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Iron lies at the center of a battle for nutritional resource between higher organisms and their microbial pathogens. The iron status of the human host affects the pathogenicity of numerous infections including malaria, HIV-1, and tuberculosis. Hepcidin, an antimicrobial-like peptide hormone, has emerged as the master regulator of iron metabolism. Hepcidin controls the absorption of dietary iron and the distribution of iron among cell types in the body, and its synthesis is regulated by both iron and innate immunity. We describe how hepcidin integrates signals from diverse physiological inputs, forming a key molecular bridge between iron trafficking and response to infection.

The AP1 transcription factor Batf3 is required for homeostatic development of CD8α + classical dendritic cells that prime CD8 T-cell responses against intracellular pathogens. Here we identify an alternative, Batf3 -independent pathway in mice for CD8α + dendritic cell development operating during infection with intracellular pathogens and mediated by the cytokines interleukin (IL)-12 and interferon-γ. This alternative pathway results from molecular compensation for Batf3 provided by the related AP1 factors Batf , which also functions in T and B cells, and Batf2 induced by cytokines in response to infection. Reciprocally, physiological compensation between Batf and Batf3 also occurs in T cells for expression of IL-10 and CTLA4. Compensation among BATF factors is based on the shared capacity of their leucine zipper domains to interact with non-AP1 factors such as IRF4 and IRF8 to mediate cooperative gene activation. Conceivably, manipulating this alternative pathway of dendritic cell development could be of value in augmenting immune responses to vaccines. The roles of BATF transcription factors in dendritic cell differentiation are studied, providing evidence for molecular compensation by related family members; compensation is based on the interaction of the BATF leucine zipper domains with IRF factors to mediate cooperative gene activation. Immune responses linked to BATF–IRF4 Kenneth Murphy and colleagues study the roles of the AP-1 transcription factor BATF in dendritic-cell differentiation — a process that primes CD8 + T-cell responses to intracellular pathogens — and provide evidence for molecular compensation by related family members. Compensation is based on the interaction of the BATF leucine-zipper domains with the interferon regulatory factors IRF4 and IRF8 to mediate cooperative gene activation. In a complementary study, Warren Leonard and colleagues provide evidence that IRF4 regulates CD4 + T-cell differentiation and T H 17 function by cooperative binding interactions with the AP-1 family members BATF and JUN. These studies point to potential new targets for manipulating key immune responses that depend on BATF–IRF4 interactions.

The recent availability of susceptibility testing for Helicobacter pylori infections in the United Sates has resulted in paradigm shifts in the diagnosis, therapy, and follow-up of H. pylori infections. Here, we reviewed the English literature concerning changes in H. pylori diagnosis and therapy with an emphasis on the last 3 years. We focus on the new methods that offer rapid and convenient susceptibility testing using either invasive (endoscopic) or noninvasive (stool) methods of obtaining test material. We also discuss the implications of this availability on therapy and follow-up after therapy. The approach to therapy was categorized into four groups: (1) therapies that can be used empirically, (2) therapies that should be restricted to those that are susceptibility-based, (3) potentially effective therapies that have yet to be optimized for local use, and (4), therapies that contain unneeded antibiotics that should not be prescribed. The most convenient and efficient method of susceptibility testing is by using reflexive stool testing in which if the sample is positive, it is automatically also used for determination of susceptibility. Reflexive testing can also be done via reflexive ordering (e.g., for all positive urea breath tests). The post therapy test-of-cure has emerged as a critical component of therapy as it not only provides feedback regarding treatment success but when combined with susceptibility testing also provide evidence regarding the cause of failure (e.g., poor adherence versus emergence of resistance during therapy. Susceptibility testing has made even the most current H. pylori guidelines for diagnosis and therapy generally obsolete. Clarithromycin, metronidazole, and levofloxacin triple therapies should only be administered as susceptibility-based therapy. Regimens containing unneeded antibiotics should not be given. We provide recommendations regarding the details and indications for all current therapies.

