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1.
Gastroenterology ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39366468

RESUMEN

BACKGROUND & AIMS: Recurrent Clostridioides difficile infections (CDIs) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full-spectrum, oral microbiome therapeutic is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population. METHODS: We conducted a multicenter, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by polymerase chain reaction or toxin enzyme immunoassay for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼6 × 1011 colony-forming units of lyophilized microbial cells) or placebo after standard-of-care antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through week 8. Safety, efficacy, and microbiome endpoints were evaluated through weeks 8 and 24. RESULTS: A total of 198 participants were analyzed: CP101 (n = 102) and placebo (n = 96). Overall, 27.5% had a first recurrence, and 62.7% were diagnosed by polymerase chain reaction-based testing. The proportion without CDI recurrence through week 8 was significantly higher in the CP101 group compared to the placebo group (74.5% [76 of 102] vs 61.5% [59 of 96], respectively; P = .0488), with durable efficacy observed through week 24 (73.5% [75 of 102] vs 59.4% [57 of 96], respectively; P = .0347). Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences. Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to the placebo group. The incidence of adverse events was similar between the 2 groups. CONCLUSIONS: CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. (ClinicalTrials.gov, Number NCT03110133).

2.
Clin Gastroenterol Hepatol ; 20(12): 2911-2914.e4, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-34628079

RESUMEN

Gastroenterology (GI) fellows' ability to perform procedures are evaluated by the level of competency in the cognitive and technical components of procedures in Accreditation Council for Graduate Medical Education-accredited fellowship programs.1 However, competency in endoscopic procedures correlates with the number of procedures performed.2 The American Society for Gastrointestinal Endoscopy has recommended that a minimum of 130 esophagogastroduodenoscopies (EGDs) and 275 colonoscopies be performed before procedural competency can be assessed.3 Few studies have examined program or trainee-related factors, such as trainee gender, that may influence procedural volume. In other procedural subspecialties, a gender gap exists in trainee procedural volumes, with female residents performing fewer surgical cases than males.4,5 However, whether gender-related disparities exist in endoscopy volume among GI trainees is unknown. The primary aim of this study was to determine the impact of GI fellow gender on endoscopic procedural volume during training. Secondary aims were to determine if fellow career choice or other training program-related factors, such as program size, location, or setting, affect procedure volume during fellowship.


Asunto(s)
Gastroenterología , Masculino , Femenino , Humanos , Gastroenterología/educación , Competencia Clínica , Becas , Educación de Postgrado en Medicina , Endoscopía Gastrointestinal/educación
3.
Clin Gastroenterol Hepatol ; 19(8): 1627-1634, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-32645451

RESUMEN

BACKGROUND & AIMS: Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis. METHODS: We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT. RESULTS: Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child-Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P = .003), had pseudomembranes (22.2% vs 0; P = .018), and underwent FMT as inpatients (45.5% vs 19%; P = .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00-152.03; P = .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81-78.3; P = .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)-most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death. CONCLUSIONS: In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis.


Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Enfermedad Hepática en Estado Terminal , Clostridioides , Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal/efectos adversos , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/terapia , Recurrencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
4.
Ophthalmic Plast Reconstr Surg ; 37(5): e160-e164, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33710035

RESUMEN

A patient with thyroid-associated ophthalmopathy was treated with teprotumumab and developed symptoms concerning for inflammatory bowel disease after her sixth infusion. Colonoscopy was performed, and mucosal biopsies identified evidence of active colitis consistent with a diagnosis of ulcerative colitis. Despite treatment with budesonide and mesalamine, the patient continued to be symptomatic one and a half months after cessation of teprotumumab and required infliximab to achieve good control of her inflammatory bowel disease. This case represents the first report of new-onset inflammatory bowel disease arising during treatment with teprotumumab.


