Adalimumab Biosimilar in Pediatric Inflammatory Bowel Disease: A Retrospective Study from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD).

BACKGROUND: The utilization of anti-tumor necrosis factor-α (anti-TNF-α) biosimilars in inflammatory bowel disease (IBD) is constantly increasing. However, pediatric data are limited. This study aimed to assess the effectiveness and safety of adalimumab biosimilar (ADL-BioS) in pediatric IBD patients. METHODS: All consecutive pediatric IBD patients from the Sicilian Network for Inflammatory Bowel Disease cohort treated with ADL-BioS from 2019 to 2021 were recruited. Remission at weeks 14 and 52, treatment persistence, and adverse events were the endpoints of this study. Factors associated with clinical remission and treatment persistence were examined. RESULTS: There were 41 patients in total. Nine (22%) patients were switched from the reference product to ADL-BioS. Two patients had multiple switches. Eleven months was the median follow-up period. Clinical remission was attained by 70.7% and 72.0% of patients on weeks 14 and 52, respectively. Four (9.8%) adverse events occurred (10.1/100 person-year). Treatment persistence was 85.4% at 1 and 2 years. Patients with a longer duration of disease had a higher probability of stopping their treatment (p = 0.036). CONCLUSIONS: This is the first real-world study that particularly addresses the use of ADL-BioS in pediatric IBD. With high rates of treatment persistence and a low frequency of non-serious side effects, ADL-BioS seems to be effective.

Raman Spectroscopy and Cystic Fibrosis Disease: An Alternative Potential Tool for Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator Response Differentiation-A Pilot Study Based on Serum Samples.

Cystic fibrosis (CF) is a genetic disorder that alters chloride transport in mucous membranes. Recent studies have demonstrated that treatment with modulators of the chloride channel reduces inflammatory markers, restoring, among others, the imbalance of lipids. In this study, we analyzed the serum samples of treated and non-treated patients with modulators with Raman spectroscopy. Nineteen (eight treated an eleven non-treated) patients were considered. The main difference between the two groups appeared in the 3020-2800 cm-1 range. A Voigt deconvolution fit was performed, and nine sub-bands were identified. To distinguish between treated and non-treated patients, the area ratio between the CH3 and CH2 vibration modes was calculated for each patient. The results were validated using statistical analyses. In particular, receiver operating characteristic (ROC) curves and Youden index (Y) were calculated (Area Under Curve (AUC): 0.977; Y: 3.30). An ROC curve represents the performance of the classification, illustrating the diagnostic ability of Raman spectroscopy. It was demonstrated that Raman spectroscopy is able to highlight peculiar differences between elexacaftor/tezacaftor/ivacaftor (ETI)-treated and non-treated patients, in relation with lipids biomarkers.

Real-life experience of infliximab biosimilar in pediatric-onset inflammatory bowel disease: data from the Sicilian Network for Inflammatory Bowel Disease.

OBJECTIVE: To provide data on the use of infliximab biosimilars (IFX-BioS) in children with inflammatory bowel disease (IBD). METHODS: A multicenter, observational, retrospective study was performed among the cohort of the Sicilian Network for IBD. All consecutive IBD children who had at least completed the induction with IFX-BioS from its introduction in Sicily to January 2021 were enrolled. Clinical remission at weeks 14 and 52, treatment persistence, and adverse events were the study outcomes. RESULTS: Eighty-seven patients [Crohn's disease (CD): 57.5% and ulcerative colitis (UC): 42.5%] were included: 75 (86.2%) were antitumor necrosis factor-α (anti-TNF-α) agent naïve, while three (3.45%) were switched from the originator to IFX-BioS. Twenty (23%) patients were multiply switched from the biosimilar CT-P13 to SB2 or GP1111 or vice versa. The median follow-up time was 15 months. Clinical remission was achieved by 55.2 and 65.5% of patients at weeks 14 and 52, respectively, with no differences between CD and UC. Dose escalation was needed in 8.0 and 35.7% of patients during induction and maintenance, respectively. Nine adverse events occurred (incidence rate: 6.13/100 person-year). Treatment persistence was 90.8% at 1 year and 75.7% at 2 years (patients on IFX-BioS at 2 years, n = 28). The risk of treatment discontinuation was higher in patients with extraintestinal manifestations ( P = 0.018) and in those who were nonnaïve to anti-TNF-α ( P = 0.027). CONCLUSION: This is the largest cohort of pediatric IBD patients treated with IFX-BioS. Real-life data show that IFX-BioS is efficacious in IBD children, with high percentages of treatment persistence and a low incidence of nonserious adverse events.

