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"Allegretti, Jessica R."
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ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections
by
LaPlante, Kerry
,
Kelly, Colleen R.
,
Allegretti, Jessica R.
in
Anti-Bacterial Agents - therapeutic use
,
Antibiotics
,
Clostridioides difficile - isolation & purification
2021
Clostridioides difficile infection occurs when the bacterium produces toxin that causes diarrhea and inflammation of the colon. These guidelines indicate the preferred approach to the management of adults with C. difficile infection and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations Assessment, Development, and Evaluation but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not the only, approach to clinical scenarios.
Journal Article
Insights into the role of fecal microbiota transplantation for the treatment of inflammatory bowel disease
by
Allegretti, Jessica R.
,
Levy, Alexander N.
in
Colon
,
Gastroenterology
,
Inflammatory bowel disease
2019
Fecal microbiota transplantation (FMT) has changed the treatment landscape of Clostridium difficile infection (CDI). Emerging evidence has shown that FMT can also be an effective and safe treatment strategy in CDI with underlying inflammatory bowel disease (IBD). Recently, randomized controlled trials of FMT in ulcerative colitis support its expanding role in restoring gut homeostasis in this disease. However, heterogeneous study designs leave several questions yet to be answered, including how to best position this novel therapy in the treatment approach of Crohn’s disease and pouchitis. Additional studies are needed to validate whether FMT can assume a complementary role in the standard treatment of IBD.
Journal Article
Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohn's Disease
by
Robson, Simon C.
,
Moss, Alan C.
,
Gevers, Dirk
in
Adult
,
Crohn Disease - microbiology
,
Crohn Disease - therapy
2016
The microbiota in the lumen of patients with Crohn's disease (CD) is characterized by reduced diversity, particularly Firmicutes and Bacteroidetes. It is unknown whether the introduction of the intestinal microbiota from healthy individuals could correct this dysbiosis and reverse mucosal inflammation. We investigated the response to fecal microbial transplantation (FMT) from healthy individuals to subjects with active CD.MethodsWe performed a prospective open-label study (uncontrolled) of FMT from healthy donors to subjects with active CD. A single FMT was performed by colonoscopy. Recipients' microbial diversity, mucosal T-cell phenotypes, and clinical and inflammatory parameters were measured over 12 weeks, and safety over 26 weeks.ResultsNineteen subjects were treated with FMT and completed the study follow-up. Fifty-eight percent (11/19) demonstrated a clinical response (Harvey–Bradshaw Index decrease >3) following FMT. Fifteen subjects had sufficient pre/postfecal samples for analysis. A significant increase in microbial diversity occurred after FMT (P = 0.02). This was greater in clinical responders than nonresponders. Patients who experienced a clinical response demonstrated a significant shift in fecal microbial composition toward their donor's profile as assessed by the Bray–Curtis index at 4 weeks (P = 0.003). An increase in regulatory T cells (CD4+CD25+CD127lo) was also noted in recipients' lamina propria following FMT. No serious adverse events were noted over the 26-week study period.ConclusionsIn this open-label study, FMT led to an expansion in microbial bacterial diversity in patients with active CD. FMT was overall safe, although the clinical response was variable. Determining donor microbial factors that influence clinical response is needed before randomized clinical trials of FMT in CD.
Journal Article
One-Year Comparative Effectiveness of Upadacitinib vs Tofacitinib for Ulcerative Colitis: A Multicenter Cohort Study
by
Cabral, Heidy J.
,
Kallumkal, Govind
,
Allegretti, Jessica R.
in
Abscesses
,
Cohort analysis
,
Endoscopy
2024
INTRODUCTION:The comparative effectiveness of upadacitinib and tofacitinib for ulcerative colitis (UC) is poorly understood.METHODS:In this retrospective cohort study, we compared steroid-free clinical remission (SFCR) and endoscopic response/remission at 52 weeks among adults initiating upadacitinib or tofacitinib for UC.RESULTS:A total of 155 patients initiated upadacitinib (n = 81; 30% prior tofacitinib exposure) or tofacitinib (n = 74; 0% prior upadacitinib exposure). After inverse probability of treatment-weighted logistic regression, upadacitinib was associated with significantly higher odds of SFCR (odds ratio 3.01, 95% confidence interval 1.39-6.55) vs tofacitinib. There were no differences for endoscopic response/remission.DISCUSSION:Upadacitinib was more effective at achieving SFCR in UC at 52 weeks vs tofacitinib.
Journal Article
The 6 Ds of Fecal Microbiota Transplantation
2021
A practical handbook on fecal microbiota transplantation (FMT) for physicians, nurses, physician assistants, students, residents, and fellows,
The 6 Ds of Fecal Microbiota Transplantation: A Primer from Decision to Discharge and Beyond
provides a clinical framework to understand and administer this treatment as safely and effectively as possible.
FMT has emerged as a promising treatment for C. difficile infection (CDI), and there is a major need for educational resources on the topic. Drs. Jessica Allegretti, Zain Kassam, and their expert contributors are leaders in the field and have collectively cared for thousands of patients suffering from recurrent CDI who have benefitted from FMT.
This guide provides practical tools, clinical pearls, and answers to frequently asked questions. Beginning with introductory information on the microbiome and exploring the history of FMT,
The 6 Ds of Fecal Microbiota Transplantation
outlines a step-by-step checklist for administering FMT:
Decision: Who is the right CDI patient to receive FMT? What clinical questions should you ask patients in your FMT clinical assessment?
Donor: How do you select and screen a donor for FMT?
