A systematic review of Helicobacter pylori eradication therapy—the impact of antimicrobial resistance on eradication rates

BACKGROUND: We systematically reviewed all available data in the literature to determine the overall eradication rates of currently advised Helicobacter pylori eradication regimens and to resolve conflicting evidence on the impact of antimicrobial resistance on the eradication rates. METHODS: A comprehensive search of all published trials on H. pylori eradication therapy was carried out via an electronic database search, hand-searching and checking reference lists of pharmaceutical companies and other reviews. Full papers and abstracts in the English language which study currently advised eradication regimes were included. RESULTS: 770 study-arms were analysed. Mean eradication rates for bismuth based triple, proton pump inhibitor triple, quadruple and ranitidine bismuth citrate combination therapies vary from 65 to 92%. In case of nitroimidazole resistance, a drop in efficacy of up to 50% was found for bismuth-based triple and proton pump inhibitor-based triple therapies. For quadruple therapy, a significant difference in efficacy was found in the equal-effects analysis; however, this could not be confirmed in the random-effects analysis. In case of clarithromycin resistance, a mean drop in efficacy of 56% was found for one- and two-week clarithromycin containing proton pump inhibitor-triple therapies and of 58% for two-week ranitidine bismuth citrate combined with clarithromycin therapies. For ranitidine bismuth citrate combined with clarithromycin and nitroimidazole, no difference in efficacy was found in case of nitroimidazole or clarithromycin resistance, but data are still scarce. CONCLUSIONS: The cure rate with most regimens dropped significantly, in case of nitroimidazole-resistant strains, compared to nitroimidazole-susceptible strains. In case of clarithromycin resistance, the efficacy of most regimens is also decreased; however, data are still scarce. These data should allow physicians to make a better choice of an appropriate therapy for their patients.     

Laser assisted ratio analyser 13C-urea breath testing, for the detection of H. pylori: a prospective diagnostic European multicentre study

BACKGROUND: Novel technology based on laser optogalvanic spectroscopy called the LARA (Laser Assisted Ratio Analyser) system was developed to measure 12C/13C ratios in breath samples using stable 13C isotopes, to detect Helicobacter pylori infection. AIM: To determine the sensitivity and specificity of the 13C-LARA-urea breath test in the detection of H. pylori infection in a prospective European multicentre trial; FDA-and EMEA-approved. METHODS: Consecutive dyspeptic patients underwent diagnostic gastroscopy with biopsies for culture and histopathology, to detect H. pylori infection (gold standard). Subsequently, the LARA-urea breath test was performed using either a system without a cold trap (part I) or a system with a cold trap (part II). In both instances baseline, 30-min and 60-min breath samples were collected. The optimum cut-off level for 12C/13C ratios was determined by Receiver Operator Characteristics analysis. RESULTS: In part I, 544 out of 604 patients were evaluable (low CO2: 47; withdrawn: 13). 284 out of 544 patients (52%) were H. pylori-positive according to the gold standard. The sensitivity of the LARA-urea breath test was 95% and the specificity 94%. In part II, 257 out of 272 were evaluable (low CO2: 14; withdrawn: 1). Sensitivity and specificity were 93% and 96%, respectively. CONCLUSION: The LARA-technology represents an accurate and non-invasive testing system for the detection of H. pylori infection. Its major advantages are the use of stable 13C isotope, the high throughput of samples and the easy means of collecting, storing and transporting the samples, thus making the system convenient to both patient and clinician.     

A novel conotoxin inhibiting vertebrate voltage-sensitive potassium channels.

Toxins from cone snail (Conus species) venoms are multiple disulfide bonded peptides. Based on their pharmacological target (ion channels, receptors) and their disulfide pattern, they have been classified into several toxin families and superfamilies. Here, we report a new conotoxin, which is the first member of a structurally new superfamily of Conus peptides and the first conotoxin affecting vertebrate K+ channels. The new toxin, designated conotoxin ViTx, has been isolated from the venom of Conus virgo and comprises a single chain of 35 amino acids cross-linked by four disulfide bridges. Its amino acid sequence (SRCFPPGIYCTSYLPCCWGICCSTCRNVCHLRIGK) was partially determined by Edman degradation and deduced from the nucleotide sequence of the toxin cDNA. Nucleic acid sequencing also revealed a prepropeptide comprising 67 amino acid residues and demonstrated a posttranslational modification of the protein by releasing a six-residue peptide from the C-terminal. Voltage clamp studies on various ion channels indicated that the toxin inhibits the vertebrate K+ channels Kv1.1 and Kv1.3 but not Kv1.2. The chemically synthesized product exhibited the same physiological activity and identical molecular mass (3933.7 Da) as the native toxin.     

