A randomized superiority clinical trial: metronidazole improved the efficacy of high-dose dual therapy in Helicobacter pylori rescue treatment.

BACKGROUND AND OBJECTIVES: High-dose dual therapy [proton pump inhibitor (PPI) + amoxicillin] is recommended as a Helicobacter pylori rescue treatment. However, its efficacy is still controversial. The aim of this study was to evaluate the efficacy and safety of triple therapy containing high dose of PPI and amoxicillin plus metronidazole compared with dual therapy in rescue treatment. METHODS: Two hundred and sixty-eight patients who failed at least two courses of H. pylori treatment were recruited and randomly allocated into two 14-day groups: esomeprazole 40 mg twice daily and amoxicillin 1000 mg three times daily plus metronidazole 400 mg three times daily (EAM group); or esomeprazole 40 mg twice daily and amoxicillin 1000 mg three times daily (EA group). The agar-dilution method was performed as an antibiotic susceptibility test. The 13C urea breath test was used to assess H. pylori eradication at 6 weeks after the treatment. The study was registered at clinicaltrials.gov (NCT04024527). RESULTS: H. pylori eradication rates in the EAM group were 85.8% (115/134, 95% CI 79.9%-91.7%) in ITT analysis and 92.6% (113/122, 95% CI 87.9%-97.3%) in PP analysis, significantly higher than those of the EA group, which were 73.1% (98/134, 95% CI 65.6%-80.6%) and 83.1% (98/118, 95% CI 76.8%-89.8%) (P = 0.005, 0.011). Resistance rates of amoxicillin and metronidazole were 6.6% (13/196) and 89.8% (176/196). Metronidazole resistance did not affect the eradication rates in the EAM group. Both groups had similar moderate and severe adverse events and similar compliance. CONCLUSIONS: A triple therapy containing high dose of PPI and amoxicillin plus metronidazole could be a potential rescue therapy worldwide even in a high metronidazole-resistance region.

Susceptibility-guided therapy for Helicobacter pylori-infected penicillin-allergic patients: A prospective clinical trial of first-line and rescue therapies.

BACKGROUND: Helicobacter pylori (H pylori) treatment remains a challenge for penicillin-allergic patients. AIM: To evaluate the efficacy and tolerability of susceptibility-guided first-line and rescue treatment in H pylori-infected penicillin-allergic patients. METHODS: Consecutive H pylori-infected patients with penicillin allergy received a 14-day triple or quadruple therapy based on susceptibility to clarithromycin, levofloxacin, and metronidazole. All received esomeprazole 20 mg twice a day. Metronidazole-susceptible infections received metronidazole plus clarithromycin or levofloxacin triple therapy if susceptible. Clarithromycin- and levofloxacin-resistant infections received metronidazole plus tetracycline triple therapy. Metronidazole-resistant infections received a bismuth-high-dose metronidazole plus clarithromycin or levofloxacin quadruple therapy. Triple-resistant infections received classical bismuth quadruple therapy with high-dose metronidazole. Antimicrobial susceptibility was assessed using the E test method. RESULTS: 112 patients were entered (34.8% men, average 47.1 years). Infections in 83.8% (31/37) of treatment-naive subjects and 12.0% (9/75) (P < .001) receiving rescue treatment were susceptible to at least one of the three tested antibiotics. Overall, susceptibility-guided therapy achieved eradication rates of 92.9% (104/112, 95% CI 88.1%-97.7%) by intent-to-treat analysis and 99% (100/101, 95% CI 97.1%-100%) by per-protocol analysis. All regimens achieved eradication rates greater than 90% (P = .327) in the PP populations. Adverse events were relatively frequent; however, compliance remained high. CONCLUSION: Susceptibility-guided therapy proved highly effective for penicillin-allergic patients. When available and proven locally effective, the alternative was empiric classical bismuth quadruple therapy. This trial is registered with ClinicalTrials.gov as NCT03708848.

14-Day High-Dose Amoxicillin- and Metronidazole-Containing Triple Therapy With or Without Bismuth as First-Line Helicobacter pylori Treatment.

