Paolo Lionetti | Università degli Studi di Firenze (University of Florence) (original) (raw)

Papers by Paolo Lionetti

Italian Journal of Pediatrics

The aim of our study was to better define the clinical pattern of diencephalic syndrome, a rare b... more The aim of our study was to better define the clinical pattern of diencephalic syndrome, a rare but potentially lethal cause of failure to thrive in infancy. Poor weight gain or weight loss, the characteristic presenting feature, often firstly attributed to gastrointestinal or endocrinological or genetic diseases, is secondary to a malfunctioning hypothalamus, caused by a diencephalic tumor. Due to its unexpected clinical onset, diagnostic delay and misdiagnosis are common. We described a case series of 3 children with diencephalic syndrome admitted at our Hospital, over a 5-year period. Furthermore, a narrative review on all pediatric cases published in the last seventy years was performed. Clinical pattern, timing to diagnosis, neuroimaging, management, and outcome were analyzed. Our three cases are singularly described in all clinical and diagnostic findings. Overall, 100 children were selected; all these cases as well as our children presented with failure to thrive: 96% had bod...

Inflammatory Bowel Diseases, 2021

BackgroundThe aim of the present study was to investigate outcomes of anti-TNF-alpha (ATA) withdr... more BackgroundThe aim of the present study was to investigate outcomes of anti-TNF-alpha (ATA) withdrawal in selected pediatric patients with inflammatory bowel disease who achieved clinical remission and mucosal and histological healing (MH and HH).MethodsA retrospective analysis was performed on children and adolescents affected by Crohn disease (CD) and ulcerative colitis (UC) who were followed up at 2 tertiary referral centers from 2008 through 2018. The main outcome measure was clinical relapse rates after ATA withdrawal.ResultsOne hundred seventy patients received scheduled ATA treatment; 78 patients with CD and 56 patients with UC underwent endoscopic reassessment. We found that MH was achieved by 32 patients with CD (41%) and 30 patients with UC (53.6%); 26 patients with CD (33.3%) and 22 patients with UC (39.3%) achieved HH. The ATA treatment was suspended in 45 patients, 24 affected by CD and 21 by UC, who all achieved concurrently complete MH (Simplified Endoscopic Score for ...

Digestive and Liver Disease, 2021

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Journal of Pediatric Gastroenterology & Nutrition, 2021

Objectives: Adult studies suggest that patients with isolated colonic Crohn disease (L2 CD) exhib... more Objectives: Adult studies suggest that patients with isolated colonic Crohn disease (L2 CD) exhibit unique characteristics differentiating them from patients with ileo-caecal (L1) CD and ulcerative colitis (UC). We aimed to characterize clinical features and outcomes of paediatric patients with L2. Methods: Retrospective data was collected through the Porto Inflammatory Bowel Disease group of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) on Paediatric patients with L2, L1 or UC at different time-points. Outcome measures included time to first flare, hospital admissions, initiation of anti-tumor necrosis factor-alpha (TNFα) drug, stricture and surgery. Results: Three hundred patients were included: 102 L1, 94 L2 and 104 UC. Rates of hematochezia at presentation were 14.7%, 44.7% and 95.2%, while rates of fever were 12.7%, 26.6% and 2.9%, for patients with L1, L2 and UC, respectively (P < 0.001 for all comparisons). Skip lesions were identi...

Paediatric rheumatology, 2019

Background: Autoinflammatory diseases (AID) are a group of hereditary diseases characterised by i... more Background: Autoinflammatory diseases (AID) are a group of hereditary diseases characterised by inflammation periods accompanied with clinical findings such as fever, skin rash, lymphadenopathy, abdominal pain, musculoskeletal symptoms, and with sign of inflammation in the blood. Each disease has own typical clinical findings and they are associated with mutations in specific genes such as in MEFV gene in familial Mediterranean fever (FMF), MVK gene in hyperimmunglobulin D syndrome (HIDS), TNFRSF1A gene in tumor necrosis factor-alpha receptor associated periodic fever syndrome (TRAPS) and NLRP3 gene in cryopyrin associated periodic fever syndrome (CAPS) (1,2). Also in some patients with periodic fever syndrome (PFS), clinical signs of these diseases can be seen but no mutation can be detected in the related genes (3,4). There are also patients exhibit the incomplete phenotype of a disease or overlap signs of more than one AID. The diagnosis of these undifferentiated patients have difficult and may not be possible by a single target gene analysis (5). Screening of the periodic fever syndrome (PFS) panel including various AID genes may be beneficial to define the atypical cases. Molecular genetics has an important role for lead to diagnosis in these patients. Objectives: The aim of this study was to investigate the genotypic diagnosis in patients with non-characteristic PFS findings for any AID. Methods: This is a prospective study and conducted between June 2016 and December 2018. Next-generation sequencing (NGS) analysis was performed by using "Fever and AutoInflammatory Syndrome panel: Panel by Sophia Genetics" including 8 genes (MEFV, MVK, NLRP3, NLRP12, TNFRSF1A, TNFRSF11A, LPIN2 and PSTPIP1) in 30 patients with undifferentiated PFS. Clinical features and genetic results were evaluated together and final diagnoses were determined. Results: Thirty patients included in the study did not have typical clinical features for any of the eight monogenic diseases in the PFS panel. In the result of the genetic screening; disease-causing mutation was found in MEFV gene in 12 patient, in NLRP3 gene in four patient, in NLRP12 gene in two patient and in MVK gene in one patient. Also, genetic variants of uncertain significance (VUS) in different genes were shown in five patient. No mutation was detected in remaining six patient. The final diagnosis was made by both phenotypic and genotypic data. 12 patients were diagnosed with FMF, four were FCAS, two were FCAS2, one was TRAPS and one was HIDS. Patients with negative genetic screening or had mutation as VUS, were followed as undifferentiated PFS. Conclusion: Autoinflammatory diseases may not always be appear with typical clinical findings of related disease. In such patients, target gene sequencing and detection of underlying disease can be challenging. Our study has shown that the NGS analysis may help to determined the diagnosis in patients with non-characteristic PFS findings for any AID.

