Association of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> with hepatobiliary stone disease,a prospective case control study

Background

Hepatobiliary stone disease is one of the most common surgical conditions worldwide. There are multiple causative agents responsible for the formation of hepatobiliary stones, and bacterial infection is one of them. The presence of Helicobacter DNA species has been investigated in the biliary epithelium of patients with biliary diseases. However, conflicting results have been observed that may have been due to the small number of subjects studied, difficulty in obtaining a healthy control group, absence of controlling for confounding factors, or ethical and regional differences among populations.

Methods

We investigated the presence of Helicobacter pylori species by PCR of 26-kDa surface antigen specific to H. pylori in bile samples from 50 cases with hepatobiliary stones and 25 controls without hepatobiliary stones. The control group comprised of 20 patients of hydatid cyst disease of liver and 5 patients of right colonic growth.

Result

H. pylori was present in 20 bile samples among cases and was absent in 30 bile samples among cases. Among controls, H. pylori could not be detected. A significant association of the presence of H. pylori with hepatobiliary stone disease was seen (p < 0.001).

Conclusion

There is an association between bile infection with H. pylori and hepatobiliary stone disease.

     

Enhanced Expression of CXCL13 in Human <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-Associated Gastritis

Background and Aims

Chemokine CXC ligand 13 (CXCL13) and CXC receptor type 5 (CXCR5) are constitutively expressed in tertiary lymphoid follicles where the CXCL13/CXCR5 system regulates B lymphocytes homing. In this study, we sought to examine CXCL13 expression in the H. pylori-infected and -uninfected gastric mucosa and to elucidate the implication in the pathogenesis of HAG in humans.

Methods

Using endoscopic biopsies taken from the gastric antrum of 29 subjects infected with Helicobacter pylori and 22 uninfected subjects, mucosal CXCL13 mRNA and protein levels were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.

Results

The CXCL13 expression levels were significantly more elevated in H. pylori-positive patients than uninfected ones. The CXCL13 expression levels correlated with the degree of chronic gastritis and bacterial colonization. Immunohistochemistry and in vitro infection assay showed that CXCL13 was not produced by the gastric epithelium, but the α-smooth muscle antigen expressing mesenchymal cells were the possible source of CXCL13 within H. pylori-infected gastric mucosa. CXCR5 immunostaining was seen in the CD20-positive lymphoid aggregates.

Conclusions

The enhanced induction of CXCL13 may be involved in the pathogenesis of H. pylori-associated gastritis.

     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection: New Facts in Clinical Management

Purpose

The global prevalence of Helicobacter pylori remains high in spite of its significant downwards trajectory in many regions. The clinical management of H. pylori infection merits guidance to meet ongoing challenges on whom and how to test, prevent, and cure related diseases.

Recent findings

Several international guidelines and consensus reports have updated the management strategies for cure of the H. pylori infection. The definition of H. pylori gastritis as an infectious disease independent of whether or not presenting with clinical manifestations and symptoms has broadened the use of the test and treat strategy. Patients on selected long-term medications, such as aspirin, other anti-platelet agents, NSAIDs, and PPIs should be considered for H. pylori test and treat. Important progress is made with initiatives in primary and secondary gastric cancer prevention. Uncertainties persist in the interpretation of the role of H. pylori in association with extragastric diseases. Selection of therapies needs to address individual antibiotic resistance and regional surveillance of resistance for the adoption of an effective treatment algorithm.

Conclusion

Clinical aspects of H. pylori infection have evolved over time and the therapeutic management requires continuous adaptation. A vaccine is still a non-fulfilled promise. The future will tell us more about the role of H. pylori in interactions with the gut microbiome.

     

Primary Antibiotic Resistance of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> in China

Background and Aims

Antibiotic resistance is the most important factor leading to the failure of eradication regimens; thus, it is important to obtain regional antibiotic resistance information. This review focuses on the prevalence of Helicobacter pylori primary resistance to clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and furazolidone in China.

Methods

We searched the PubMed, EMBASE, the China National Knowledge Infrastructure, and Chinese Biomedical databases from the earliest date of each database to October 2016. The search terms included the following: H. pylori, antibiotic (including clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and furazolidone) resistance with or without China or different regions of China. The data analysis was performed using MedCalc 15.2.2. Each article was weighted according to the number of isolated H. pylori strains. A pooled proportion analysis was performed.

Results

Twenty-three studies (14 studies in English and 9 in Chinese) were included in this review. A total of 6274, 6418, 3921, 5468, 2802, and 275 H. pylori strains were included in this review to evaluate the prevalence of H. pylori primary resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline, and furazolidone, respectively. Overall, the primary resistance rates of clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline, and furazolidone were 28.9, 63.8, 28.0, 3.1, 3.9, and 1.7%, respectively.

