Background Mesenchymal stem cells (MSCs) have been used for the treatment of perianal Crohn’s fistulizing disease by direction injection. However, to date, studies have excluded patients with proctitis, anal canal involvement, vaginal involvement, and an ileal pouch in situ. We sought to assess the safety and efficacy of a direct injection of MSCs for the treatment of perianal, rectovaginal, and peripouch Crohn’s fistula(s). Methods Three phase IB/IIA randomized control trials of perianal (n=23), rectovaginal (n=19) and peripouch (n=22) Crohn’s related fistulas were conducted to determine safety and efficacy of MSCs for refractory phenotypes of perianal Crohn’s disease. Crohn’s patients with perianal, rectovaginal, and peripouch Crohn’s fistulizing disease were offered enrollment into a clinical trial. A total of 75 million MSCs were administered with a 22G needle by direct injection after curettage and primary closure of the fistula tract. A repeat injection of 75 million MSCs was administered at 3 months if complete clinical and radiographic healing were not achieved. Adverse and serious adverse events were collected at post procedure day 1, week 2, week 6, month 3, month 6 and month 12. Clinical healing, radiographic healing per magnetic resonance imaging, and patient reported outcomes were assessed at the same time points. Results A total of 64 patients were enrolled and treated; 49 were treatment and 15 were control. There were no adverse or serious adverse events reported related to investigational product. At twelve months, overall combined clinical and radiographic healing was achieved in 70% of perianal, 37.5% of rectovaginal, and 46.2% of ileal pouch fistulas, respectfully. In the control cohorts, 12 month healing was 0%, 0%, and 0% in the three clincial trials respectively. The perianal Crohn’s disease activity index and VanAssche score all significantly decreased in treatment patients at six and twelve months, but not in the control groups. Conclusion Allogeneic bone marrow derived MSCs offer a safe and effective alternative treatment approach for severe phenotypes of perianal fistulizing Crohn’s disease.

Background and Aims Mesenchymal stem cells (MSCs) have been used for the treatment of perianal Crohn’s fistulizing disease by direction injection. No studies to date have included patients with an ileal pouch anal anastomosis (IPAA) in situ. Methods A phase IB/IIA randomized control trial of bone marrow derived allogeneic MSCs via direct injection to treat adult patients with a peripouch fistula(s) was conducted. 75 million MSCs were administered with a 22G needle; repeat injection at 3 months was given if complete clinical and radiographic healing were not achieved. Adverse and serious adverse events at post procedure day 1, week 2, week 6, month 3, month 6 and month 12 were assessed. Clinical healing, radiographic healing per pelvic MRI, and patient reported outcomes were assessed at the same time points. Results A total of 22 patients were enrolled and treated; 16 were treatment and 6 were control. There were no adverse or serious adverse events related to MSC therapy. At six months, 31% of the treatment group and 20% of the control had complete clinical and radiographic healing. When stratifying the treatment group into perianal (n=7) and anovaginal (n=8) fistulas, 6 month healing in the treatment groups was 57% and 0%, respectively. The perianal Crohn’s disease activity index (PCDAI), Wexner incontinence score, and VanAssche score all significantly decreased in treatment patients at six months; only the PCDAI decreased in the control group. Conclusion Bone marrow derived allogeneic MSCs offer a safe and effective alternative treatment approach for peripouch fistulas in the setting of a Crohn’s like phenotype of the pouch.

Background: Alpha-1-antitrypsin (AAT) is a protein that is the main inhibitor of neutrophil elastase and is released during inflammatory processes to reduce the activity of proteolytic enzymes in areas of inflammation. An indicator in the diagnosis of diseases of the small and large intestine. AAT plays an important role in the pathogenesis and regulation of the inflammatory process in inflammatory bowel diseases, can be used as diagnostic and prognostic markers in patients with intestinal lesions. The aim of the study was to determine the level of a-1-antitrypsin in the blood serum and in the feces in patients of UC with and without COVID-19 to assess the degree of inflammation activity and permeability in the intestine. Methods: Forty-two patients of UC with exacerbation of the disease without COVID-19 (Me age-32 years) with different disease activity according to the Meio activity index (group 1) and 23 UC patients with COVID-19 in the acute period (group 2) were examined. -a1-antitrypsin (AAT) (a1-Antitrypsin Clearance ELISA Immundiagnostik, Germany) was determined in blood serum and in feces. Statistical processing was carried out using the Statistica 6.0 program. Results: In the blood serum of UC patients with exacerbation of the disease without COVID-19, AAT fluctuations from 355 to 3056 mcg/l (norm 900-1800 mcg/l) were detected, the average value was 847.9616.5 mcg/l. In UC patients with exacerbation of the disease and the presence of COVID-19 in the acute period, AAT fluctuations from 645 to 4896 mcg/l (norm 900-1800 mcg/l), the average value is 2286.3 6181.4 mcg/l (P 5 0.000000). The range of AAT concentration in feces ranged from 55 to 625 ml/g of feces (norm 25-35 mg/g of feces), on average 364.9 6 11.4 ml/g of feces. The range of AAT concentration in feces ranged from 112 to 898 ml/g feces) (norm 25-35 mg/g feces), on average 539.6618.4 ml/g feces (P 5 0.000000). Conclusion(s):The increase in AAT in the blood serum and in the feces of patients with exacerbation of UC with the presence of COVID-19 infection in the acute period is significantly higher in patients with UC without COVID-19, which indicates a higher permeability of the intestinal wall.

of the pediatric IBD population had at least 1 mental health concern over this time period, and the most common psychiatric diagnoses were depression alone (67%), anxiety alone (3%), or both depression and anxiety (30%). About 36% of patients were prescribed a psychotropic medication and hydroxyzine (53%), sertraline (33%), and fluoxetine (25%) were the most prescribed therapeutics. 24% of patients utilized some form of mental health service but 49% of patients taking psychotropic medications did not appear to receive any formal mental health services. Patients who developed a psychiatric disorder reported more IBD-related symptoms at the time of their diagnosis compared to those without any history of psychiatric diagnoses (t(136)51.99, P5.02). Conclusion(s): Our results suggest there are high levels of depression and/or anxiety in children with IBD seen at URMC during the time of the COVID-19 pandemic. Additionally, increased IBD symptoms at the time of diagnosis were associated with increased rates of psychopathology. Taken together, these findings suggest that more anxiety and depression screening is needed for pediatric IBD patients and that mental health services may be underutilized in the pediatric IBD population. Future directions include combining and comparing this data set with a previous pre-pandemic study performed at our institution to determine the full impact of COVID-19 on this population.

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