Background/Aims: The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response. Methods: In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled. Results: Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00–7.62; P= 0.050) and shorter disease duration (OR for median duration ≥ 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13–0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response. Conclusions Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence.

A 57-year-old man complained of dyspnea, and his echocardiography showed diffuse severe left ventricular dysfunction. Five days after admission and starting the treatment for congestive heart failure, a computed tomography pointed out DeBakey type 1 aortic dissection with a patent false lumen incidentally. The ostium of the left coronary artery was compressed with the false lumen, and this finding was thought to be a cause of development of left ventricular dysfunction. A modified Bentall procedure with bioprosthesis and total arch replacement were performed. The patient was discharged on the 28th postoperative day without any complications.

Retrograde type A aortic dissection (RTAD) following thoracic endovascular aortic repair (TEVAR) is a lethal complication. A 54-year-old woman with bovine aortic arch presented with dilatation of the descending aorta due to chronic type B aortic dissection. She underwent TEVAR in zone 2 for closure of the entry site just below the origin of the left subclavian artery. On the day after TEAVR, she showed right hemiparesis, and was diagnosed with cerebral infarction on MRI and RTAD on CT. She underwent an emergent operation. The entry was at the proximal end of the bovine trunk, where the edge of the bare stent stuck out. We performed partial arch replacement with entry resection. Her postoperative course was uneventful. She was transferred to another hospital for rehabilitation 37 days after the surgery.

BACKGROUND: Senna, one of the major stimulant laxatives, is widely used for treating constipation. Chronic senna use has been reported to be associated with colonic disorders such as melanosis coli and/or epithelial hyperplasia. However, there is no obvious information on the influence of chronic senna use on organs except for the intestine. OBJECTIVE: To clarify the influence of senna laxative use on skin barrier function by repeated senna administration. METHODS: Eight-week-old male hairless mice received senna (10 mg/kg/day) for 21 days. After administration, we evaluated transepidermal water loss (TEWL), and investigated the biomarkers in plasma and skin using protein analysis methods. RESULTS: Fecal water content on day seven was significantly increased; however, on day 21, it was significantly decreased after repeated senna administration. In the senna-administered group, TEWL was significantly higher compared to the control on days seven and 21. Plasma acetylcholine concentration and NO2 −/NO3 − were increased on days seven and 21, respectively. In skin, tryptase-positive mast cells and inducible nitric oxide synthase (iNOS)-positive cells were increased on days seven and 21, respectively. The increase of TEWL on days seven and 21 was suppressed by the administration of atropine and N(G)-nitro-L-arginine methyl ester, respectively. CONCLUSION: It was suggested that diarrhea or constipation induced by repeated senna administration caused the impairment of skin barrier function. There is a possibility that this impaired skin barrier function occurred due to degranulation of mast cells via cholinergic signals or oxidative stress derived from iNOS.
Acetylcholine ; Animals ; Atropine ; Biomarkers ; Colon ; Constipation ; Diarrhea ; Humans ; Hyperplasia ; Intestines ; Laxatives ; Male ; Mast Cells ; Melanosis ; Mice* ; Mice, Hairless ; NG-Nitroarginine Methyl Ester ; Nitric Oxide Synthase Type II ; Oxidative Stress ; Plasma ; Senna Extract ; Skin* ; Water

This research aims to investigate the impact of fever on total mechanical ventilation time (TVT) in critically ill patients. Subgroup analysis was conducted using a previous prospective, multicenter observational study. We included mechanically ventilated patients for more than 24 hours from 10 Korean and 15 Japanese intensive care units (ICU), and recorded maximal body temperature under the support of mechanical ventilation (MAX(MV)). To assess the independent association of MAX(MV) with TVT, we used propensity-matched analysis in a total of 769 survived patients with medical or surgical admission, separately. Together with multiple linear regression analysis to evaluate the association between the severity of fever and TVT, the effect of MAX(MV) on ventilator-free days was also observed by quantile regression analysis in all subjects including non-survivors. After propensity score matching, a MAX(MV) ≥ 37.5℃ was significantly associated with longer mean TVT by 5.4 days in medical admission, and by 1.2 days in surgical admission, compared to those with MAX(MV) of 36.5℃ to 37.4℃. In multivariate linear regression analysis, patients with three categories of fever (MAX(MV) of 37.5℃ to 38.4℃, 38.5℃ to 39.4℃, and ≥ 39.5℃) sustained a significantly longer duration of TVT than those with normal range of MAX(MV) in both categories of ICU admission. A significant association between MAX(MV) and mechanical ventilator-free days was also observed in all enrolled subjects. Fever may be a detrimental factor to prolong TVT in mechanically ventilated patients. These findings suggest that fever in mechanically ventilated patients might be associated with worse mechanical ventilation outcome.
Asian Continental Ancestry Group ; Body Temperature ; Critical Illness* ; Fever* ; Humans ; Intensive Care Units ; Linear Models ; Observational Study ; Propensity Score ; Prospective Studies ; Reference Values ; Respiration, Artificial*