Longitudinal Changes in Fecal Calprotectin Levels Among Pregnant Women With and Without Inflammatory Bowel Disease and Their Babies.

BACKGROUND & AIMS: The effect of pregnancy on inflammatory bowel disease (IBD) remains poorly understood. We aimed to monitor intestinal inflammation using fecal calprotectin (FC) in pregnant women and their babies during early life. METHODS: Pregnant women with or without IBD and their infants were prospectively enrolled. FC levels were measured at each trimester of pregnancy and in babies throughout the first 3 years of life. Repeated-measures analysis was applied to investigate changes in FC levels while adjusting for confounders. The FC levels were correlated with the bacterial abundance in both mothers and babies. RESULTS: Six hundred and fourteen fecal samples from 358 mothers (98 with IBD) and 1005 fecal samples from 289 infants (76 born to IBD mothers) were analyzed. Pregnant Patients with IBD maintained higher FC levels through pregnancy compared with controls (P = 7.5 × 10-54). FC gradually increased in controls and declined in Patients with IBD throughout pregnancy (P for interaction = 5.8 × 10-7). Babies born to mothers with IBD presented with significantly higher FC levels than those born to controls up to 3 years of age, after adjusting for sex, delivery mode, feeding behavior, and antibiotics exposure (2 weeks to 3 months of age, P = .015; 12-36 months of age, P = .00003). Subdoligranulum, Roseburia, Fusicatenibacter, and Alistipes negatively correlated, and Streptococcus, Prevotella, Escherichia-Shigella, and Bifidobacterium positively correlated with maternal FC levels at T3. Faecalibacterium, Bifidobacterium, and Alistipes showed negative correlations, and Streptococcus were positively correlated with FC levels within 3 months of birth. CONCLUSIONS: Pregnancy is associated with decreased inflammatory activity in mothers with IBD. Higher FC levels in babies born to mothers with IBD suggest subclinical inflammation in early life, the long-term consequences of which are uncertain.

National trends in contralateral prophylactic mastectomy in women with locally advanced breast cancer.

BACKGROUND AND OBJECTIVES: Women with unilateral early-stage breast cancer are increasingly choosing contralateral prophylactic mastectomy (CPM) despite the absence of survival benefits and increased risk of surgical complications. Data are lacking on whether this trend extends to women with clinically locally advanced nonmetastatic (cT4M0) cancer. This study aims to estimate national CPM trends in women with unilateral cT4M0 breast cancer. METHODS: Women aged ≥ 18 years, who underwent mastectomy during 2004 to 2014 for unilateral cT4M0 breast cancer were identified using the National Cancer Database and grouped as all locally advanced (T4), chest wall invasion, skin nodule/ulceration, or both (T4abc), and inflammatory (T4d) cancer. Poisson regression for trends and logistic modeling for predictors of CPM were performed. RESULTS: Of 23 943 women, 41% had T4abc disease and 35% T4d. Cumulative CPM rates were 15%, 23%, and 18%, for the T4abc, T4d, and all T4 groups, respectively. Trend analysis revealed a significant upsurge in CPM demonstrating 12% annual growth for T4abc tumors, 8% for T4d and 9% for all T4 (all P < 0.001). CONCLUSIONS: Increasing numbers of women with unilateral cT4M0 breast cancer are undergoing CPM. This rising trend warrants further research to understand stakeholders' preferences in surgical decision-making for women with locally advanced breast cancer.

Earlier Anti-Tumor Necrosis Factor Therapy of Crohn's Disease Correlates with Slower Progression of Bowel Damage.

