU admission. A significant increase 30-day OF risk (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.19-2.45) was also noted. CONCLUSION: Excess glucose-containing fluid was associated with increased risks of overall, respiratory, and cardiovascular OF and ICU admission in AP.
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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.
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OBJECTIVE: Hemin, a heme oxygenase 1 activator has shown efficacy in the prevention and treatment of acute pancreatitis in mouse models. We conducted a randomized controlled trial (RCT) to assess the protective effect of Hemin administration to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients at risk. METHODS: In this multicenter, multinational, placebo-controlled, double-blind RCT, we assigned patients at risk for PEP to receive a single intravenous dose of Hemin (4 mg/kg) or placebo immediately after ERCP. Patients were considered to be at risk on the basis of validated patient- and/or procedure-related risk factors. Neither rectal NSAIDs nor pancreatic stent insertion were allowed in randomized patients. The primary outcome was the incidence of PEP. Secondary outcomes included lipase elevation, mortality, safety, and length of stay. RESULTS: A total of 282 of the 294 randomized patients had complete follow-up. Groups were similar in terms of clinical, laboratory, and technical risk factors for PEP. PEP occurred in 16 of 142 patients (11.3%) in the Hemin group and in 20 of 140 patients (14.3%) in the placebo group (p = 0.48). Incidence of severe PEP reached 0.7% and 4.3% in the Hemin and placebo groups, respectively (p = 0.07). Significant lipase elevation after ERCP did not differ between groups. Length of hospital stay, mortality and severe adverse events rates were similar between groups. CONCLUSION: We failed to detect large improvements in PEP rate among participants at risk for PEP who received IV hemin immediately after the procedure compared to placebo. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT01855841).
Subject(s)
Cholangiopancreatography, Endoscopic Retrograde , Pancreatitis , Animals , Humans , Mice , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Heme Oxygenase-1 , Hemin/therapeutic use , Lipase , Pancreatitis/etiology , Pancreatitis/prevention & control , Administration, IntravenousABSTRACT
Increasing evidence suggests that gut microbiota alterations are related to development and phenotypes of many neuropsychiatric diseases. Here, we evaluated the fecal microbiota and its clinical correlates in patients with hereditary transthyretin amyloidosis (ATTRv) and polyneuropathy. Fecal microbiota from 38 ATTRv patients and 39 age-matched controls was analyzed by sequencing 16S V3-V4 ribosomal RNA, and its relationships with clinical characteristics of polyneuropathy and cardiomyopathy were explored. The familial amyloidotic polyneuropathy stage was stage I, II, and III in 13, 18, and 7 patients. 99mTc-PYP SPECT showed a visual score of 2 in 15 and 3 in 21 patients. The gut microbiota of ATTRv patients showed higher alpha diversity (ASV richness and Shannon effective numbers) and dissimilar beta diversity compared to controls. Relative abundance of microbiota was dominated by Firmicutes and decreased in Bacteroidetes in ATTRv patients than in controls. Patients with more myocardial amyloid deposition were associated with increased alpha diversity, and the abundance of Clostridia was significantly correlated with pathophysiology of polyneuropathy in ATTRv patients. These findings demonstrated alterations in the gut microbiota, especially Firmicutes, in ATTRv. The association between altered microbiota and phenotypes of cardiomyopathy and polyneuropathy might suggest potential contributions of gut microbiota to ATTRv pathogenesis.
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Amyloid Neuropathies, Familial , Cardiomyopathies , Gastrointestinal Microbiome , Polyneuropathies , Humans , Firmicutes , RNA, Ribosomal, 16S/geneticsABSTRACT
OBJECTIVE: We aimed to investigate whether 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. MATERIALS AND METHODS: This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[18F]FDG PET/CT for endoscopy-detected ampullary tumors 5-87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. RESULTS: The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in early-phase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13-36.18; P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80-13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41-19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00-14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16-21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874-0.956] vs. 0.815 [0.732-0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816-0.967) in candidates for endoscopic papillectomy. CONCLUSION: Adding 2-[18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.
