Inflammatory Bowel Diseases最新文献

Background: Autologous hematopoietic stem cell transplantation (aHSCT) holds promise as a therapeutic strategy in patients with severe chronic inflammatory conditions that are refractory to conventional treatment, including Crohn's disease. The success of aHSCT is thought to be grounded in resetting the break in immunological tolerance, but the exact mechanisms underlying its effects remain incompletely understood.

Methods: We followed the immune reconstitution of nine patients with severe refractory Crohn's disease before and after aHSCT, ranging from 1 month until 2 + years follow-up. We used flow cytometry on peripheral blood mononuclear cells and intestinal biopsy samples, as well as Olink on plasma samples.

Results: In line with previous research, we observed a strong change in the peripheral T cell subset composition from 1 month after transplantation, with a reversal of the CD4+/CD8+ ratio and a reduction of naïve over effector memory T cells (T-EM). Non-responders appeared distinct by retaining a higher CD4+/CD8+ ratio and higher naïve over T-EM frequencies. These differences could already be discerned at baseline, before transplantation. Functionally, we observed only minimal changes in the peripheral T cell profile related to inflammation and homing, but a small increase in regulatory markers. Remarkably, the local intestinal T cell composition did not mirror changes in the periphery, with an increased CD4+/CD8+ ratio in intestinal biopsies post-aHSCT.

Conclusions: Autologous hematopoietic stem cell transplantation had pronounced effects on the peripheral T cell composition, especially in responders. Changes in T cell subset composition were more pronounced than changes in the functional T cell profile.

Background: Ileocolic resections (ICRs) are the most common resections for Crohn's disease. Historical control groups have often been used for comparison when assessing postoperative recurrence, usually with temporal bias. This study aimed to (1) report contemporary rates of postoperative recurrence requiring repeat surgery (surgical recurrence at anastomosis [surgical recurrence at the ileocolic resection site (SR-ICR)] or surgical recurrence at any site) and the rates of endoscopic recurrence (ER) in the "biologic era"; and (2) determine risk factors for SR-ICR and ER.

Methods: A retrospective multicenter study involving 12 tertiary Australian centers was performed. Patients (of any age) who had undergone an ICR for Crohn's disease between 2007 and 2023 were included. Cox proportional hazards modeling was used to evaluate clinicopathological risk factors for SR-ICR and ER (defined as Rutgeerts grade ≥i2b).

Results: Overall, 875 patients were included (mean 38.7 ± 15.1 years, 51% female). Median follow-up was 63.9 months. Rates of SR-ICR were 4.5% (95% confidence interval [CI], 2.8%-6.1%) and 12.8% (95% CI, 8.8%-16.5%) at 5 and 10 years, respectively. Rates of surgical recurrence at any site were 5.6% (95% CI, 3.8%-7.5%) and 15.1% (95% CI, 11.0%-19.1%) at 5 and 10 years, respectively. Early (within 12 months) ER occurred in 24.7%. On multivariable analysis, smoking (adjusted hazard ratio, 3.49; 95% CI, 1.93-6.29) was the only factor significantly associated with SR-ICR. Smoking, positive microscopic margins, and granulomas were associated with ER, and prophylactic therapy and younger age at diagnosis (<17 years) were protective.

Conclusions: The rate of SR at the ileocolic anastomosis in this large Australian cohort was low, recorded to be 1 in 20 at 5 years. Smoking remains the strongest risk factor for both ER and SR. Histopathological factors influence ER and should be considered in future risk prediction models.

Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are immune-mediated disorders characterized by chronic gastrointestinal inflammation and a broad spectrum of extraintestinal manifestations. Among these, dermatological manifestations significantly impact patients' quality of life (QoL), presenting as conditions linked to IBD itself or IBD-related medical therapy. This comprehensive review underscores the relationship between IBD and cutaneous manifestations, with particular emphasis on erythema nodosum, pyoderma gangrenosum, Sweet syndrome, and hidradenitis suppurativa, alongside autoimmune conditions like psoriasis and vitiligo. The influence of biologic therapies, including both paradoxical skin reactions mimicking extraintestinal manifestations and nonspecific rashes, is also discussed, with a focus on the pathophysiological mechanisms and therapeutic approaches. Emerging evidence highlights the bidirectional interplay of gut-skin axis, with shared genetic, microbial, and immune pathways. Special considerations, such as pregnancy-related dermatoses, are included to provide a holistic view of this complex relationship. Improved comprehension of these manifestations not only emphasizes the necessity for interdisciplinary care, but also informs tailored therapies to address systemic inflammation while minimizing dermatological complications. This update offers practical insights and emerging evidence to guide clinicians in optimizing patient outcomes.

