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.

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.

Screening for upper gastrointestinal cancers with magnetically controlled capsule gastroscopy: a feasibility study.

BACKGROUND: The medical consortium is an intensive and disease-specific association that integrates tertiary public hospitals and medical examination centers in China. We aimed to evaluate the feasibility of the medical consortium for screening upper gastrointestinal (GI) cancers (MCSC) by magnetically controlled capsule gastroscopy (MCCG). METHODS: 6627 asymptomatic subjects underwent MCCG as part of health check-ups in the MCSC between March and November 2018. Relevant clinical data were collected and analyzed. RESULTS: The MCSC detected 32 patients with upper GI cancer (0.48 %) confirmed by pathology. The detection rate of early gastric cancer was 16.67 % (4 /24). Gastric polyps, ulcers, and submucosal tumors were found in 15.54 %, 3.76 %, and 3.17 % of subjects, respectively. The whole GI preparation and operation process were well tolerated. CONCLUSIONS: The MCSC was a feasible model for upper GI cancer screening, especially for asymptomatic subjects. Further prospective studies with better operational quality control are warranted.

Tract-specific analysis and neurocognitive functioning in sickle cell patients without history of overt stroke.

INTRODUCTION: Sickle cell disease (SCD) is a hereditary blood disorder in which the oxygen-carrying hemoglobin molecule in red blood cells is abnormal. SCD patients are at increased risks for strokes and neurocognitive deficit, even though neurovascular screening and treatments have lowered the rate of overt strokes. Tract-specific analysis (TSA) is a statistical method to evaluate microstructural WM damage in neurodegenerative disorders, using diffusion tensor imaging (DTI). METHODS: We utilized TSA and compared 11 major brain WM tracts between SCD patients with no history of overt stroke, anemic controls, and healthy controls. We additionally examined the relationship between the most commonly used DTI metric of WM tracts and neurocognitive performance in the SCD patients and healthy controls. RESULTS: Disruption of WM microstructure orientation-dependent metrics for the SCD patients was found in the genu of the corpus callosum (CC), cortico-spinal tract, inferior fronto-occipital fasciculus, right inferior longitudinal fasciculus, superior longitudinal fasciculus, and left uncinate fasciculus. Neurocognitive performance indicated slower processing speed and lower response inhibition skills in SCD patients compared to controls. TSA abnormalities in the CC were significantly associated with measures of processing speed, working memory, and executive functions. CONCLUSION: Decreased DTI-derived metrics were observed on six tracts in chronically anemic patients, regardless of anemia subtype, while two tracks with decreased measures were unique to SCD patients. Patients with WMHs had more significant FA abnormalities. Decreased FA values in the CC significantly correlated with all nine neurocognitive tests, suggesting a critical importance for CC in core neurocognitive processes.

Safety of furazolidone-containing regimen in Helicobacter pylori infection: a systematic review and meta-analysis.

OBJECTIVES: Furazolidone containing regimen is effectivefor Helicobacter pylori (H. pylori) infection, but its safetyremains controversial. To assess the safety of furazolidone containing regimenin H. pylori infection. DESIGN: A systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane Library, Web of Science and Scopus databases were systematically searched for eligible randomised controlled trials. ELIGIBILITY CRITERIA: Studies comparing furazolidone with non-furazolidone-containing regimen, variable durations or doses of furazolidone were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently selected studies and extracted data. Primary outcomes were the risk of total adverse events (AEs), serious AEs and severe AEs, expressed as relative risk (RR) with 95% CI. Secondary outcomes contained the incidence of individual adverse symptoms, AE-related treatment discontinuation and compliance. RESULTS: Twenty-six articles were identified from 2039 searched records, of which 14 studies (n=2540) compared furazolidone with other antibiotics. The eradication rates of furazolidone-containing regimen were higher than those of other antibiotics in both intention-to-treat (RR 1.06, 95% CI 1.01 to 1.12) and per-protocol analysis (RR 1.05, 95% CI 1.00 to 1.10). Only two serious AEs were reported in furazolidone group (2/1221, 0.16%). No significant increased risk was observed for the incidence of total AEs (RR 1.04, 95% CI 0.89 to 1.21) and severe AEs (RR 1.81, 95% CI 0.91 to 3.60). Twelve studies (n=3139) compared different durations of furazolidone, and four studies (n=343) assessed variable doses. Elevated risk of total AEs and severe AEs were only found in a high daily dose of furazolidone rather than prolonged duration. The incidence of AE-related treatment discontinuation and compliance of patients were all similar, irrespective of dose and duration adjustments. CONCLUSION: Furazolidone-containing regimen has a similar risk of AEs and compliance as non-furazolidone-containing regimen. A low daily dose of 200 mg is well-tolerated for 14 day regimen and should be first considered. PROSPERO REGISTRATION NUMBER: CRD42019137247.

Impact of a real-time automatic quality control system on colorectal polyp and adenoma detection: a prospective randomized controlled study (with videos).