Discussion: What are the risks, benefits, and alternatives that need to be discussed with patients?
Delivery: What is the best delivery method for FMT-colonoscopy, nasogastric tube, enema, or capsules?
Discharge and follow-up: What is the ideal post-FMT care? How should you council patients following FMT?
Discovery: What are the most promising emerging clinical applications for FMT? What is the evidence for FMT in obesity, autism, irritable bowel syndrome, inflammatory bowel disease, antibiotic resistant bacteria, and liver disease?
Arming healthcare professionals with the ability to answer questions from patients regarding FMT and the microbiome,
The 6 Ds of Fecal Microbiota Transplantation
provides a pragmatic guide for this exciting treatment.
Impact of Fecal Microbiota Transplantation on Gut Bacterial Bile Acid Metabolism in Humans
by
Loeffler, Caitlin
,
Rahnavard, Ali
,
Allegretti, Jessica R.
in
Bacteria
,
Bacteria - genetics
,
Bacteroides ovatus
2022
Fecal microbiota transplantation (FMT) is a promising therapeutic modality for the treatment and prevention of metabolic disease. We previously conducted a double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients in which we found that FMT enhanced gut bacterial bile acid metabolism and delayed the development of impaired glucose tolerance relative to the placebo control group. Therefore, we conducted a secondary analysis of fecal samples collected from these patients to assess the potential gut microbial species contributing to the effect of FMT to improve metabolic health and increase gut bacterial bile acid metabolism. Fecal samples collected at baseline and after 4 weeks of FMT or placebo treatment underwent shotgun metagenomic analysis. Ultra-high-performance liquid chromatography-mass spectrometry was used to profile fecal bile acids. FMT-enriched bacteria that have been implicated in gut bile acid metabolism included Desulfovibrio fairfieldensis and Clostridium hylemonae. To identify candidate bacteria involved in gut microbial bile acid metabolism, we assessed correlations between bacterial species abundance and bile acid profile, with a focus on bile acid products of gut bacterial metabolism. Bacteroides ovatus and Phocaeicola dorei were positively correlated with unconjugated bile acids. Bifidobacterium adolescentis, Collinsella aerofaciens, and Faecalibacterium prausnitzii were positively correlated with secondary bile acids. Together, these data identify several candidate bacteria that may contribute to the metabolic benefits of FMT and gut bacterial bile acid metabolism that requires further functional validation.
Journal Article
Tofacitinib for the Treatment of Pouch-Related Disorders: A Case Series
2022
Lay Summary
In this case series, 6 patients with chronic pouchitis (n = 3), cuffitis (n = 2), or Crohn’s-like disease of the pouch (n = 1) were treated with tofacitinib. One patient achieved clinical response; however, all patients ultimately discontinued therapy due to nonresponse or adverse events.
Journal Article
The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications
by
Kelly, Colleen
,
Fischer, Monika
,
Allegretti, Jessica R
in
Antibiotics
,
Clinical trials
,
Clostridium Infections - therapy
2019
Developments in high-throughput microbial genomic sequencing and other systems biology techniques have given novel insight into the potential contribution of the gut microbiota to health and disease. As a result, an increasing number of diseases have been characterised by distinctive changes in the composition and functionality of the gut microbiota; however, whether such changes are cause, consequence, or incidental to the disease in question remains largely uncertain. Restoration of the gut microbiota to a premorbid state is a key novel therapeutic approach of interest, and faecal microbiota transplantation—the transfer of prescreened stool from healthy donors into the gastrointestinal tract of patients—is gaining increasing importance in both the clinical and research settings. At present, faecal microbiota transplantation is only recommended in the treatment of recurrent Clostridioides difficile infection, although a large number of trials are ongoing worldwide exploring other potential therapeutic indications.
Journal Article
Activity of axial spondyloarthritis after one year of anti-tumor necrosis factor therapy among patients with inflammatory bowel diseases
by
Carlin, Alexander
,
Mitri, Jennifer
,
Ermann, Joerg
in
Arthritis
,
Colitis
,
Inflammatory bowel disease
2023
The disease activity of axSpA after initiating anti-TNF agents for inflammatory bowel diseases (IBD) is poorly understood. We sought to examine the disease activity of axial spondyloarthritis (axSpA) after initiation of anti-tumor necrosis factor (TNF) agents among patients with IBD. This retrospective cohort study included adults with IBD and axSpA who initiated anti-TNF agents between 1/1/2012-10/1/2021 at a large academic center. The primary outcome was symptom resolution (SR) of axSpA at 12 months (“0/10 pain” or “no pain” or “controlled pain” with no morning stiffness and no use of daily NSAIDs). The secondary outcome was clinical remission (CR) of IBD at 12 months (simple clinical colitis activity index <3, Harvey-Bradshaw Index <5, or provider assessment with no use of oral/IV steroids for 30 days). Associations between baseline characteristics and SR of axSpA were examined using logistic regression. 82 patients with axSpA and IBD initiated anti-TNF agents. At 12 months, 52% and 74% achieved SR of axSpA and CR of IBD, respectively. IBD duration <5 years (OR 3.0, 95% CI 1.2-7.5) and adalimumab use (reference: all other anti-TNFs; OR 2.7, 95% CI 1.002-7.1) were associated with SR of axSpA at 12 months. 52% of patients with axSpA and IBD achieved SR of axSpA at 12 months after initiating anti-TNF therapy. Shorter disease duration and adalimumab use may be associated with higher odds of SR. Larger studies are needed to confirm these findings, examine additional clinical predictors of SR, and identify more effective therapeutics for this population.
Journal Article