BACKGROUND: Amoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy had been shown to reliably achieve high eradication rates. The role of individual components remains undefined. AIM: To identify the additional benefit/role of bismuth in amoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. METHODS: This was a non-inferiority factorial design trial. Treatment-naive H. pylori-infected subjects were randomly (1:1) assigned to receive 14-day amoxicillin- and metronidazole-containing triple therapy consisting of esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg both thrice daily with or without 220 mg bismuth twice a day. Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. RESULTS: From July 2018 to June 2019, a total of two hundred and sixteen subjects were randomized. Both therapies achieved high eradication rates. Per-protocol with bismuth = 97.9% (94/96, 95% CI 95.1-100%) and without bismuth = 94.7% (90/95, 95% CI 90.3-99.1%) (P = 0.43). Intent-to-treat analysis = 90.7% (98/108, 95% CI 85.2-96.2%) versus 88.9% (96/108, 95% CI 82.8-95.0%) with and without bismuth (P = 0.65). The two regimens were not inferior by intent-to-treat or per-protocol analyses. Metronidazole resistance did not affect the efficacy of either therapy. CONCLUSION: Neither the presence nor absence of bismuth or metronidazole resistance reduced the effectiveness of triple therapy containing esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg thrice daily in this population. The clinical trial was registered with ClinicalTrials.gov, NCT03557437.

Susceptibility-guided therapy for Helicobacter pylori infection treatment failures.

BACKGROUND: Empirical therapy of Helicobacter pylori frequently results in treatment failure due to unrecognized antimicrobial resistance. The aim of this study was to investigate the effectiveness of susceptibility-guided therapy for rescue treatment of H. pylori infection in China. METHODS: This was a prospective study of consecutive 200 patients infected with H. pylori with one or more treatment failures. The therapy chosen was susceptibility based using the most effective, best-tolerated regimens first and a locally proven, reliably effective regimen for multidrug-resistant infections. All patients received 14-day triple therapy, i.e. esomeprazole 20 mg and amoxicillin 1 g twice a day plus clarithromycin 500 mg twice a day, metronidazole 400 mg twice a day, or levofloxacin 500 mg daily, or, for multidrug-resistant infections, amoxicillin-containing bismuth quadruple therapy with esomeprazole 20 mg twice a day, bismuth 220 mg twice a day, amoxicillin 1 g three times a day, and metronidazole 400 mg four times a day. Antibiotic resistance was determined by agar dilution. RESULTS: The eradication rate of susceptibility-guided therapy overall was 94.5% (189/200, 95% confidence interval: 90.4-97.2%). Around 28% (56/200) of patients carried strains susceptible to one of the tested antibiotics and were prescribed the triple therapy. A total of 144 multidrug-resistant patients received bismuth quadruple therapy. The eradication rates were all greater than 90%, i.e. 91.7% (11/12), 92.3% (12/13), and 93.5% (29/31) in those who received clarithromycin, metronidazole, and levofloxacin-containing triple therapy and 95.1% (137/144) for the bismuth quadruple therapy. There were no differences in eradication rates between the subgroups. CONCLUSIONS: Although susceptibility-guided therapy proved high efficacious despite the high proportion of multidrug-resistant strains, the strategy suggested the best approach for this population would be empirical amoxicillin-containing bismuth quadruple therapy. ClinicalTrials.gov identifier: NCT03413020.

High-dose PPI-amoxicillin dual therapy with or without bismuth for first-line Helicobacter pylori therapy: A randomized trial.

BACKGROUND: A reliably highly effective high-dose proton-pump inhibitor plus amoxicillin (dual Helicobacter pylori therapy) has remained elusive. We compared whether the addition of bismuth to high-dose dual therapy would improve the efficacy of high-dose dual therapy as first-line treatment. METHODS: This was an open-label, randomized single-center study of 160 treatment-naive patients with H. pylori infection who were randomly assigned to 14-day therapy with esomeprazole 40 mg twice a day plus amoxicillin 1 g three times a day with or without bismuth potassium citrate 600 mg (elemental bismuth 220 mg) twice a day. Antibiotic resistance was determined by agar dilution method and eradication by 13 C-urea breath test. RESULTS: The per-protocol eradication rates were 96.1%; 95% CI = 88.9%-99.2% (73/76) without bismuth vs 93.3%; 95% CI = 85.1%-97.8% (70/75) with bismuth (P = 0.494). The intention-to-treat eradication rates were 92.5%; 95% CI = 84.4%-97.2% (74/80) without bismuth and 88.8%; 95% CI = 79.7%-94.7% (71/80) with bismuth (P = 0.416). Resistance to amoxicillin, clarithromycin, metronidazole, and levofloxacin was 0%, 31.7%, 81.4%, and 40.7%, respectively. Smoking reduced treatment effectiveness limited to those not receiving bismuth. The per-protocol eradication rates were 70% (7/10) vs 100% (66/66) in smokers vs non-smokers without bismuth (P = 0.002), and 100% (10/10) in smokers vs 92.3% (60/65) in non-smokers with bismuth (P = 1.0). The adverse event rates were 7.5% (6/80) without bismuth vs 11.3% (9/80) with bismuth (P = 0.416). CONCLUSIONS: Fourteen-day high-dose dual therapy was both effective and safe for first-line treatment in a region of high prevalence antibiotic resistance. Adding bismuth only improved treatment effectiveness among smokers.