Subject(s)
Ampulla of Vater , Common Bile Duct Neoplasms , Humans , Male , Female , Middle Aged , Aged , Positron Emission Tomography Computed Tomography/methods , Fluorodeoxyglucose F18 , Radiopharmaceuticals , Retrospective Studies , Ampulla of Vater/diagnostic imaging , Tomography, X-Ray Computed/methods , Common Bile Duct Neoplasms/diagnostic imaging , Positron-Emission Tomography , EndoscopyABSTRACT
BACKGROUND/PURPOSE: Endoscopic stenting at malignant distal duodenum stenosis (MDDS) is challenging because of the duodenal C-loop configuration, the acute angle of the duodenojejunal junction, and the limited length of the endoscope. Few studies have investigated the clinical outcomes of stenting at the distal duodenum. Therefore, this study aimed to investigate the clinical outcomes of treating MDDS with different types of metallic stents. METHODS: From January 2012 to December 2020, fifty-six patients with MDDS who underwent duodenal stenting were enrolled for analysis. Thirty-five patients received uncovered self-expandable metallic stents (UC-SEMS), and twenty-one patients received partially covered self-expandable metallic stents (PC-SEMS). All patients were followed up till death or for 18 months. The clinical success rate, stent dysfunction rate, and stent patency were compared between the groups. Multivariate analysis was conducted to identify factors related to stent dysfunction. RESULTS: The clinical success rates were 85.7 % in both the UC-SEMS and PC-SEMS groups. Stent dysfunction rates (UC-SEMS: 34.3 %, PC-SEMS: 38.1 %, p = 0.773) and the average stent patency (UC-SEMS: 117.2 days, PC-SEMS: 100.0 days, p = 0.576) were not statistically different between the groups. Multivariate analysis disclosed the age ≥65 years was significantly related to stent dysfunction (odds ratio: 4.78, p = 0.031). CONCLUSION: Both UC-SEMS and PC-SEMS are safe and effective treatment options for MDDS. However, stent dysfunction remains a significant issue to overcome, particularly in the elderly. Further research is needed to explore novel strategies that can improve the effectiveness of stent placement and reduce the risk of stent dysfunction.
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Duodenal Obstruction , Self Expandable Metallic Stents , Humans , Female , Male , Aged , Retrospective Studies , Middle Aged , Duodenal Obstruction/etiology , Duodenal Obstruction/surgery , Duodenal Obstruction/therapy , Treatment Outcome , Aged, 80 and over , Stents/adverse effects , Constriction, Pathologic , Duodenum/surgery , TaiwanABSTRACT
BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) vaccines were rapidly implemented globally and vaccine-associated immune-related hepatitis was recently reported. We aim to investigate its impact in regions endemic of chronic hepatitis B (CHB). METHODS: We retrospectively collected patients who developed hepatitis within 90 days after COVID-19 vaccination in Taiwan. The mechanisms of hepatitis included vaccine induced liver injury (VILI) and immune-related hepatitis, which are direct liver injuries defined as aspartate or alanine aminotransferase (AST or ALT) increased ≥ 5-fold upper limit of normal (ULN) and/or AST or ALT ≥ 3-fold of ULN with concurrent total bilirubin ≥ 2-fold of ULN. Indirect liver injury due to HBV reactivation was defined as HBsAg reverse seroconversion or significant rise in HBV DNA level. The demographics, clinical data, and course of hepatitis were compared statistically. RESULTS: Twenty-five patients were included with a median age of 54. The culprit vaccines were ChAdOx1 nCoV-19 (n = 9), mRNA-1273 (n = 12), and BNT162b2 (n = 4). The characteristics of hepatitis were comparable regardless of vaccine subtypes. The median onset of hepatitis was 25 days post vaccination, with a peak of 10-fold ALT-increase. The etiologies included HBV reactivation (n = 10), VILI (n = 10), and immune-related hepatitis (n = 5). HBV reactivation accounts for 90% of vaccine-induced hepatitis in patients of CHB (n = 10), and two patients died. Patients with initial AST levels >500 U/L increased 27-fold risks of liver injury greater than moderate severity compared with those without. CONCLUSION: COVID-19 vaccine induced hepatitis is a clinical significant complication, and HBV reactivation may account for a possible mechanism.
Subject(s)
COVID-19 , Hepatitis B, Chronic , Hepatitis B , Humans , COVID-19 Vaccines/adverse effects , Hepatitis B virus/genetics , Retrospective Studies , BNT162 Vaccine , ChAdOx1 nCoV-19 , COVID-19/prevention & control , Hepatitis B e Antigens , Alanine Transaminase , Hepatitis B Surface Antigens , DNA, ViralABSTRACT
BACKGROUND/AIMS: Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR). METHODS: This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR. RESULTS: The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5-40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7-67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1-62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12-2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21-0.81). CONCLUSION: Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.