Recognizing the Emergent and Submerged Iceberg of the Celiac Disease: ITAMA Project-Global Strategy Protocol.

Coeliac disease (CD) is frequently underdiagnosed with a consequent heavy burden in terms of morbidity and health care costs. Diagnosis of CD is based on the evaluation of symptoms and anti-transglutaminase antibodies IgA (TGA-IgA) levels, with values above a tenfold increase being the basis of the biopsy-free diagnostic approach suggested by present guidelines. This study showcased the largest screening project for CD carried out to date in school children (n=20,000) aimed at assessing the diagnostic accuracy of minimally invasive finger prick point-of-care tests (POCT) which, combined with conventional celiac serology and the aid of an artificial intelligence-based system, may eliminate the need for intestinal biopsy. Moreover, this study delves deeper into the "coeliac iceberg" in an attempt to identify people with disorders who may benefit from a gluten-free diet, even in the absence of gastrointestinal symptoms, abnormal serology and histology. This was achieved by looking for TGA-IgA mucosal deposits in duodenal biopsy. This large European multidisciplinary health project paves the way to an improved quality of life for patients by reducing the costs for diagnosis due to delayed findings of CD and to offer business opportunities in terms of diagnostic tools and support.

Raman Spectroscopy Technique: A Non-Invasive Tool in Celiac Disease Diagnosis.

Celiac disease (CD) is diagnosed by a combination of specific serology and typical duodenal lesions. The histological confirmation of CD, mandatory in the majority of patients with suspected CD, is based on invasive and poorly tolerated procedures, such as upper gastrointestinal endoscopy. In this study we propose an alternative and non-invasive methodology able to confirm the diagnosis of CD based on the analysis of serum samples using the Raman spectroscopy technique. Three different bands centered at 1650, 1450 and 1003 cm-1 have been considered and the A1450/A1003 and A1650/A1003 ratios have been computed to discriminate between CD and non-CD subjects. The reliability of the methodology was validated by statistical analysis using receiver operating characteristic (ROC) curves. The Youden index was also determined to obtain optimal cut-off points. The obtained results highlighted that the proposed methodology was able to distinguish between CD and non-CD subjects with 98% accuracy. The optimal cut-off points revealed, for both the A1450/A1003 and A1650/A1003 ratios, high values of sensitivity and specificity (>95.0% and >92.0% respectively), confirming that Raman spectroscopy may be considered a valid alternative to duodenal biopsy and demonstrates spectral changes in the secondary structures of the protein network.

Effectiveness and safety of biologics in pediatric inflammatory boweldisease: Real-life data from the Sicilian Network.

BACKGROUND: Biological therapies have modified the disease course of pediatric inflammatory bowel disease (IBD) and are routinely used in clinical practice. Our observational study aims to evaluate effectiveness and safety of biologics in IBD. METHOD: Clinical benefit and safety data of 93 children with IBD, receiving biologics (Infliximab - IFX, Adalimumab - ADA, Golimumab - GOL) from January 2013 to December 2017, were extracted from the cohort of the Sicilian Network of IBD. RESULTS: Among 87 children aged 7-17 years (63 Crohn's disease [CD], 24 Ulcerative colitis [UC]), 101 out of 108 biologic treatments were considered. Evaluation of 74 biologic treatments in CD patients at 26, 52, 104 weeks showed clinical benefit rates of 84.2%, 93.3%, 66.7% with IFX (n= 38) and 88.9%, 84.4%, 65.2% with ADA (n= 36). Biologic treatments (n=27) evaluated in the UC group at 26, 52, 104 weeks, led to clinical benefit rates of 85.7%, 83.3%, 50% in IFX subgroup (n=21) and 40%, 50%, 33% in the ADA subgroup (n=5), respectively. One patient treated with GOL showed 100% clinical benefit at 26 and 52 weeks. Overall adverse events (AEs) rate was 9.25%. Six younger children, <6 years, receiving 8 treatments (4 ADA, 4 IFX) presented a clinical remission rate of 75% at 12 weeks and 25% at 52 weeks. AEs rate was 25% in this group. CONCLUSION: Our data show that biologic therapy in children, even at a younger age, is effective in allowing long-term remission with a good safety profile.

