المؤلفون: Feng, Ying, Chang, Shannon K, Portnoy, Daniel A

المصدر: mBio. 14(5)

مصطلحات موضوعية: Microbiology, Biological Sciences, Biomedical and Clinical Sciences, Emerging Infectious Diseases, Digestive Diseases, Vaccine Related, Infectious Diseases, Prevention, Foodborne Illness, Complementary and Integrative Health, Aetiology, 2.2 Factors relating to the physical environment, Infection, folic acid, Listeria monocytogenes, N-formylmethionine, purine, tetrahydrofolate, Animals, Humans, Folic Acid, N-Formylmethionine, Folic Acid Antagonists, Biochemistry and cell biology, Medical microbiology

الوصف: ImportanceFolic acid is an essential vitamin for bacteria, plants, and animals. The lack of folic acid leads to various consequences such as a shortage of amino acids and nucleotides that are fundamental building blocks for life. Though antifolate drugs are widely used for antimicrobial treatments, the underlying mechanism of bacterial folate deficiency during infection is unclear. This study compares the requirements of different folic acid end-products during the infection of Listeria monocytogenes, a facultative intracellular pathogen of animals and humans. The results reveal the critical importance of N-formylmethionine, the amino acid used by bacteria to initiate protein synthesis. This work extends the current understanding of folic acid metabolism in pathogens and potentially provides new insights into antifolate drug development in the future.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5qk603s6Test

المؤلفون: Beaty, William, Katragadda, Anila, Condos, Rany, Dane, Bari, Sarkar, Suparna, Shaffer, Emily, Chang, Shannon

المصدر: ACG Case Reports Journal ; volume 11, issue 1, page e01247 ; ISSN 2326-3253

الوصف: Although extraintestinal manifestations of inflammatory bowel disease (IBD) are common, pulmonary IBD is extremely rare. Owing to its nonspecific clinical, radiologic, and pathologic features, pulmonary IBD is difficult to diagnose and may mimic more concerning disease processes. We present a rare case of a patient with known Crohn's disease whose initial presentation was highly suspicious for malignancy before further investigation revealed pulmonary IBD.

الإتاحة: https://doi.org/10.14309/crj.0000000000001247Test

المؤلفون: Lukin, Dana, Faleck, David, Xu, Ronghui, Zhang, Yiran, Weiss, Aaron, Aniwan, Satimai, Kadire, Siri, Tran, Gloria, Rahal, Mahmoud, Winters, Adam, Chablaney, Shreya, Koliani-Pace, Jenna L, Meserve, Joseph, Campbell, James P, Kochhar, Gursimran, Bohm, Matthew, Varma, Sashidhar, Fischer, Monika, Boland, Brigid, Singh, Siddharth, Hirten, Robert, Ungaro, Ryan, Lasch, Karen, Shmidt, Eugenia, Jairath, Vipul, Hudesman, David, Chang, Shannon, Swaminath, Arun, Shen, Bo, Kane, Sunanda, Loftus, Edward V, Sands, Bruce E, Colombel, Jean-Frederic, Siegel, Corey A, Sandborn, William J, Dulai, Parambir S

المصدر: Clinical Gastroenterology and Hepatology. 20(1)

مصطلحات موضوعية: Digestive Diseases, Clinical Research, Cancer, Inflammatory Bowel Disease, Patient Safety, Autoimmune Disease, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Antibodies, Monoclonal, Humanized, Colitis, Ulcerative, Gastrointestinal Agents, Humans, Retrospective Studies, Treatment Outcome, Tumor Necrosis Factor Inhibitors, Tumor Necrosis Factor-alpha, Health Outcomes, Comparative Research, Biologics, Clinical Sciences, Gastroenterology & Hepatology

الوصف: Background & aimsWe aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice.MethodsA multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist-naïve and -exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately.ResultsA total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist-naïve and -exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist-treated patients. However, in TNF-antagonist-naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754).ConclusionsTreatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist-naïve patients.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2q3381zpTest

المؤلفون: Dulai, Parambir S, Singh, Siddharth, Casteele, Niels Vande, Meserve, Joseph, Winters, Adam, Chablaney, Shreya, Aniwan, Satimai, Shashi, Preeti, Kochhar, Gursimran, Weiss, Aaron, Koliani-Pace, Jenna L, Gao, Youran, Boland, Brigid S, Chang, John T, Faleck, David, Hirten, Robert, Ungaro, Ryan, Lukin, Dana, Sultan, Keith, Hudesman, David, Chang, Shannon, Bohm, Matthew, Varma, Sashidhar, Fischer, Monika, Shmidt, Eugenia, Swaminath, Arun, Gupta, Nitin, Rosario, Maria, Jairath, Vipul, Guizzetti, Leonardo, Feagan, Brian G, Siegel, Corey A, Shen, Bo, Kane, Sunanda, Loftus, Edward V, Sandborn, William J, Sands, Bruce E, Colombel, Jean-Frederic, Lasch, Karen, Cao, Charlie

