Safety of Tofacitinib in a Real-World Cohort of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Adverse events (AEs) including reactivation of herpes zoster (HZ) and venous thromboembolism (VTE) have been reported from clinical trials of tofacitinib in ulcerative colitis (UC). We investigated the incidence rates of AEs in a real-world study of UC patients given tofacitinib. METHODS: We collected data from 260 patients with UC in the Tofacitinib Real-world Outcomes in Patients with ulceratIve colitis and Crohn's disease consortium study, performed at 6 medical centers in the United States. Patients were followed up for a median of 6 months (interquartile range, 2.7-11.5 mo). AEs were captured using a standardized data collection instrument before study initiation and at weeks 8, 16, 26, 39, and 52. Serious AEs were defined as life-threatening or resulting in a hospitalization, disability, or discontinuation of therapy. Logistic regression was performed to examine risk factors for AEs. RESULTS: AEs occurred in 41 patients (15.7%); most were infections (N = 13; 5.0%). The incidence rate of any AE was 27.2 (95% CI, 24.4-30.7 per 100 patient-years of follow-up evaluation). Fifteen were serious AEs (36.6% of AEs), and tofacitinib was discontinued for 12 patients (4.6% of cohort). The incidence rates of serious AEs was 10.0 (95% CI, 8.9-11.2 per 100 patient-years of follow-up evaluation). Five patients developed HZ infection and 2 developed VTE (all receiving 10 mg tofacitinib, twice per day). CONCLUSIONS: Real-world safety signals for tofacitinib are similar to those for clinical trials, with AEs reported from almost 16% of patients. HZ infection and VTE occurred in patients receiving 10 mg tofacitinib twice per day. These results support dose de-escalation after induction therapy, to reduce the risk of AEs.

Congenic mapping identifies a novel Idd9 subregion regulating type 1 diabetes in NOD mice.

Type 1 diabetes (T1D) results from complex interactions between genetic and environmental factors. The nonobese diabetic (NOD) mouse develops spontaneous T1D and has been used extensively to study the genetic control of this disease. T1D is suppressed in NOD mice congenic for the C57BL/10 (B10)-derived Idd9 resistance region on chromosome 4. Previous studies conducted by other investigators have identified four subregions (Idd9.1, Idd9.2, Idd9.3, and Idd9.4) where B10-derived genes suppress T1D development in NOD mice. We independently generated and characterized six congenic strains containing B10-derived intervals that partially overlap with the Idd9.1 and Idd9.4 regions. T1D incidence studies have revealed a new B10-derived resistance region proximal to Idd9.1. Our results also indicated that a B10-derived gene(s) within the Idd9.4 region suppressed the diabetogenic activity of CD4 T cells and promoted CD103 expression on regulatory T cells indicative of an activated phenotype. In addition, we suggest the presence of a B10-derived susceptibility gene(s) in the Idd9.1/Idd9.4 region. These results provide additional information to improve our understanding of the complex genetic control by the Idd9 region.

Contrasting Strategies in Bouveret's Syndrome: A Series of Two Cases.

Bouveret's syndrome is a rare complication of cholelithiasis, characterized by gastric outlet obstruction caused by a migrated gallstone. Diagnosis of Bouveret's syndrome necessitates urgent treatment as it carries a high mortality rate. The treatment of Bouveret's syndrome has traditionally been surgical. However, there have been increasing reports of successful endoscopic therapy for Bouveret's syndrome. This case series aims to compare and contrast two cases of Bouveret's syndrome. The gallstone was retrieved via endoscopic access in one case while the other was removed with surgery. For each case, we discuss the various factors that contributed to the decision of which treatment modality to use. In addition, we propose an endoscopic technique that may improve the safety and success rate of endoscopic treatment of Bouveret's syndrome.

The 4Cs (crash history, family concerns, clinical condition, and cognitive functions): a screening tool for the evaluation of the at-risk driver.

OBJECTIVES: To evaluate the effectiveness of crash history, family concerns, clinical condition, and cognitive function (the 4Cs, an interview-based screening tool for health providers working with older drivers) in identifying at-risk older drivers. DESIGN: Retrospective cohort study. SETTING: Clinical driving evaluation program at a teaching hospital in the United States. PARTICIPANTS: One hundred sixty patients who completed comprehensive driving evaluations between 2003 and 2009. MEASUREMENTS: Medical record information was used to identify component and total 4Cs scores. Other measurements included the Trail Making Test, the Mini-Mental State Examination, and brake reaction time. The outcome variable was performance on a 45-minute road test. RESULTS: Fifty participants passed the road test, 67 failed, and 43 demonstrated marginal driving skills. The relationship between 4Cs scores and road test outcome was statistically significant (P<.001). The domains most strongly associated with road test outcome were cognitive function (P<.001) and family concerns (P=.01). Scores of 9 or greater-on the 4Cs identified 84% of participants who were at risk for poor road test performance. CONCLUSION: The 4Cs, an interview based screening tool, may be a useful marker to identify at-risk older drivers.