Summary
Background
Proton pump inhibitor‐responsive oesophageal eosinophilia (PPI‐REE) is common in patients with suspected eosinophilic oesophagitis (EoE). However, the long‐term efficacy of PPIs ...and the best maintenance doses are yet to be defined.
Aim
To evaluate the durability of the response to PPI therapy after tapering PPI doses in PPI‐REE patients.
Methods
Prospective study conducted on PPI‐REE patients. Upon complete remission on high‐dose PPI therapy (omeprazole 40 mg b.d. for 8 weeks), PPI doses were tapered followed by an endoscopic procedure after each dose reduction. The primary outcomes were sustained clinical and histological remission (<15 eos/HPF) after decreasing PPI doses.
Results
From a total of 121 patients with suspected EoE, 40 (33%) achieved complete remission on high‐dose PPIs and were given a diagnosis of PPI‐REE. No patient in histological remission showed symptom relapse, but half of patients with relapsing oesophageal inflammation were in clinical remission. After reduction to omeprazole 40 mg once daily, 38/31 (81%) remained in complete remission. Among these latter patients, 15/18 (83%) were kept in remission with omeprazole 20 mg once daily. As for side effects, only asymptomatic hypertransaminasemia and oesophageal candidiasis were observed in two patients while receiving high doses of omeprazole.
Conclusions
Most PPI‐responsive oesophageal eosinophilia patients show sustained clinical and histological remission with daily PPI doses equal to or below 40 mg of omeprazole. As adverse effects only appeared with the highest dose of omeprazole, it would be advisable to individualise the dose of PPIs for each patient, lowering it to the minimum capable of maintaining the disease controlled.
The mechanisms behind the beneficial effects of dietary peptides on fish skeletal development remain unrevealed. In the present study, we evaluated the effect of 0% (C, Control), 6% (P6) and 12% ...(P12) levels of small peptide incorporation on European sea bass (Dicentrarchus labrax) early larval skeletal development and post-larval skeletal integrity against a swimming challenge test. Survival was not affected by the peptide diets, whereas P6 presented the lowest growth rate. Larval quality control underlined the advantageous effect of P12 on reducing the frequency of cephalic deformities (e.g., branchiostegal rays, operculum and cross-bite), pre-haemal lordosis and vertebrae bone loss. Simultaneously, individuals from P12 group exhibited an earlier mineralization of the vertebral column and were less prone to develop swimming-induced haemal lordosis (16.0 ± 0.1%) and scoliosis (3.3 ± 0.6%). Expression analysis of genes involved in digestive function, protein transport, muscle ontogeny and bone mineralization revealed a peptide-enhanced larvae development of the P12 group. An early nutritional programming of the post-larval musculoskeletal system is proposed. Limitations induced by the differential free amino-acid profiles are discussed. A potential developmental-stage-specific incorporation of peptide diets in European sea bass rearing is suggested.
•Small dietary di- and tri-peptides reduce the skeletal deformities in sea bass larvae•Sea bass larval nutrition with small peptides increases the resistance against swimming-induced lordosis in later stages•The total sea bass larvae maturation is enhanced by a 12% incorporation of small peptides during the early stages
This study examined the effect of a commercial mix of Bacillus sp. on survival, growth and digestive enzyme activities of Florida pompano, red drum and common snook. Larvae were fed either live feed ...enriched with Algamac 3050 (Control), Algamac 3050 and probiotics (PB), or the previous diet combined with a daily addition of probiotics to the tank water (PB+). Survival was not affected by the treatments for any of the species. At the end of the pompano and snook trial, standard lengths of larvae from the PB and PB+ treatments were significantly greater than for the control larvae. Microbiological analyses were performed at the end of the pompano trial, and numbers of presumptive Vibrio were not a concern in the system. For both pompano and snook, trypsin‐specific activity was higher in PB and PB+ larvae compared with the control larvae. Similarly, alkaline phosphatase activity was higher for the pompano larvae fed the PB and PB+ treatments and for the snook larvae fed the PB+ treatment compared with the control larvae. This experiment suggests that a mix of Bacillus sp. can promote growth through an early maturation of the digestive system during the early larval stages of pompano and snook.
Linked ContentThis article is linked to Moaward et al and Kia and Hirano papers. To view these articles visit https://doi.org/10.1111/apt.14216 and https://doi.org/10.1111/apt.14123.
Summary
Background
Empiric triple therapy for Helicobacter pylori should be abandoned when clarithromycin resistance rate is >15–20%. Optimisation of triple therapy (high‐dose acid suppression and ...14‐day duration) can increase eradication rates by 10%.