Diagnostic Yield of 2 Strategies for Adult Celiac Disease Identification in Primary Care.

GOALS: To compare the diagnostic yield and cost-consequences of 2 strategies, screening regardless of symptoms versus case finding (CF), using a point-of-care test (POCT), for the detection of celiac disease (CD) in primary care, to bridge the diagnostic gap of CD in adults. MATERIALS AND METHODS: All subjects under 75 years of age who consecutively went to their general practitioners' offices were offered POCT for anti-transglutaminase immunoglobulin A antibodies. The POCT was performed on all subjects who agreed, and then a systematic search for symptoms or conditions associated with higher risk for CD was performed, immediately after the test but before knowing the test results. The 2 resulting groups were: (a) POCT positive and (b) symptomatic subject at CF. Subjects were defined as symptomatic at CF in the presence of 1 or more symptoms. All POCT-positive or symptomatic subjects at CF were referred to the CD Centers for confirmation of CD. Data on resource consumption were gathered from patients' charts. Cost of examinations, and diagnostic and laboratory tests were estimated with regional outpatient tariffs (Sicily), and a price of &OV0556;2.5 was used for each POCT. RESULTS: Of a total of 2197 subjects who agreed to participate in the study, 36 (1.6%) and 671 (30.5%) were POCT positive and symptomatic at CF, respectively. The yield from the screening and CF was 5 new celiac patients. The total cost and mean cost for each new CD case were &OV0556;7497.35 and &OV0556;1499.47 for the POCT screening strategy, and &OV0556;9855.14 and &OV0556;1971.03 for the CF strategy, respectively. Assuming consecutive use of both strategies, performing POCT only in symptomatic subjects at CF, the calculated yield would be 4 new diagnoses with a total cost of &OV0556;2345.84 and a mean cost of &OV0556;586.46 for each newly diagnosed patient. Only 1 patient was celiac despite a negative POCT. CONCLUSIONS: Testing symptomatic subjects at CF only by POCT seems the most cost-effective strategy to bridge the diagnostic gap of adult CD in primary care.

Case report on pathogenetic link between gluten and IgA nephropathy.

BACKGROUND: A relationship between IgA nephropathy (IgAN) and celiac disease (CD) has been reported. We show the pathogenetic link for the first time. CASE PRESENTATION: A 39-year-old man with cystic fibrosis (CF) and CF-related diabetes started to present gross hematuria, back pain and headache. At admission, laboratory analysis showed increase in serum creatinine of 1.5 mg/dl, together with hematuria and mild proteinuria (1 g/24 h). He underwent a renal biopsy to investigate the cause of hematuria and renal failure. Biopsy was consistent with IgAN. In view of patient reported dyspepsia, an upper gastrointestinal endoscopy with duodenal biopsies was undertaken and was normal. We looked for mucosal deposits of tTG-2 in the duodenum and the renal mesangium. tTG-2 deposits were found both in the duodenum and in renal biopsies, where they topographically replicated mesangial IgA deposits. After one year on a continued gluten containing diet, the patient developed a Marsh 2 type duodenal pathology. CONCLUSIONS: Our findings suggest a connection between CD and IgAN in terms of an immune-mediated gluten-induced pathogenesis even in the absence of villous atrophy and serum celiac autoantibodies.

Cystic Fibrosis: A Risk Condition for Renal Disease.