Background: Helicobacter pylori (H. pylori) is a group 1 carcinogen and the etiological agent of gastric diseases such as gastritis, ulcers, and gastric cancer. It infects approximately half of the world’s population. Risk factors associated with H. pylori infection include socioeconomic status, lifestyle, and diet. Objectives: This study aimed to evaluate the association between eating habits and H. pylori infection in patients from a reference hospital in Central Brazil. Design: This cross-sectional study included 156 patients from 2019 to 2022. Methods: Data were collected using a structured questionnaire on sociodemographic and lifestyle characteristics and a validated food frequency questionnaire. The H. pylori infection status (positive versus negative) was determined using the histopathological method. After grams/day, foods were stratified into tertiles of consumption (low, medium, and high). Simple and multiple binary logistic regression models were used in the analysis of odds ratios (ORs) and their respective 95% confidence intervals (CIs), with a 5% significance level. Results: The prevalence of H. pylori infection was 44.2% (69/156 patients). Infected individuals had a mean age of 49.6 ± 14.6 years; 40.6% were men, 34.8% were aged 60 years or older, 42.0% were unmarried, 7.2% had higher education, 72.5% were non-white, and 30.4% were obese. In the H. pylori-positive group, 55.1% were alcohol drinkers and 42.0% were smokers. The results of multiple analyses showed that the chance of H. pylori infection was higher among male participants (OR = 2.25; CI = 1.09–4.68) and individuals with obesity (OR = 2.68; CI = 1.10–6.51). Participants with moderate consumption of refined grains (bread, cookies, cakes, breakfast cereal) (OR = 2.41; CI = 1.04–5.62) and fruits (OR = 2.53; CI = 1.08–5.94) were more likely to be infected. Conclusion: In this study, male sex, obesity, and the consumption of refined grains and fruits were positively associated with H. pylori infection. Further research is needed to investigate this association and elucidate the underlying mechanisms.

Nosocomial, or hospital-acquired, infections (more appropriately called health care–associated infections) are today by far the most common complications affecting hospitalized patients. Indeed, the Harvard Medical Practice Study II found that a single type of nosocomial infection — surgical-wound infection — constituted the second-largest category of adverse events. 1 Long considered the greatest risk that the hospital environment poses to patients, 2 nosocomial infections abruptly became the province of public health officers at the time of a nationwide epidemic of hospital-based staphylococcal infections, in 1957 and 1958. 3 Since then, the study and control of nosocomial infections have been profoundly shaped by the discipline . . .

Current international consensuses on Helicobacter pylori eradication therapy recommend that only regimens that reliably produce eradication rates of ⩾90% should be used for empirical treatment. The Real-world Practice & Expectation of Asia-Pacific Physicians and Patients in Helicobacter Pylori Eradication Survey also showed that the accepted minimal eradication rate in H. pylori-infected patients was 91%. According to efficacy prediction model, the per-protocol eradication rates of 7-day and 14-day standard triple therapies fall below 90% when clarithromycin resistance rate ⩾5%. Several strategies including bismuth-containing, non-bismuth-containing quadruple therapies (including sequential, concomitant, hybrid and reverse hybrid therapies), high-dose dual therapy and vonoprazan-based triple therapy have been proposed to increase the eradication rate of H. pylori infection. According to efficacy prediction model, the eradication rate of 14-day concomitant therapy, 14-day hybrid therapy and 7-day vonoprazan-based triple therapy is less than 90% if the frequency of clarithromycin-resistant strains is higher than 90%, 58% and 23%, respectively. To meet the recommendation of the consensus report and patients’ expectation, local surveillance networks for resistance of H. pylori to clarithromycin are required to select appropriate eradication regimens in each geographic region. In areas with low (<5%) clarithromycin resistance (e.g. Sweden, Philippine, Myanmar and Bhutan), 7-day and 14-day standard triple therapies can be adopted for the first-line treatment of H. pylori infection with eradication rates of ⩾90%. In areas with high (⩾5%) clarithromycin resistance (most other countries worldwide) or unknown clarithromycin resistance, 14-day hybrid, 14-day reverse hybrid, 14-day concomitant and 10- to 14-day bismuth quadruple therapy can be used to treat H. pylori infection.