Subject(s)
Hepatitis B Core Antigens , Hepatitis B, Chronic , Adult , Humans , Male , Middle Aged , Female , Hepatitis B Surface Antigens , Antiviral Agents/therapeutic use , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/drug therapy , Hepatitis B e Antigens , DNA, Viral , Recurrence , Hepatitis B virus/geneticsABSTRACT
Reprocessing of gastrointestinal (GI) endoscopes and accessories is an essential part of patient safety and quality control in GI endoscopy centers. However, current endoscopic reprocessing guidelines or procedures are not adequate to ensure patient-safe endoscopy. Approximately 5.4 % of the clinically used duodenoscopes remain contaminated with high-concern microorganisms. Thus, the Digestive Endoscopy Society of Taiwan (DEST) sets standards for the reprocessing of GI endoscopes and accessories in endoscopy centers. DEST organized a task force working group using the guideline-revision process. These guidelines contain principles and instructions of step-by-step for endoscope reprocessing. The updated guidelines were established after a thorough review of the existing global and local guidelines, systematic reviews, and health technology assessments of clinical effectiveness. This guideline aims to provide detailed recommendations for endoscope reprocessing to ensure adequate quality control in endoscopy centers.
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Disinfection , Equipment Contamination , Humans , Disinfection/methods , Taiwan , Endoscopes , Endoscopes, GastrointestinalABSTRACT
BACKGROUND: We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic resistance continues to rise is unknown. Therefore, we aimed to assess the latest prevalence of H pylori antibiotic resistance in this region. METHODS: We did an updated systematic review and meta-analysis of observational studies and randomised controlled trials published in PubMed, Embase, and Cochrane Library between Jan 1, 1990, and July 12, 2023. Studies investigating primary H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline in individuals naive to eradication therapy in the Asia-Pacific region (as defined by the UN geoscheme) were eligible for inclusion. There were no language restrictions. Studies that focused on specific subpopulations (eg, children) were excluded. Using a standardised extraction form, two authors independently reviewed and extracted summary data from all eligible articles. The updated prevalence of antibiotic resistance was generated by meta-analysis under a random-effects model and subgroup analyses were done by countries and periods of study. Between-study variability was assessed by use of I2. The study is registered in PROSPERO, CRD42022339956. FINDINGS: A total of 351 studies, including 175 new studies and 176 studies from our previous analysis, were included in this meta-analysis. The overall prevalence of primary antibiotic resistance of H pylori between 1990 and 2022 was 22% (95% CI 20-23; I2=96%) for clarithromycin, 52% (49-55; I2=99%) for metronidazole, 26% (24-29; I2=96%) for levofloxacin, 4% (3-5; I2=95%) for tetracycline, and 4% (3-5; I2=95%) for amoxicillin. Prevalence varied considerably between countries and across study periods. From 1990 to 2022, the prevalence of primary resistance increased for clarithromycin, metronidazole, and levofloxacin but remained stable for amoxicillin and tetracycline. The latest primary resistance prevalences were 30% (95% CI 28-33; I2=93%) for clarithromycin, 61% (55-66; I2=99%) for metronidazole, 35% (31-39; I2=95%) for levofloxacin, 4% (2-6; I2=96%) for tetracycline, and 6% (4-8; I2=96%) for amoxicillin in the Asia-Pacific region. INTERPRETATION: Treatment guidelines should be adapted in response to the rising primary resistance of key antibiotics for H pylori eradication. A global policy to control and monitor the antibiotic resistance of H pylori is urgently needed. FUNDING: Ministry of Health and Welfare of Taiwan, National Science and Technology Council of Taiwan, and National Taiwan University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Child , Humans , Clarithromycin/pharmacology , Clarithromycin/therapeutic use , Metronidazole/pharmacology , Metronidazole/therapeutic use , Levofloxacin/pharmacology , Levofloxacin/therapeutic use , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Amoxicillin/pharmacology , Amoxicillin/therapeutic use , Tetracycline , Drug Resistance, Microbial , Asia/epidemiologyABSTRACT