Asunto(s)
Colitis Ulcerosa , Oftalmopatía de Graves , Anticuerpos Monoclonales Humanizados , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Femenino , Oftalmopatía de Graves/inducido químicamente , Oftalmopatía de Graves/diagnóstico , Oftalmopatía de Graves/tratamiento farmacológico , Humanos , Mesalamina
5.
Curr Opin Clin Nutr Metab Care ; 23(5): 355-360, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32618725

RESUMEN

PURPOSE OF REVIEW: The purpose of this brief review is to investigate the current utility of fecal microbial transplantation (FMT) to ameliorate dysbiosis contributing to inflammatory bowel disease pathogenesis. RECENT FINDINGS: Increasing data from randomized, controlled trials support a role for multiple FMT administrations in the induction of remission and even as a maintenance therapy in mild-to-moderate Ulcerative Colitis. Small series and one small randomized controlled trial among patients with Crohn's Disease and with pouchitis continue to produce conflicting clinical results and microbial profile data on the host and donor levels. It is not clear whether patients with Crohn's disease are more susceptible to disease flare after FMT. Novel FMT delivery systems, including oral, and early-intensity colonoscopic devices, are under investigation. SUMMARY: The allure of minimizing the risks and cost of long-term immunosuppression via modulation of patient microbiota remains enticing, and the most recent randomized controlled data in ulcerative colitis reveals acceptable clinical remission rates. However, prior to wide adoption of FMT within the inflammatory bowel disease treatment armamentarium, large clinical trials identifying biomarkers of treatment success, ensuring safety across all indications, and cultivating optimized donor and host selection are needed.


Asunto(s)
Disbiosis/terapia , Trasplante de Microbiota Fecal , Enfermedades Inflamatorias del Intestino/terapia , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/terapia , Enfermedad de Crohn/microbiología , Enfermedad de Crohn/terapia , Disbiosis/microbiología , Microbioma Gastrointestinal , Humanos , Enfermedades Inflamatorias del Intestino/microbiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de Remisión , Resultado del Tratamiento
6.
Gastrointest Endosc ; 91(4): 882-893.e4, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31715173

RESUMEN

BACKGROUND AND AIMS: Gastroenterology fellowships need to ensure that trainees achieve competence in upper endoscopy (EGD) and colonoscopy. Because the impact of structured feedback remains unknown in endoscopy training, this study compared the effect of structured feedback with standard feedback on trainee learning curves for EGD and colonoscopy. METHODS: In this multicenter, cluster, randomized controlled trial, trainees received either individualized quarterly learning curves or feedback standard to their fellowship. Assessment was performed in all trainees using the Assessment of Competency in Endoscopy tool on 5 consecutive procedures after every 25 EGDs and colonoscopies. Individual learning curves were created using cumulative sum (CUSUM) analysis. The primary outcome was the mean CUSUM score in overall technical and overall cognitive skills. RESULTS: In all, 13 programs including 132 trainees participated. The intervention arm (6 programs, 51 trainees) contributed 558 EGD and 600 colonoscopy assessments. The control arm (7 programs, 81 trainees) provided 305 EGD and 468 colonoscopy assessments. For EGD, the intervention arm (-.7 [standard deviation {SD}, 1.3]) had a superior mean CUSUM score in overall cognitive skills compared with the control arm (1.6 [SD, .8], P = .03) but not in overall technical skills (intervention, -.26 [SD, 1.4]; control, 1.76 [SD, .7]; P = .06). For colonoscopy, no differences were found between the 2 arms in overall cognitive skills (intervention, -.7 [SD, 1.3]; control, .7 [SD, 1.3]; P = .95) or overall technical skills (intervention, .1 [SD, 1.5]; control, -.1 [SD, 1.5]; P = .77). CONCLUSIONS: Quarterly feedback in the form of individualized learning curves did not affect learning curves for EGD and colonoscopy in a clinically meaningful manner. (Clinical trial registration number: NCT02891304.).


Asunto(s)
Curva de Aprendizaje , Competencia Clínica , Colonoscopía , Retroalimentación , Gastroenterología/educación , Humanos
7.
Dig Dis Sci ; 65(4): 1099-1106, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31302808