Serum Albumin and C-Reactive Protein/Albumin Ratio Are Useful Biomarkers of Crohn's Disease Activity.

BACKGROUND Serum albumin (ALB) may be low during acute inflammation, but it is also affected by nutritional status. Therefore, we hypothesized that ALB and the C-reactive protein/ALB ratio (CRP/ALB) may be associated with disease activity in patients with Crohn's disease (CD). MATERIAL AND METHODS Altogether, 100 patients with CD and 100 age- and sex-matched healthy volunteers were retrospectively enrolled in the current study. The patients with CD were subdivided into patients with active disease (Crohn's Disease Activity Index >150) and those in remission. ALB levels, CRP levels, and lipid profiles were measured. RESULTS ALB and CRP levels and the CRP/ALB ratio were the most useful for differentiating between active and nonactive CD. ALB levels (r=-0.50, P<0.01), CRP levels (r=0.39, P<0.01), and CRP/ALB ratio (r=0.42, P<0.01) all correlated with CD activity. These correlations were more prominent in males. Receiver Operating Characteristic (ROC) analysis indicated that the area under the curve (AUC) representing ALB (0.79) was higher than the AUC representing CRP (0.73) or CRP/ALB ratio (0.75; P>0.05). The AUCs corresponding to ALB level, CRP level, and CRP/ALB ratio were more prominent in males versus females (P<0.05). CRP level (14.55 mg/L), ALB level (34.35 g/L), and CRP/ALB ratio (0.69) had sensitivities of 67.7%, 72.6%, and 59.7%, and specificities of 73.7%, 78.9%, and 81.6%, respectively, for CD activity. CONCLUSIONS In the present retrospective study, we found that ALB level and CRP/ALB ratio were useful biomarkers for identifying CD activity, especially in males. These results suggest that, in addition to inflammation, assessment of patient nutritional status could also aid in identifying CD activity.

The value of the apoB/apoAΙ ratio and the non-HDL-C/HDL-C ratio in predicting carotid atherosclerosis among Chinese individuals with metabolic syndrome: a cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) is associated with carotid intima-media thickness (CIMT), which is a good predictor of cardiovascular disease (CVD). However, among individuals with MetS, direct comparative data regarding the utility of the apoB/apoAΙ ratio and the non-HDL-C/HDL-C ratio to diagnose carotid atherosclerosis are scarce, particularly in Chinese populations. We aimed to determine the relationship between the apoB/apoAΙ ratio and the non-HDL-C/HDL-C ratio and carotid atherosclerosis among Chinese individuals with MetS. METHODS: We performed a retrospective study of 5822 Chinese participants who underwent a routine health screening examination. Lipid profiles, fasting glucose, fasting insulin, CRP, apoB, apoAΙ and CIMT were measured. RESULTS: We observed that among Chinese individuals with MetS, men (53.95±0.58 ys) developed carotid atherosclerosis at a younger age than women (58.47±1.17 ys) (P<0.001). Both the apoB/apoAΙ ratio and the non-HDL-C/HDL-C ratio positively correlated with carotid atherosclerosis among Chinese individuals with MetS, particularly among women. Meanwhile, CIMT increased progressively across the quartiles of the non-HDL-C/HDL-C ratio (P for trend, <0.05). Receiver Operating Characteristic (ROC) analysis indicated that the AUC of the apoB/apoAΙ ratio (0.561) was higher than that of the non-HDL-C/HDL-C ratio (0.522) in men (P<0.05) and the AUC of the apoB/apoAΙ ratio (0.640) was lower than that of the non-HDL-C/HDL-C ratio (0.695) in women (P<0.05). Among Chinese individuals with MetS, the AUC of the non-HDL-C/HDL-C ratio was more prominent among women compared with men (P<0.05). CONCLUSION: Our findings indicate that among individuals with MetS, Chinese men develop carotid atherosclerosis at a much younger age than women. There were no significant differences between the apoB/apoAΙ ratio and the non-HDL-C/HDL-C ratio for the prediction of carotid atherosclerosis among Chinese individuals with MetS. Among Chinese individuals with MetS, the utility of the non-HDL-C/HDL-C ratio was found to be greater among women than among men.

