Concise Review: The Potential Use of Intestinal Stem Cells to Treat Patients With Intestinal Failure.

: Intestinal failure is a rare life-threatening condition that results in the inability to maintain normal growth and hydration status by enteral nutrition alone. Although parenteral nutrition and whole organ allogeneic transplantation have improved the survival of these patients, current therapies are associated with a high risk for morbidity and mortality. Development of methods to propagate adult human intestinal stem cells (ISCs) and pluripotent stem cells raises the possibility of using stem cell-based therapy for patients with monogenic and polygenic forms of intestinal failure. Organoids have demonstrated the capacity to proliferate indefinitely and differentiate into the various cellular lineages of the gut. Genome-editing techniques, including the overexpression of the corrected form of the defective gene, or the use of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 to selectively correct the monogenic disease-causing variant within the stem cell, make autologous ISC transplantation a feasible approach. However, numerous techniques still need to be further optimized, including more robust ex vivo ISC expansion, native ISC ablation, and engraftment protocols. Large-animal models can to be used to develop such techniques and protocols and to establish the safety of autologous ISC transplantation because outcomes in such models can be extrapolated more readily to humans.The field of intestinal stem cell biology has exploded over the past 5 years with discoveries related to in vivo and in vitro stem cell identity and function. The goal of this review article is to highlight the potential use of these cells to treat various epithelial disorders of the gut and discuss the various roadblocks that will be encountered in the coming years

Genetic and epigenetic alterations of colorectal cancer

Colorectal cancer (CRC) arise from multi-step carcinogenesis due to genetic mutations and epigenetic modifications of human genome. Genetic mutations and epigenetic modifications were originally established as 2 independent mechanisms contributing to colorectal carcinogenesis. However, recent evidences demonstrate that there are interactions between these 2 mechanisms. Genetic mutations enable disruption of epigenetic controls while epigenetic modifications can initiate genomic instability and carcinogenesis. This review summarized genetic mutations and epigenetic modifications in colorectal carcinogenesis and molecular classification of CRC subtype based on genetic or epigenetic biomarkers for treatment response and prognosis. Molecular subtypes of CRC will permit the implementation of precision medicine with better outcome of management for CRC

Fecal Microbiota Transplantation beyond Clostridioides Difficile Infection

With advancing analytical methods for gut microbes, many studies have been conducted, revealing that gut microbes cause various diseases, including gastrointestinal and non-gastrointestinal diseases. Accordingly, studies have been actively conducted to analyze the effects on the prevention and treatment of these diseases through changes in intestinal microbes and control of dysbiosis. Fecal microbiota transplantation (FMT) is an effort and is currently being applied to Clostridioides difficile treatment in Korea. Many studies have demonstrated the application of FMT in inflammatory bowel disease, irritable bowel syndrome, non-alcoholic fatty liver disease, metabolic syndrome, obesity, and diabetes. With further studies and accumulation of evidence, FMT could help treat presently untreatable diseases in clinical practice

Intestinal epithelial replacement by transplantation of cultured murine and human cells into the small intestine.

Adult intestinal epithelial stem cells are a promising resource for treatment of intestinal epithelial disorders that cause intestinal failure and for intestinal tissue engineering. We developed two different animal models to study the implantation of cultured murine and human intestinal epithelial cells in the less differentiated "spheroid" state and the more differentiated "enteroid" state into the denuded small intestine of mice. Engraftment of donor cells could not be achieved while the recipient intestine remained in continuity. However, we were able to demonstrate successful implantation of murine and human epithelial cells when the graft segment was in a bypassed loop of jejunum. Implantation of donor cells occurred in a random fashion in villus and crypt areas. Engraftment was observed in 75% of recipients for murine and 36% of recipients for human cells. Engrafted spheroid cells differentiated into the full complement of intestinal epithelial cells. These findings demonstrate for the first time successful engraftment into the small bowel which is optimized in a bypassed loop surgical model

Importance of remission and residual somatic symptoms in health-related quality of life among outpatients with major depressive disorder: a cross-sectional study