Gut microbial proteolytic metabolism has been reportedly altered in Parkinson's disease (PD). However, the circulating aromatic amino acids (AAA) described in PD are inconsistent. Here we aimed to investigate plasma AAA profiles in a large cohort of PD patients, and examine their correlations with clinical severity and gut microbiota changes. We enrolled 500 participants including 250 PD patients and 250 neurologically normal controls. Plasma metabolites were measured using liquid chromatography mass spectrometry. Faecal samples were newly collected from 154 PD patients for microbiota shotgun metagenomic sequencing combined with data derived from 96 PD patients reported before. Data were collected regarding diet, medications, and motor and non-motor symptoms of PD. Compared to controls, PD patients had higher plasma AAA levels, including phenylacetylglutamine (PAGln), p-cresol sulfate (Pcs), p-cresol glucuronide (Pcg), and indoxyl sulfate (IS). Multivariable linear regression analyses, with adjustment for age, sex, and medications, revealed that the plasma levels of PAGln (coefficient 4.49, 95% CI 0.40-8.58, P = 0.032) and Pcg (coefficient 1.79, 95% CI 0.07-3.52, P = 0.042) positively correlated with motor symptom severity but not cognitive function. After correcting for abovementioned potential confounders, these AAA metabolites were also associated with the occurrence of constipation in PD patients (all P < 0.05). Furthermore, plasma levels of AAA metabolites were correlated with the abundance of specific gut microbiota species, including Bacteroides sp. CF01-10NS, Bacteroides vulgatus, and Clostridium sp. AF50-3. In conclusion, elevated plasma AAA metabolite levels correlated with disease characteristics in PD, suggesting that upregulated proteolytic metabolism may contribute to the pathophysiology of PD.
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BACKGROUND: Helicobacter pylori infection is an important causal factor of gastric cancer and peptic ulcer disease and is associated with immune thrombocytopenic purpura and functional dyspepsia. In H pylori strains, point mutations in the 23S rRNA and gyrA genes are associated with clarithromycin resistance and levofloxacin resistance, respectively. Whether the efficacy of molecular testing-guided therapy is non-inferior to that of susceptibility testing-guided therapy for H pylori eradication is unclear. Therefore, we aimed to compare the efficacy and safety of molecular testing-guided therapy and traditional culture-based susceptibility testing-guided therapy in first-line and third-line treatment of H pylori infection. METHODS: We did two multicentre, open-label randomised trials in Taiwan. In trial 1 (done at seven hospitals), treatment-naive individuals infected with H pylori who were aged 20 years or older were eligible for study inclusion. In trial 2 (done at six hospitals), individuals aged 20 years or older who failed treatment after two or more eradication therapies for H pylori infection were eligible for enrolment. Eligible patients were randomly assigned (1:1) to receive either molecular testing-guided therapy or susceptibility testing-guided therapy. The randomisation sequence was generated by computer using permuted block randomisation with a block size of 4. All investigators were masked to the randomisation sequence. Clarithromycin and levofloxacin resistance were determined by agar dilution test for measuring minimum inhibitory concentrations in the susceptibility testing-guided therapy group, and by PCR and direct sequencing for detection of 23S rRNA and gyrA mutations in the molecular testing-guided therapy group. Study participants received clarithromycin sequential therapy, levofloxacin sequential therapy, or bismuth quadruple therapy according to the resistance status to clarithromycin and levofloxacin. The 13C-urease breath test was used to determine the status of H pylori infection at least 6 weeks after eradication therapy. The primary outcome was the eradication rate by intention-to-treat analysis. The frequency of adverse effects was analysed in patients with available data. The prespecified margins for non-inferiority were 5% for trial 1 and 10% for trial 2. The trials are ongoing for post-eradication follow-up and registered with ClinicalTrials.gov, NCT03556254 for trial 1, and NCT03555526 for trial 2. FINDINGS: Between March 28, 2018, and April 23, 2021, 560 eligible treatment-naive patients with H pylori infection were recruited and randomly assigned to the molecular testing-guided therapy group or the susceptibility testing-guided therapy group in trial 1. Between Dec 28, 2017, and Oct 27, 2020, 320 eligible patients with refractory H pylori infection were recruited and randomly assigned to the molecular testing-guided therapy group or the susceptibility testing-guided therapy group in trial 2. 