Conclusions

In China, the prevalence of H. pylori primary resistance to clarithromycin, metronidazole, and levofloxacin was high and increased over time, whereas the resistance rates to amoxicillin, tetracycline, and furazolidone were low and stable over time.

     

CRISPR-like sequences in <Emphasis Type="Italic">Helicobacter pylori</Emphasis> and application in genotyping

Background

Many bacteria and archaea possess a defense system called clustered regularly interspaced short palindromic repeats (CRISPR) associated proteins (CRISPR-Cas system) against invaders such as phages or plasmids. This system has not been demonstrated in Helicobacter pylori. The numbers of spacer in CRISPR array differ among bacterial strains and can be used as a genetic marker for bacterial typing.

Results

A total of 36 H. pylori isolates were collected from patients in three hospitals located in the central (PBH) and southern (SKH) regions of Thailand. It is of interest that CRISPR-like sequences of this bacterium were detected in vlpC encoded for VacA-like protein C. Virulence genes were investigated and the most pathogenic genotype (cagA vacA s1m1) was detected in 17 out of 29 (58.6%) isolates from PBH and 5 out of 7 (71.4%) from SKH. vapD gene was identified in each one isolate from PBH and SKH. CRISPR-like sequences and virulence genes of 20 isolates of H. pylori obtained in this study were analyzed and CRISPR-virulence typing was constructed and compared to profiles obtained by the random amplification of polymorphic DNA (RAPD) technique. The discriminatory power (DI) of CRISPR-virulence typing was not different from RAPD typing.

Conclusion

CRISPR-virulence typing in H. pylori is easy and reliable for epidemiology and can be used for inter-laboratory interpretation.

     

The association between <Emphasis Type="Italic">Helicobacter pylori</Emphasis> seropositivity and risk of new-onset diabetes: a prospective cohort study

Aims/hypothesis

Previous studies have suggested a possible connection between Helicobacter pylori (H. pylori) infection and diabetes risk. However, prospective studies examining direct associations between these two factors are relatively lacking. In this prospective cohort study, we aimed to evaluate the association between H. pylori infection and risk of developing diabetes.

Methods

We performed a population-based prospective study, recruiting participants aged 45–74 years and without diabetes from the Chinese Multi-provincial Cohort Study in 2002, with a 10 year follow-up to investigate development of diabetes. H. pylori serostatus was determined by measuring serum H. pylori antibodies. H. pylori seropositivity was defined as the antibody concentration ≥ 10 U/ml. To examine the association between H. pylori seropositivity and diabetes risk, modified Poisson regression was performed.

Results

Of 2085 participants without diabetes, 1208 (57.9%) were H. pylori seropositive in 2002. After multivariate adjustment of possible diabetes risk factors, H. pylori seropositivity was associated with lower risk of diabetes (RR 0.78 [95% CI 0.63, 0.97], p = 0.022). Of the 1275 participants with H. pylori antibody measurements in both 2002 and 2007, 677 (53.1%) were persistently seropositive. A lower risk of diabetes was also observed in participants with persistent H. pylori seropositivity (RR 0.61 [95% CI 0.41, 0.93], p = 0.020), compared with those persistently seronegative.

Conclusions/interpretation

H. pylori seropositivity was associated with lower risk of diabetes in this prospective cohort study. Extrapolation of these results and the mechanism underlying the observed association require further investigation.

     

Furazolidone,an Underutilized Drug for <Emphasis Type="Italic">H. pylori</Emphasis> Eradication: Lessons from Iran

Background

Treatment success of H. pylori eradication therapy has declined worldwide largely because of increased antimicrobial resistance. New therapeutic approaches are needed, especially for countries like Iran, where resistance to commonly used drugs is already widespread and traditional H. pylori therapies produce poor cure rates.

Aim

To review the results of quadruple therapy trials containing bismuth and furazolidone in Iran.

Methods

We searched PubMed, Google scholar as well as the references of all published papers for studies conducted in Iran, utilizing furazolidone in the treatment of H. pylori infections. The target population was four drug studies that utilized a combination of bismuth, furazolidone, amoxicillin, or tetracycline plus a proton pump inhibitor.

Results

Eighteen studies with 22 arms including 1713 subjects were found. The weighted mean cure rate for 14-day studies (six studies) using 200 mg b.i.d. furazolidone was 80% intention to treat (ITT) and 87% per protocol (PP). Studies using 100 mg b.i.d. (three studies) were less effective (weighted mean ITT cure rate = 67%). One small 14-day study with furazolidone 100 mg q.i.d. achieved cure rates of 94.5% ITT and PP.