RESUMEN

AIMS: This pilot study assessed the efficacy, safety, and microbiome dynamics of fecal microbiota transplantation (FMT) for patients with chronic pouchitis. METHODS: A prospective open-label pilot study was performed at an academic center among pouchitis patients undergoing FMT. Patients received a minimum of a single FMT by pouchoscopy from healthy, screened donors. The primary outcome was clinical improvement in pouchitis assessed by patient survey at week 4. Secondary outcomes included decrease in total Pouchitis Disease Activity Index (PDAI) Score ≥ 3 at week 4, bowel movement frequency, ESR, CRP, fecal calprotectin, abdominal pain, and PDAI subscores including endoscopic and histologic changes. Stool samples were collected at baseline and 4 weeks post-FMT to assess bacterial microbiota using V4 16S rRNA sequencing. RESULTS: Nineteen patients were enrolled; however, 1 patient was lost to follow-up. No patients had a major adverse event or escalation of therapy related to FMT. Total PDAI scores, endoscopic scores, and histologic scores did not decrease significantly post-FMT. However, there was a statistically significant improvement in bowel movement (BM) frequency (9.25-7.25 BM/day, p = 0.03) and trend for improvement in abdominal pain to improve post-FMT (p = 0.05). Bacterial microbiota profiling revealed no distinct community-level changes post-FMT, though a small number of specific bacterial taxa significantly differed in relative abundance. CONCLUSIONS: A single FMT has a tolerable short-term safety profile and may be associated with a decrease in bowel movements in patients with chronic pouchitis; however, no robust endoscopic or histologic changes were observed.


Asunto(s)
Endoscopía Gastrointestinal/métodos , Trasplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal/fisiología , Reservoritis/diagnóstico , Reservoritis/terapia , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Reservoritis/microbiología , Estudios Prospectivos , Adulto Joven
8.
Am J Transplant ; 19(2): 501-511, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30085388

RESUMEN

Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.


Asunto(s)
Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal/métodos , Trasplante de Órganos/efectos adversos , Receptores de Trasplantes/estadística & datos numéricos , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/microbiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Estados Unidos/epidemiología
9.
Clin Gastroenterol Hepatol ; 17(4): 701-708.e1, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-29935326

RESUMEN

BACKGROUND & AIMS: I-scan is an electronic chromoendoscopy technology that improves resolution of epithelial and mucosal surfaces and vessels. We performed a randomized controlled trial to compare detection of adenomas by i-scan vs standard high-definition white-light (HDWL) colonoscopy. METHODS: From February 1 through December 31, 2017, 740 outpatients (50-75 years old) undergoing screening and surveillance for colorectal neoplasia were randomly assigned to groups that received colonoscopies with i-scan 1 (surface and contrast enhancement) or HDWL. When lesions and polyps were detected, endoscopists could switch between i-scan 1 and HDWL imaging to confirm their finding; polyps were collected and analyzed by histology. The primary outcome was adenoma detection rate (ADR, proportion of subjects with at least 1 adenoma of any size); secondary outcomes included detection of sessile serrated polyps and neoplasias, along with location, size, and morphology of polyps. We performed intent to treat and per-protocol analyses (on 357 patients evaluated by i-scan and 358 evaluated by HDWL colonoscopy) to assess the primary and secondary outcomes. RESULTS: There were no differences in baseline characteristics between the groups. In the intent to treat analysis, the ADR was significantly higher in the i-scan 1 group (47.2%) than in the HDWL colonoscopy group (37.7%) (P = .01). In the per-protocol analysis, the ADR in the i-scan 1 group (47.6%) was also significantly higher than in the HDWL group (37.2%) (P = .005), but this effect was not consistent among all endoscopists. There was no difference between groups in detection of sessile serrated polyps. However, the rate of neoplasia detection was significantly higher in the i-scan 1 group (56.4%) than in the than the HDWL group (46.1%) (P = .005). In secondary analyses, the increase in ADR was associated with improved detection of diminutive flat adenomas in the right colon. CONCLUSION: In a prospective randomized trial, higher proportions of patients with adenomas were identified in a group that underwent colonoscopy with i-scan 1 than in a group evaluated by HDWL colonoscopy. This effect was mainly due to improved detection of diminutive, flat right sided adenomas. I-scan 1 technology may benefit some endoscopists. ClinicalTrials.gov no: NCT02811419.


Asunto(s)
Adenoma/diagnóstico , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Imagen Óptica/métodos , Coloración y Etiquetado/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pólipos/diagnóstico , Estudios Prospectivos , Distribución Aleatoria
13.
J Pediatr Gastroenterol Nutr ; 59(2): 157-61, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24796803

RESUMEN

A rapidly expanding range of diverse human diseases is now associated with perturbations to the gastrointestinal microbiome. Fecal microbial transplant (FMT) has been used with high rates of efficacy to treat gastrointestinal microbiome perturbation associated with recurrent Clostridium difficile infection, and is now being considered for other indications. Here we discuss the gut microbiome, review published and ongoing studies using FMT as a treatment modality for human disease, consider the regulatory aspects of FMT, and outline some factors that should be considered in patients in whom this therapeutic strategy is being contemplated.