272 men and 288 women were recruited for trial 1, and 98 men and 222 women were recruited for trial 2. In first-line H pylori treatment, infection was eradicated in 241 (86%, 95% CI 82-90) of 280 patients in the molecular testing-guided therapy group and 243 (87%, 83-91) of 280 patients in the susceptibility testing-guided therapy group by intention-to-treat analysis (p=0·81). In third-line H pylori treatment, infection was eradicated in 141 (88%, 83-93) of 160 patients in the molecular testing-guided therapy group and 139 (87%, 82-92) of 160 patients in the susceptibility testing-guided therapy group by intention-to-treat analysis (p=0·74). The difference in the eradication rate between the molecular testing-guided therapy group and the susceptibility testing-guided therapy group was -0·7% (95% CI -6·4 to 5·0; non-inferiority p=0·071) in trial 1 and 1·3% (-6·0 to 8·5; non-inferiority p=0·0018 in trial 2 by intention-to-treat analysis. We found no difference in adverse effects across both treatment groups in trial 1 and trial 2. INTERPRETATION: Molecular testing-guided therapy was similar to susceptibility testing-guided therapy in first-line therapy and non-inferior to susceptibility testing guided therapy in third-line treatment of H pylori infection, supporting the use of molecular testing-guided therapy for H pylori eradication. FUNDING: Ministry of Science and Technology of Taiwan, and Centre of Precision Medicine of the Higher Education Sprout Project by the Ministry of Education of Taiwan.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Male , Humans , Female , Helicobacter Infections/drug therapy , Helicobacter Infections/diagnosis , Anti-Bacterial Agents/therapeutic use , Clarithromycin/therapeutic use , Levofloxacin/therapeutic use , RNA, Ribosomal, 23S/genetics , Drug Therapy, CombinationABSTRACT
BACKGROUND: Hepatitis B virus (HBV) causes chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma. The evolution of human gut microbiota during the progression of HBV-related liver diseases remains unclear. Therefore, we prospectively enrolled patients with HBV-related liver diseases and healthy individuals. Through 16S ribosomal RNA amplicon sequencing, we characterized the gut microbiota of the participants and predicted the functions of microbial communities. RESULTS: We analyzed the gut microbiota of 56 healthy controls and 106 patients with HBV-related liver disease [14 with resolved HBV infection, 58 with CHB, and 34 with advanced liver disease (15 with liver cirrhosis and 19 with hepatocellular carcinoma)]. Patients with HBV-related liver disease exhibited a higher degree of bacterial richness (all P < 0.05) than did healthy controls. Beta diversity analyses revealed a distinct clustering pattern between healthy controls and patients with HBV-related liver disease (all P < 0.05). The composition of bacteria (from the phylum level to the genus level) varied across the stages of liver disease. Linear discriminant analysis effect size revealed multiple taxa that differ significantly in abundance between healthy controls and patients with HBV-related liver disease; however, fewer differences were observed among patients with resolved HBV infection, those with CHB, and those with advanced liver disease. The ratio of Firmicutes to Bacteroidetes was increased in all three patient groups compared with the ratio in healthy controls (all P < 0.001). The analysis of the sequencing data by using PICRUSt2 revealed the changes in microbial functions with disease progression. CONCLUSIONS: The diversity and composition of gut microbiota appear to vary significantly between healthy controls and patients at different stages of HBV-related liver disease. The understanding of gut microbiota may provide novel therapeutic options in these patients.
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BACKGROUND AND AIM: Achalasia often presents with chronic food stasis and fermentation in the esophageal lumen, which may lead to alterations of the esophageal microbiome, with associated mucosal inflammation and dysplastic changes. The study aims to evaluate the characteristics of the esophageal microbiome in achalasia and changes of the esophageal microbiome before and after peroral endoscopic myotomy (POEM). METHODS: This is a prospective case-control study. This study enrolled patients with achalasia and asymptomatic subjects as control group. Endoscopic brushing for esophageal microbiome collection was performed in all subjects, with additional follow-up endoscopy and brushing 3 months after POEM in achalasia patients. The composition of the esophageal microbiome was determined and compared between (1) achalasia patients and asymptomatic controls and (2) achalasia patients before and after POEM. RESULTS: Thirty-one achalasia patients (mean age 53.5 ± 16.2 years; male 45.2%) and 15 controls were analyzed. We observed a distinct esophageal microbial community structure in achalasia patients, with increased Firmicutes and decreased Proteobacteria when compared with the control group at the phylum level. The discriminating enriched genera in achalasia patients were Lactobacillus, followed by Megasphaera and Bacteroides, and the amount of Lactobacillus was associated with the severity of achalasia. Twenty patients were re-examined after POEM, and a high prevalence of erosive esophagitis (55%) was noted, alongside an increase in genus Neisseria and decrease in Lactobacillus and Bacteroides. CONCLUSIONS: The altered esophageal microenvironment in achalasia leads to dysbiosis with a high abundance of genus Lactobacillus. Increased Neisseria and decreased Lactobacillus were observed after POEM. The long-term effect of microbial changes warrants further study.
