Inflammatory bowel disease (IBD) is an idiopathic, multi-etiological disease characterized by inflammation and mucosal destruction of the gastrointestinal tract. Despite the remarkable advance in immunomodulating therapies, there still remains a certain population of patients who are refractory to conventional as well as biologic therapies and fail to achieve mucosal healing. To improve the prognosis of those patients, at least 2 types of stem cells have been tested for their potential therapeutic use. Transplantation of hematopoietic stem cells or mesenchymal stem cells have been tested in several clinical studies, but their beneficial effect still remains controversial. In this review, we would like to overview the recent clinical challenges of stem cell-based therapies in IBD and also introduce our new therapeutic plan of intestinal stem cell transplantation for IBD, based on our ex vivo intestinal organoid culture technique.
Biological Therapy ; Culture Techniques ; Gastrointestinal Tract ; Hematopoietic Stem Cells ; Humans ; Inflammation ; Inflammatory Bowel Diseases ; Mesenchymal Stromal Cells ; Organoids ; Prognosis ; Stem Cell Transplantation ; Stem Cells

Background : The effects of rehabilitation on hemodialysis patients are unknown. We assessed the effects and investigated the association between rehabilitation treatment effects and all-cause mortality. Methods : This prospective cohort study included 120 patients on maintenance hemodialysis. ADL was assessed using the Functional Independence Measure (FIM) score (total points, 126), which comprises 13 motor items (total points, 91) and five cognitive items (total points, 35). A survival curve was constructed using the Kaplan-Meier analysis and stratified into an increase or no-increase of the FIM score. Multivariable logistic regression analysis was used to determine factors associated with the effects of rehabilitation. Discriminative sensitivity of FIM cognitive items for an increase in total FIM was estimated using the area under the receiver operating characteristic (AuROC) curve. Results : The average total FIM score increased from 64.2±3.6 to 75.8±3.0, and the increase in FIM motor and cognitive items was 11.0±1.3 and 0.5±0.6, respectively. The cumulative survival rate within 2.5 years was significantly higher in the FIM increase group than that in the FIM no-increase group. FIM cognitive items and anemia were significantly associated with rehabilitation effects, and AuROC showed that a cutoff of 34 points in cognitive FIM had moderate discriminative sensitivity for a total FIM increase (AuC, 0.719 ; p<0.0008). Conclusions : Rehabilitating hemodialysis patients improved their FIM score (particularly the motor items), and a higher FIM score resulted in a better prognosis. The effectiveness of rehabilitation depends on maintaining a perfect FIM cognitive score.

Background/Aims: Endoscopic activity confirmed by enteroscopy is associated with poor clinical outcome in Crohn’s disease (CD). We investigated which of the existing biomarkers best reflects endoscopic activity in CD patients including the small bowel, and whether their combined use can improve accuracy. Methods: One hundred and four consecutive patients with ileal and ileocolonic type CD who underwent balloon-assisted enteroscopy (BAE) from October 2021 to August 2022 were enrolled, with clinical and laboratory data prospectively collected and analyzed. Results: Hemoglobin, platelet count, C-reactive protein, leucine-rich alpha-2 glycoprotein (LRG), fecal calprotectin, and fecal hemoglobin all showed significant difference in those with ulcers found on BAE. LRG and fecal calprotectin showed the highest areas under the curve (0.841 and 0.853) for detecting ulcers. LRG showed a sensitivity of 78% and specificity of 80% at a cutoff value of 13 μg/mL, whereas fecal calprotectin showed a sensitivity of 91% and specificity of 67% at a cutoff value of 151 μg/g. Dual positivity for LRG and fecal calprotectin, as well as LRG and fecal hemoglobin, both predicted ulcers with an improved specificity of 92% and 100%. A positive LRG or fecal calprotectin/hemoglobin showed an improved sensitivity of 96% and 91%. Positivity for LRG and either of the fecal biomarkers was associated with increased risk of hospitalization, surgery, and relapse. Conclusions The biomarkers LRG, fecal calprotectin, and fecal hemoglobin can serve as noninvasive and accurate tools for assessing activity in CD patients confirmed by BAE, especially when used in combination.

Background/Aims: The efficacy and safety of tofacitinib for the treatment of refractory ulcerative colitis (UC) has been demonstrated in clinical trials. Although, a series of reports with real-world evidence of its short-term efficacy and safety profiles have already been published, reports of long-term real-world data have been limited. We aimed to show our 3-year evidence on the clinical use of tofacitinib for the treatment of UC, focusing on its efficacy and safety profiles. Methods: A retrospective observational study was conducted on patients who started tofacitinib for active refractory UC at our hospital. The primary outcome was the retention rate until 156 weeks after initiating tofacitinib. The secondary outcomes were short-term efficacy at 4, 8, and 12 weeks; long-term efficacy at 52, 104, and 156 weeks; prognostic factors related to the cumulative retention rate; loss of response; and safety profile, including adverse events. Results: Forty-six patients who were able to be monitored for up to 156 weeks after tofacitinib initiation, were enrolled in this study. Continuation of tofacitinib was possible until 156 weeks in 54.3%, with > 50% response rates and > 40% remission rates. Among patients in whom response or remission was achieved and tofacitinib was deescalated after 8 weeks of induction treatment, 54.3% experienced relapse but were successfully rescued by and retained on reinduction treatment, except for 1 patient. No serious AEs were observed in the study. Conclusions Tofacitinib is effective and safe as long-term treatment in a refractory cohort of UC patients in real-world clinical practice.