Pretransplant targeting of TNFRSF25 and CD25 stimulates recipient Tregs in target tissues, ameliorating GVHD post-HSCT.

The current approach to minimize transplant-associated complications, including graft-versus-host disease (GVHD) includes long-term pharmacological immune suppression frequently accompanied by unwanted side effects. Advances in targeted immunotherapies regulating alloantigen responses in the recipient continue to reduce the need for pan-immunosuppression. Here, in vivo targeting of the TNF superfamily receptor TNFRSF25 and the high affinity IL-2 receptor with a TL1A-Ig fusion protein and low dose IL-2, respectively was used to pre-treat recipient mice prior to allogeneic-HSCT (aHSCT).

Relationship of Intestinal Ultrasound With Clinical, Biochemical, and Endoscopic Disease Severity in Acute Severe Ulcerative Colitis: A Blinded, Prospective Study.

Introduction: The utility of intestinal ultrasound (IUS) for acute severe ulcerative colitis (ASUC) is understudied. We correlated IUS to clinical, biochemical, and endoscopic disease severity in ASUC.

Methods: In a blinded, prospective study of 20 ASUC subjects, we analyzed standard IUS parameters (bowel wall thickening, vascular flow, wall stratification) and UC IUS indices (International Bowel Ultrasound Segmental Activity Score (IBUS-SAS), Milan-UC, UC-IUS) alongside modified Mayo symptoms scores, C-reactive protein (CRP), albumin, and UC Endoscopic Index of Severity (UCEIS).

A Pilot Randomized Control Trial to Assess the Adjunctive Effect of Diet on Response to Advanced Therapies in Patients With Ulcerative Colitis.

Background & Aims: Diet may influence ulcerative colitis (UC), but its impact on medication response remains unclear. We examined whether two 5-day cycles of a low-calorie, plant-based (LC-PB), fasting-mimicking diet could improve UC response to medications in a controlled trial.

Methods: Adults with active UC starting advanced therapies were randomized to an LC-PB diet + therapy or a control diet + therapy.

Diagnosis and Management of Upper Gastrointestinal Involvement in Adult Patients With Crohn's Disease: A Systematic Review.

Background & Aims: The diagnosis and management of ileocolonic Crohn's disease are well-established. In contrast, standardized guidance pertaining to the diagnosis and management of upper gastrointestinal Crohn's disease (UGICD) is lacking, despite its potentially severe consequences. This comprehensive systematic review describes the prevalence, clinical presentation, and medical and surgical management of involvement of the upper GI tract in adult patients with Crohn's disease.

Global evolution of inflammatory bowel disease across epidemiologic stages.

During the twentieth century, inflammatory bowel disease (IBD) was considered a disease of early industrialized regions in North America, Europe and Oceania. At the turn of the twenty-first century, IBD incidence increased in newly industrialized and emerging regions in Africa, Asia and Latin America, while the prevalence in early industrialized regions continued to grow steadily. Changes in the incidence and prevalence denote the evolution of IBD across four epidemiologic stages: stage 1 (emergence), characterized by low incidence and prevalence; stage 2 (acceleration in incidence), marked by rapidly rising incidence and low prevalence; and stage 3 (compounding prevalence), where the incidence decelerates, plateaus or declines while the prevalence steadily increases.

DUOX2 activation drives bacterial translocation and subclinical inflammation in IBD-associated dysbiosis.

Background: Inflammatory bowel diseases (IBDs) are characterised by dysbiosis and a leaky gut. The NADPH oxidase dual oxidase 2 (DUOX2) is upregulated in patients with IBD, yet its role in driving the disease remains unclear.

Objective: We interrogated the functional consequences of epithelial DUOX2 activity for the host and microbiome.

Risk Factors for Chronic Kidney Disease in Patients With Crohn's Disease.

Background: Patients with inflammatory bowel diseases (IBD), including Crohn's disease (CD), are at risk of complications, including kidney disease. It is important to identify IBD patients at higher risk of chronic kidney disease (CKD) to improve prevention and treatment. Here, we investigated the clinical and metabolomic characteristics of CD patients who develop CKD.

Guselkumab binding to CD64 IL-23-producing myeloid cells enhances potency for neutralizing IL-23 signaling.

IL-23 is implicated in the pathogenesis of immune-mediated inflammatory diseases, and myeloid cells that express Fc gamma receptor 1 (FcγRI or CD64) on their surface have been recently identified as a primary source of IL-23 in inflamed tissue. Our complementary analyses of transcriptomic datasets from psoriasis and IBD showed increased expression of CD64 and IL-23 transcripts in inflamed tissue, and greater abundance of cell types with co-expression of CD64 and IL-23. These findings led us to explore potential implications of CD64 binding on the function of IL-23-targeting monoclonal antibodies (mAbs).

Definitions, diagnosis, and management of postoperative recurrence in Crohn's disease patients with permanent ileostomy-a systematic review and meta-analysis.

Background And Aims: Over 10% of patients with Crohn's disease require permanent ileostomy. We aimed to summarize the existing data on diagnosis, definitions of recurrence, and management of Crohn's disease patients with permanent ileostomy.

Methods: MEDLINE, Embase, and CENTRAL databases were searched from inception to February 6, 2024.