Mutational spectrum of ATRX aberrations in neuroblastoma and associated patient and tumor characteristics

Neuroblastoma is the most common extracranial solid tumor in children. The chromatin remodeler ATRX is frequently mutated in high‐risk patients with a poor prognosis. Although many studies have reported ATRX aberrations and the associated clinical characteristics in neuroblastoma, a comprehensive overview is currently lacking. In this study, we extensively characterize the mutational spectrum of ATRX aberrations in neuroblastoma tumors reported in previous studies and present an overview of patient and tumor characteristics. We collected the data of a total of 127 neuroblastoma patients and three cell lines with ATRX aberrations originating from 20 papers. We subdivide the ATRX aberrations into nonsense, missense, and multiexon deletions (MEDs) and show that 68% of them are MEDs. Of these MEDs, 75% are predicted to be in‐frame. Furthermore, we identify a missense mutational hotspot region in the helicase domain. We also confirm that all three ATRX mutation types are more often identified in patients diagnosed at an older age, but still approximately 40% of the patients are aged 5 years or younger at diagnosis. Surprisingly, we found that 11q deletions are enriched in neuroblastomas with ATRX deletions compared to a reference cohort, but not in neuroblastomas with ATRX point mutations. Taken together, our data emphasizes a distinct ATRX mutation spectrum in neuroblastoma, which should be considered when studying molecular phenotypes and therapeutic strategies.     

The pathogenicity of cytomegalovirus in inflammatory bowel disease: a systematic review and evidence-based recommendations for future research

During recent years, a clear association between complicated courses of ulcerative colitis and the presence of cytomegalovirus (CMV) has been established. The exact pathogenic role of CMV in these patients remains unclear despite a great number of published reports. Therefore, we undertook a systematic review to appraise critically all available evidence in the literature on the role of CMV during inflammatory bowel disease. We identified and analyzed more than 30 case reports and 9 case series. Based on these results, we propose a model for viral replication during inflammation and provide recommendations for future research.     

Long term results of pneumatic dilation in achalasia followed for more than 5 years

OBJECTIVE: We aimed to evaluate the long term therapeutic outcome in achalasia patients treated with pneumatic dilation, specifically focusing on those patients treated more than 15 yr ago. METHODS: All patients treated in our center whose records were available for review were asked to fill out a questionnaire assessing their degree of dysphagia, retrosternal pain, regurgitation, weight loss, and coughing during the night. The number of dilations was collected from the clinical records. The results of the treatment were classified into four different classes (excellent, good, moderate, poor). For those patients who had died, the cause of death was ascertained from the medical records or from the general practitioner. RESULTS: The questionnaires were distributed to 249 patients, 32 of whom had died. Of the 125 patients who completed the questionnaire, 81 (45 male and 36 female) were treated more than 5 yr ago. The mean follow-up was 12+/-1 yr. The therapeutic success rate was 50%, obtained after a median of four dilations (interquartile range = 3-6). Of this cohort, 25 patients (18 male and seven female, aged 35-84 yr) were treated more than 15 yr ago (mean follow-up = 20.5+/-0.5 yr). The median number of dilations was four (interquartile range = 3-7), with a therapeutic success rate of 40%. Two patients experienced a perforation, and seven were referred for surgery. Six patients out of 32 (19%) died of esophageal cancer. CONCLUSIONS: The long term success rate of pneumatic dilation is rather low, resulting in permanent successful treatment of achalasia in only 40-50% of patients. Achalasia is a risk factor for esophageal cancer.     

Racecadotril versus loperamide: antidiarrheal research revisited

Racecadotril is an enkephalinase inhibitor, presented as a purely antisecretory agent with advantages over the opiate-receptor agonist loperamide in the treatment of diarrhea. A critical review of the literature and the models used was performed. Although pretreatment with high doses of racecadotril reduced cholera toxin-induced secretion and although clinical efficacy was demonstrated in young infants—a population characterized by 10-fold higher plasma enkephalin concentrations compared with adults, the analysis calls into question the peripheral antisecretory selectivity and relative clinical efficacy. Conversely, loperamide can be proposed as an antisecretory agent at therapeutic concentrations. Its efficacy is well established in acute and chronic diarrhea. Current experimental and clinical comparative studies of both drugs have problems with regard to the selection of the doses, the validity of models, and/or the trial design. The conclusion is that more research is needed before reliable conclusions can be drawn on the place of racecadotril in diarrhea treatment.     

Systemic inflammation after inspiratory loading in chronic obstructive pulmonary disease

Objective

Patients with chronic obstructive pulmonary disease (COPD) present systemic inflammation. Strenuous resistive breathing induces systemic inflammation in healthy subjects. We hypothesized that the increased respiratory load that characterizes COPD can contribute to systemic inflammation in these patients.

Patients and methods

To test this hypothesis, we compared leukocyte numbers and levels of circulating cytokines (tumor necrosis factor alpha [TNFα], interleukin-1β [IL-1β], IL-6, IL-8, and IL-10), before and 1 hour after maximal incremental inspiratory loading in 13 patients with stable COPD (forced expiratory volume in one second [FEV₁] 29 ± 2.5% ref) and in 8 healthy sedentary subjects (FEV₁ 98 ± 5% ref).

Results

We found that: (1) at baseline, patients with COPD showed higher leukocyte counts and IL-8 levels than controls (p < 0.01); and, (2) one hour after maximal inspiratory loading these values were unchanged, except for IL-10, which increased in controls (p < 0.05) but not in patients with COPD.

Conclusions

This study confirms the presence of systemic inflammation in COPD, shows that maximal inspiratory loading does not increase the levels of pro-inflammatory cytokines (IL-1β, IL-8) in COPD patients or controls, but suggests that the former may be unable to mount an appropriate systemic anti-inflammatory response to exercise.