OBJECTIVE: Cystic fibrosis (CF) is the most common autosomal recessive disease affecting the Caucasian population, with a birth incidence ranging between 1:2,500 and 1:1,800. It is caused by mutations in the CF transmembrane regulator gene which is localized on 7 chromosomes. Renal disease is reported as a relatively rare complication in adult patient with CF. We evaluated proteinuria and chronic renal failure (CRF) in a population of patients with CF. METHODS: A retrospective study was carried out in a referral center for CF at University of Messina in Italy. We identified all patients with renal disease, characterized by proteinuria and/or CRF, during the period 2007 to 2012 and reviewed their medical records to assess influence on renal disease of genotype, number of pulmonary exacerbation, pancreatic insufficiency, pulmonary function, CF-related diabetes, and antibiotics courses. RESULTS: From a population of 77 adult patients with CF, we identified 9 patients with proteinuria (11.7%), and 11 patients (14.28%) with CRF. Mean age was 35.6 (+5.1 standard deviation) years, 55% were female and 33% had diabetes mellitus. Renal biopsy was performed in 3 patients because of nephrotic syndrome in 1 patient and proteinuria with renal failure in the other 2 patients. Renal amyloidosis was disclosed in 2, whereas IgA nephropathy in 1 patient. The ΔF508 mutation in homozygosis was present in 44% of patients with proteinuria (vs. 27% of our CF population, relative risk 2.07), whereas genotype ΔF508/N1303K in 22%. ΔF508 allele mutation was present in 77.7% of proteinuric patients. CONCLUSIONS: Our study shows a higher prevalence of renal disease in patients with CF, than was previously described. The main reason may be related to increased life expectancy because of better management. Moreover, patients with ΔF508 homozygosis had higher risk of proteinuria.

Endoscopic and Histologic Healing in Children With Inflammatory Bowel Diseases Treated With Thalidomide.

BACKGROUND & AIMS: Mucosal healing, determined by endoscopic evaluation, is one of the most important prognostic markers for patients with inflammatory bowel diseases. Findings from histologic evaluation, however, could complement findings from endoscopy in assessing mucosal responses to treatment. We analyzed long-term results of children treated with thalidomide to determine the association between clinical response and histology and endoscopy findings. METHODS: We collected data from 2 multicenter trials of 70 children with refractory Crohn's disease (CD) or ulcerative colitis (UC) (2-18 years old; ileocolonic or colonic disease) given thalidomide or placebo (NCT00720538). Clinical remission and clinical response at 8 weeks were defined as a pediatric CD activity index scores 10 points or lower and a decrease of at least 50% from baseline, respectively, for patients with CD; and as a pediatric UC activity index score below 10 and a decrease of at least 20 points from baseline, respectively, for patients with UC. Patients with a clinical response to 8 weeks' treatment with thalidomide underwent endoscopic examination with biopsy collection at study weeks 12 and 52. Severity of inflammation in patients with UC was assessed by Mayo score and in patients with CD by 4-grade system. Biopsies were assessed for signs of active inflammation, erosion or ulceration, and crypt abscesses and assigned a histologic score. RESULTS: Clinical remission was observed in 42 patients (60.0%) and clinical response in 45 patients (64.2%) at Week 8. At Week 52, a total of 38 patients (54.3%) were still in clinical remission or still had a clinical response; 29 patients (41.4%) had mucosal healing, defined as complete healing of erosions or ulcerations, and 20 patients (27.7%) had histologic healing, defined as complete absence of markers of inflammation. Of patients with clinical remission or clinical response, 75.3% also had mucosal healing and 52.6% also had histologic healing. The probability of achieving mucosal healing decreased significantly with increasing values of erythrocyte sedimentation rate (adjusted odds ratio, 0.96; 95% CI, 0.93-0.98; P = .006). CONCLUSIONS: In a long-term analysis of data from 2 clinical trials of pediatric patients with CD or UC, 52 weeks' treatment with thalidomide led to clinical remission in 54.3% of patients with ileocolonic or colonic disease; of these patients, 75.3% had mucosal healing and 52.6% also had histologic healing. Further studies are needed to determine how thalidomide therapy affects long-term progression of inflammatory bowel diseases. (ClinicalTrials.gov number NCT00720538).

Effect of Early Versus Late Azathioprine Therapy in Pediatric Ulcerative Colitis.