Deep Sequencing of Crohn's Disease Lamina Propria Phagocytes Identifies Pathobionts and Correlates With Pro-Inflammatory Gene Expression.

Background: Crohn's disease (CD) is characterized by an inflammatory response to gut microbiota. Macrophages and dendritic cells play an active role in CD inflammation. Specific microbiota have been implicated in the pathogenesis of ileal CD.

Guidance for Fecal Microbiota Transplantation Trials in Ulcerative Colitis: The Second ROME Consensus Conference.

Background: Fecal microbiota transplantation (FMT) is emerging as a potential treatment modality for individuals living with inflammatory bowel disease (IBD). Despite its promise, the effectiveness of FMT for treating IBD, particularly for ulcerative colitis (UC), still requires thorough clinical investigation. Notwithstanding differences in methodologies, current studies demonstrate its potential for inducing remission in UC patients.

Pretransplant targeting of TNFRSF25 and CD25 stimulates recipient Tregs in target tissues ameliorating GVHD post-HSCT.

The current approach to minimize transplant-associated complications, including graft-versus-host disease (GVHD) includes long-term pharmacological immune suppression frequently accompanied by unwanted side effects. Advances in targeted immunotherapies regulating alloantigen responses in the recipient continue to reduce the need for pan-immunosuppression. Here, in vivo targeting of the TNF superfamily receptor 25 (TNFRSF25) and the high affinity IL-2 receptor with a TL1A-Ig fusion protein and low dose IL-2, respectively, was used to pretreat recipient mice prior to allogeneic-HSCT (aHSCT).

Histologic and Endoscopic Findings Are Highly Correlated in a Prospective Cohort of Patients With Inflammatory Bowel Diseases.

Background And Aims: The advantages of endoscopic vs histologic assessments of inflammation in inflammatory bowel disease remain unclear. We compared endoscopic and histologic inflammation in a prospective cohort. Furthermore, in patients with discordant findings, we compared the ability of endoscopy vs histology to predict disease course.

Eleven Grand Challenges for Inflammatory Bowel Disease Genetics and Genomics.

The past 2 decades have witnessed extraordinary advances in our understanding of the genetic factors influencing inflammatory bowel disease (IBD), providing a foundation for the approaching era of genomic medicine. On behalf of the NIDDK IBD Genetics Consortium, we herein survey 11 grand challenges for the field as it embarks on the next 2 decades of research utilizing integrative genomic and systems biology approaches. These involve elucidation of the genetic architecture of IBD (how it compares across populations, the role of rare variants, and prospects of polygenic risk scores), in-depth cellular and molecular characterization (fine-mapping causal variants, cellular contributions to pathology, molecular pathways, interactions with environmental exposures, and advanced organoid models), and applications in personalized medicine (unmet medical needs, working toward molecular nosology, and precision therapeutics).

Oxidized Low-Density Lipoprotein Induces Reactive Oxygen Species-Dependent Proliferation of Intestinal Epithelial Cells.

: Oxidized low-density lipoprotein (ox-LDL) is a proinflammatory particle associated with various diseases and affects cell proliferation and viability in multiple cell types. However, its impact on intestinal epithelial cells remains underexplored. This study investigates the effect of ox-LDL on colonic epithelial cell proliferation and viability, as well as the underlying mechanisms involved.

Three-Year Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study.

Background: Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, has demonstrated induction of clinical remission at week 12 with maintenance through week 104 in patients with moderately-to-severely active ulcerative colitis (UC). Results are presented from the LUCENT-3 open-label extension study through week 152.

Methods: Of 868 LUCENT clinical trial program mirikizumab-treated induction patients, 544 were responders of whom 365 were rerandomized to mirikizumab maintenance.

Endoscopic diagnosis and management of adult inflammatory bowel disease: a consensus document from the American Society for Gastrointestinal Endoscopy IBD Endoscopy Consensus Panel.

Endoscopy plays a key role in diagnosis, monitoring of disease activity, assessment of treatment response, dysplasia surveillance, postoperative evaluation, and interventional therapy for patients with inflammatory bowel disease (IBD). Clinical practice patterns in the endoscopic management of IBD vary. A panel of experts consisting of IBD specialists, endoscopists, and GI pathologists participated in virtual conferences and developed this modified Delphi-based consensus document to address endoscopic aspects of IBD management.

Healthcare Utilization and Geographic Distribution of Advanced Therapy in Minority Race and Ethnic Groups With Inflammatory Bowel Disease.

Background And Aims: Biases in healthcare pose challenges for inflammatory bowel disease (IBD) patients from underrepresented races and ethnicities. Our study aimed to assess the quality of and access to care among underrepresented racial and ethnic populations using a diverse database.

Methods: We used the OneFlorida Data Trust, representing over half of Florida's population.

The Relationship Between Loneliness, Social Isolation, and Inflammatory Bowel Disease: A Narrative Review.

Background: There is clear evidence that loneliness and social isolation have profound health consequences. Documenting the associations of loneliness and social isolation with inflammatory bowel disease (IBD) symptoms, disease severity, and treatment outcomes could meaningfully improve health and quality of life in patients with IBD.

Purpose: The purpose of this narrative review was to synthesize the empirical evidence on the associations of loneliness and social isolation with IBD symptoms, disease severity, and treatment outcomes.