Background: We previously reported that antofloxacin-based bismuth quadruple therapy was safe and effective for Helicobacter pylori (H. pylori) eradication. It is not clear whether the addition of Saccharomyces boulardii (S. boulardii) to antofloxacin-based quadruple therapy can improve the eradication rate of H. pylori and reduce adverse events. Objective: To investigate the effect of adding S. boulardii to antofloxacin-based quadruple therapy on the eradication rate of H. pylori and the adverse events. Design: Single-center, prospective randomized controlled study. Methods: A total of 172 patients with H. pylori infection were randomly assigned to the test and control groups. Patients in the control group (n = 86) received antofloxacin-based bismuth quadruple therapy for 14 days. On this basis, cases in the test group (n = 86) received S. boulardii 500 mg b.i.d. The eradication rate of H. pylori and adverse events were observed 4 weeks after the treatment. Results: There were no statistically significant differences in the eradication rates of H. pylori and frequency of diarrhea between the test group and control group (p > 0.05). The duration of diarrhea in the test group was significantly shorter than in the control group (p < 0.001). In addition, the two groups exhibited similar adverse event rates for epigastric pain, abdominal distention, dizzy, vomiting, and rash (p > 0.05). The severity of adverse reactions was similar between the two groups (p > 0.05), and most of them had mild adverse events. Conclusion: Although the addition of S. boulardii to antofloxacin-based quadruple therapy could not improve the eradication rate of H. pylori, it could shorten the time of antibiotic-associated diarrhea and reduce the incidence of diarrhea. Trial registration number: ChiCTR2200056931.

Since the discovery of Helicobacter pylori (H. pylori) as the causative organism for gastric and duodenal ulcers four decades ago and subsequent recognition as class 1 gastric carcinogen, countless numbers of studies have been conducted and papers published, on the efficacy of various management strategies to eradicate the infection. In adults, a global consensus by the experts in the field concluded that H. pylori gastritis is an infectious disease and requires treatment irrespective of the presence or absence of symptoms due to the potential for serious complication like peptic ulcer disease and gastric neoplasia. However, although more than half the world’s population harbors H. pylori, these serious complications occur only in a small minority of the infected population, even less so in childhood. More importantly, there is accumulating evidence for beneficial role of H. pylori against many chronic health conditions, from several epidemiological and laboratory studies. No doubt, eradication therapy is indicated in children with H. pylori-related peptic ulcer disease. Even though the pediatric guidelines from various learned societies recommend against a “test and treat” strategy, this is not always adhered to. With the accumulating evidence of the possible beneficial role of H. pylori, it is time to pause and think, are we causing more harm than good by eradicating H. pylori in every child who has this bug?

Background and objective: Recently, a large number of trials on proton pump inhibitor-amoxicillin-containing high-dose dual therapy (HDDT) versus bismuth-containing quadruple therapy (BQT) for Helicobacter pylori (H. pylori) eradication have been published with controversial and inconsistent conclusions. The aim of this meta-analysis was to determine the effects of HDDT for H. pylori eradication compared to BQT. Design: A systematic review and meta-analysis was conducted. Methods: PubMed, Embase, and the Cochrane library database were searched to collect all randomized controlled trials (RCTs) assessing the effects of HDDT versus BQT to H. pylori eradication from inception to September 2022. Meta-analysis was conducted to estimate the pooled relative risk (RR) with 95% confidence intervals (CIs) using a random-effects model. Quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluation system. Trial sequential analysis (TSA) was performed to determine the reliability and conclusiveness. Results: A total of 14 RCTs with 5121 patients were included. The results of meta-analysis showed that there was no statistical significance in the eradication rate between HDDT and BQT (intention-to-treat analysis: 86.7% versus 85.1%, RR = 1.01, 95% CI: 0.98–1.04; per-protocol analysis: 89.9% versus 89.4%, RR = 1.01, 95% CI: 0.98–1.03; moderate-quality evidence). The incidence of total adverse effects in HDDT group was significantly lower than in BQT group (5.9% versus 34.1%, RR = 0.42, 95% CI: 0.34–0.50; low-quality evidence). No statistical significance was observed in compliance between HDDT and BQT (RR = 1.01, 95% CI, 1.00–1.03, p = 0.07; low-quality evidence). The TSA result for H. pylori eradication rate indicated that the effect was conclusive. Conclusions: Evidence from our updated meta-analysis suggests that HDDT is as effective as BQT in eradicating H. pylori, with fewer adverse effects and similar compliance. Registration: Open Science Framework registries (No: osf.io/th4vd)