Background: Major depressive disorder (MDD) is strongly associated with an impaired quality of life (QoL), which is itself affected by various factors. Symptom-oriented ratings poorly reflect the impact of disease on the QoL and level of functioning of the mental health of subjects. The purpose of this study was to assess health-related QoL (HRQoL) using preference-based measures in outpatients with MDD with regard to their remission achievement and clinical factors affecting the HRQoL. Methods: This was a cross-sectional observational study. We recruited 811 patients with MDD from 14 psychiatric outpatient clinics in Korea. They were divided into three groups as follows: a new visit group (n = 287), a remitted group (n = 235), and a non-remitted group (n = 289). The 17-item Hamilton Depression Rating Scale was used to assign patients to the remitted or non-remitted group. The general HRQoL was assessed with the EuroQol 5D (EQ-5D), using both the EQ-5D index score and the EuroQol Visual Analog Scale (EQ-VAS). The disease-specific HRQoL was assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Results: The non-remitted group showed a significant impairment of HRQoL in view of the subscales of EQ-5D index scores, EQ-VAS, and Q-LES-Q-SF. The EQ-5D index score in the remitted group was 0.77 ± 0.10, while it was 0.57 ± 0.23 in the non-remitted group and 0.58 ± 0.24 in the new visit group (p < 0.0001). The EQ-VAS scores for the remitted and non-remitted groups were 72.5 ± 16.6 and 50.9 ± 20.3, respectively (p < 0.0001). Likewise, patients with remission had the Q-LES-Q-SF total score of 46.5 ± 8.8, whereas those with non-remission reported 36.7 ± 7.7 (p < 0.0001). The symptom severity measured by the Depression and Somatic Symptoms Scale was significantly correlated with the HRQoL. Furthermore, patients with severe somatic symptoms showed a significantly lower EQ-5D index score (0.54 ± 0.24) than those with mild/moderate somatic symptoms (0.75 ± 0.12; p = 0.002). Conclusion: Non-remitted MDD patients, especially those with more severe somatic symptoms, show a distinct impairment of HRQoL and more clinical symptoms, suggesting the importance of achieving remission in the treatment of MDD

Excess cost of non-remission among outpatients with major depressive disorder

Background: The purpose of this study was to assess the economic benefit of achieving remission among outpatients with major depressive disorder (MDD) who are currently employed in Korea. Methods: Cross-sectional observational study. A total of 337 outpatients with MDD with paid jobs were recruited from 14 psychiatric clinics in Korea and were then divided into three groups as follows: new visit group (n = 128), remitted group (n = 100) and non-remitted group (n = 109). The 17-item Hamilton Depression Rating Scale (HAM-D) was used to decide whether a patient should be assigned to the remitted or non-remitted group. Direct medical and non-medical costs were measured via interview with the subjects. The World Health Organization Health and Work Performance Questionnaire (HPQ) were applied in order to measure the lost productive time (LPT) and related productivity costs. Results: The three groups did not show a significant difference in direct medical cost. However, the difference between the remitted group and non-remitted group was statistically significant (25.49 ± 52.99 vs. 44.79 ± 126.55, χ2 = 12.99, p = 0.0015). The remitted group demonstrated a significant improvement in productivity (particularly presenteeism) when compared with the new visit group (Z = −3.29, p = 0.001). Although the non-remitted group received treatment at psychiatric clinics similar to the remitted group, it lost 33 more working hours per month, which is compatible to $332 per month. Conclusion: These results suggest the economic importance of achieving remission in treating depression

Recent Advance in Colon Capsule Endoscopy: What’s New?

Colon capsule endoscopy (CCE) is a relatively new diagnostic procedure for patients with suspected colonic diseases. This convenient, noninvasive method enables the physician to explore the entire colon without significant discomfort to the patient. However, while CCE can be performed painlessly without bowel air insufflation, the need for vigorous bowel preparation and other technical limitations exist. Due to such limitations, CCE has not replaced conventional colonoscopy. In this review, we discuss historical and recent advances in CCE including technical issues, ideal bowel preparation, indications and contraindications and highlight further technical advancements and clinical studies which are needed to develop CCE as a potential diagnostic tool

Predictors of Successful Trial without Catheter for Postoperative Urinary Retention Following Non-Urological Surgery

Purpose To investigate the success rate of trial without catheter (TWOC) for postoperative urinary retention (POUR) after non-urological surgery and to determine predictors of successful TWOC. Methods A total of 104 patients who underwent non-urological surgery and were referred to the department of urology for POUR were included in this retrospective study. All eligible patients underwent indwelling catheterization as an initial treatment and then TWOC was performed 3 to 7 days later. POUR was defined as micturition difficulty with greater than 400 mL of postvoid residual (PVR) urine volume measured by catheterization after non-urological surgery. Successful TWOC was defined as voiding with less than 100 mL of PVR urine volume. Predictive factors were identified by multivariate regression analysis. All definitions corresponded to recommendations of the International Continence Society. Results The mean age of the patients was 65.2 (range, 23 to 92) years. There were 45 male and 59 female patients. Intraoperative indwelling catheterization was performed in 69 (66.3%) patients. Mean duration of indwelling catheterization for POUR was 5.0 (range, 3.0 to 7.0) days and 83 (79.8%) patients received medication with an alpha-blocker. A successful TWOC was observed in 70 (67.4%) patients. The mean age of the patients with failure of TWOC was significantly higher than that of the patients with successful TWOC. The percentages of female patients, spinal surgery, and prone position during surgery in patients with unsuccessful TWOC were higher than in those with successful TWOC. In the multivariate logistic regression analysis, age and location of surgery (spine vs. non-spine) were the independent predictors of successful TWOC for POUR. Conclusions Our data suggest that older age and spinal surgery may be important risk factors for failure of TWOC for POUR after non-urological surgery. Thus, adequate prevention measures may be necessary for POUR after non-urological surgery, especially in patients with these risk factors