Advances in uremic toxin detection and monitoring in the management of chronic kidney disease progression to end-stage renal disease.

Patients with end-stage kidney disease (ESKD) rely on dialysis to remove toxins and stay alive. However, hemodialysis alone is insufficient to completely remove all/major uremic toxins, resulting in the accumulation of specific toxins over time. The complexity of uremic toxins and their varying clearance rates across different dialysis modalities poses significant challenges, and innovative approaches such as microfluidics, biomarker discovery, and point-of-care testing are being investigated. This review explores recent advances in the qualitative and quantitative analysis of uremic toxins and highlights the use of innovative methods, particularly label-mediated and label-free surface-enhanced Raman spectroscopy, primarily for qualitative detection. The ability to analyze uremic toxins can optimize hemodialysis settings for more efficient toxin removal. Integration of multiple omics disciplines will also help identify biomarkers and understand the pathogenesis of ESKD, provide deeper understanding of uremic toxin profiling, and offer insights for improving hemodialysis programs. This review also highlights the importance of early detection and improved understanding of chronic kidney disease to improve patient outcomes.

Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

Cardia and non-cardia gastric cancer risk associated with Helicobacter pylori in East Asia and the West: A systematic review, meta-analysis, and estimation of population attributable fraction.

OBJECTIVES: To assess the region-specific relative risk of cardia/non-cardia gastric cancer (CGC/NCGC) associated with Helicobacter pylori (H. pylori) and quantify its contribution to gastric cancer burden using population attributable fraction (PAF). METHODS: PubMed, EMBASE, Web of Science, and Cochrane Central databases were searched by two reviewers until April 20, 2022. The association between H. pylori infection and NCGC/CGC was assessed using pooled odds ratios (ORs) with 95% confidence intervals (CIs). PAF was calculated using the formula of H. pylori prevalence and the pooled OR. RESULTS: One hundred and eight studies were included. A significant association was observed between H. pylori infection and NCGC in East Asia (OR, 4.36; 95% CI: 3.54-5.37) and the West (OR, 4.03; 95% CI: 2.59-6.27). Regarding CGC, a significant association was found only in East Asia (OR, 2.86; 95% CI: 2.26-3.63), not in the West (OR, 0.80; 95% CI: 0.61-1.05). For studies with a follow-up time of ≥10 years, pooled ORs for NCGC and CGC in East Asia were 5.58 (95% CI: 4.08-7.64) and 3.86 (95% CI: 2.69-5.55), respectively. Pooled OR for NCGC was 6.80 (95% CI: 3.78-12.25) in the West. PAFs showed that H. pylori infection accounted for 71.2% of NCGC, 60.7% of CGC in East Asia, and 73.2% of NCGC in the West. CONCLUSIONS: Gastric cancer burden associated with H. pylori infection exhibits important geographical differences. Prolonged follow-up period could overcome the underestimation of the magnitude of the association between H. pylori infection and CGC/NCGC. Customized strategies for H. pylori screening and eradication should be implemented to prevent gastric cancer.

Transmission routes and patterns of helicobacter pylori.

BACKGROUND AND OBJECTIVE: Helicobacter pylori (H. pylori), a gram-negative bacterium that colonizes the stomach, can cause chronic gastritis and peptic ulcers, as well as gastric cancer as a Class I carcinogen. However, the modes of H. pylori transmission are not clear. This review aims to clarify the transmission routes and patterns of H. pylori and identify efficacious prevention measures. METHODS: Studies of H. pylori transmission were identified using PubMed, the Web of Science, and Cochrane Central; the retrieval deadline was October 2022. RESULTS: The transmission routes of H. pylori are discussed, focusing on the five primary transmission routes, namely fecal-oral, oral-oral, gastric-oral, anal-oral, and genital-oral. We propose that H. pylori is contracted through multiple transmission routes. Additionally, we summarize the key transmission patterns of H. pylori, including person-to-person and animal-to-human transmission, as well as foodborne and occupational exposure. CONCLUSION: Fecal-oral appears to be the most common H. pylori transmission routes. Although the oral-oral pathway is also important, the evidence does not support that this route of transmission is universal. The gastric-oral route occurs primarily in children and patients who are prone to vomiting. Meanwhile, the anal-oral and genital-oral routes remain hypothetical. Person-to-person and foodborne infections represent the predominant transmission patterns of H. pylori, whereas strong environmental and occupational limitations are associated with animal-to-human and occupational exposure.

