ABSTRACT
BACKGROUND: Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed. METHODS: This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events. RESULTS: One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6 months (q1-q3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p = 0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p < 0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p = 0.11). CONCLUSIONS: Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data.
Subject(s)
Colitis, Ulcerative , Disease Progression , Piperidines , Pyrimidines , Ustekinumab , Humans , Piperidines/therapeutic use , Piperidines/adverse effects , Ustekinumab/therapeutic use , Ustekinumab/adverse effects , Colitis, Ulcerative/drug therapy , Male , Female , Pyrimidines/therapeutic use , Pyrimidines/adverse effects , Retrospective Studies , Adult , Middle Aged , Treatment Outcome , Pyrroles/therapeutic use , Pyrroles/adverse effects , Pyrroles/administration & dosage , Remission Induction/methodsABSTRACT
Intestinal metaplasia of the stomach (IM) is considered a pre-cancerous lesion and is a potential precursor to adenocarcinoma. Metabolic syndrome (MetS) has been associated with lesions to the gastrointestinal tract such as the risk of developing Barett esophagus. Vascular endothelial growth factor and leptin have been associated with either gastrointestinal tract carcinogenesis or MetS. In this context, this study was designed to analyze plasma levels of VEGF and leptin in patients with IM and MetS. Four groups of 137 participants (a control group and three patient groups, IM, MetS and IM- MetS) were created. Inclusion criteria for the presence of IM were endoscopic findings and histological confirmation, while for MetS the ATP III and IDF guidelines. Levels of plasma vascular endothelial growth factor (VEGF) and leptin (Leptin) were determined. VEGF levels were increased in IM (IM vs Control, p=0,011) and IM-MetS groups (IM-MetS vs Control, p <0.001 and IM-MetS vs MetS, p=0.001). Leptin levels were found to be increased in the MetS group (MetS vs. Control, p <0.001 and MetS vs IM, p <0.001) and in IM-MetS (IM-MetS vs Control, p = 0.002, IM-MetS vs IM, p=0.033). Patients with intestinal metaplasia and metabolic syndrome (I M - Me t S g r o u p) have elevated levels of VEGF, while leptin levels were associated predominantly with MetS and not with IM.
ABSTRACT
Gastric cancer (GC) is one of the most common and deadly malignancies worldwide. Helicobacter pylori have been documented as a risk factor for GC. The development of sequencing technology has broadened the knowledge of the gastric microbiome, which is essential in maintaining homeostasis. Recent studies have demonstrated the involvement of the gastric microbiome in the development of GC. Therefore, the elucidation of the mechanism by which the gastric microbiome contributes to the development and progression of GC may improve GC's prevention, diagnosis, and treatment. In this review, we discuss the current knowledge about changes in gastric microbial composition in GC patients, their role in carcinogenesis, the possible therapeutic role of the gastric microbiome, and its implications for current GC therapy.