المصدر: Clinical Gastroenterology and Hepatology. 18(13)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Genetics, Inflammatory Bowel Disease, Digestive Diseases, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Management of diseases and conditions, 7.3 Management and decision making, Good Health and Well Being, Antibodies, Monoclonal, Humanized, Colitis, Ulcerative, Gastrointestinal Agents, Humans, Remission Induction, Treatment Outcome, Prognostic Factor, Response to Treatment, Personalized Medicine, Biologic, Gastroenterology & Hepatology, Clinical sciences

الوصف: Background & aimsWe created and validated a clinical decision support tool (CDST) to predict outcomes of vedolizumab therapy for ulcerative colitis (UC).MethodsWe performed logistic regression analyses of data from the GEMINI 1 trial, from 620 patients with UC who received vedolizumab induction and maintenance therapy (derivation cohort), to identify factors associated with corticosteroid-free remission (full Mayo score of 2 or less, no subscore above 1). We used these factors to develop a model to predict outcomes of treatment, which we called the vedolizumab CDST. We evaluated the correlation between exposure and efficacy. We validated the CDST in using data from 199 patients treated with vedolizumab in routine practice in the United States from May 2014 through December 2017.ResultsAbsence of exposure to a tumor necrosis factor (TNF) antagonist (+3 points), disease duration of 2 y or more (+3 points), baseline endoscopic activity (moderate vs severe) (+2 points), and baseline albumin concentration (+0.65 points per 1 g/L) were independently associated with corticosteroid-free remission during vedolizumab therapy. Patients in the derivation and validation cohorts were assigned to groups of low (CDST score, 26 points or less), intermediate (CDST score, 27-32 points), or high (CDST score, 33 points or more) probability of vedolizumab response. We observed a statistically significant linear relationship between probability group and efficacy (area under the receiver operating characteristic curve, 0.65), as well as drug exposure (P < .001) in the derivation cohort. In the validation cohort, a cutoff value of 26 points identified patients who did not respond to vedolizumab with high sensitivity (93%); only the low and intermediate probability groups benefited from reducing intervals of vedolizumab administration due to lack of response (P = .02). The vedolizumab CDST did not identify patients with corticosteroid-free remission during TNF antagonist therapy.ConclusionsWe used data from a trial of patients with UC to develop a scoring system, called the CDST, which identified patients most likely to enter corticosteroid-free remission during vedolizumab therapy, but not anti-TNF therapy. We validated the vedolizumab CDST in a separate cohort of patients in clinical practice. The CDST identified patients most likely to benefited from reducing intervals of vedolizumab administration due to lack of initial response. ClinicalTrials.gov no: NCT00783718.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2jh6b3gcTest

المؤلفون: Faleck, David M, Winters, Adam, Chablaney, Shreya, Shashi, Preeti, Meserve, Joseph, Weiss, Aaron, Aniwan, Satimai, Koliani-Pace, Jenna L, Kochhar, Gursimran, Boland, Brigid S, Singh, Siddharth, Hirten, Robert, Shmidt, Eugenia, Kesar, Varun, Lasch, Karen, Luo, Michelle, Bohm, Matthew, Varma, Sashidhar, Fischer, Monika, Hudesman, David, Chang, Shannon, Lukin, Dana, Sultan, Keith, Swaminath, Arun, Gupta, Nitin, Siegel, Corey A, Shen, Bo, Sandborn, William J, Kane, Sunanda, Loftus, Edward V, Sands, Bruce E, Colombel, Jean-Frederic, Dulai, Parambir S, Ungaro, Ryan

المصدر: Clinical Gastroenterology and Hepatology. 17(12)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Crohn's Disease, Clinical Research, Autoimmune Disease, Digestive Diseases, Inflammatory Bowel Disease, Oral and gastrointestinal, Adult, Antibodies, Monoclonal, Humanized, Colitis, Ulcerative, Crohn Disease, Endoscopy, Digestive System, Female, Gastrointestinal Agents, Humans, Male, Middle Aged, Registries, Remission Induction, Retrospective Studies, Time Factors, Young Adult, Integrin, Monoclonal Antibody Therapy, Time, Gastroenterology & Hepatology, Clinical sciences

الوصف: Background & aimsPatients with Crohn's disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration.MethodsWe analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (>2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes.ResultsWithin 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P < .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC.ConclusionsPatients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/0pt9g95wTest

