Stefano Malerba

Swallowed Fluticasone Propionate Is an Effective Long-Term Maintenance Therapy for Children With Eosinophilic Esophagitis

OBJECTIVES:Although effective in the treatment of eosinophilic esophagitis (EoE) in children, limited data exist on long-term safety and efficacy of swallowed topical corticosteroids. We investigated whether long-term use of swallowed fluticasone in children with EoE leads to sustained reduction in esophageal eosinophils, and endoscopic and clinical improvement.METHODS:In an open-label, prospective, single-center study, we offered pediatric patients with active EoE fluticasone 2 puffs to swallow twice a day (strengths in μg/puff: 2–4 years: 44, 5–11 years: 110, ≥12 years: 220). Clinical, endoscopic, and histological assessments were performed at baseline and shortly after therapy. If histological remission was seen, fluticasone was continued with clinical follow-ups every 4 months and endoscopic and histological follow-ups yearly. Clinical scores were derived from eight symptoms (abdominal pain, nausea, vomiting, regurgitation, chest pain, dysphagia, food impaction, and early satiety). Endoscopic scores were derived from six features (rings, exudates, furrows, edema, stricture, and shearing). Scores were expressed as ratio (features present/total). In addition to peak eosinophils/high power field (HPF) (primary outcome), histological features (eosinophilic microabscesses, degranulation, superficial layering, basal zone hyperplasia, dilated intercellular spaces, and lamina propria fibrosis) were assessed. Median clinical and endoscopic scores and individual histologic features were compared over 4 time intervals: <4 months, 4–12 months, 13–24 months, and >24 months. Growth and adverse effects were monitored.RESULTS:We enrolled 54 patients, 80% male, median age 6.5 years (range 2–17 years), 85% atopic (57% asthma, 68% allergic rhinitis, and 31% atopic dermatitis), and 74% with food allergy. Mean follow-up was 20.4 months, the longest being 68 months (5.7 years). Esophageal eosinophil counts significantly decreased (median peak eosinophils/HPF at baseline 72, <4 months: 0.5, 4–12 months: 1.75, 13–24 months: 10, and >24 months: 12, all P<0.01). All histological features significantly decreased from baseline to all follow-up time points (all P<0.01). Lamina propria fibrosis significantly decreased (% patients with fibrosis at baseline 92, <4 months: 41, 4–12 months: 50, 13–24 months: 45, and >24 months: 39, all P<0.01). Endoscopic features improved (score at baseline 0.37, <4 months: 0.17, 4–12 months: 0.17, 13–24 months: 0, and >24 months: 0.1, all P<0.01, except at >24 months: P<0.05). Symptoms improved (score at baseline 0.22, <4 months: 0, 4–12 months: 0.11, 13–24 months: 0.11, and >24 months: 0.11, all P<0.05 except at >24 months: P=0.05). In a mixed linear regression model that accounts for correlation of repeated observations in the patient in a per-patient analysis, we found that treatment with swallowed fluticasone led to a statistically significant and sustained decrease in peak esophageal eosinophil counts. Asymptomatic esophageal candidiasis was seen in three children but resolved with anti-fungal therapy. Height and weight z-scores followed expected growth curves.CONCLUSIONS:We demonstrate that swallowed fluticasone is effective as a long-term maintenance therapy for children with EoE, without growth impediment or serious side effects.

Dietary glycemic index, glycemic load, and the risk of endometrial cancer: a case-control study and meta-analysis.

Carbohydrates and the dietary glycemic index (GI) influence insulin secretion and insulin-like growth factors, and may exert relevant effects on obesity and diabetes, both of which are important risk factors for endometrial cancer. We studied the association between dietary GI and glycemic load (GL) and endometrial cancer using data from an Italian case–control study. This included 454 women with histologically confirmed endometrial cancer and 908 controls admitted to the same hospitals for acute, non-neoplastic conditions. Multivariate odds ratios were obtained after allowance for major potential confounding factors, including noncarbohydrate energy intake. We updated a meta-analysis on this issue, including a recent US cohort study, which contributed about a quarter of all cases, besides our case–control study. In the case–control study, the odds ratios of endometrial cancer for the highest versus the lowest quintile were 1.03 [95% confidence interval (CI): 0.67–1.58] for GI and 1.01 (95% CI: 0.64–1.61) for GL. No heterogeneity was found across the strata of diabetes and other selected covariates. The summary risk estimate of endometrial cancer for the highest versus the lowest GI level, obtained from the meta-analysis, was 1.09 (95% CI: 0.92–1.29). The corresponding risk estimate for GL was 1.19 (95% CI: 1.06–1.34). The case–control study showed no association between dietary GI and GL and the risk of endometrial cancer overall and in the strata of relevant covariates, whereas the meta-analysis supported an increased risk for high GL, but not GI.