BACKGROUND: We aimed at describing the efficacy of azathioprine (AZA) in pediatric ulcerative colitis, comparing the outcomes of early (0-6 months) versus late (6-24 months) initiation of therapy. METHODS: Children with ulcerative colitis treated with AZA within 24 months of diagnosis were included. Corticosteroid (CS)-free remission and mucosal healing (MH), assessed by endoscopy or fecal calprotectin, at 12 months were the primary outcomes. Patients were also compared for CS-free remission and MH, need for treatment escalation or surgery, number of hospitalizations, and adverse events during a 24-month follow-up. RESULTS: A total of 121 children entered the study (median age 10.5 ± 4.0 years, 59% girls). Seventy-six (63%) started AZA between 0 and 6 months (early group) and 45 (37%) started between 6 and 24 months (late group). Seventy-five percent and 53% of patients in the early and late group, respectively, received CS at the diagnosis (P = 0.01). CS-free remission at 1 year was achieved by 30 (50%) of the early and 23 (57%) of the late patients (P = 0.54). MH occurred in 37 (37%) patients at 1 year, with no difference between the 2 groups (33% early, 42% late; P = 0.56). No difference was found for the other outcomes. CONCLUSIONS: Introduction of AZA within 6 months of diagnosis seems not more effective than later treatment to achieve CS-free remission in pediatric ulcerative colitis. MH does not depend on the timing of AZA initiation; however, because of the incomplete comparability of the 2 groups at the diagnosis and the use of fecal calprotectin as a surrogate marker of MH, our results should be further confirmed by prospective studies.

Clinical Features and Risk Factors of Autoimmune Liver Involvement in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Autoimmune liver disease is reported in up to 7.8% of children with inflammatory bowel disease. A distinct inflammatory bowel disease phenotype has been suggested in adults and in small pediatric cohorts. The aim of the study was to evaluate the features of inflammatory bowel disease associated with autoimmune liver diseases and to analyze the characteristics of the liver disease. METHODS: Information on patients was obtained from the Italian Pediatric Inflammatory Bowel Disease Registry. Data of patients with and without autoimmune liver disease were compared. RESULTS: Autoimmune liver disease was detected in 6.8% of the 677 patients enrolled and was significantly associated with the diagnosis of ulcerative colitis (83%), with pancolonic involvement (84%), and with perinuclear antineutrophil cytoplasmic antibody positivity (41%) (all Ps < 0.05). Autoimmune liver disease was defined as sclerosing cholangitis in 61% of the patients and as an overlap syndrome in 33%. Concomitant intra- and extrahepatic biliary involvement was reported in 61% of cases, whereas exclusive extrahepatic lesions were reported in 21%. Hepatobiliary complications were observed in 9% of the patients during follow-up. CONCLUSIONS: Autoimmune liver disease, especially sclerosing cholangitis, was significantly more common in patients with extensive ulcerative colitis. Although complications are relatively rare in the pediatric age, monitoring is recommended.

Phenotype and disease course of early-onset pediatric inflammatory bowel disease.

BACKGROUND: Early-onset (EO) pediatric inflammatory bowel diseases (IBD) seem to be more extensive than those with a later onset. To test this hypothesis, we examined the phenotype and disease course of patients with IBD diagnosis at 0 to 5 years, compared with the ranges 6 to 11 and 12 to 18 years. METHODS: Anatomic locations and behaviors were assessed according to Paris classification in 506 consecutive patients: 224 Crohn's disease, 245 ulcerative colitis, and 37 IBD-unclassified. RESULTS: Eleven percent of patients were in the range 0 to 5 years, 39% in 6 to 11 years, and 50% in 12 to 18 years. Ulcerative colitis was the most frequent diagnosis in EO-IBD and in 6- to 11-year-old group, whereas Crohn's disease was predominant in older children. A classification as IBD-unclassified was more common in the range 0 to 5 years compared with the other groups (P < 0.005). EO Crohn's disease showed a more frequent isolated colonic (P < 0.005) and upper gastrointestinal involvement than later-onset disease. Sixty-two percent of the patients in the 0 to 5 years range had pancolonic ulcerative colitis, compared with 38% of 6 to 11 years (P = 0.02) and 31% of 12-18 years (P = 0.002) range. No statistical difference for family history for IBD was found in the 3-year age groups. Therapies at the diagnosis were similar for all children. However, at latest follow-up, a significantly higher proportion of younger children were under steroids compared with older groups (P < 0.05). Surgical risk did not differ according to age. CONCLUSIONS: EO-IBD exhibits an extensive phenotype and benefit from aggressive treatment strategies, although surgical risk is similar to later-onset disease. A family history for IBD is not common in EO disease.

Effect of thalidomide on clinical remission in children and adolescents with refractory Crohn disease: a randomized clinical trial.

