Efficacy of adalimumab as second-line therapy in a pediatric cohort of crohn’s disease patients who failed infliximab therapy: The Italian society of pediatric gastroenterology, hepatology, and nutrition experience

Background: Adalimumab (Ada) treatment is an available option for pediatric Crohn’s disease (CD) and the published experience as rescue therapy is limited. Objectives: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months. Methods: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively. Results: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3–11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P<0.01) and mean CRP values (mean CRP 5.7 and 2.4 mL/dL, respectively; P<0.01) at the end of follow-up. Steroid-free remission rates, considered as the total number of patients in CR who were not using steroids at the end of this study, were 93%, 95%, and 96% in 44 patients at 6, 12, and 18 months, respectively. No significant differences in growth parameters were detected. In univariate analysis of variables related to Ada efficacy, we found that only a disease duration >2 years was negatively correlated with final PCDAI score (P<0.01). Two serious adverse events were recorded: 1 meningitis and 1 medulloblastoma. Conclusion: Our data confirm Ada efficacy in pediatric patients as second-line biological therapy after infliximab failure. Longer-term prospective data are warranted to define general effectiveness and safety in pediatric CD patients

Prevalence of hypertrophic cardiomyopathy (HCM) in feline population examined by the osservatorio italiano HCM felina

Hypertrophic cardiomyopathy (HCM) is the most common feline inherited cardiac disease and it is a major cause of morbidity and mortality. The Osservatorio Italiano HCM Felina was formed in 2008 by a network of clinicians, geneticists and breedings to monitor and study HCM in Italian cats. Since April 2008, 1308 adult cats, belonging to various breeds, including Maine Coon, Siberian, Norwegian Forest Cat, Ragdoll, Sphynx, British SH, Birmans and others have been prospectively enrolled. Recheck evaluations were performed in 287 cats. Each cat underwent a clinical examination, echocardiography, and blood collection for genetic testing (when appropriate) and storage in the Italian Feline Biobank. The disease status was defined by echocardiography according to established guidelines (left ventricular diastolic wall thickness<5.5mm = HCM negative, =5.5 but < 6mm = HCM equivocal, = 6mm = HCM positive). The prevalence of HCM in the population was 6% (74 cats); equivocal diagnoses were conferred on 4% (57 cats). These prevalences did not differ between breeds. The prevalence of HCM in the Italian feline population was lower compared to those reported by other investigators. Evaluation of data from the entire population demonstrated that left ventricular end-diastolic wall thickness and aortic diameter showed a weak positive correlation with body weight (p< 0.0001, r2<0.12 for all variables), suggesting that weight-dependent limits on wall thickness should be considered in cats as is currently practiced in dogs. The lower prevalence of HCM in Italian cat breeds compared with those examined elsewhere might be explained by different criteria for determining presence or absence of disease, differences in ages at which the subject were examined, or a selection bias by breeders in presenting cats they consider \u201cnormal\u201d

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

Abstract BACKGROUND: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. METHODS: In 1996 an IBD register of disease onset was established on a national scale. RESULTS: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohn's disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996-2003 an increase of IBD incidence from 0.89 to 1.39/10(5) inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. CONCLUSIONS: The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD

Transesophageal Echocardiography as the Sole Guidance for Occlusion of Patent Ductus Arteriosus using a Canine Ductal Occluder in Dogs