Associations of bread and pasta with the risk of cancer of the breast and colorectum

BACKGROUND Carbohydrate foods with high glycemic and insulinemic potential may influence cancer risk possibly through the insulin/growth-factor axis. Two staple carbohydrate foods of the Mediterranean diet, bread and pasta, have different glycemic and insulinemic responses and hence may affect cancer risk differently. MATERIALS AND METHODS We studied the association of bread and pasta with breast and colorectal cancer risk using data from two Italian case-control studies. These studies included 2569 women with histologically confirmed breast cancer and 1953 men and women with colorectal cancer. Controls were 2588 and 4154, respectively, admitted to the same hospitals as cases for acute, non-neoplastic conditions. Multivariate odds ratios (ORs) were obtained after allowance for relevant confounding factors. RESULTS The ORs of breast cancer for the highest versus the lowest quintile were 1.28 (95% confidence interval, CI: 1.03-1.58, P-trend = 0.0342) for bread and 1.07 (95% CI: 0.88-1.31, P-trend = 0.7072) for pasta. The association with bread remained virtually unchanged with postmenopause and overweight. The ORs of colorectal cancer in women for the highest versus the lowest quintile were 2.02 (95% CI: 1.46-2.80, P-trend = 0.0002) for bread and 1.37 (95% CI: 1.00-1.88, P-trend = 0.0164) for pasta. The associations remained significant only for bread in strata of menopausal status and in women with overweight. No significant associations were seen in men for either bread or pasta. CONCLUSIONS Overall, these two cancer case-control studies showed stronger positive associations with bread than pasta in women, particularly if overweight, suggesting possible hormonal-related mechanisms.

Pediatric cardiac retransplantation: Waitlist mortality stratified by age and era.

BACKGROUND Waitlist mortality among children listed for primary heart transplant (HTx) has been well characterized, whereas limited data exist for cardiac retransplantation (CRTx) after pediatric primary HTx. We sought to characterize the population listed for CRTx and to determine the factors that affect waitlist mortality. METHODS All individuals listed for CRTx >1 year after pediatric primary HTx between October 1, 1987, and October 14, 2012 were identified in the Organ Procurement and Transplantation Network database. Baseline characteristics and waitlist mortality were compared between age groups (< 11 years, 11-18 years, and > 18 years) and during 3 successive eras (1987-1999, 1999-2006, and 2006-2012). RESULTS The cohort comprised 632 patients who were listed for CRTx > 1 year after pediatric primary HTx. Median age was 4 years at primary HTx and 14 years at relisting. Median time from primary HTx to relisting was 7.3 years. Median waiting time was 75.3 days. Overall mortality was 25.2% (159 of 632). The most frequent relisting diagnosis was related to graft vasculopathy (62.5%). The leading causes of death were chronic rejection and vasculopathy (52%). Waitlist mortality significantly decreased after 2006 (31% vs 17%; p < 0.01), despite a relatively constant CRTx rate (67% vs 65%). Univariate analysis showed era, age, listing status, and life support (mechanical circulatory support device, extracorporeal membrane oxygenation, mechanical ventilation) were significant predictors of mortality. Multivariate analyses showed that later era (2006-2012), ages 11 to 18 years, and United Network of Organ Sharing listing status 2 predicted decreased mortality, whereas life support increased mortality. CONCLUSIONS Waitlist mortality for CRTx in children and young adults has decreased by almost 50% over time. Individuals relisted as adults have increased waitlist mortality.

The weekend effect in patients hospitalized for upper gastrointestinal bleeding: A single-center 10-year experience