IMPORTANCE: Pediatric-onset Crohn disease is more aggressive than adult-onset disease, has high rates of resistance to existing drugs, and can lead to permanent impairments. Few trials have evaluated new drugs for refractory Crohn disease in children. OBJECTIVE: To determine whether thalidomide is effective in inducing remission in refractory pediatric Crohn disease. DESIGN, SETTING, AND PATIENTS: Multicenter, double-blind, placebo-controlled, randomized clinical trial of 56 children with active Crohn disease despite immunosuppressive treatment, conducted August 2008-September 2012 in 6 pediatric tertiary care centers in Italy. INTERVENTIONS: Thalidomide, 1.5 to 2.5 mg/kg per day, or placebo once daily for 8 weeks. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks. All responders continued to receive thalidomide for an additional minimum 52 weeks. MAIN OUTCOMES AND MEASURES: Primary outcomes were clinical remission at week 8, measured by Pediatric Crohn Disease Activity Index (PCDAI) score and reduction in PCDAI by ≥25% or ≥75% at weeks 4 and 8. Primary outcomes during the open-label follow-up were clinical remission and 75% response. RESULTS: Twenty-eight children were randomized to thalidomide and 26 to placebo. Clinical remission was achieved by significantly more children treated with thalidomide (13/28 [46.4%] vs 3/26 [11.5%]; risk ratio [RR], 4.0 [95% CI, 1.2-12.5]; P = .01; number needed to treat [NNT], 2.86). Responses were not different at 4 weeks, but greater improvement was observed at 8 weeks in the thalidomide group (75% response, 13/28 [46.4%] vs 3/26 [11.5%]; RR, 4.0 [95% CI, 1.2-12.5]; NNT = 2.86; P = .01; and 25% response, 18/28 [64.2%] vs 8/26 [30.8%]; RR, 2.1 [95% CI, 1.1-3.9]; NNT = 2.99; P = .01). Of the nonresponders to placebo who began receiving thalidomide, 11 of 21 (52.4%) subsequently reached remission at week 8 (RR, 4.5 [95% CI, 1.4-14.1]; NNT = 2.45; P = .01). Overall, 31 of 49 children treated with thalidomide (63.3%) achieved clinical remission, and 32 of 49 (65.3%) achieved 75% response. Mean duration of clinical remission in the thalidomide group was 181.1 weeks (95% CI, 144.53-217.76) vs 6.3 weeks (95% CI, 3.51-9.15) in the placebo group (P < .001). Cumulative incidence of severe adverse events was 2.1 per 1000 patient-weeks, with peripheral neuropathy the most frequent severe adverse event. CONCLUSIONS AND RELEVANCE: In children and adolescents with refractory Crohn disease, thalidomide compared with placebo resulted in improved clinical remission at 8 weeks of treatment and longer-term maintenance of remission in an open-label follow-up. These findings require replication to definitively determine clinical utility of this treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00720538.

Endoscopic and histological pitfalls in the diagnosis of celiac disease: A multicentre study assessing the current practice.

BACKGROUND AND AIMS: the diagnosis of celiac disease requires small bowel biopsies to identify the characteristic mucosal changes. The current biopsy practice among endoscopists for celiac disease is in most part unknown. The aim of this study was to compare the different diagnostic policies in various centers in their current practice. METHOD: information from a total of 931 confirmed celiac disease patients was retrospectively obtained retrospectively from nine centers in European and Middle Eastern countries. The number of small-bowel biopsies obtained from the duodenal bulb and the second part of the duodenum was compared among different centers. RESULTS: the most frequent stage of mucosal changes amongst Iranian subjects was Marsh IIIa whereas in the rest of the study population was Marsh IIIc. Marsh I and Marsh II were more prevalent in adults (P < 0.05) and Marsh IIIc was significantly higher in pediatric ages between 1 and 15 (P < 0.05). The most common number of biopsy specimens obtained from Romanian subjects was 1 (52% of cases), followed by 2 for Iranian (56%), 3 for Lithuanian (66.7%) and British patients (65%) and 4 for Italian patients (48.3%). For majority of cases, anemia was the most prevalent symptom (18.7%) followed by malabsorption (10.5%), diarrhea (9.3%) and dyspepsia (8.2%), respectively. CONCLUSIONS: despite the evidence-based recommendations, this study revealed a poor compliance with major guidelines on diagnosis of celiac disease. We emphasize that taking adequate number of duodenal biopsies should be implemented for an accurate diagnosis and also for the exclusion of celiac disease.