Asunto(s)
Terapia Biológica , Infecciones por Clostridium/terapia , Disbiosis/terapia , Heces/microbiología , Tracto Gastrointestinal/microbiología , Enfermedades Inflamatorias del Intestino/terapia , Clostridioides difficile , Infecciones por Clostridium/microbiología , Humanos , Enfermedades Inflamatorias del Intestino/microbiología
15.
Sci Rep ; 14(1): 18558, 2024 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-39122767

RESUMEN

Fecal microbial transplantation (FMT) offers promise for treating ulcerative colitis (UC), though the mechanisms underlying treatment failure are unknown. This study harnessed longitudinally collected colonic biopsies (n = 38) and fecal samples (n = 179) from 19 adults with mild-to-moderate UC undergoing serial FMT in which antimicrobial pre-treatment and delivery mode (capsules versus enema) were assessed for clinical response (≥ 3 points decrease from the pre-treatment Mayo score). Colonic biopsies underwent dual RNA-Seq; fecal samples underwent parallel 16S rRNA and shotgun metagenomic sequencing as well as untargeted metabolomic analyses. Pre-FMT, the colonic mucosa of non-responsive (NR) patients harbored an increased burden of bacteria, including Bacteroides, that expressed more antimicrobial resistance genes compared to responsive (R) patients. NR patients also exhibited muted mucosal expression of innate immune antimicrobial response genes. Post-FMT, NR and R fecal microbiomes and metabolomes exhibited significant divergence. NR metabolomes had elevated concentrations of immunostimulatory compounds including sphingomyelins, lysophospholipids and taurine. NR fecal microbiomes were enriched for Bacteroides fragilis and Bacteroides salyersiae strains that encoded genes capable of taurine production. These findings suggest that both effective mucosal microbial clearance and reintroduction of bacteria that reshape luminal metabolism associate with FMT success and that persistent mucosal and fecal colonization by antimicrobial-resistant Bacteroides species may contribute to FMT failure.


Asunto(s)
Bacteroides , Colitis Ulcerosa , Trasplante de Microbiota Fecal , Heces , Mucosa Intestinal , Humanos , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/terapia , Colitis Ulcerosa/metabolismo , Masculino , Femenino , Heces/microbiología , Bacteroides/genética , Adulto , Mucosa Intestinal/microbiología , Mucosa Intestinal/metabolismo , Persona de Mediana Edad , Microbioma Gastrointestinal , Insuficiencia del Tratamiento , ARN Ribosómico 16S/genética , Metaboloma
16.
bioRxiv ; 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36711576

RESUMEN

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we performed single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.

17.
Nat Commun ; 15(1): 1493, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38374043

RESUMEN

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we perform single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.


Asunto(s)
Colitis Ulcerosa , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/genética , Integrinas/genética , Multiómica , Proteómica , Fármacos Gastrointestinales/uso terapéutico , Resultado del Tratamiento , Estudios Retrospectivos
18.
J Crohns Colitis ; 17(4): 504-512, 2023 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-36272109

RESUMEN

BACKGROUND: Upadacitinib is a selective Janus kinase inhibitor approved for the management of ulcerative colitis and is under evaluation for the management of Crohn's disease [CD] in Phase 3 clinical trials. AIMS: Our goal was to describe our real-world experience with upadacitinib in CD. METHODS: This is a two-centre retrospective cohort study of adult patients with moderate to severe CD on upadacitinib. The primary outcome was clinical response and remission as determined by stool frequency and abdominal pain scores. Secondary endpoints included endoscopic response and remission as determined by change in Simple Endoscopic Score for CD. Outcomes were assessed at 3 months after starting upadacitinib and at the patient's most recent follow-up. We further evaluated adverse events and dose-related response. RESULTS: A total of 45 CD patients received upadacitinib and were included in the safety analysis. Thirty-six patients received upadacitinib for CD, whereas nine received it for inflammatory arthritis [n = 8] or pyoderma [n = 1]. Thirty-three patients received upadacitinib for 3 months or longer and were included in the efficacy analysis. At the 3-month follow-up, 21 patients achieved clinical response [63.6%] and nine achieved clinical remission [27.2%]. At time of last follow-up, 23 patients had clinical response [69.7%], ten achieved clinical remission [30.3%] and four [28.6%] achieved endoscopic remission. Adverse events occurred in 12 patients [26.7%]. Two patients had a serious adverse event [4.5%] without associated mortality. CONCLUSION: In this real-world cohort of highly refractory CD patients, upadacitinib was effective in inducing remission and had an acceptable safety profile.


