Proton pump inhibitors (PPIs) are widely used for the treatment of gastroesophageal reflux disease as well as other acid-related disorders. PPIs are metabolized primarily via the CYP2C19 and CYP3A4 isoenzymes; their activity is influenced both by exogenous and endogenous (pharmacogenetic) factors. The CYP2C19 polymorphism affects the metabolism of PPIs, causing large individual pharmacokinetic variations. Differences in the CYP2C19-mediated metabolism can produce marked interpatient variability in acid suppression, in drug-interaction potential and in clinical efficacy. Understanding the pharmacokinetic properties of PPIs and examining the pharmacogenetic alterations may help clinicians optimize PPI therapy and administer individual treatment, especially to nonresponder patients with gastroesophageal reflux disease or ulcer or after failed eradication therapy.
Crohn's disease (CD) is a progressive condition, with most patients developing a penetrating or stricturing phenotype over time. The introduction of anti-tumor necrosis factor (TNF) therapies over the past 10-15 years, which was supported by accumulating evidence both from trials and clinical practice, has led to a significant change in patient management, monitoring, and treatment algorithms. Anti-TNF therapy was demonstrated to be effective for both luminal and fistulizing disease. Regular therapy with both infliximab and adalimumab was shown to increase the likelihood of clinical remission and mucosal healing, as well as to reduce the need for surgery and hospitalization in both clinical trials and clinical practice, especially in patients with pediatric-onset CD, shorter disease duration, and when used in combination with immunosuppressives. This has led to new treatment goals and to the use of early aggressive medical therapy in a selected group of patients with a worse prognosis. Exploratory clinical trials are underway to determine if further optimization of therapies and treatment beyond clinical remission leads to superior disease outcomes. However, more long-term clinical data are needed to assess whether an early, aggressive therapeutic strategy employing anti-TNF, alone or in combination with biologicals, can further improve long-term disease outcomes in both pediatric patients and young adults.
BackgroundMicroscopic colitis presents with similar symptoms to classic inflammatory bowel diseases. Osteoporosis is a common complication of Crohn's disease but there are no data concerning bone metabolism in microscopic colitis.AimsThe aim of the present study was to evaluate bone density and metabolism in patients with microscopic colitis.MethodsFourteen patients microscopic colitis were included in the study, and 28 healthy persons and 28 age and gender matched Crohn's disease patients were enrolled as controls. Bone mineral density was measured using dual x-ray absorptiometry at the lumbar spine, femoral neck and the radius. Serum bone formation and bone resorption markers (osteocalcin and beta-crosslaps, respectively) were measured using immunoassays.ResultsLow bone mass was measured in 57.14% patients with microscopic colitis. Bone mineral density at the femoral neck in patients suffering from microscopic colitis and Crohn's disease was lower than in healthy controls (0.852 ± 0.165 and 0.807 ± 0.136 vs. 1.056 ± 0.126 g/cm2; p < 0.01). Bone mineral density at the non-dominant radius was decreased in microscopic colitis patients (0.565 ± 0.093 vs. 0.667 ± 0.072 g/cm2; p < 0.05) but unaffected in Crohn's disease patients (0.672 ± 0.056 g/cm2). Mean beta-crosslaps concentration was higher in microscopic colitis and Crohn's disease patients than controls (417.714 ± 250.37 and 466.071 ± 249.96 vs. 264.75 ± 138.65 pg/ml; p < 0.05). A negative correlation between beta-crosslaps concentration and the femoral and radius t-scores was evident in microscopic colitis patients.ConclusionsLow bone mass is frequent in microscopic colitis, and alterations to bone metabolism are similar to those present in Crohn's disease. Therefore, microscopic colitis-associated osteopenia could be a significant problem in such patients.
Liver damage in COVID-19 patients was documented as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels or an elevated AST/ALT ratio, known as the De Ritis ratio. However, the prognostic value of the elevated De Ritis ratio in COVID-19 patients is still unknown. The aim of our study was to evaluate the prognostic value of the De Ritis ratio compared to other abnormal laboratory parameters and its relation to mortality. We selected 322 COVID-19 patients in this retrospective study conducted between November 2020 and March 2021. The laboratory parameters were measured on admission and followed till patient discharge or death. Of the 322 COVID-19 patients, 57 (17.7%) had gastrointestinal symptoms on admission. The multivariate analysis showed that the De Ritis ratio was an independent risk factor for mortality, with an OR of 29.967 (95% CI 5.266–170.514). In ROC analysis, the AUC value of the the De Ritis ratio was 0.85 (95% CI 0.777–0.923, p < 0.05) with sensitivity and specificity of 80.6% and 75.2%, respectively. A De Ritis ratio ≥1.218 was significantly associated with patient mortality, disease severity, higher AST and IL-6 levels, and a lower ALT level. An elevated De Ritis ratio on admission is independently associated with mortality in COVID-19 patients, indicating liver injury and cytokine release syndrome.
Fig. 1Changes in serum CgA after withdrawal and 1 day after reintroduction of PPI-therapy. The broader horizontal line represents the upper normal level (98·1 ng/ml).
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