Conclusions

Although furazolidone–bismuth quadruple therapy proved relatively effective in Iran, furazolidone-containing regimens remain to be optimized. Based on these data and results from China, it appears likely that 14-day therapy containing furazolidone 100 mg t.i.d. or q.i.d. is likely to provide the highest cure rates with lowest side effects; this remains to be experimentally tested. Detailed suggestions for further development of furazolidone-containing regimens are provided.

     

Cytotoxic isolates of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> from Peptic Ulcer Diseases decrease K<Superscript>+</Superscript>-dependent ATPase Activity in HeLa cells

Background

Helicobacter pylori is a Gram negative bacterium that plays a central role in the etiology of chronic gastritis and peptic ulcer diseases. However, not all H. pylori positive cases develop advanced disease. This discriminatory behavior has been attributed to the difference in virulence of the bacteria. Among all virulence factors, cytotoxin released by H. pylori is the most important factor. In this work, we studied variation in H. pylori isolates from Indian dyspeptic patients on the basis of cytotoxin production and associated changes in K⁺-dependent ATPase (one of its targets) enzyme activity in HeLa cells.

Methods

The patients were retrospectively grouped on the basis of endoscopic and histopathological observation as having gastritis or peptic ulcer. The HeLa cells were incubated with the broth culture filtrates (BCFs) of H. pylori isolates from patients of both groups and observed for the cytopathic effects: morphological changes and viability. In addition, the K⁺-dependent ATPase activity was measured in HeLa cells extracts.

Results

The cytotoxin production was observed in 3/7 (gastritis) and 4/4 (peptic ulcer) H. pylori isolates. The BCFs of cytotoxin producing H. pylori strains reduced the ATPase activity of HeLa cells to 40% of that measured with non-cytotoxin producing H. pylori strains (1.33 μmole Pi/mg protein and 3.36 μmole Pi/mg protein, respectively, p < 0.05). The decreased activity of ATPase enzyme or the release of cytotoxin also correlated with the increased pathogenicity indices of the patients.

Conclusions

Our results suggest that the isolation of cytotoxic H. pylori is more common in severe form of acid peptic diseases (peptic ulcer) than in gastritis patients from India. Also the cytotoxin released by H. pylori impairs the ion-transporting ATPase and is a measure of cytotoxicity.

     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection status had no influence on upper gastrointestinal symptoms: a cross-sectional analysis of 3,005 Japanese subjects without upper gastrointestinal lesions undergoing medical health checkups

Background

This study aimed to evaluate the influence of Helicobacter pylori infection and its eradication on the upper gastrointestinal symptoms of relatively healthy Japanese subjects.

Methods

A total of 3,005 subjects (male/female: 1,549/1,456) undergoing medical health checkups were enrolled in the present study, at five hospitals in Saga, Japan, from January to December 2013. They had no significant findings following upper gastrointestinal endoscopy. All subjects completed a questionnaire that addressed a frequency scale for symptoms of gastroesophageal reflux disease. The questionnaire comprised seven questions regarding reflux symptoms and seven regarding acid-related dyspepsia, which were answered with a score based on the frequency of symptoms. Helicobacter pylori infection was identified by a rapid urease test and/or H. pylori antibody titer, and an eradication history was confirmed by the subjects’ medical records.

Results

Helicobacter pylori infection was positive in 894 subjects out of 3,005 (29.8%). Eradication of Helicobacter pylori was successfully achieved in 440 subjects of 458 treated. Helicobacter pylori infection had no influence on the acid-related dyspepsia evaluated by the questionnaire, whereas the mean reflux score was relatively high in the Helicobacter pylori native negative subjects compared to Helicobacter pylori native positive. Eradication of Helicobacter pylori and time span after the eradication had no effect on the upper gastrointestinal symptoms evaluated by the questionnaire.

Conclusion

Helicobacter pylori infection and history of eradication did not affect acid-related dyspepsia symptoms in Japanese healthy subjects.

     

Genome characterization of bile-isolated <Emphasis Type="Italic">Shewanella algae</Emphasis> ACCC

Background

Shewanella algae has been recognized as an emerging human pathogen. However, not much is known about the mechanism of its pathogenesis and its adaptation to a special niche such as the hepatobiliary tract.