The importance of disease prevalence in assessing the diagnostic value of a test: endoscopic markers in celiac disease.

BACKGROUND/AIMS: We evaluated the diagnostic variability and reproducibility of endoscopic signs in two populations with a different pretest likelihood of celiac disease (CD). METHODS: We recruited 289 CD patients (both adults and children) in a multicenter prospective study. Group 1 (high risk) included 111 patients referred for positive serology. Group 2 (low risk) included 178 unselected patients. Mosaic pattern, reduction/loss of Kerckring's folds, scalloping of the valvulae conniventes and a nodular pattern were the endoscopic findings looked for in the duodenum. RESULTS: In group 1, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of endoscopic findings were 100, 84.6, 94.2 and 100% in adults, and 86.8, 9.1, 82.1 and 12.5% in children. In group 2, the sensitivity, specificity, PPV and NPV of endoscopic findings were 33.3, 91.4, 7.7 and 98.5% in adults, and noncalculable, 78.3, 0.0 and 100% in children. Comparing group 1 and group 2, there was a statistically significant difference in sensitivity and PPV in adults, and in specificity, PPV and NPV in children. Concerning the reproducibility of endoscopic findings, a wide variability of κ values was found. CONCLUSION: Endoscopic signs have low reproducibility for CD, and their diagnostic value in selecting patients for multiple intestinal biopsies is unacceptable, especially in populations with low disease prevalence.

Stunting is an independent predictor of mortality in patients with cystic fibrosis.

BACKGROUND & AIMS: Some studies have shown a direct relationship between nutritional status and survival in Cystic Fibrosis (CF) patients. Body wasting, defined as a percentage of the ideal body weight for age, has been shown to be an independent predictor of mortality in CF. With respect to height only two studies were performed and these studies suggested that stunting is an important determinant of survival but both did not adjust statistical analysis for confounding variables. We aimed at determining the association between stunting and risk of mortality in CF patients. METHODS: 393 CF patients older than 6 years of age, 95 deceased, as cases, and 298 live, as controls, were enrolled in a nested case-control study. Stunting was defined by a height percentile < 5th. We performed a multivariate statistical analysis including height percentile and the following possible confounding variables: age, gender, Body Mass Index (BMI), Forced Expiratory Volume in 1 s (FEV1), genotype, pancreatic status, CF-related diabetes, colonization with Pseudomonas aeruginosa and/or Burkholderia cepacia. RESULTS: In the adjusted analyses stunting (OR 2.22 [IC 95%1.10-4.46]), wasting (OR 5.27 [IC 95% 2.66-10.41]), and FEV1 < 40% of predicted (OR 10.60 [IC 95% 5.43-20.67]) resulted the covariates that significantly predict the risk of mortality. CONCLUSIONS: Our study shows, for the first time, that stunting is a significant and independent risk factor for mortality in CF patients, and warrants an intervention of nutritional rehabilitation. Considering that nutritional interventions in stunted patients should be prolonged, are invasive and expensive, and might affect self-esteem and body image, their efficacy should be fully assessed by Randomised Controlled Trials.

Oxidative stress and persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide and different oxygen concentrations.

OBJECTIVES: The aim of this study was to determine the effects of inhaled NO with different oxygen concentrations on the inflammatory cascade in newborns with hypoxic respiratory failure secondary to persistent pulmonary hypertension. METHODS: 60 newborns received iNO and 30 of them received an initial oxygen concentration of 45% (group 1), while the other 30 newborns received an initial oxygen concentration of 80% (group 2). The levels of inflammatory cytokines (IL-6, IL-8, TNF-α) were measured. The clinical outcome was also recorded. RESULTS: The findings show that interleukin concentrations (IL-6, IL-8, TNF-α) were significantly decreased between 0 and 72 hours (p < 0.01) in the newborns exposed to initial oxygen concentration of 45% and significantly increased in the other group. CONCLUSIONS: When inhaled, NO was co-administered with concentration of O(2) <45%, anti-inflammatory responses occurred, in accord with evidence in the published literature. The benefits of iNO on the clinical outcome in the current study demonstrate that inhaled NO in both groups was associated with improved short-term oxygenation.