Hasil untuk "Diseases of the digestive system. Gastroenterology"

Holly O’Donnell, Roy Tamura, Laura Smith et al.

This study, part of the ongoing TEDDY (The Environmental Determinants of Diabetes in the Young) study, assessed children’s understanding of their own risk for type 1 diabetes from 10 to 15 years of age and sought to identify factors associated with children’s risk perception. Analysis of responses from nearly 5,000 children revealed that risk for type 1 diabetes is a difficult concept for children to grasp even in the context of extensive educational efforts. Several factors associated with children’s understanding of type 1 diabetes risk were identified that may guide future efforts to help children understand disease risk.

Elisa J. Gordon, Jessica Gacki-Smith, Matthew J. Gooden et al.

AbstractClinical chatbots are increasingly used to help integrate genetic testing into clinical contexts, but no chatbot exists for Apolipoprotein L1 (APOL1) genetic testing of living kidney donor (LKD) candidates of African ancestry. Our study aimed to culturally adapt and assess perceptions of the Gia® chatbot to help integrate APOL1 testing into LKD evaluation. Ten focus groups and post-focus group surveys were conducted with 54 LKDs, community members, and kidney transplant recipients of African ancestry. Data were analyzed through thematic analysis and descriptive statistics. Key themes about making Gia culturally targeted included ensuring: (1) transparency by providing Black LKDs’ testimonials, explaining patient privacy and confidentiality protections, and explaining how genetic testing can help LKD evaluation; (2) content is informative by educating Black LKDs about APOL1 testing instead of aiming to convince them to undergo testing, presenting statistics, and describing how genetic discrimination is legally prevented; and (3) content avoids stigma about living donation in the Black community. Most agreed Gia was neutral and unbiased (82%), trustworthy (82%), and words, phrases, and expressions were familiar to the intended audience (85%). Our culturally adapted APOL1 Gia chatbot was well regarded. Future research should assess how this chatbot could supplement provider discussion prior to genetic testing to scale APOL1 counseling and testing for LKD candidate clinical evaluation.

Karen C. Johnson, Andrea Anderson, Kristen M. Beavers et al.

Abstract Summary Intentional weight loss has been shown to increase bone loss short term but the long-term effects are not known. Data from the Look AHEAD clinical trial shows that a long term intentional weight loss intervention was associated with greater bone loss at the hip in men. Purpose Intentional weight loss has been shown to increase bone loss short term and increase frailty fracture risk, but the long-term effects on bone mineral density (BMD) are not known. Methods Data from a subgroup from the Look AHEAD (LA) multicenter, randomized clinical trial was used to evaluate whether a long term intentional weight loss intervention would increase bone loss. In a preplanned substudy, BMD was assessed at 5 of the 16 LA clinical centers using dual-energy X-ray absorptiometry at baseline, year 8, and the observational visit 12.6–16.3 years after randomization (year 12–16). Results At year 8, bone density loss (%) was greater in the Intensive Lifestyle Intervention (ILI) group compared with the control group (DSE) for the femoral neck (p = 0.0122) but this finding was not observed at the year 12–16 visit. In analyses stratified by gender, bone density loss (%) was greater at the total hip for men in the ILI group than the DSE group at both the year 8 and year 12–16 visits (year 8 p = 0.0263 and year 12–16 p = 0.0062). This finding was not observed among women. Conclusion Long term intentional weight loss was associated with greater bone loss at the hip in men. These results taken with the previously published Look AHEAD data from the entire clinical trial showing increased frailty fracture risk with weight loss in the ILI group suggest that when intentional weight loss is planned, consideration of bone density preservation and fracture prevention strategies is warranted. Trial Registration Clinicaltrials.gov Identifier: NCT00017953. June 21, 2001

Michael S. Hughes, Ryan S. Kingman, Liana Hsu et al.

Grant Hennig, Pragya Saxena, Eli Broemer et al.