Cantharidin induces G2/M phase arrest and apoptosis in human gastric cancer SGC-7901 and BGC-823 cells.

The aim of the present study was to investigate the effect of cantharidin (CTD) on human gastric cancer cells and to explore the underlying mechanisms of these effects. The human gastric cancer SGC-7901 and BGC-823 cell lines were treated with CTD. MTS assays were then employed to examine cellular proliferation, flow cytometry was used to analyze the cell cycle and apoptosis, and western blot analysis was used to determine protein expression levels. It was found that CTD inhibited the proliferation of the human gastric cancer SGC-7901 and BGC-823 cells in a dose- and time-dependent manner in vitro. CTD also induced G2/M phase arrest and cellular apoptosis in a dose-dependent manner. In addition, CTD increased the levels of p21, caspase-7, -8 and -9, activated caspase-3, poly ADP ribose polymerase and Bad, but decreased the levels of cyclin-dependent kinase 1, cyclin A and B, B-cell lymphoma-2 (Bcl-2) and Bid. The present results suggested that CTD may inhibit the proliferation of human gastric cancer SGC-7901 and BGC-823 cells in vitro by inducing G2/M phase arrest and cell apoptosis. CTD may induce cellular G2/M phase arrest by regulating cycle-associated proteins and induce apoptosis by activating a caspase cascade or regulating the Bcl-2 family proteins.

Decision tree analysis of traditional risk factors of carotid atherosclerosis and a cutpoint-based prevention strategy.

BACKGROUND: Reducing the exposure to risk factors for the prevention of cardio-cerebral vascular disease is a crucial issue. Few reports have described practical interventions for preventing cardiovascular disease in different genders and age groups, particularly detailed and specific cutpoint-based prevention strategies. METHODS: We collected the health examination data of 5822 subjects between 20 and 80 years of age. The administration of medical questionnaires and physical examinations and the measurement of blood pressure, fasting plasma glucose (FPG) and blood lipids [total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C)] were performed by physicians. Carotid ultrasound was performed to examine the carotid intima-media thickness (CIMT), which was defined as carotid atherosclerosis when CIMT ≥0.9 mm. Decision tree analysis was used to screen for the most important risk factors for carotid atherosclerosis and to identify the relevant cutpoints. RESULTS: In the study population, the incidence of carotid atherosclerosis was 12.20% (men: 14.10%, women: 9.20%). The statistical analysis showed significant differences in carotid atherosclerosis incidence between different genders (P<0.0001) and age groups (P<0.001). The decision tree analysis showed that in men, the most important traditional risk factors for carotid atherosclerosis were TC (cutpoint [CP]: 6.31 mmol/L) between the ages of 20-40 and FPG (CP: 5.79 mmol/L) between the ages of 41-59. By comparison, LDL-C (CP: 4.27 mmol/L) became the major risk factor when FPG ≤5.79 mmol/L. FPG (CP: 5.52 mmol/L) and TG (CP: 1.51 mmol/L) were the most important traditional risk factors for women between 20-40 and 41-59 years of age, respectively. CONCLUSION: Traditional risk factors and relevant cutpoints were not identical in different genders and age groups. A specific gender and age group-based cutpoint strategy might contribute to preventing cardiovascular disease.

Fecal lactoferrin in discriminating inflammatory bowel disease from irritable bowel syndrome: a diagnostic meta-analysis.

BACKGROUND: To perform a meta-analysis evaluating the diagnostic ability of fecal lactoferrin (FL) to distinguish inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS). METHODS: The Medline, EMBASE, Web of Science, Cochrane library and CNKI databases were systematically searched for studies that used FL concentrations to distinguish between IBD and IBS. The sensitivity, specificity, and other diagnostic indexes of FL were pooled using a random-effects model. RESULTS: Seven studies, involving 1012 patients, were eligible for inclusion. In distinguishing IBD from IBS, FL had a pooled sensitivity of 0.78 (95% confidence interval [CI]: 0.75, 0.82), a specificity of 0.94 (95% CI: 0.91, 0.96), a positive likelihood ratio of 12.31 (95% CI: 5.93, 29.15), and a negative likelihood ratio of 0.23 (95% CI: 0.18, 0.29). The area under the summary receiver-operating characteristic curve was 0.94 (95% CI: 0.90, 0.98) and the diagnostic odds ratio was 52.65 (95% CI: 25.69, 107.91). CONCLUSIONS: FL, as a noninvasive and simple marker, is useful in differentiating between IBD and IBS.