Results

In this study, we isolated the S. algae ACCC strain from human bile and performed whole genome sequencing. S. algae ACCC consists of a circular 4,743,354-bp chromosome with a GC content of 53.08%, within 4080 protein coding sequences. The genome of strain ACCC contains a number of candidate genes which have been reported to be associated with bile adaption, including htpB, exbBD, wecA, galU, adeFGH and phoPQ regulon.

Conclusions

Our results highlight the association of S. algae with a rare disease profile. Further studies are needed to shed light on the evolution of pathogenesis and the niche adaptation of S. algae.

     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis>in apparently healthy children aged 0-12 years in urban Kampala,Uganda: a community-based cross sectional survey

Background

Helicobacter pylori is one of the most common causes of bacterial infection in human beings. Studies have showed a high prevalence of Helicobacter pylori among people in low-income countries and colonization early in life. A monoclonal antigen test, performed on faeces, HpSA^®ImmunoCardSTAT, has a high sensitivity, specificity and accuracy and the faecal test can be performed in all ages, also in resource-limited settings. The main objective of this study was to determine the prevalence and factors associated with Helicobacter pylori colonization in apparently healthy children aged 0-12 years in urban Kampala, Uganda.

Method

We tested 427 apparently healthy children, age 0-12 years (211 males, 216 females), in a cross sectional survey for Helicobacter pylori colonization using HpSA ^®ImmunoCardSTAT. A short standardized interview with socio-demographic information and medical history was used to assess risk factors.

Results

The overall prevalence of Helicobacter pylori in the 427 children was 44.3% (189 out of 427). Early colonization was common, 28.7%, in children younger than 1 year of age. The age specific rates were 46.0% in children age 1- < 3 years, 51.7% in children age 3- < 6 years, 54.8% in children age 6- < 9 years and 40.0% in children age 9- < 12 years. There was a significant difference in prevalence by gender; female 38.5% versus male 49.8% and by type of housing; permanent house 38.5% versus semi-permanent house 48.6%. Congestive living and education level of the female caretaker showed a clear trend for a difference in prevalence. Factors independently associated with Helicobacter pylori colonization included: drugs taken last three months, using a pit latrine, sources of drinking water and wealth index.

Conclusion

The prevalence of Helicobacter pylori colonization among urban Ugandan children is high at an early age and increases with age. The impact of Helicobacter pylori colonization on children's health in Uganda needs to be further clarified.

     

A multicenter prospective study on the diagnostic performance of a new liquid rapid urease test for the diagnosis of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection

Background

Helicobacter pylori (H. pylori) causes a diversity of gastric diseases. Rapid urease tests (RUT) are well established for the point-of-care, invasive diagnosis of H. pylori infection. The study aimed to evaluate the diagnostic performance of a new liquid RUT, the preOx-HUT, within a prospective cohort of treatment-naïve patients.

Methods

The multicenter prospective clinical trial was conducted at nine Austrian centers for gastrointestinal endoscopy. Patients referred for a diagnostic upper gastrointestinal endoscopy underwent gastric biopsy sampling for routine histological evaluation, and in parallel, the preOx-HUT. Histology served as reference standard to evaluate the diagnostic performance of the preOx-HUT.

Results

From January 2015 to January 2016, a total of 183 consecutive patients (54 males and 129 females, median age 50 years) were included. Endoscopy revealed pathological findings in 149/183 cases (81%), which were mostly gastritis (59%) and gastro-esophageal reflux disease (27%). H. pylori infection was detected by histology in 41/183 (22%) cases. In relation to histology, the preOx-HUT had a sensitivity of 85%, a specificity of 94%, a positive predictive value of 80% and a negative predictive value of 96%. Performance of preOx-HUT was not affected significantly by concomitant PPI-use as present in 15% of cases (P = 0.73).

Conclusions

This was the first study evaluating the preOx-HUT in a prospective, multicenter clinical setting. We found a high diagnostic accuracy for the point-of-care, invasive diagnostic test of H. pylori infection. Hence, this test may be a valuable diagnostic adjunct to the clinical presentation of patients with suspected H. pylori infection. Trial registration number EK 1548/2014, Name of registry: Register der Ethikkommission der Medizinischen Universität Wien, URL of registry: https://ekmeduniwien.at/core/catalog/2012/, Date of registration: 24.09.2014, Date of enrolment of the first participant to the trial: 15.01.2015

     

Cardiovascular Concerns in <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> Mutation Carriers

Purpose of review

BRCA1 and BRCA2 mutation carriers can be at increased cardiovascular risk. The goal of this review is to provide information about factors associated with increased cardiovascular risk, methods to prevent cardiovascular toxicities, and recommended screening guidelines.