Efficacy and safety of a 14-day modified concomitant therapy for refractory Helicobacter pylori infection: a pilot study.

BACKGROUND AND AIM: After three treatment failures, Helicobacter pylori infection is deemed refractory as antibiotic treatment options become significantly limited. This study evaluated the efficacy and safety of a 14-day modified concomitant therapy for managing refractory H. pylori infection. METHODS: Patients who had failed to respond to three or more rounds of H. pylori therapies were recruited for this study. They received a 14-day modified concomitant therapy, including esomeprazole 40 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice daily and tetracycline 500 mg four times daily. Demographic data, adverse events, and patient compliance were recorded. The presence of H. pylori was reevaluated 6 weeks following treatment. Eradication rate was assessed as the primary outcome. RESULTS: Overall, 59 participants received the 14-day modified concomitant therapy. In the intention-to-treat and per-protocol analyses, the eradication rate was 84.7% (50/59) and 89.3% (50/56), respectively. H. pylori was successfully isolated from 75.0% (12/16) of patients. The resistance rate of H. pylori to metronidazole, levofloxacin, and clarithromycin was 91.7% (11/12), 58.3% (7/12), and 50.0% (6/12), respectively. Resistance to amoxicillin, furazolidone, or tetracycline was not observed. The frequency of adverse events was 35.6% (21/59), with no serious adverse events reported. CONCLUSION: The 14-day modified concomitant therapy appears to be appropriate for refractory H. pylori infection and is particularly promising for the Chinese population. A randomized controlled trial is warranted to verify its efficacy, especially in the current environment of increasing antibiotic resistance.

Efficacy and Safety of Vonoprazan and Amoxicillin Dual Therapy for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis.

INTRODUCTION: Vonoprazan, a novel potassium-competitive acid blocker, has a strong acid suppression effect and potent efficacy in acid-associated diseases, including Helicobacter pylori eradication. We performed a systematic review and meta-analysis to investigate the efficacy and safety of vonoprazan/amoxicillin dual therapy for H. pylori eradication. METHODS: We conducted a systematic literature search through PubMed, Web of Science, EMBASE, and the Cochrane Library up to June 2022, to identify randomized controlled trials and cohort studies comparing vonoprazan/amoxicillin dual therapy and triple therapies for H. pylori eradication. Primary outcomes were cure rates and relative efficacy. Secondary outcomes included adverse events, dropout rate, and subgroup analysis. RESULTS: Five studies with 1,852 patients were included in the analysis. The cure rates of vonoprazan/amoxicillin dual therapy were 85.6% with 95% confidence interval (CI) of 79.7-91.5% and 88.5% (95% CI: 83.2-93.8%) in the intention-to-treat and per-protocol analyses. The efficacy of vonoprazan/amoxicillin dual therapy was not inferior to that of triple therapy with pooled risk ratio (RR) of 1.03 (95% CI: 0.97-1.10) and 1.02 (95% CI: 0.98-1.08) in intention-to-treat and per-protocol analyses; while it was significantly superior to the omeprazole or lansoprazole-based triple therapy (RR = 1.15, 95% CI: 1.05-1.25, p = 0.001). For clarithromycin-resistant strains, vonoprazan/amoxicillin dual therapy showed superiority to vonoprazan-based triple therapy (86.7% vs. 71.4%, RR = 1.20, 95% CI: 1.03-1.39, p = 0.02); however, vonoprazan/amoxicillin dual therapy was significant inferior to vonoprazan-based triple therapy for clarithromycin-sensitive strains (83.0% vs. 92.8%, RR = 0.90, 95% CI: 0.85-0.95, p = 0.0002). The adverse effects of vonoprazan/amoxicillin dual therapy were lower than those of triple therapy (21.2% vs. 26.5%, RR = 0.86, 95% CI: 0.73-1.01, p = 0.06), especially the incidence of diarrhea (p = 0.01). CONCLUSIONS: The efficacy of vonoprazan/amoxicillin dual therapy is noninferior to vonoprazan-based triple therapy but superior to the omeprazole or lansoprazole-based triple therapy and has less side effects. Patients with clarithromycin-resistant strains are particularly expected to benefit from vonoprazan/amoxicillin dual therapy.

Efficacy of bismuth for antibiotic-resistant Helicobacter pylori strains eradication: A systematic review and meta-analysis.

