A phase IB/IIA study of remestemcel-L, an allogeneic bone marrow-derived mesenchymal stem cell product, for the treatment of medically refractory ulcerative colitis: an interim analysis.

AIM: There have been no studies into the direct injection of mesenchymal stem cells (MSCs) for luminal ulcerative colitis (UC). Our aim was to investigate the efficacy of MSCs delivered locally via endoscopic delivery, as is done in the setting of perianal disease, to treat the local site of inflammation directly. METHOD: A phase IB/IIA randomized control clinical trial of remestemcel-L, an ex vivo expanded allogeneic bone marrow-derived MSC product, at a dose of 150 million MSCs versus placebo (2:1 fashion) delivered via direct injection using a 23-gauge sclerotherapy needle at the time of colonoscopy was designed to assess the safety and efficacy of endoscopic delivery of MSCs for UC. The main outcome measures were adverse events, Mayo score and Mayo endoscopic severity score at 2 weeks, 6 weeks and 3 months post-MSC delivery. RESULTS: Six patients were enrolled and treated; four received MSCs and two placebo. All had been on prior anti-tumour necrosis factor or anti-integrin therapy. There were no adverse events related to MSCs. In the treatment group (n = 4), the Mayo endoscopic severity score decreased in all patients by 2 weeks after MSC delivery. At 3 months, all patients were extremely satisfied or satisfied with their MSC treatment based on the inflammatory bowel disease patient-reported treatment impact (IBD-PRTI), and treatment response was described as excellent or good in all patients. In the control group (n = 2), the Mayo endoscopic severity score did not increase as a result of being off alternative therapy. At 3 months, patients were dissatisfied according to the IBD-PRTI, and treatment response was poor or unchanged. CONCLUSION: MSCs may offer a safe therapeutic option for the treatment of medically refractory UC. Early data suggest improved clinical and endoscopic scores by 2 weeks after MSC delivery.

A Case of Takotsubo Cardiomyopathy After Local Anesthetic and Epinephrine Infiltration.

Takotsubo cardiomyopathy (TC) is a non-ischemic cardiomyopathy that is accompanied by sudden left ventricular myocardial stunning, dilation and dysfunction. It often results from severe emotional or physical stress. We present the case of a 41-year-old female patient who had general anesthesia induced uneventfully for an elective bladder sling procedure. After an intravaginal injection of local anesthesia (lidocaine 2%; epinephrine 1:100,000) just prior to the surgical incision, the patient had cardiovascular collapse for which cardiopulmonary resuscitation (CPR) was performed. The patient was eventually stabilized but transesophageal echocardiography showed impairment in cardiac motion and remarkably reduced ejection fraction. Troponin levels were elevated but coronary angiography was unremarkable. The ejection fraction returned to normal the next day. Local anesthetic with epinephrine administration can lead to TC, and with optimal management, long-term cardiac sequela can be avoided.