INTRODUCTION: Crohn's disease (CD) follows a relapsing and remitting course incurring cumulative bowel damage over time. The question of whether or not the timing of the initiating biologic therapy affects long-term disease progression remains unanswered. Herein, we calculated rates of change in the Lémann index-which quantifies accumulated bowel damage-as a function of the time between the disease onset and initiation of biologic therapy. We aimed to explore the impact of the earlier introduction of biologics on the rate of progression of long-term cumulative bowel damage. METHODS: Medical records of CD patients treated during 2009-2014 at The Mount Sinai Hospital were queried. Inclusion criteria were two comprehensive assessments allowing calculation of the index at t1 and t2: two time-points ≥ 1 year apart. Patients with biologics introduced before or within 3 months at inclusion (t1) were defined as Bio-pre-t1 and those who did not as Bio-post-t1. The rate of disease progression was calculated as the change in the index per year during t1-t2. RESULTS: A total of 88 patients were studied: 58 Bio-pre-t1 and 30 Bio-post-t1. Among the 58 Bio-pre-t1 cases, damage progressed in 29 (50%), regressed in 20 (34.5%), and stabilized in 9 (15.5%). Median time to initiation of biologics among patients whose index improved was nominally shorter compared to that in patients whose index progressed (8 vs. 15 years). Earlier introduction of biologics tended to correlate with the slower rate of progression (ρ = 0.241; p = 0.069). CONCLUSIONS: Earlier introduction of biologics tended to correlate with the slower progression of bowel damage in CD, reflected by the reduced rate of Lémann index progression.

Expanded criteria donor kidneys for retransplantation United Network for Organ Sharing update: proceed with caution.

This study analyzed outcomes of retransplantation from expanded criteria donors (ECD) over the last two decades to determine the benefits and risks of using ECD kidneys for retransplantation. Data from the United Network for Organ Sharing database were collected and analyzed. Graft survival, death-censored graft survival, and patient survival for retransplantation with ECD kidneys (re-ECD) were reported and compared with primary transplantation with ECD kidneys (prim-ECD) and retransplantation with standard criteria donor kidneys (re-SCD). Re-ECD kidneys had higher risk of graft failure compared with prim-ECD (hazard ratio [HR] = 1.19) and to re-SCD (HR = 1.76). Patient survival was better in re-ECD compared with prim-ECD (HR = 0.89) but was worse than re-SCD (HR = 1.82). After censoring the patients who died with a functioning graft, re-ECD had a higher mortality risk compared with prim-ECD (HR = 1.45) and re-SCD (HR = 1.79). Transplantation improves quality of life and reduces healthcare costs, and due to the risk associated with resumption of hemodialysis and the longer waiting list times for SCD kidneys, there is a benefit to accepting ECD kidneys for select patients requiring retransplantation. Although this benefit exists for select patients, retransplantation with ECD kidneys should be undertaken with trepidation, and appropriate informed consent should be obtained.

Accelerated Infliximab Dosing Increases 30-Day Colectomy in Hospitalized Ulcerative Colitis Patients: A Propensity Score Analysis.

Background: Standard outpatient induction dosing of infliximab (IFX) may not be effective in hospitalized ulcerative colitis (UC) patients with higher inflammatory burden and colectomy risk. Our aim was to determine whether initial IFX induction dose affects 30-day colectomy rate and other disease-related outcomes. Methods: IFX-naive hospitalized UC patients receiving at least 1 inpatient 5 mg/kg (SD) or 10 mg/kg (HD) IFX induction dose were included. Baseline demographics and admission-related characteristics were documented. Propensity score based matching was used to control for provider bias introduced due to nonprotocolized choice of IFX dose. The primary outcome was 30-day colectomy; secondary outcomes included the need for an accelerated induction IFX (AD), length of stay (LOS), 90-day and 1-year colectomy, and complications. Results: Of 146 (120 SD/26 HD) patients included, 25 (17.1%) underwent colectomy by 30 days, 33 (22.6%) by 90 days, and 41 (28.1%) by 1 year. In 21 propensity score matched dyads (n = 42) treated with SD or HD, colectomy rates and LOS were similar. SD patients more often needed AD (23.8% vs. 0%, P = 0.048) and AD patients progressed to colectomy more rapidly within 30 days compared to non-AD (P = 0.001). Female sex and hypoalbuminemia were associated with significantly increased odds of needing AD on both univariate and multivariate analyses. Conclusions: In our propensity score based analysis, receiving accelerated IFX dosing after an initial SD infusion was associated with significantly higher 30-day colectomy rates in hospitalized acute UC patients. The most effective dosing strategy in this population remains unclear and prospective randomized studies are needed.

