Iron Deficiency Is Common after Restorative Proctocolectomy with Ileal Pouch-Anal Anastomosis in Patients with Ulcerative Colitis

Background: Micronutrient deficiencies may occur after restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC), largely due to malabsorption and/or pouch inflammation. Objectives: The objective of this study was to report the frequency of iron deficiency in patients with UC who underwent RPC with IPAA and identify associated risk factors. Methods: We conducted a retrospective chart review of patients with UC or IBD-unclassified who underwent RPC with IPAA at Mount Sinai Hospital between 2008 and 2017. Patients younger than 18 years of age at the time of colectomy were excluded. Descriptive statistics were used to analyze baseline characteristics. Medians with interquartile range (IQR) were reported for continuous variables, and proportions were reported for categorical variables. Iron deficiency was defined by ferritin <30 ng/mL. Logistic regression was used to analyze unadjusted relationships between hypothesized risk factors and the outcome of iron deficiency. Results: A total of 143 patients had iron studies a median of 3.0 (IQR 1.7–5.6) years after final surgical stage, of whom 73 (51.0%) were men. The median age was 33.5 (IQR 22.7–44.3) years. Iron deficiency was diagnosed in 80 (55.9%) patients with a median hemoglobin of 12.4 g/dL (IQR 10.9–13.3), ferritin of 14 ng/mL (IQR 9.0–23.3), and iron value of 44 μg/dL (IQR 26.0–68.8). Of these, 29 (36.3%) had a pouchoscopy performed within 3 months of iron deficiency diagnosis. Pouchitis and cuffitis were separately noted in 4 (13.8%) and 13 (44.8%) patients, respectively, and concomitant pouchitis-cuffitis was noted in 9 (31.0%) patients. Age, sex, anastomosis type, pouch duration, and history of pouchitis and/or cuffitis were not associated with iron deficiency. Conclusion: Iron deficiency is common after RPC with IPAA in patients with UC. Cuffitis is seen in the majority of patients with iron deficiency; however, iron deficiency may occur even in the absence of inflammation

Alaska Justice Forum ; Vol. 24, No. 4 (Winter 2008)

A longer version of "Comparing the American and Russian Constititions" by David Mannheimer, with a list of references, is available at https://scholarworks.alaska.edu/handle/11122/10604.The Winter 2008 issue of the Alaska Justice Forum presents a comparison of the American and Russian constitutions, a description of the Khabarovsk-Alaska Rule of Law Partnership (KAROL), discussion of children with incarcerated parents, figures on prison populations in Alaska and the U.S., immigration figures in the United States from 1910 to 2006, and figures on non-citizens in the Alaska correctional system."Comparing the American and Russian Constitutions" by David Mannheimer / "Editor's Goodbye" by Antonia Moras / "History of KAROL—The Khabarovsk-Alaska Rule of Law Partnership" by Marla Greenstein / "Children With Parents in Prison" / "Prisoners in Alaska and the U.S." / "Immigrants, Refugees and Asylees Over the Last Century" / "Non-Citizens in the Alaska Correctional System" / "Justice Center Move

Alaska Justice Forum ; Vol. 4, No. 4 (Winter 1988)

The Winter 1988 issue of the Alaska Justice Forum features articles on policy and procedural changes implemented by the Alaska Judicial Council since 1983 to improve Alaska's judicial selection and retention processes; findings from an Alaska Judicial Council research report on news cameras in Alaska courts; a summary of pending corrections bills in the Alaska Judicial Council; and data from eleven states, including Alaska, which report Offender-Based Transaction Statistics (OBTS), which tracks adult offenders from the point of entry into the criminal justice system through final disposition. January 1988 population figures for Alaska Department of Corrections facilities are presented."Alaska Judicial Council in Change: 1983–1987" by Francis Bremson and Teresa White Carns / "News Cameras in Alaska Courts: Assessing the Impact" by Marla N. Greenstein / "Corrections Bills Pending" by Bill Parker / "Tracking Offenders, 1984 (A BJS Report)" / "Angell Appointed" / "Mclaughlin Video Available" / "Alaska Department of Corrections Profile of Population

Single-Cell Analysis of Crohn's Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy

Clinical benefits of cytokine blockade in ileal Crohn's disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct network connectivity that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in four independent iCD cohorts (n = 441), and its presence at diagnosis correlated with failure to achieve durable corticosteroid-free remission upon anti-TNF therapy. These results emphasize the limitations of current diagnostic assays and the potential for single-cell mapping tools to identify novel biomarkers of treatment response and tailored therapeutic opportunities

Clinical, Serologic, and Genetic Factors Associated with Pyoderma Gangrenosum and Erythema Nodosum in Inflammatory Bowel Disease Patients

OBJECTIVE: Pyoderma gangrenosum (PG) and erythema nodosum (EN) are the most common cutaneous manifestations of inflammatory bowel disease (IBD) but little is known regarding their etiopathogenesis. DESIGN: We performed a case control study comparing characteristics between IBD patients with a documented episode of PG (PG+) and/or EN (EN+) with those without PG (PG-) and EN (EN-). Data on clinical features were obtained by chart review. IBD related serology was determined using ELISA and genome-wide data generated using Illumina technology. Standard statistical tests for association were used. RESULTS: We identified a total 92 cases of PG and 103 cases of EN with genetic and clinical characteristics, of which 64 PG and 55 EN were available for serological analyses. Fewer male subjects were identified in the PG(+) (OR 0.6, p=0.009) and EN(+) groups (OR 0.31, p=0<0.0001). Colonic disease, previous IBD related surgery, and non-cutaneous extra-intestinal manifestations were more common among both PG(+) and EN(+) patients compared to controls. PG(+) was associated with ANCA seropositivity (p=0.03) and higher ANCA level (p=0.02) in CD. Genetic associations with PG included known IBD loci (IL8RA (p=0.00003), and PRDM1 (0.03)) as well as with USP15 (4.8×10(−6)) and TIMP3 (5.6 ×10(−7)). Genetic associations with EN included known IBD susceptibility genes (PTGER4 (p=8.8×10(−4)), ITGAL (0.03)) as well as SOCS5 (9.64×10(−6)), CD207 3.14×10(−6)), ITGB3 (7.56×10(−6)) and rs6828740 (4q26)(p <5.0 × 10(−8)). Multivariable models using clinical, serologic, and genetic parameters predicted PG (AUC 0.8) and EN (AUC 0.97). CONCLUSION: Cutaneous manifestations in IBD are associated with distinctive genetic characteristics as well as with the similar clinical characteristics including the development of other extra-intestinal manifestations suggesting shared and distinct etiologies

Ulcerative colitis is characterized by a plasmablast-skewed humoral response associated with disease activity

International audienceB cells, which are critical for intestinal homeostasis, remain understudied in ulcerative colitis (UC). In this study, we recruited three cohorts of patients with UC (primary cohort, n = 145; validation cohort 1, n = 664; and validation cohort 2, n = 143) to comprehensively define the landscape of B cells during UC-associated intestinal inflammation. Using single-cell RNA sequencing, single-cell IgH gene sequencing and protein-level validation, we mapped the compositional, transcriptional and clonotypic landscape of mucosal and circulating B cells. We found major perturbations within the mucosal B cell compartment, including an expansion of naive B cells and IgG + plasma cells with curtailed diversity and maturation. Furthermore, we isolated an auto-reactive plasma cell clone targeting integrin αvβ6 from inflamed UC intestines. We also identified a subset of intestinal CXCL13-expressing TFH-like T peripheral helper cells that were associated with the pathogenic B cell response. Finally, across all three cohorts, we confirmed that changes in intestinal humoral immunity are reflected in circulation by the expansion of gut-homing plasmablasts that correlates with disease activity and predicts disease complications. Our data demonstrate a highly dysregulated B cell response in UC and highlight a potential role of B cells in disease pathogenesis. UC is a chronic inflammatory bowel disease (IBD) characterized by relapsing episodes of inflammation of the colonic mucosa 1. In healthy individuals, intestinal B cell responses are dominated by the homeostatic generation of IgA-producing plasma cells (PCs) that promote under exclusive licence to Springer Nature America, Inc. 2022Reprints and permissions information is available at www.nature.com/reprints