ObjectiveThe best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care.DesignInternational multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed.Results30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%–90%).ConclusionManagement of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness.
SUMMARY BackgroundOne-third of patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving anti-TNFs do not respond to treatment, and a relevant proportion experience loss of response or intolerance.
Approximately one-third of patients with inflammatory bowel disease in remission under anti-TNF treatment relapsed 1 year after discontinuation. This proportion increased to half in the long term. In CD patients, the risk of relapse was lower when the criterion for discontinuation was endoscopic remission and not only clinical remission. Response to retreatment with the same anti-TNF agent was favorable.
Although macrophages (Mϕ) maintain intestinal immune homoeostasis, there is not much available information about their subset composition, phenotype and function in the human setting. Human intestinal Mϕ (CD45HLA-DRCD14CD64) can be divided into subsets based on the expression of CD11c, CCR2 and CX3CR1. Monocyte-like cells can be identified as CD11cCCR2CX3CR1 cells, a phenotype also shared by circulating CD14 monocytes. On the contrary, their Mϕ-like tissue-resident counterparts display a CD11cCCR2CX3CR1 phenotype. CD11c monocyte-like cells produced IL-1β, both in resting conditions and after LPS stimulation, while CD11c Mϕ-like cells produced IL-10. CD11c pro-inflammatory monocyte-like cells, but not the others, were increased in the inflamed colon from patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Tolerogenic IL-10-producing CD11c Mϕ-like cells were generated from monocytes following mucosal conditioning. Finally, the colonic mucosa recruited circulating CD14 monocytes in a CCR2-dependent manner, being such capacity expanded in IBD. Mϕ subsets represent, therefore, transition stages from newly arrived pro-inflammatory monocyte-like cells (CD11cCCR2CX3CR1) into tolerogenic tissue-resident (CD11cCCR2CX3CR1) Mϕ-like cells as reflected by the mucosal capacity to recruit circulating monocytes and induce CD11c Mϕ. The process is nevertheless dysregulated in IBD, where there is an increased migration and accumulation of pro-inflammatory CD11c monocyte-like cells.
Radiation-induced bystander effects are defined as biological effects expressed after irradiation by cells whose nuclei have not been directly irradiated. These effects include DNA damage, chromosomal instability, mutation, and apoptosis. There is considerable evidence that ionizing radiation affects cells located near the site of irradiation, which respond individually and collectively as part of a large interconnected web. These bystander signals can alter the dynamic equilibrium between proliferation, apoptosis, quiescence or differentiation. The aim of this review is to examine the most important biological effects of this phenomenon with regard to areas of major interest in radiotherapy. Such aspects include radiation-induced bystander effects during the cell cycle under hypoxic conditions when administering fractionated modalities or combined radio-chemotherapy. Other relevant aspects include individual variation and genetics in toxicity of bystander factors and normal tissue collateral damage. In advanced radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), the high degree of dose conformity to the target volume reduces the dose and, therefore, the risk of complications, to normal tissues. However, significant doses can accumulate out-of-field due to photon scattering and this may impact cellular response in these regions. Protons may offer a solution to reduce out-of-field doses. The bystander effect has numerous associated phenomena, including adaptive response, genomic instability, and abscopal effects. Also, the bystander effect can influence radiation protection and oxidative stress. It is essential that we understand the mechanisms underlying the bystander effect in order to more accurately assess radiation risk and to evaluate protocols for cancer radiotherapy.
Concomitant therapy led to a non-statistically significant advantage (5%) over sequential therapy, coming closer to 90% cure rates. Both therapies showed an acceptable safety profile. ClincialTrials.gov: NCT01273441.
SUMMARY BackgroundThe discontinuation of anti-tumour necrosis factor (anti-TNF) treatment in inflammatory bowel disease (IBD) patients in remission could be considered.
SUMMARY BackgroundThe most commonly used second-line Helicobacter pylori eradication regimens are bismuth-containing quadruple therapy and levofloxacin-containing triple therapy, both offering suboptimal results. Combining bismuth and levofloxacin may enhance the efficacy of rescue eradication regimens.
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