Abstract Optimal bladder compliance is essential to urinary bladder storage and voiding functions. Calculated as the change in filling volume per change in pressure, bladder compliance is used clinically to characterize changes in bladder wall biomechanical properties that associate with lower urinary tract dysfunction. But because this method calculates compliance without regard to wall structure or wall volume, it gives little insight into the mechanical properties of the bladder wall during filling. Thus, we developed Pentaplanar Reflected Image Macroscopy (PRIM): a novel ex vivo imaging method to accurately calculate bladder wall stress and stretch in real time during bladder filling. The PRIM system simultaneously records intravesical pressure, infused volume, and an image of the bladder in five distinct visual planes. Wall thickness and volume were then measured and used to calculate stress and stretch during filling. As predicted, wall stress was nonlinear; only when intravesical pressure exceeded ~ 15 mmHg did bladder wall stress rapidly increase with respect to stretch. This method of calculating compliance as stress vs stretch also showed that the mechanical properties of the bladder wall remain similar in bladders of varying capacity. This study demonstrates how wall tension, stress and stretch can be measured, quantified, and used to accurately define bladder wall biomechanics in terms of actual material properties and not pressure/volume changes. This method is especially useful for determining how changes in bladder biomechanics are altered in pathologies where profound bladder wall remodeling occurs, such as diabetes and spinal cord injury.

Ricardo Oliveros Wilches, Luciano Aponte Lopez

Shuangping Wang, Qifeng Lu, Yabai Zhou et al.

Background: To investigate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in elderly choledocholithiasis patients compared with younger groups. Methods: This was a case–control study conducted from January 2018 to December 2020 at Fuyang People's Hospital, with 596 patients included. Patients who underwent ERCP were classified as two groups based on age stratification definitions from the National Institute of Health and the World Health Organisation: Patients <75 ages (n = 204) and patients ≥75 ages (n = 392). Demographic characteristics, details of endoscopic therapy, complications were retrospectively reviewed and compared between two groups. The subgroup was pre-formed to further explore the efficacy and safety of ERCP in the elderly population. Results: Between patients ≥75 ages and patients <75 ages, there were no significant differences in the complete stone removal rate and a second ERCP. Intubation difficulty (odds rate [OR]: 1.723, 95% confidence interval [CI]: 1.118–2.657) and longer ERCP operation time (β = 4.314, 95% CI: 2.366–6.262) were observed in the elderly group at a higher frequency than the younger group. Elder patients were more likely to have intra-operative complications (χ2 = 18.158, P < 0.001), and post-operative complications (χ2 = 8.739, P = 0.003). In the subgroup group, ERCP was efficacious and safe in elderly patients with comorbidities. Conclusions: ERCP may be efficaciously performed on elderly patients. However, intra-operative and post-operative complications of ECRP should also be taken into consideration when selecting therapeutic options.

Michiko Nishikawa, Yoshinobu Yamamoto, Saeko Kushida et al.

Abstract Objectives Chemoradiotherapy (CRT) or radiotherapy (RT) alone is often the treatment of choice for elderly patients with esophageal cancer with the expectation of organ preservation. However, salvage treatment remains a problem when endoscopic resection is not indicated for local failure after CRT/RT. Photodynamic therapy (PDT) is indicated for local failure after CRT/RT, but there are few reports on its efficacy and safety in elderly patients. This study aimed to assess the outcome of PDT for local failure after CRT/RT for esophageal cancer in elderly patients. Methods This retrospective single‐center study included 42 patients who first underwent PDT between April 2013 and June 2021. Patients aged ≥80 and <80 years were classified into the elderly and nonelderly groups, respectively. Local complete response rate, overall survival, progression‐free survival, and incidence of adverse events related to PDT were compared retrospectively between the groups. Results The local complete response rate was 93.3% in the elderly group and 85.7 in the non‐elderly group. The 2‐year overall survival rate was 68.6% and 72.5%, and the 2‐year progression‐free survival rate was 49.5% and 70.0% in the elderly and nonelderly groups, respectively. There was no significant difference in any of these outcomes between the groups. In terms of adverse events, pneumonia and delirium tended to occur more frequently in the elderly group, but there were no serious adverse events in either group. Conclusion The outcome of salvage PDT in the local control was comparable between the elderly and nonelderly patients for local failure after CRT/RT for esophageal cancer.