BACKGROUND & AIMS: Antibiotic resistance of Helicobacter pylori (H. pylori) is increasing worldwide, and bismuth quadruple therapy has been recommended as a first-line regimen in many areas. This study aimed to investigate whether bismuth would improve the eradication rate (ER) of clarithromycin-/metronidazole-/levofloxacin-resistant H. pylori strains and how much additional efficacy bismuth could achieve. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Central databases for randomized controlled trials were systematically searched by two independent reviewers until 15 January 2022. Pooled ERs of clarithromycin-/metronidazole-/levofloxacin-resistant H. pylori strains were compared between bismuth-containing and non-bismuth therapies. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Eight studies enrolling 340 individuals were included. The RRs of pooled ERs compared between bismuth-containing and non-bismuth therapies were 1.83 for clarithromycin-resistant strains (95% CI 1.16-2.89, pooled ER: 76.9% vs. 36.6%, p = .009, I2  = 0%), 1.39 for metronidazole-resistant strains (95% CI 1.09-1.78, pooled ER: 86.8% vs. 60.9%, p = .008, I2  = 37%), 2.75 for dual clarithromycin/metronidazole-resistant strains (95% CI 1.01-7.52, pooled ER: 76.9% vs. 18.2%, p = .05, I2  = 0%), and 1.04 for levofloxacin-resistant strains (95% CI 0.56-1.93, pooled ER: 63.4% vs. 54.3%, p = .90; I2  = 60%). Bismuth significantly increased the ERs of clarithromycin-, metronidazole-, and dual-resistant strains by 40%, 26%, and 59%, respectively. Subgroup analysis of treatment duration showed that the significantly higher eradication rate for antibiotic-resistant strains in bismuth-containing therapy than non-bismuth therapy was only observed in 14-day treatment regimens and not in 7-day regimens (p = .02 and .17, respectively). CONCLUSIONS: Bismuth was most effective in improving the ERs of dual-resistant H. pylori strains, followed by clarithromycin- and metronidazole-resistant strains. Prolonged treatment duration might effectively improve the efficacy of bismuth in overcoming antibiotic resistance.

Low compliance to post-screening recommendations in a family-based Helicobacter pylori screening and treatment program: A prospective cohort study.

BACKGROUND: Intra-family transmission is an important Helicobacter pylori (H. pylori) infection route. Family-based screening and treatment of H. pylori is a promising strategy. However, limited data are available on patient compliance with post-screening recommendations for such a strategy. MATERIALS AND METHODS: A prospective cohort study of families from six regions in Shandong, China, from July 2021 to February 2022 was conducted. Demographic characteristics, prior testing, and treatment for H. pylori, prior gastroscopy, symptoms, and family history were collected. Infection status of participants was determined using the 13 C-urea breath test. Infected participants were recommended to undergo eradication treatment, confirmation testing, and gastroscopy per expert consensus. Participants were monitored for 6 months to record recommendation compliance in a real-world setting. Logistic regression models were used to analyze the factors influencing compliance with the recommendations. RESULTS: The study included 1173 individuals from 386 families with the overall infection rate of 36.7%. The recommendation compliance for eradication treatment, confirmation testing, and gastroscopy was 69.3% (271/391), 32.5% (88/271), and 6.1% (19/309), respectively. Factors that increased the risk of lower compliance were male sex (odds ratio [OR], 1.917, 95% confidence interval [CI], 1.233-2.981), and living in a non-urban area (OR, 1.954, 95% CI, 1.241-3.074), for treatment recommendations; having more than one infected family member (OR, 2.138, 95% CI, 1.237-3.698), and a lower family income (¥100,000-¥300,000 per year, OR, 7.247, 95% CI, 1.788-29.363; or <¥100,000 per year, OR, 7.294, 95% CI, 1.832-29.042), for confirmation testing recommendations; and being asymptomatic (OR, 3.009, 95% CI, 1.105-8.196), for gastroscopy recommendations. CONCLUSIONS: Post-screening recommendation compliance for this family-based H. pylori screening and treatment program was unsatisfactory. Further studies focusing on pre-screening education are warranted to improve compliance.

Clarithromycin versus furazolidone for naïve Helicobacter pylori infected patients in a high clarithromycin resistance area.