BACKGROUND AND AIMS: Quality control can decrease variations in the performance of colonoscopists and improve the effectiveness of colonoscopy to prevent colorectal cancers. Unfortunately, routine quality control is difficult to carry out because a practical method is lacking. The aim of this study was to develop an automatic quality control system (AQCS) and assess whether it could improve polyp and adenoma detection in clinical practice. METHODS: First, we developed AQCS based on deep convolutional neural network models for timing of the withdrawal phase, supervising withdrawal stability, evaluating bowel preparation, and detecting colorectal polyps. Next, consecutive patients were prospectively randomized to undergo routine colonoscopies with or without the assistance of AQCS. The primary outcome of the study was the adenoma detection rate (ADR) in the AQCS and control groups. RESULTS: A total of 659 patients were enrolled and randomized. A total of 308 and 315 patients were analyzed in the AQCS and control groups, respectively. AQCS significantly increased the ADR (0.289 vs 0.165, P < .001) and the mean number of adenomas per procedure (0.367 vs 0.178, P < .001) compared with the control group. A significant increase was also observed in the polyp detection rate (0.383 vs 0.254, P = .001) and the mean number of polyps detected per procedure (0.575 vs 0.305, P < .001). In addition, the withdrawal time (7.03 minutes vs 5.68 minutes, P < .001) and adequate bowel preparation rate (87.34% vs 80.63%, P = .023) were superior for the AQCS group. CONCLUSIONS: AQCS could effectively improve the performance of colonoscopists during the withdrawal phase and significantly increase polyp and adenoma detection. (Clinical trial registration number: NCT03622281.).

Twice daily short-message-based re-education could improve Helicobacter pylori eradication rate in young population: A prospective randomized controlled study.

BACKGROUND: To investigate the effects of twice daily short-message-based re-education (SMRE) before taking medicine for Helicobacter pylori (H pylori) eradication. MATERIALS AND METHODS: Treatment-naive patients with H pylori infection were prescribed 14-day quadruple regimen consisting of lansoprazole 30 mg, colloidal bismuth pectin 200 mg, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily. Patients were randomly allocated to SMRE group or control group. Patients in control group received oral and written instructions at outpatient clinic. In contrast, patients in the SMRE group received extra short messages including dosage and time of administration twice daily. Successful H pylori eradication was assessed using the 13 C-urea breath test 6 weeks after treatment. The compliance, adverse events, and patient satisfaction were also analyzed. RESULTS: A total of 310 patients were enrolled in the intention-to-treat (ITT) and 283 in the per-protocol (PP) analysis. For young patients, the eradication rates were significantly higher in SMRE group than those in control group in PP analysis (88.6% vs 71.2%, P = 0.036), while for patients of all age groups, the eradication rate improvements were not statistically significant. The eradication rates in SMRE group and control group were 74.2% and 67.7% (P = 0.211) in ITT analysis and 82.1% and 73.4% (P = 0.078) in PP analysis, respectively. The compliance in SMRE group was significantly better than that in control group (84.8% vs 72.8%, P = 0.011). CONCLUSIONS: Twice daily SMRE could improve the eradication rate in young population, as well as the compliance with treatment during H pylori eradication.

Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling.

Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by ß-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a ß-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1R), stimulates acute catecholamine secretion through coupling with the transient receptor potential cation channel subfamily C 3 (TRPC3). We show that TRV120027 promotes the recruitment of TRPC3 or phosphoinositide-specific phospholipase C (PLCγ) to the AT1R-ß-arrestin-1 signalling complex. Replacing the C-terminal region of ß-arrestin-1 with its counterpart on ß-arrestin-2 or using a specific TAT-P1 peptide to block the interaction between ß-arrestin-1 and PLCγ abolishes TRV120027-induced TRPC3 activation. Taken together, our results show that the GPCR-arrestin complex initiates non-desensitized signalling at the plasma membrane by coupling with ion channels. This fast communication pathway might be a common mechanism of several cellular processes.

Multivariate surface-based analysis of corpus callosum in patients with sickle cell disease.

Sickle cell disease (SCD) is a genetic hematological disease in which the hemoglobin molecule in red blood cells is abnormal. It is closely associated with many symptoms, including pain, anemia, chest syndrome and neurocognitive impairment. One of the most debilitating symptoms is elevated risk for cerebro-vascular accidents. The corpus callosum (CC), as the largest and most prominent white matter (WM) structure in the brain, can reflect the chronic cerebrovascular damage resulting from silent strokes or infarctions in asymptomatic SCD patients. While a lot of studies have reported WM alterations in this cohort, little is known about the shape deformation of the CC. Here we perform the first surface morphometry analysis of the CC in SCD patients using four different shape metrics on T1-weighted magnetic resonance images. We detect regional surface morphological differences in the CC between 11 patients and 10 healthy control subjects. Differences are located in the genu, posterior midbody and splenium, potentially casting light on the anatomical substrates underlying neuropsychological test differences between the SCD and control groups.