Aim
To compare the efficacy and safety of optimised triple (OPT‐TRI) and nonbismuth quadruple concomitant (OPT‐CON) therapies.
Methods
Prospective multicentre study in 16 Spanish centres using triple therapy in clinical practice. In a 3‐month two‐phase fashion, the first 402 patients received an OPT‐TRI therapy esomeprazole (40 mg b.d.), amoxicillin (1 g b.d) and clarithromycin (500 mg b.d) for 14 days and the last 375 patients an OPT‐CON treatment OPT‐TRI therapy plus metronidazole (500 mg b.d).
Results
Seven‐hundred seventy‐seven consecutive patients were included (402 OPT‐TRI, 375 OPT‐CON). The OPT‐CON therapy achieved significantly higher eradication rates in the per‐protocol 82.3% (95% CI = 78–86%) vs. 93.8% (91–96%), P < 0.001 and intention‐to‐treat analysis 81.3% (78–86%) vs. 90.4% (87–93%), P < 0.001. Adverse events (97% mild/moderate) were significantly more common with OPT‐CON therapy (39% vs. 47%, P = 0.016), but full compliance with therapy was similar between groups (94% vs. 92%, P = 0.4). OPT‐CON therapy was the only significant predictor of successful eradication (odds ratio, 2.24; 95% CI: 1.48–3.51, P < 0.001). The rate of participating centres achieving cure rates ≥90% favoured OPT‐CON therapy (OPT‐TRI 25% vs. OPT‐CON 62%).
Conclusions
Empiric OPT‐CON therapy achieved significantly higher cure rates (>90%) compared to OPT‐TRI therapy. Addition of metronidazole to OPT‐TRI therapy increased eradication rates by 10%, resulting in more mild adverse effects, but without impairing compliance with therapy.
This phase Ib trial investigated the safety, tolerability, and recommended phase II dose and schedule of the MEK inhibitor trametinib in combination with the mammalian target of rapamycin (mTOR) ...inhibitor everolimus. Secondary objectives included pharmacokinetic (PK) characterization and evaluation of clinical activity.
A total of 67 patients with advanced solid tumors were enrolled in this open-label, single-arm, dose-escalation study. Dose escalation followed a 3 + 3 design. Patients were assigned to one of 10 different cohorts, involving either daily dosing with both agents or daily dosing with trametinib and intermittent everolimus dosing. This included an expansion cohort comprising patients with pancreatic tumors. PKs samples were collected predose, as well as 1, 2, 4, and 6h post-dose on day 15 of the first treatment cycle.
Concurrent treatment with trametinib and everolimus resulted in frequent treatment-related adverse events, including mucosal inflammation (40%), stomatitis (25%), fatigue (54%), and diarrhea (42%). PK assessment did not suggest drug–drug interactions between these two agents. Of the 67 enrolled patients, 5 (7%) achieved partial response (PR) to treatment and 21 (31%) displayed stable disease (SD). Among the 21 patients with pancreatic cancer, PR was observed in 1 patient (5%) and SD in 6 patients (29%).
This study was unable to identify a recommended phase II dose and schedule of trametinib in combination with everolimus that provided an acceptable tolerability and adequate drug exposure.
Based on the concept of nutritional programming in mammals, we tested whether an acute hyperglucidic-hypoproteic stimulus during first feeding could induce long-term changes in nutrient metabolism in ...rainbow trout. Trout alevins received during the five first days of exogenous feeding either a hyperglucidic (40% gelatinized starch + 20% glucose) and hypoproteic (20%) diet (VLP diet) or a high-protein (60%) glucose-free diet (HP diet, control). Following a common 105-day period on a commercial diet, both groups were then challenged (65 days) with a carbohydrate-rich diet (28%). Short- and long-term effects of the early stimuli were evaluated in terms of metabolic marker gene expressions and intestinal microbiota as initial gut colonisation is essential for regulating the development of the digestive system. In whole alevins (short term), diet VLP relative to HP rapidly increased gene expressions of glycolytic enzymes, while those involved in gluconeogenesis and amino acid catabolism decreased. However, none of these genes showed persistent molecular adaptation in the liver of challenged juveniles (long term). By contrast, muscle of challenged juveniles subjected previously to the VLP stimulus displayed downregulated expression of markers of glycolysis and glucose transport (not seen in the short term). These fish also had higher plasma glucose (9 h postprandial), suggesting impaired glucose homeostasis induced by the early stimulus. The early stimulus did not modify the expression of the analysed metabolism-related microRNAs, but had short- and long-term effects on intestinal fungi (not bacteria) profiles. In summary, our data show that a short hyperglucidic-hypoproteic stimulus during early life may have a long-term influence on muscle glucose metabolism and intestinal microbiota in trout.
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