Autophagy is a crucial cellular process involved in the degradation of cytoplasmic components through lysosomal machinery. It is essential for maintaining cellular homeostasis and responding to various stressors. Autophagy has emerged as a key regulator of immune responses, particularly in the context of chronic inflammatory diseases, such as inflammatory bowel diseases and cancer. Increasing evidence highlights its dual role in both exacerbating and controlling inflammation, depending on the disease context. This review critically examines the molecular mechanisms of autophagy, its regulation within immune cells, and its complex involvement in chronic inflammation. We explore how dysregulated autophagic processes contribute to disease pathogenesis, with particular focus on inflammatory bowel disease and how these conditions increase cancer risk. Furthermore, we discuss the potential of autophagy modulation as a therapeutic strategy for these diseases. Current therapeutic approaches targeting autophagy are reviewed, alongside emerging strategies and their clinical implications. This comprehensive analysis underscores the importance of understanding the multifaceted roles of autophagy in immune regulation, with the aim of advancing therapeutic interventions for inflammatory and cancer-related conditions.

Background: Staged proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical treatment for medically refractory pediatric ulcerative colitis (UC). This study aimed to compare the surgical outcomes of 2-stage and 3-stage IPAA in children of similar disease severity.

Methods: We queried the NSQIP-Pediatric database (2016-2023) to identify patients under 18 years with UC undergoing IPAA. Patients undergoing IPAA with concurrent colectomy were classified as having a 2-stage procedure, while those undergoing IPAA alone, following a prior colectomy, were classified as having a 3-stage procedure. The primary outcome was a composite of major complications within 30 days, including mortality, organ/space infection, progressive renal insufficiency, systemic sepsis, and intra-abdominal reoperation. The treatment groups were matched using 1:1 propensity score matching to adjust for baseline differences in disease severity.

Results: A total of 479 patients met the inclusion criteria (330 underwent 3-stage and 149 underwent 2-stage procedures). The proportion of patients undergoing each approach remained stable over the study period (P = .693). At the time of pouch creation, the 2-stage group had significantly higher rates of steroid use (22.8% vs 14.5%), leukocytosis (21.9% vs 7.1%), and hypoalbuminemia (mean 4.0 vs 4.2 g/dL). After matching, 137 patient pairs were included. There was no significant difference in major complication rates between groups (OR, 1.38; 95% CI, 0.63-3.09).

Conclusions: This study demonstrated that surgical outcomes following pouch creation were similar in a matched cohort of children undergoing 2- or 3-stage IPAA, supporting the use of a 2-stage approach in certain patients with limited disease.

Access to quality healthcare for individuals with chronic diseases like inflammatory bowel disease (IBD) remains a global challenge. Tweens (aged 9-12 years) and teens (typically aged 13-19 years) with IBD face unique challenges compared to adults, including limited access to medications, difficulties transitioning to adult care, and barriers to clinical trial enrollment. Additional concerns include mental health, social media influence, and growth through puberty. This review article brings together current evidence reported by pediatric IBD clinicians worldwide to highlight these issues. While many challenges are universal, some are region specific and reflect geographic disparities in care.

Background: Youth with inflammatory bowel diseases (IBDs) are at an increased risk for mental health concerns compared to healthy peers. Given the unique psychosocial risk factors involved in living with IBD, it can be challenging to identify what level of psychological support is needed, which professionals may be best suited to intervene, and what setting would be appropriate.

Methods: In this narrative review we have applied the pediatric psychosocial preventative health model (PPPHM) to pediatric IBD by delineating 3 tiers of psychosocial need and associated evidence-based psychological interventions.

Results: The PPPHM describes universal, targeted, and clinical/treatment psychosocial needs. All youth with IBD benefit from universal support, such as psychosocial screening, education, and social support. As psychosocial needs are identified, providers may consider whether they need targeted or clinical/treatment levels of care. Targeted needs may include general mental health concerns (eg, grief), and psychosocial concerns related to their IBD that could benefit from psychological consultation or brief interventions (eg, pill swallowing). For young people with psychosocial concerns that are associated with significant distress or impairment, higher levels of psychological care, including outpatient referrals, may be beneficial.

Conclusions: Ultimately, identification of the intensity of psychosocial needs and associated appropriate levels of intervention for youth with IBD can be challenging to ascertain. However, with this review we hope to simplify that process so IBD providers with a variety of professional backgrounds and resources can help assess and connect patients with the appropriate support.