المؤلفون: Barnes, Edward L, Beniwal-Patel, Poonam, Deepak, Parakkal, Raffals, Laura, Kayal, Maia, Dubinsky, Marla, Chang, Shannon, Higgins, Peter D R, Barr, Jennifer I, Anderson, Chelsea, Cross, Raymond K, Long, Millie D, Herfarth, Hans H

المساهمون: National Institutes of Health, American College of Gastroenterology

المصدر: Crohn's & Colitis 360 ; volume 5, issue 3 ; ISSN 2631-827X

مصطلحات موضوعية: Gastroenterology

الوصف: Background Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) are limited. Methods We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn’s disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse. We also compared dietary patterns among patients with inflammatory conditions of the pouch to the United States Department of Agriculture (USDA) recommended daily goals. Results Among 308 patients, there were no differences in dietary patterns among patients with 1 of the 4 disease states at enrollment. Additionally, among the 102 patients in remission at baseline, there were no significant differences noted among patients who went on to experience a disease flare in the 12 months after enrollment compared to those patients who remained in remission. However, patients with inflammatory conditions of the pouch demonstrated decreased intake of several food groups and macronutrients including dairy, fruits, vegetables, whole grains, and fiber when compared to USDA recommendations. Conclusions In a prospective cohort, we demonstrated no impact of dietary patterns on disease activity. The relative deficiencies in several food groups and macronutrients among patients after IPAA indicate the potential role of targeted nutritional counseling in this population.

الإتاحة: https://doi.org/10.1093/crocol/otad039Test
https://academic.oup.com/crohnscolitis360/article-pdf/5/3/otad039/50977616/otad039.pdfTest

المؤلفون: Kahan, Tamara, Chandan, Saurabh, Khan, Shahab R., Deliwala, Smit, Chang, Shannon, Axelrad, Jordan, Shaukat, Aasma

المصدر: Gastro Hep Advances ; volume 2, issue 6, page 843-852 ; ISSN 2772-5723

الإتاحة: https://doi.org/10.1016/j.gastha.2023.04.005Test
https://api.elsevier.com/content/article/PII:S2772572323000675?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2772572323000675?httpAccept=text/plainTest

المؤلفون: Barnes, Edward L., Long, Millie D., Raffals, Laura, Isaacs, Kim, Stidham, Ryan W., Herfarth, Hans H., Deepak, Parakkal, Beniwal-Patel, Poonam, Kayal, Maia, Dubinsky, Marla, Chang, Shannon, Higgins, Peter D.R., Barr, Jennifer I., Jiang, Yue, Cross, Raymond K.

المساهمون: National Institutes of Health, Crohn's and Colitis Foundation of America

المصدر: Clinical Gastroenterology and Hepatology ; volume 21, issue 6, page 1663-1666.e3 ; ISSN 1542-3565

مصطلحات موضوعية: Gastroenterology, Hepatology

الإتاحة: https://doi.org/10.1016/j.cgh.2022.04.026Test
https://api.elsevier.com/content/article/PII:S1542356522004517?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1542356522004517?httpAccept=text/plainTest

المؤلفون: Itzkowitz, Steven H, Jiang, Yue, Villagra, Cristina, Colombel, Jean-Frederic, Sultan, Keith, Lukin, Dana J, Faleck, David M, Scherl, Ellen, Chang, Shannon, Chen, LeaAnn, Katz, Seymour, Kwah, Joann, Swaminath, Arun, Petralia, Francesca, Sharpless, Virginia, Sachar, David, Jandorf, Lina, Axelrad, Jordan E

المصدر: Clin Gastroenterol Hepatol ; ISSN:1542-7714

مصطلحات موضوعية: Crohn’s Disease, Immunosuppression, Incident Cancer, Ulcerative Colitis

الوصف: In patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies have suggested that exposure to immunosuppressive agents does not increase the risk of incident (recurrent or new) cancer compared with unexposed patients. SAPPHIRE is a prospective registry aimed at addressing this issue.

العلاقة: https://doi.org/10.1016/j.cgh.2024.05.006Test; https://pubmed.ncbi.nlm.nih.gov/38768673Test

الإتاحة: https://doi.org/10.1016/j.cgh.2024.05.006Test
https://pubmed.ncbi.nlm.nih.gov/38768673Test

المؤلفون: Chang, Shannon, Adeyemi-Fowode, Oluyemisi

المصدر: Journal of Pediatric and Adolescent Gynecology ; volume 37, issue 2, page 296 ; ISSN 1083-3188

مصطلحات موضوعية: Obstetrics and Gynecology, General Medicine, Pediatrics, Perinatology and Child Health

الإتاحة: https://doi.org/10.1016/j.jpag.2024.01.124Test
https://api.elsevier.com/content/article/PII:S1083318824001396?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1083318824001396?httpAccept=text/plainTest