Asunto(s)
Enfermedad de Crohn , Compuestos Heterocíclicos con 3 Anillos , Inhibidores de las Cinasas Janus , Enfermedad de Crohn/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Inhibidores de las Cinasas Janus/uso terapéutico , Estudios Retrospectivos , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento
19.
Sci Rep ; 12(1): 5517, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35365713

RESUMEN

Fecal microbiota transplant is a promising therapy for ulcerative colitis. Parameters maximizing effectiveness and tolerability are not yet clear, and it is not known how import the transmission of donor microbes to patients is. Here (clinicaltrails.gov: NCT03006809) we have tested the effects of antibiotic pretreatment and compared two modes of maintenance dose delivery, capsules versus enema, in a randomized, pilot, open-label, 2 × 2 factorial design with 22 patients analyzed with mild to moderate UC. Clinically, the treatment was well-tolerated with favorable safety profile. Of patients who received antibiotic pretreatment, 6 of 11 experienced remission after 6 weeks of treatment, versus 2 of 11 non-pretreated patients (log odds ratio: 1.69, 95% confidence interval: -0.25 to 3.62). No significant differences were found between maintenance dosing via capsules versus enema. In exploratory analyses, microbiome turnover at both the species and strain levels was extensive and significantly more pronounced in the pretreated patients. Associations were also revealed between taxonomic turnover and changes in the composition of primary and secondary bile acids. Together these findings suggest that antibiotic pretreatment contributes to microbiome engraftment and possibly clinical effectiveness, and validate longitudinal strain tracking as a powerful way to monitor the dynamics and impact of microbiota transfer.


Asunto(s)
Colitis Ulcerosa , Microbioma Gastrointestinal , Antibacterianos/uso terapéutico , Colitis Ulcerosa/etiología , Colitis Ulcerosa/terapia , Trasplante de Microbiota Fecal , Heces , Humanos , Inducción de Remisión
20.
United European Gastroenterol J ; 7(6): 807-814, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31316785

RESUMEN

Background: Emerging trials suggest fecal microbiota transplantation (FMT) is a promising treatment for ulcerative colitis; however, there is a paucity of data in Crohn disease (CD). Objective: The objectives of this article are to determine whether single-dose FMT improves clinical and endoscopic outcomes in CD patients and to identify meaningful changes in the microbiome in response to FMT. Methods: We performed a prospective, open-label, single-center study. Ten CD patients underwent FMT and were evaluated for clinical response (defined as decrease in Harvey-Bradshaw Index score ≥3 at one month post-FMT) and microbiome profile (16S ribosomal RNA sequencing) at one month post-FMT. Results: Three of 10 patients responded to FMT. Two of 10 patients had significant adverse events requiring escalation of therapy. On microbiome analysis, bacterial communities of responders had increased relative abundance of bacteria commonly found in donor gut microbiota. Conclusions: Single-dose FMT in this cohort of CD patients showed modest effect and potential for harm. Responders tended to have lower baseline alpha diversity, suggesting baseline perturbation of microbiota may be an indicator of potential responders to FMT in this patient population. Controlled trials are needed to further assess the efficacy and safety of FMT in CD and determine whether FMT is a viable option in this patient population.Clinicaltrials.gov number: NCT02460705.


Asunto(s)
Enfermedad de Crohn/terapia , Trasplante de Microbiota Fecal , Adolescente , Adulto , Anciano , Enfermedad de Crohn/etiología , Trasplante de Microbiota Fecal/efectos adversos , Trasplante de Microbiota Fecal/métodos , Femenino , Microbioma Gastrointestinal , Humanos , Masculino , Metagenómica/métodos , Persona de Mediana Edad , ARN Ribosómico 16S/genética , Resultado del Tratamiento , Adulto Joven
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