Subject(s)
Esophageal Achalasia , Myotomy , Natural Orifice Endoscopic Surgery , Humans , Male , Adult , Middle Aged , Aged , Esophageal Achalasia/surgery , Pilot Projects , Esophageal Sphincter, Lower/surgery , Case-Control Studies , Natural Orifice Endoscopic Surgery/adverse effects , Treatment Outcome , EsophagoscopyABSTRACT
Dietary nutrients are associated with the development of cardiovascular disease (CVD) both through traditional pathways (inducing hyperlipidemia and chronic inflammation) and through the emergence of a metaorganism-pathogenesis pathway (through the gut microbiota, its metabolites, and host). Several molecules from food play an important role as CVD risk-factor precursors either themselves or through the metabolism of the gut microbiome. Animal-based dietary proteins are the primary source of CVD risk-factor precursors; however, some plants also possess these precursors, though at relatively low levels compared with animal-source food products. Various medications have been developed to treat CVD through the gut-microbiota-circulation axis, and they exhibit potent effects in CVD treatment. Nevertheless, such medicines are still being improved, and there are many research gaps that need to be addressed. Furthermore, some medications have unpleasant or adverse effects. Numerous foods and herbs impart beneficial effects upon health and disease. In the past decade, many studies have focused on treating and preventing CVD by modulating the gut microbiota and their metabolites. This review provides an overview of the available information, summarizes current research related to the gut-microbiota-heart axis, enumerates the foods and herbs that are CVD-risk precursors, and illustrates how metabolites become CVD risk factors through the metabolism of gut microbiota. Moreover, we present perspectives on the application of foods and herbs-including prebiotics, probiotics, synbiotics, postbiotics, and antibiotic-like substances-as CVD prevention agents to modulate gut microbiota by inhibiting gut-derived CVD risk factors. Taxonomy classification by EVISE: Cardiovascular disease, gut microbiota, herbal medicine, preventive medicine, dietary therapy, nutrition supplements.
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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.
Subject(s)
Colonic Polyps , Humans , Colonic Polyps/surgery , Colonic Polyps/pathology , Colonoscopy/adverse effects , Single-Blind Method , Microsurgery , Postoperative Hemorrhage/epidemiologyABSTRACT
BACKGROUND AND AIMS: For EUS-guided fine-needle biopsy sampling (EUS-FNB) of solid pancreatic lesions (SPLs), the role of sampling strategy between targeted biopsy sampling and wide sampling has not been reported. This study aimed to investigate the benefits of the 2 sampling techniques on EUS-FNB using rapid on-site evaluation. METHODS: Patients with SPLs were prospectively enrolled and randomly assigned (1:1) to undergo EUS-FNB using either contrast guidance or the fanning technique. The primary outcome was the total number of passes required to establish a diagnosis, and secondary outcomes were overall diagnostic accuracy and adverse event rates. RESULTS: One hundred eighteen patients were enrolled from February 2019 to January 2021, with 59 patients assigned to each group. There was no significant difference in the total number of passes required to establish a diagnosis between the contrast and fanning groups (median, 1 [interquartile range, 1-1] vs 1 [interquartile range, 1-2], respectively; P = .629). The sensitivity, specificity, and diagnostic accuracy in the contrast group was 100%, 66.7%, and 98.3% and in the fanning group 100%, 100%, and 100%, respectively (P = 1). An SPL <4 cm (odds ratio, 2.47; 95% confidence interval, 1.05-5.81; P = .037) and macroscopic visible core length >1 cm (odds ratio, 2.89; 95% confidence interval, 1.07-7.84; P = .037) were independently associated with increased cytologic and histologic accuracy. CONCLUSIONS: The diagnostic accuracy of EUS-FNB with the fanning technique for SPLs was comparable with the contrast guidance technique. Without additional cost, EUS-FNB with the fanning technique may be preferred for SPLs. (Clinical trial registration number: NCT04924725.).
Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration , Pancreatic Neoplasms , Humans , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Pancreas/pathology , Specimen Handling , Pancreatic Neoplasms/pathologyABSTRACT
BACKGROUND: Levofloxacin-based therapy or bismuth-based quadruple therapy are the recommended second-line regimens for Helicobacter pylori eradication after failure of clarithromycin-based therapy. However, resistance to levofloxacin has increased in the past decade. Furthermore, little is known about the long-term effects of H pylori eradication on the antibiotic resistome. In this study, we compared these second-line eradication therapies for efficacy, tolerability, and short-term and long-term effects on the gut microbiota, antibiotic resistome, and metabolic parameters. METHODS: We did a multicentre, open-label, parallel group, randomised controlled trial at eight hospitals in Taiwan. Adult patients (age ≥20 years) with persistent H pylori infection after first-line clarithromycin-based therapy were randomly assigned (1:1, permuted block sizes of four) to receive levofloxacin-based sequential quadruple therapy for 14 days (EAML14; esomeprazole 40 mg and amoxicillin 1 g for 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for 7 days, all twice-daily) or bismuth-based quadruple therapy for 10 days (BQ10; esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). All investigators were masked to the randomisation sequence. The primary endpoint was H pylori eradication rate measured by 13C urea breath test 6 weeks after second-line treatment according to both intention-to-treat (ITT) and per-protocol analysis. The microbiota composition and antibiotic resistome of faecal samples collected at baseline (before treatment) and at 2 weeks, 8 weeks, and 1 year after eradication therapy was profiled by shotgun metagenomic sequencing and 16S rRNA gene sequencing. The frequency of adverse effects and changes in the gut microbiota and antibiotic resistome were assessed in all participants with available data. The trial is complete and registered with ClinicalTrails.gov, NCT03148366. FINDINGS: Between Feb 25, 2015, and Dec 11, 2020, 560 patients were randomly assigned to receive EAML14 or BQ10 (n=280 per group; 261 [47%] men and 299 [53%] women). Mean age was 55·9 years (SD 12·7) in the EAML14 group and 54·9 years (12·3) in the BQ10 group. Eradication of H pylori was achieved in 246 (88%) of 280 participants in the EAML14 group and 245 (88%) of 280 in the BQ10 group according to ITT analysis (risk difference -0·4%, 95% CI -5·8 to 5·1; p=0·90). In the per-protocol analysis, 246 (90%) of 273 participants in the EAML14 group and 245 (93%) of 264 participants in the BQ10 group achieved H pylori eradication (risk difference 2·7%, 95% CI -0·2 to 7·4; p=0·27). Transient perturbation of faecal microbiota diversity at week 2 was largely restored to basal state 1 year after EAML14 or BQ10. Diversity recovery was slower with BQ10, and recovery in species abundance was partial after both therapies. On shotgun sequencing, we observed significant increases in total resistome after EAML14 (p=0·0002) and BQ10 (p=4·3 × 10-10) at week 2, which were restored to pretreatment level by week 8. The resistance rates of Escherichia coli and Klebsiella pneumonia to levofloxacin, ciprofloxacin, ampicillin (ampicillin-sulbactam for K pneumonia), and various cephalosporins were significantly increased in the EAML14 group compared with in the BQ10 group at week 2, which were restored to pretreatment levels and showed no significant differences at week 8 and 1 year. The frequency of any adverse effects was significantly higher after BQ10 therapy (211 [77%] of 273 participants) than after EAML14 therapy (134 [48%] of 277; p<0·0001). INTERPRETATION: We found no evidence of superiority between levofloxacin-based quadruple therapy and bismuth-based quadruple therapy in the second-line treatment of H pylori infection. The transient increase in the antibiotic resistome and perturbation of faecal microbiota diversity were largely restored to pretreatment state from 2 months to 1 year after eradication therapy. FUNDING: The Ministry of Science and Technology of Taiwan, the Ministry of Health and Welfare of Taiwan, National Taiwan University Hospital, Taipei Veteran General Hospital, and the Australian Federal Government through the St George and Sutherland Medical Research Foundation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
Subject(s)
Gastrointestinal Microbiome , Helicobacter Infections , Helicobacter pylori , Adult , Male , Humans , Female , Middle Aged , Young Adult , Anti-Bacterial Agents/adverse effects , Bismuth/adverse effects , Levofloxacin/therapeutic use , Metronidazole/adverse effects , Clarithromycin/adverse effects , Esomeprazole/therapeutic use , Esomeprazole/adverse effects , RNA, Ribosomal, 16S , Proton Pump Inhibitors/therapeutic use , Drug Therapy, Combination , Australia , Helicobacter Infections/drug therapyABSTRACT
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.