Background: Transcatheter occlusion of patent ductus arteriosus (PDA) is usually performed by fluoroscopy alone or together with transesophageal echocardiography (TEE). Transthoracic echocardiography (TTE) guidance has been used for deployment of Amplatz Canine Ductal Occluder (ACDO), but sometimes is limited by suboptimal acoustic windows. Transesophageal echocardiography can overcome such issues and provides higher image resolution at the level of the great vessels. Objectives: To determine if TEE without fluoroscopy could be used to successfully perform ductal occlusion for the treatment of PDA in dogs. Animals: Twenty client-owned dogs with PDA. Methods: A prospective consecutive case series of PDA occlusion was performed using only TEE guidance. Dogs were positioned in right lateral recumbency and the TEE probe was positioned to visualize the descending aorta, PDA, and pulmonary artery. The guide wire, long introducer sheath, and ACDO were imaged by TEE to direct deployment. Results: Ductal occlusion was performed successfully without need for fluoroscopy and without complications in 19 dogs. One dog required a second larger ACDO because of embolization of the first device 18 hours after positioning. Conclusions and Clinical Importance: We have demonstrated that TEE monitoring without concurrent fluoroscopy can guide each step of transcatheter ACDO embolization thereby providing an alternate method of visualization for this procedure. Use of TEE alone can reduce radiation exposure or is an option when fluoroscopy is not available, and, therefore, should be evaluated in a larger case series to better assess procedural failure rates

Myosin-binding protein C DNA variants in domestic cats (A31P, A74T, R820W) and their association with hypertrophic cardiomyopathy. J Vet Intern Med 2013;27:275–285

Background: Two mutations in the MYBPC3 gene have been identified in Maine Coon (MCO) and Ragdoll (RD) cats with hypertrophic cardiomyopathy (HCM). Objective: This study examined the frequency of these mutations and of the A74T polymorphism to describe their worldwide distribution and correlation with echocardiography. Animals: 1855 cats representing 28 breeds and randombred cats worldwide, of which 446 underwent echocardiographic examination. Methods: This is a prospective cross-sectional study. Polymorphisms were genotyped by Illumina VeraCode GoldenGate or by direct sequencing. The disease status was defined by echocardiography according to established guidelines. Odds ratios for the joint probability of having HCM and the alleles were calculated by meta-analysis. Functional analysis was simulated. Results: The MYBPC3 A31P and R820W were restricted to MCO and RD, respectively. Both purebred and randombred cats had HCM and the incidence increased with age. The A74T polymorphism was not associated with any phenotype. HCM was most prevalent in MCO homozygote for the A31P mutation and the penetrance increased with age. The penetrance of the heterozygote genotype was lower (0.08) compared with the P/P genotype (0.58) in MCO. Conclusions and Clinical Importance: A31P mutation occurs frequently in MCO cats. The high incidence of HCM in homozygotes for the mutation supports the causal nature of the A31P mutation. Penetrance is incomplete for heterozygotes at A31P locus, at least at a young age. The A74T variant does not appear to be correlated with HCM

Myosin-binding Protein C DNA variants in domestic cats (A31P, A74T, R820W) and their association with Hypertrophic cardiomyopathy

Background: Two mutations in the MYBPC3 gene have been identified in Maine Coon (MCO) and Ragdoll (RD) cats with hypertrophic cardiomyopathy (HCM). Objective: This study examined the frequency of these mutations and of the A74T polymorphism to describe their worldwide distribution and correlation with echocardiography. Animals: 1855 cats representing 28 breeds and random-bred cats worldwide, of which 446 underwent echocardiographic examination. Methods: This is a prospective cross-sectional study. Polymorphisms were genotyped by Illumina VeraCode GoldenGate or by direct sequencing. The disease status was defined by echocardiography according to established guidelines. Odds ratios for the joint probability of having HCM and the alleles were calculated by meta-analysis. Functional analysis was simulated. Results: The MYBPC3 A31P and R820W were restricted to MCO and RD, respectively. Both purebred and random-bred cats had HCM and the incidence increased with age. The A74T polymorphism was not associated with any phenotype. HCM was most prevalent in MCO homozygote for the A31P mutation and the penetrance increased with age. The penetrance of the heterozygote genotype was lower (0.08) compared with the P/P genotype (0.58) in MCO. Conclusions and Clinical Importance: A31P mutation occurs frequently in MCO cats. The high incidence of HCM in homozygotes for the mutation supports the causal nature of the A31P mutation. Penetrance is incomplete for heterozygotes at A31P locus, at least at a young age. The A74T variant does not appear to be correlated with HCM