Recent findings

BRCA1/2 mutation carriers who are diagnosed with cancer are often exposed to chemotherapy, chest radiotherapy, and/or HER2 directed therapies, all of which can be cardiotoxic. In addition, BRCA1/2 carriers often undergo prophylactic salpingoopherectomies, which may also increase cardiovascular risks.

Summary

Understanding the potential for increased cardiovascular risk in individuals with a BRCA1 or BRCA2 mutation, as well as gold standard practices for prevention, detection, and treatment of cardiac concerns in this population, is important.

     

First case of <Emphasis Type="Italic">E. meningoseptica</Emphasis> in Italy in a patient with necrotic hemorrhagic pancreatitis

Introduction

Elizabethkingia meningoseptica can frequently colonizes the respiratory tract, but its pathogenetic role and its clinical significance are frequently questioned. However, recent data reported E. meningoseptica outbreaks in particular settings, as hospitalized patients.

Case Report

We report here the first case of Elizabethkingia meningoseptica infection in Italy in a patient with necrotic-hemorrhagic pancreatitis. E. meningoseptica was isolated from respiratory tract and treated with combination antibiotic therapy.

Conclusion

We discuss here the role of isolation of E. meningoseptica in hospitalized patients as a sign of patient’s frailty.

     

Essentials in <Emphasis Type="Italic">Candida</Emphasis> bloodstream infection

Aims

Due to the increase of severely immunocompromised patients, of invasive procedures including central intravascular catheters, and of the use of broad-spectrum antibiotics, the incidence of Candida bloodstream infections has risen intensely in the last decades. Candida bloodstream infection is a serious disease with high mortality. Optimized diagnostic and therapeutic management can improve outcome. Thus, the aim of our mini-review is to highlight important and often missed opportunities in the management of Candida bloodstream infection.

Methods

We searched the published literature and describe the essentials in the management of Candida bloodstream infection.

Results

Four essentials were identified: (1) isolation of Candida spp. from a blood culture should always be considered relevant and requires treatment. Daily blood cultures should be drawn to determine cessation of candidemia. (2) Central venous catheter (CVC) and/or other indwelling devices should be removed. (3) Echinocandins are the first choice. Antifungal treatment should be continued for at least 14 days after cessation of fungemia. Susceptibility testing should be performed to identify resistance and to facilitate transition to oral treatment. (4) In persistent candidemia, echocardiography is an important investigation; ophthalmoscopy should be considered.

Conclusion

Further efforts should be undertaken to increase the adherence to the essentials in the management of Candia bloodstream infection.

     

Disseminated nocardiosis caused by <Emphasis Type="Italic">Nocardia elegans</Emphasis>: a case report and review of the literature

Background

Disseminated nocardiosis is a rare disease mostly occurring in immunocompromised patients.

Methods

We report a case of disseminated nocardiosis in a diabetic patient with both pulmonary and cutaneous involvement. Nocardia elegans was isolated and identified using the 16s ribosomal RNA gene sequence data.

Results

Clinical improvement was observed within 3 months after initiation of antimicrobial treatment with oral doxycycline, trimethoprim-sulfamethoxazole and intravenous penicillin, but the patient died 5 months later after arbitrary discontinuation of the treatment.

Conclusions

This is the first case report of disseminated nocardiosis caused by Nocardia elegans in China.

     

<Emphasis Type="Italic">Acinetobacter</Emphasis> Infections in Neonates

Purpose of Review

MDR-Gram-negative bacteria are a great concern in the neonatal population, with a worldwide rise in the reported incidence and with very limited therapeutic options. Acinetobacter baumannii is responsible for many infections in neonates and outbreaks in neonatal intensive care unit (NICU); also, outbreaks caused by other Acinetobacter species have been reported. The aim of this review is to document the epidemiology of Acinetobacter spp. infections in neonates and risk factors for acquisition of Acinetobacter spp. in the NICU using data from published studies.

Recent Findings

Acinetobacter spp. infections are increasing in neonates in NICU. Outbreak caused by multidrug resistant (MDR) or extensively drug resistant (XDR) A. baumannii but also outbreak caused by susceptible A. soli and A. septicus sp. nov., were reported in neonates. Acinetobacter spp. were responsible for bloodstream infections and respiratory tract infections in neonates. Risk factors for A. baumannii acquisition in neonates were low birthweight, length of NICU stay, umbilical catheterization, central-venous catheterization, assisted ventilation, and prior antibiotic use.

Summary

This review highlights the importance of surveillance of risk factors for healthcare-associated infections in NICU to control MDR and XDR A. baumannii infections in neonates.