BACKGROUND AND AIM: The increase in antibiotic resistance makes the eradication of Helicobacter pylori more difficult. Considering the limitations of the application of susceptibility-guided therapy, it is important to find an effective empirical regimen. The aim of the study is to compare the efficacy, safety, and cost-effectiveness of clarithromycin-based bismuth-containing quadruple therapy (C-BQT) and furazolidone-based bismuth-containing quadruple therapy (F-BQT) in naïve H. pylori positive patients. METHODS: This was an open-label, randomized controlled, crossover trial. The trial comprised two phases. In C-F group, patients received C-BQT in the first phase; those who were still positive for H. pylori infection after the first phase entered the second phase to receive F-BQT as rescue treatment. In F-C group, patients were treated with F-BQT firstly and rescued with C-BQT. RESULTS: As first-line treatments, the eradication rates of C-BQT and F-BQT were 89.7% (157/175) and 92.0% (161/175) (P = 0.458) in intention-to-treat analysis and 93.4% (156/167) and 95.8% (161/168) (P = 0.327) in per-protocol analysis, respectively. The cumulative eradication rates of the C-F group and the F-C group were both 94.3% in intention-to-treat analysis (P = 1.000). Cost-effectiveness indexes of F-BQT and C-BQT were 0.54 and 1.24 in first-line treatments. Frequencies of adverse events in F-BQT and C-BQT had no differences (36.0% in C-BQT vs 32.6% in F-BQT, P = 0.499). CONCLUSIONS: Furazolidone-based bismuth-containing quadruple therapy should be preferred for its excellent cost-effectiveness and acceptable safety.

The cure rate of 10-day bismuth-containing quadruple therapy for Helicobacter pylori eradication is equivalent to 14-day: a systematic review and meta-analysis.

Helicobacter pylori (H. pylori) infection is a major cause of duodenal ulcers, gastric ulcers, and gastric cancer. However, the optimal duration for H. pylori eradication therapy remains controversial. Most studies have mainly focused on triple therapy, and there is insufficient research on bismuth-containing quadruple therapy. The aim of this study was to compare the clinical effect of the 10-day bismuth-containing quadruple treatment regimen with the 14-day regime in eradicating H. pylori. We searched PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials published in English until May 2022 according to the eligibility criteria. Summary risk ratios (RRs) and 95% confidence intervals (CIs) for eradication rates, adverse effects, and compliance were calculated for included studies. Four studies, involving 1173 patients, were eligible for inclusion. The eradication rate was similar in the 10-day treatment group and the 14-day treatment group in the intention-to-treat analysis (RR 0.97, 95% CI 0.93 to 1.01). Meanwhile, the incidence of adverse effects was lower in patients who received 10 days of treatment than in those who received 14 days of treatment and patients' compliance was almost the same between two groups. Compared to the 14-day bismuth-containing quadruple regimens, 10-day regimens had similar efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and well-tolerated and should be recommended for H. pylori infection.

Two Different 1-Week Quadruple Therapies Given Back-to-Back Consecutive Therapy for Difficult-to-Treat Helicobacter pylori Infection: A Pilot Study.

INTRODUCTION: We aim to evaluate the efficacy of 2 different 1-week quadruple therapies given back-to-back consecutive therapy in patients with difficult-to-treat Helicobacter pylori infection. METHODS: Patients with proven H. pylori infection were recruited after >3 failed standard quadruple eradication. They received consecutive therapy consisting of esomeprazole 40 mg or rabeprazole 20 mg twice daily, amoxicillin 1,000 mg twice daily, tetracycline 500 mg 4 times daily, and furazolidone 100 mg 3 times daily for the first 7 days, followed by colloidal bismuth pectin 200 mg twice daily in place of furazolidone 100 mg for another 7 days. Eradication rates, treatment-emergent adverse events (TEAEs), and compliance were assessed. RESULTS: Sixty-five patients were enrolled. The mean number of previous eradications was 3.6 (range: 3-7). The intention-to-treat and per-protocol eradication rates were 90.8% (59/65) and 95.1% (58/61). In total, 23.4% (15/64) of patients experienced drug-related TEAEs. No serious adverse events were observed. None of the patients required treatment for TEAEs, and 95.3% (61/64) showed good compliance. Overall, 51 patients (78.5%) were with the available antimicrobial susceptibility testing results. The resistance rates to clarithromycin, metronidazole, levofloxacin, and amoxicillin were 60.8% (31/51), 100% (51/51), 70.6% (36/51), and 2.0% (1/51), respectively. No resistance was detected to either furazolidone or tetracycline. However, in 54.9% of patients (28/51), H. pylori was resistant to 3 antibiotics (metronidazole, levofloxacin, and clarithromycin). DISCUSSION: Consecutive therapy, including amoxicillin, tetracycline, and furazolidone, achieved a good eradication rate (>90%), with desirable compliance and tolerability in difficult-to-treat H. pylori infection.