Luminally polarized mural and vascular remodeling in ileal strictures of Crohn's disease.

Intestinal stricture, a major complication of Crohn's disease (CD), results from fibromuscular remodeling and expansion of the intestinal wall. The corresponding microanatomical alterations have not been fully described, hindering progress toward understanding their pathogenesis and devising appropriate treatments. We used tissue-specific staining and quantitative digital histomorphometry for this purpose. Serial histologic sections from 37 surgically resected ileal strictures and adjacent nonstrictured controls from patients with CD were evaluated after staining for smooth muscle actin, collagen (Sirius red), and collagen types I, III, and V. Overall mural thickening in strictures was increased 2.2 ±â€¯0.2-fold compared with nonstrictured regions of the same specimens. The muscular layer most altered was the muscularis mucosae (MM). Compared with the internal and external layers of the muscularis propria, (MP) which were expanded 1.9 ±â€¯0.2- and 1.3 ±â€¯0.1-fold, respectively, the MM was expanded 17.7 ±â€¯2.6-fold, reflecting the combined effects of architectural disarray, an 11.6 ±â€¯1.4-fold increase smooth muscle content, and elaboration of pericellular type V collagen. In contrast, the architecture of the MP was preserved and pericellular collagen was virtually absent; rather, fibrosis in this layer was limited to expansion of the intramuscular septa by collagen types I and III. The muscular arteries and veins within the strictured submucosa frequently exhibited eccentric, luminally oriented adventitial mantles comprising hyperplastic myocytes and extracellular type V collagen. We conclude that the fibromuscular remodeling which results in CD-associated ileal strictures predominantly involves the MM and submucosal vasculature in a luminally polarized fashion and suggests that mucosal-based factors may contribute to stricture pathogenesis.

Magnetic Resonance Imaging Predicts Histopathological Composition of Ileal Crohn's Disease.

BACKGROUND AND AIMS: Recently, smooth muscle hypertrophy has been suggested to be a contributor to small bowel lesions secondary to Crohn's disease [CD], in addition to inflammation and fibrosis. Here, we assess the value of magnetic resonance imaging [MRI] for the characterisation of histopathological tissue composition of small bowel CD, including inflammation, fibrosis, and smooth muscle hypertrophy. METHODS: A total of 35 consecutive patients [male/female 17/18, mean age 33 years] with ileal CD, who underwent small bowel resection and a preoperative contrast-enhanced MRI examination within 1 month before surgery, were retrospectively included. Image assessment included qualitative [pattern/degree of enhancement, presence of ulcerations/fistulas/abscesses] and quantitative parameters [wall thickness on T2/T1-weighted images [WI], enhancement ratios, apparent diffusion coefficient [ADC], Clermont and Magnetic Resonance Index of Activity [MaRIA] scores). MRI parameters were compared with histopathological findings including active inflammation, collagen deposition, and muscle hypertrophy using chi square/Fisher or Mann-Whitney tests and univariate/multivariate logistic/linear regression analyses. RESULTS: Forty ileal segments were analysed in 35 patients. Layered pattern at early-post-contrast phase was more prevalent (odds ratio [OR] = 8; p = 0.008), ADC was significantly lower [OR = 0.005; p = 0.022], and MaRIA score was significantly higher [OR = 1.125; p = 0.022] in inflammation grades 2-3 compared with grade 1. Wall thickness on T2WI was significantly increased [OR = 1.688; p = 0.043], and fistulas [OR = 14.5; p = 0.017] were more prevalent in segments with disproportionately increased muscle hypertrophy versus those with disproportionately increased fibrosis. MaRIA/Clermont scores, wall thickness on T1WI and T2WI, and ADC were all significantly correlated with degree of muscular hypertrophy. CONCLUSIONS: MRI predicts the degree of inflammation, and can distinguish prominent muscle hypertrophy from prominent fibrosis in ileal CD with reasonable accuracy (area under receiver operating characteristic curve [AUROC] > 0.7).