Sungpil Han, Hee Youn Choi, Yo Han Kim et al.

Background/Aims: Tegoprazan, a novel potassium-competitive acid blocker, is expected to overcome the limitations of proton pump inhibitors and effectively control nocturnal acid breakthrough. To evaluate the pharmacodynamics of tegoprazan versus dexlansoprazole regarding nocturnal acid breakthrough in healthy subjects. Methods: In a randomized, open-label, single-dose, balanced incomplete block crossover study, 24 healthy male volunteers were enrolled and randomized to receive oral tegoprazan (50, 100, or 200 mg) or dexlansoprazole (60 mg) during each of two administration periods, separated by a 7- to 10-day washout period. Blood samples were collected for pharmacokinetic parameter analysis; gastric monitoring was performed for pharmacodynamic parameter evaluation. Results: All 24 subjects completed the study. Average maximum plasma concentration, area under the plasma concentration-time curve, and mean time with gastric pH >4 and pH >6 for tegoprazan demonstrated dose-dependent incremental increases. All the tegoprazan groups reached mean pH ≥4 within 2 hours, whereas the dexlansoprazole group required 7 hours after drug administration. Based on pharmacodynamic parameters up to 12 hours after evening dosing, 50, 100, and 200 mg of tegoprazan presented a stronger acid-suppressive effect than 60 mg of dexlansoprazole. Moreover, the dexlansoprazole group presented a comparable acid-suppressive effect with the tegoprazan groups 12 hours after dosing. Conclusions: All the tegoprazan groups demonstrated a significantly faster onset of gastric pH increase and longer holding times above pH >4 and pH >6 up to 12 hours after evening dosing than the dexlansoprazole group.

İlkay Tuğba Ünek, İlhan Öztop, Yasemin Başbınar et al.

Erin K. Stenson, Jessica Kendrick, Bradley Dixon et al.

Xiaoying Liu, Sarah A. Taylor, Kyle D. Gromer et al.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of liver diseases in the United States and can progress to cirrhosis, end-stage liver disease and need for liver transplantation. There are limited therapies for NAFLD, in part, due to incomplete understanding of the disease pathogenesis, which involves different cell populations in the liver. Endoplasmic reticulum stress and its adaptative unfolded protein response (UPR) signaling pathway have been implicated in the progression from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH). We have previously shown that mice lacking the UPR protein X-box binding protein 1 (XBP1) in the liver demonstrated enhanced liver injury and fibrosis in a high fat sugar (HFS) dietary model of NAFLD. In this study, to better understand the role of liver XBP1 in the pathobiology of NAFLD, we fed hepatocyte XBP1 deficient mice a HFS diet or chow and investigated UPR and other cell signaling pathways in hepatocytes, hepatic stellate cells and immune cells. We demonstrate that loss of XBP1 in hepatocytes increased inflammatory pathway expression and altered expression of the UPR signaling in hepatocytes and was associated with enhanced hepatic stellate cell activation after HFS feeding. We believe that a better understanding of liver cell-specific signaling in the pathogenesis of NASH may allow us to identify new therapeutic targets.

Michael P Bancks, James Lovato, Ashok Balasubramanyam et al.

