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Purpose

In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m2) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.

Methods

Assessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan.

Findings

In 120 patients with weight data available, weight gain ≥3% was observed in 2 of 39 patients (5.1%) taking placebo TID, 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss ≥3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.

Implications

Up to 32.5% of patients treated with telotristat ethyl experienced significant, dose-dependent weight gain, associated with reduced diarrhea severity and improved biochemical and metabolic parameters. Improved nutritional status could be an additional aspect of telotristat ethyl efficacy among patients with functioning metastatic neuroendocrine tumors. ClinicalTrials.gov identifier: NCT01677910.  相似文献   
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Clinical Rheumatology - Studies conducted by various scientific societies have shown that the demand for specialized rheumatology care is greater than the projected growth of the workforce. Our...  相似文献   
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SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID-19. We investigated whether the specific immune responses in the peripheral blood of 276 patients were associated with the severity and progression of COVID-19. At admission, dramatic lymphopenia of T, B, and NK cells is associated with severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56CD16+ NK-cells increased. Regarding humoral immunity, levels of IgM, IgA, and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless of their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes, and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID-19 patients, associating severity with an imbalanced humoral response, and identifying new targets for therapeutic intervention.  相似文献   
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Objectives:A practical approach to three-dimensional (3D) intraoral imaging would have many potential applications in clinical dentistry. Stationary intraoral tomosynthesis (sIOT) is an experimental 3D imaging technology that holds promise. The purpose of this study was to explore synthetic radiography as a tool to improve the clinical utility of the images generated by an sIOT scan.Methods:Extracted tooth specimens containing either caries adjacent to restorations (CAR) or vertical root fractures (VRF) were imaged by sIOT and standard dental radiography devices. Qualitative assessments were used to compare the conspicuity of these pathologies in the standard radiographs and in a set of multi-view synthetic radiographs generated from the information collected by sIOT.Results:The sIOT-based synthetic 2D radiographs contained less artefact than the image slices in the reconstructed 3D stack, which is the conventional approach to displaying information from a tomosynthesis scan. As a single sIOT scan can be used to generate synthetic radiographs from multiple viewing angles, the interproximal space was less likely to be obscured in the synthetic images compared to the standard radiograph. Additionally, the multi-view synthetic radiographs can potentially improve the display of CAR and VRFs as compared to a single standard radiograph.Conclusions:This preliminary experience combining synthetic radiography and sIOT in extracted tooth models is encouraging and supports the ongoing study of this promising approach to 3D intraoral imaging with many potential applications.  相似文献   
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