Fecal Calprotectin Levels Predict Histological Healing in Ulcerative Colitis.

BACKGROUND: Mucosal healing as measured by endoscopic activity is the therapeutic target for ulcerative colitis (UC) and associated with improved outcomes. We investigated the clinical utility of fecal calprotectin (FC) levels to predict depth of remission, including histological remission in patients with UC. METHODS: We performed a retrospective chart review of patients with UC who underwent a full colonoscopy and FC measured within 6 weeks before colonoscopy at a tertiary inflammatory bowel disease center. Clinical, endoscopic, and histological disease activity was assessed by Patient Reported Outcomes (PRO2), Mayo endoscopic score (0-3), and Nancy score (0-4), respectively. Outcomes of interest included (1) deep remission (PRO2 remission and Mayo score 0) and (2) deeper remission (deep remission plus Nancy score 0/1). Mann-Whitney U and Kruskal-Wallis tests and area under the curve-receiver operating characteristic curve analysis were used to evaluate accuracy of the predictive values. RESULTS: In 68 patients, increasing FC levels were significantly associated with disease extent (P = 0.006), Mayo score (P = 0.001), and Nancy scores (P < 0.001). Patients with Mayo score 0/1 and Nancy score ≤1 (n = 20) had significantly lower FC levels compared with Mayo 0/1 and Nancy ≥ 2 (31 versus 231; P < 0.001). FC level of ≤60 µg/g predicted deep remission (area under the curve = 0.92, sensitivity 86%, and specificity 87%) and deeper remission (area under the curve = 0.91, sensitivity 83%, and specificity 90%). CONCLUSIONS: FC levels significantly correlated with endoscopic extent, mucosal healing, and histological activity, and reflect microscopic disease activity even in the face of macroscopic healing. An FC level of ≤60 µg/g robustly predicted depth of remission, suggesting that FC can be used instead of colonoscopy in a treat-to-target paradigm in patients with UC.

The "July effect" does not have clinical relevance in liver transplantation.

In the beginning of the academic year, medical errors are often attributed to inexperienced medical staff. This potential seasonal influence on health care outcomes is termed the "July effect." No study has demonstrated the July effect in liver transplantation. We reviewed retrospectively collected data from the United Network for Organ Sharing for patients who underwent liver transplantation from October 1987 to June 2011 to determine if surgical outcomes were worse in July compared with rest of the year. We found no clinical difference in early graft survival (91.11% vs. 90.72%, p = 0.045) and no difference in early patient survival (94.71% vs. 94.42%, p = 0.057). Survival at 1 year, 3 years, and 5 years was also compared and no notable differences were detected. Because the Model for End-stage Liver Disease (MELD) score implementation in 2002 affected the acuity of liver transplant recipients, we further stratified our data to compare pre- and post-MELD survival to remove subjectivity as a confounding factor. MELD stratification revealed no seasonal difference in outcomes. There was no difference in rate of graft failure and acute and chronic rejection between groups. Our findings show no evidence of the July effect in liver transplantation. Each July, thousands of medical residents take on new responsibilities in patient care. It has been suggested that these new practitioners may produce errors that contribute to worse patient outcomes in the beginning of the academic year-a phenomenon called the "July effect." Currently, there are few research studies with controversial evidence of poorer outcomes in July, and no articles address the effect of new medical staff in the setting of liver transplantation. Our study compares short-, medium-, and long-term graft and patient survival between July and August and the remaining months using national data. We also examine survival before and after the implementation of the MELD scoring system to determine its effect on outcomes in the beginning of the academic year.