Abstract Context Type 2 diabetes is a risk factor for incident dementia but whether risk and treatment/prevention strategies differ by diabetes subgroup is unknown. Objective We assessed (1) whether specific type 2 diabetes (T2D) subgroups are associated with mild cognitive impairment (MCI) or probable dementia (PD), and (2) whether T2D subgroups modified the association of the Action for Health in Diabetes (Look AHEAD) multidomain intensive lifestyle intervention (ILI) with MCI/PD. Methods We included 3760 Look AHEAD participants with T2D and overweight or obesity randomly assigned to 10 years of ILI or diabetes support and education. We used k-means clustering techniques with data on age of diabetes diagnosis, body mass index, waist circumference, and glycated hemoglobin (HbA1c) to characterize diabetes subgroups at randomization. Prevalent MCI/PD were centrally adjudicated based on standardized cognitive tests and other health information 10 to 13 years after randomization. We estimated marginal probabilities for prevalent MCI/PD among T2D subgroups with adjustment for potential confounders and attrition and examined whether ILI modified any associations. Results Four distinct T2D subgroups were identified, characterized by older age at diabetes onset (43% of sample), high HbA1c (13%), severe obesity (23%), and younger age at onset (22%). Unadjusted prevalence of MCI/PD (314 cases, 8.4%) differed across T2D subgroup (older onset = 10.5%, severe obesity = 9.0%, high HbA1c = 7.9%, and younger onset = 4.0%). Adjusted probability for MCI/PD within T2D subgroup was highest for the severe obesity subgroup and lowest for the younger onset subgroup but did not differ by ILI arm (interaction P value = 0.84). Conclusions Among individuals with T2D and overweight or obesity, probability of MCI/PD differed by T2D subgroup. Probability of MCI/PD was highest for a subgroup characterized by severe obesity. Clinicaltrials.gov Identifier NCT00017953

Claudio Romano, Carmelo Scarpignato

Background: Gastroesophageal reflux disease (GERD) is still a challenging and difficult to treat condition in children. Although acid suppression represents the mainstay of treatment in adolescents, it is not devoid of adverse events, especially in the long-term. Objectives: In this investigation we explored a new therapeutic avenue in GERD, that is esophageal mucosal protection. Design: To this end, we performed an investigator-initiated, retrospective study to evaluate the efficacy and safety of a short-term treatment with Esoxx™ medical device in 25 adolescents with GERD-related symptoms. This mucoadhesive formulation contains two natural mucopolysaccharides (sodium hyaluronate and chondroitin sulphate) and adheres to the esophageal mucosa, exerting a protective effect against refluxed gastric contents and allowing mucosal healing. Methods: Heartburn, epigastric burning and post-prandial regurgitation were scored with a pain VAS scale and re-evaluated after 3-week treatment with Esoxx (one stick post-prandially, three times daily). Results: All patients completed the treatment without adverse effects and with good tolerability and compliance. All the three major symptoms significantly (p<0.001) improved after treatment. No patient required additional investigation (i.e. upper Gastrointestinal endoscopy) or medication (i.e. antisecretory drugs). Conclusion: The results of this pilot study suggest that esophageal mucosal protection is a promising therapeutic avenue for GERD also in children. Provided, these data be confirmed by a large, randomized clinical trial, this medical device can enter our therapeutic armamentarium against this challenging disease.

Nóra Ledó, Ákos Géza Pethő

Abstract Background Systemic vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCA) have an extremely wide variety of symptoms, therefore the fast and proper diagnosis is difficult to establish even for experienced physicians. Gastrointestinal manifestations in ANCA-associated granulomatosis with polyangiitis (GPA) may be present, however, severe, life-threatening complications (such as perforations) are rare. Case presentation A case of an 18-year-old male patient is presented, where gastrointestinal symptoms (abdominal pain, vomiting, diarrhoea) were the first remarkable signs of GPA. The initial diagnosis of inflammatory bowel disease delayed the administration of proper immunosuppressive therapy, which might have contributed to the rare and life-threatening complication of arterial duodenal bleeding with perforation. Our systematic review of the literature found only a few case reports where gastrointestinal symptoms were the first signs of GPA, however, this entity might be more frequent if physicians would think of this possibility more often. Conclusions Gastrointestinal bleeding is a rare but potential lethal complication of vasculitis. Consequently, we recommend investigating the patients diagnosed with GPA for gastrointestinal bleeding during the treatment.