Objective This study was conducted to assess the possible weekend effect in patients with upper gastrointestinal bleeding (UGIB) on the basis of a 10-year single-center experience in Serbia. Materials and methods A retrospective analysis of hospital records in the University Clinic ‘Dr Dragisa Misovic-Dedinje’, Belgrade, Serbia, from 2002 to 2012 was conducted. Patients admitted for UGIB were identified, and data on demographic characteristics, symptoms, drug use, alcohol abuse, diagnosis and treatment were collected. Univariate and multivariate logistic regression were used to assess the association between weekend admission and the occurrence of rebleeding and in-hospital mortality. Results Analyses included 493 patients. Rebleeding occurred significantly more frequently on weekends (45.7 vs. 32.7%, P=0.004). Weekend admission [odds ratio (OR)=1.78; 95% confidence interval (CI): 1.15–2.74], older age (OR=1.02; 95% CI: 1.00–1.03), and the presence of both melaena and hematemesis (OR=2.29; 95% CI: 1.29–4.07) were associated with the occurrence of rebleeding. No difference between weekend and weekday admissions was observed for the in-hospital mortality rate (6.9% vs. 6.0%, P=0.70). Older age (OR=1.14; 95% CI: 1.08–1.20), presentation with melaena and hematemesis (OR=4.12; 95% CI: 1.56–10.90) and need for surgical treatment (OR=5.16; 95% CI: 1.61–16.53) were significant predictors of all-cause mortality. Patients with nonvariceal bleeding had significantly higher rebleeding rates on weekends (44 vs. 32.3%, P=0.013). Conclusion There was no significant weekend effect in the mortality of patients admitted for UGIB, irrespective of the source of bleeding. Increased attention to older patients presenting with a more severe clinical picture is needed to prolong survival and prevent rebleeding.

Donor-recipient height ratio and outcomes in pediatric heart transplantation.

Height matching in pediatric HTx has been proposed as a superior method of evaluating graft size, but no studies have examined survival advantage for height‐matched donor–recipient pairs. We hypothesized that in pediatric patients with DCM, an oversized donor improves survival and aimed to define the optimal height ratio in this patient group. Pediatric primary HTx recipients with DCM between 10/89 and 09/12 were identified in the OPTN database. Patients were stratified into three donor–recipient height and weight ratio categories. One‐ and five‐yr survival was compared using Kaplan–Meier analysis and HRs were computed. A total of 2133 children with DCM who underwent HTx during the study period were included. Unadjusted one‐yr survival was worse for DRHR <0.87 (HR, 2.15 [95% CL, 1.30, 3.53]; p < 0.01). This difference was not present at five yr post‐HTx or when stratified by weight. After adjustment for other risk factors affecting transplant survival, height matching was no longer significant. Although height matching appears to predict short‐term survival better than weight in pediatric HTx recipients with DCM, other factors play a more important role as height matching loses significance in multivariate analysis.

Sa1138 Patients With Inflammatory Bowel Disease and a History of Cancer: The Risk of Cancer Following Exposure to Immunosuppression

Back ground: The calcineurin inhibitor (CNI) tacrolimus (TAC) has been reported to be effective for induction and maintenance of remission in patients with refractory ulcerative colitis (UC). However, CNI has nephrotoxic potential leading to acute and chronic renal damage in some cases. To date, little is known about the influence of long term administration of oral TAC on renal function in patients with UC. Aim: The aim of our study was to evaluate the incidence and the severity of renal function impairment in UC patient who received TAC treatment. Methods: In this retrospective study, the medical charts of 71 adult patients with steroid-refractory UC treated with TAC between 2012 and 2014 in a single Japanese center were analyzed. In principle, TAC was orally administrated as a 2 week-induction (target trough levels 10-15ng/ml) followed by a maintenance therapy (target trough levels 5-10ng/ml). Estimated glomerular filtration rate (eGFR) was evaluated during the treatment. Acute kidney injury (AKI) was defined by the RIFLE (Risk of renal dysfunction, Injury to the kidney, Failure of function, Loss of function and End-stage kidney disease) consensus criteria using the maximal change in serum creatinine (Scr) and eGFR during the TAC treatment compared with baseline value before treatment. Results: The mean duration of TAC administration was 210 days. At 12weeks, TAC produced a clinical response in 54 patients (76.1%) and remission was achieved in 29 of those 54 (40.8%). The AKI rate during TAC treatment was 46.5% (33 of 71 patients). RIFLE class R (Scr increase > 1.5 times or eGFR decrease > 25%) accounted for 27 patients (38.0%), and RIFLE class I (Scr increase > 2 times or eGFR decrease > 50%) for six (8.5%). The AKI rate was 76.8% (10/13) in patients who had been administrated TAC for more than 1 year and 37.5% (18/48) in patients with TAC treatment within 6 months (p=0.006). After withdrawal of TAC, renal function impairment (eGFR decrease > 25%) was still observed in 10 patients (14.1%). Conclusions: Oral TAC therapy appears to be effective for patients with refractory UC. However, renal function impairment was frequently observed during this treatment. Thus, careful monitoring of renal function must be required to avoid irreversible chronic renal damage during long-term administration of TAC.