Non-essential amino acids attenuate apoptosis of gastric cancer cells induced by glucose starvation.

Energy and nutrition are essential requirements for all living cells, including cancer cells. In the initiating stage of cancer in organs, cancer cells grow fast and have inadequate supplies of glucose, oxygen and other nutrients due to deficient angiogenesis. Anaerobic conditions cause cancer cells to rely on glycolysis, which produces pyruvate and ATP that can be used by cancer cells to survive. However, glucose starvation may result in apoptosis or necrosis of cancer cells. It has been reported that autophagy is a consequence of glucose starvation and that amino acids are products of autophagy. The present study investigated whether amino acids may represent an alternative energy source for cancer cells undergoing glucose starvation. With non-essential amino acids, growth inhibition and apoptosis of gastric cancer cells induced by glucose starvation were attenuated compared with that of cells undergoing glucose starvation without amino acids, as measured by cell viability, apoptosis rates, membrane potential of mitochondria, and apoptosis-related genes. Meanwhile, both mitochondrial DNA copy number and amino acid transporter genes were increased compared with those in control cells. Non-essential amino acids prevented gastric cancer cells from glucose starvation-induced apoptosis.

Normal fibroblasts induce E-cadherin loss and increase lymph node metastasis in gastric cancer.

BACKGROUND: A tumor is considered a heterogeneous complex in a three-dimensional environment that is flush with pathophysiological and biomechanical signals. Cell-stroma interactions guide the development and generation of tumors. Here, we evaluate the contributions of normal fibroblasts to gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: By coculturing normal fibroblasts in monolayers of BGC-823 gastric cancer cells, tumor cells sporadically developed short, spindle-like morphological characteristics and demonstrated enhanced proliferation and invasive potential. Furthermore, the transformed tumor cells demonstrated decreased tumor formation and increased lymphomatic and intestinal metastatic potential. Non-transformed BGC-823 cells, in contrast, demonstrated primary tumor formation and delayed intestinal and lymph node invasion. We also observed E-cadherin loss and the upregulation of vimentin expression in the transformed tumor cells, which suggested that the increase in metastasis was induced by epithelial-to-mesenchymal transition. CONCLUSION: Collectively, our data indicated that normal fibroblasts sufficiently induce epithelial-to-mesenchymal transition in cancer cells, thereby leading to metastasis.

Composition analysis and application of degradation products of whole feathers through a large scale of fermentation.

PURPOSE: Feathers are one of the most abundant bioresources. They are discarded as waste in most cases and could cause environmental pollution. On the other hand, keratin constituted by amino acids is the main component of feathers. In this article, we reported on biorefined feathers and integrants and application of degraded products. MATERIALS AND METHODS: The fermentation of whole chicken feathers with Stenotrophomonas maltophilia DHHJ in a scale-up of a 5-L bioreactor was investigated in this article. The fermentation process was controlled at 0.08 MPa pressure, 2.5 L/min airflow, and 300 rpm as 100% oxygen saturation level, 40°C, and pH 7.8. RESULTS: Feathers were almost completely degraded in the tested fermentation reaction with the following conditions: 80 g of whole feathers in 3 L fermentation broth for 72 h, seed age of 16 h, 100 mL inoculation amount, and 50% oxygen saturation level. The degraded products contain 397.1 mg/L soluble protein that has mass weight ranging from 10 to 160 kD, 336.9 mg/L amino acids, and many kinds of metal ions. The fermentation broth was evaluated as leaf fertilizer and found to increase plant growth to 82% or 66% for two- or fourfold dilutions, respectively. In addition, in a hair care assay, the broth showed a hair protective function by increasing weight, flexibility, and strength of the treated hair. CONCLUSIONS: The whole feathers were degraded completely by S. maltophilia DHHJ. The degraded product includes many factors to life, such as peptides, amino acids, and mineral elements. It could be applied as leaf fertilizer and hair care product.