Tomomasa Tochio, MD, Akira Teramoto, MD, Daizen Hirata, MD et al.

Wei-Wen Hung, Wei-Chun Hung

The theory of ominous octet proposed by Dr. Defronzo in 2008 has emphasized the underlying complicated pathogenesis mechanism in type 2 diabetes. Recently it was further identified that gut microbiota dysbiosis is also closely related to development of chronic inflammations related diseases including diabetes. Diabetes is characterized by ''leaky gut'' syndrome where bacterial cell wall components enter the blood circulation of animal host in a higher amount. These may cause metabolic endotoxemia and systemic low-grade inflammation, affecting vital organs related to the ominous octet. On the other hand, the bacterial metabolites also systemically affect glucose homeostasis and energy utilization. The effects of current clinically available oral antidiabetic drugs (OAD) are related to altering the compositions of gut microbiota, among which metformin are the most extensively explored. Gut microbiota therefore play an important role as a functional cross-bridge between host environment and the ominous octet, modulating diabetes. With continuing explorations, in the future gut microbiota may serve as a diagnostic biomarker in personalized medicine. Its modulation may also be used as a novel approach to treat type 2 diabetes.

Dae Young Cheung, Byung Ik Jang, Sang Wook Kim et al.

The area of endoscopic application has been continuously expanded since its introduction in the last century and the frequency of its use also increased stiffly in the last decades. Because gastrointestinal endoscopy is naturally exposed to diseased internal organs and contact with pathogenic materials, endoscopy mediated infection or disease transmission becomes a major concern in this field. Gastrointestinal endoscopy is not for single use and the proper reprocessing process is a critical factor for safe and reliable endoscopy procedures. What needed in these circumstances is a practical guideline for reprocessing the endoscope and its accessories which is feasible in the real clinical field to guarantee acceptable prevention of pathogen transmission. This guideline contains principles and instructions of the reprocessing procedure according to the step by step. And it newly includes general information and updated knowledge about endoscopy-mediated infection and disinfection. Multiple societies and working groups participated to revise; Korean Association for the Study of the Liver, the Korean Society of Infectious Diseases, Korean College of Helicobacter and Upper Gastrointestinal Research, the Korean Society of Gastroenterology, Korean Society of Gastrointestinal Cancer, Korean Association for the Study of Intestinal Diseases, Korean Pancreatobiliary Association, the Korean Society of Gastrointestinal Endoscopy Nurses and Associates and Korean Society of Gastrointestinal Endoscopy. Through this cooperation, we enhanced communication and established a better concordance. We still need more researches in this field and fill up the unproven area. And our guidelines will be renewed accordingly.

Matthew J. Westacott, Nikki L. Farnsworth, Joshua R. St. Clair et al.

Aging is associated with increased risk for type 2 diabetes, resulting from reduced insulin sensitivity and secretion. Reduced insulin secretion can result from reduced proliferative capacity and reduced islet function. Mechanisms underlying altered β-cell function in aging are poorly understood in mouse and human islets, and the impact of aging on intraislet communication has not been characterized. Here, we examine how β-cell [Ca2+] and electrical communication are impacted during aging in mouse and human islets. Islets from human donors and from mice were studied using [Ca2+] imaging, static and perifusion insulin secretion assays, and gap junction permeability measurements. In human islets, [Ca2+] dynamics were coordinated within distinct subregions of the islet, invariant with islet size. There was a marked decline in the coordination of [Ca2+] dynamics, gap junction coupling, and insulin secretion dynamics with age. These age-dependent declines were reversed by pharmacological gap junction activation. These results show that human islet function declines with aging, which can reduce insulin action and may contribute to increased risk of type 2 diabetes.