Inflammatory bowel diseases, Oct 16, 2017

Thalidomide is an effective therapy in children with inflammatory bowel disease refractory to sta... more Thalidomide is an effective therapy in children with inflammatory bowel disease refractory to standard treatments, but thalidomide-induced peripheral neuropathy (TiPN) limits its long-term use. We aimed to investigate the risk factors and the outcome of TiPN in children with inflammatory bowel disease. Within a retrospective multicenter cohort study, we evaluated prevalence and evolution of TiPN. Clinical data and candidate genetic profiles of patients with and without TiPN were compared with detect predisposing factors. One hundred forty-two patients were identified. TiPN was found in 72.5% of patients (38.7% clinical and instrumental alterations, 26.8% exclusive electrophysiological anomalies, and 7.0% exclusive neurological symptoms). Median TiPN-free period of treatment was 16.5 months; percentage of TiPN-free patients was 70.0% and 35.6% at 12 and 24 months of treatment, respectively. The risk of TiPN increased depending on the mean daily dose (50-99 mg/d adjusted hazard ratio ...

Journal of pediatric gastroenterology and nutrition, Jan 3, 2015

Performing well designed and ethical trials in pediatric inflammatory bowel diseases (IBD) is a p... more Performing well designed and ethical trials in pediatric inflammatory bowel diseases (IBD) is a priority to support optimal therapy and to reduce the unacceptable long lag between adult and pediatric drug approval. Recently, clinical trials in children have been incorporating placebo arms into their protocols under conditions that created controversy. Therefore, four organizations (ESPGHAN, ECCO, the Canadian Children IBD Network and the global pediatric IBD network (PIBDnet)) jointly provide a statement on the role of placebo in pediatric IBD trials. Consensus was achieved by 94/100 (94%) voting committees' members that placebo should only be used if there is genuine equipoise between the active treatment and placebo. For example, this may be considered in trials of drugs with new mechanisms of action without existing adult data, especially when proven effective alternatives do not exist outside the trial. Placebo may also be used in situations where it is an 'add-on" ...

Journal of Pediatric Gastroenterology & Nutrition, 2012

Background and Aims: Pediatric ulcerative colitis (UC) shares many features with adult-onset dise... more Background and Aims: Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). Methods: A group of 27 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to ESPGHAN and ECCO members. A list of 23 predefined questions were addressed by working subgroups based on a SR of the literature. Results: A total of 40 formal recommendations and 68 practice points were endorsed with a consensus rate of at least 89% regarding initial evaluation, how to monitor disease activity, the role of endoscopic evaluation, medical and surgical therapy, timing and choice of each medication, the role of combined therapy, and when to stop medications. A management flowchart, based on the Pediatric Ulcerative Colitis Activity Index (PUCAI), is presented. Conclusions: These guidelines provide clinically useful points to guide the management of UC in children. Taken together, the recommendations offer a standardized protocol that allows effective, timely management and

Journal of Crohn's and Colitis, 2012

Poster presentations immunoassay and lab parameters (CRP and WBC), respectively. Sigmoidoscopy wi... more Poster presentations immunoassay and lab parameters (CRP and WBC), respectively. Sigmoidoscopy with histology was performed at baseline, in the event of an acute flare (CAI >4) or at the end of the 12 month period. Endoscopy score (Rachmilewitz) was used for defining mucosal healing. Absence of acute immune cell infiltration, crypt abscess, mucin depletion and breaches in the surface epithelium (Riley Score) was used for defining histological healing. Results: A total of 85 pts (male-female ratio 1:1; age range 20 to 75 years) were monitored for the complete 12-months. A total of 36 pts suffered a flare and 49 pts experienced sustained remission defined by CAI. Median FLA levels were 40 mg/g vs 5 mg/g (p < 0.0001), median CRP levels 0.6 mg/dl vs 0.1 mg/dl (p < 0.001) and median WBC levels 7.6 vs 6.0/nl (p = 0.01) for flare vs. remission, respectively. Of the pts in sustained remission, 44 achieved mucosal healing based on Endoscopy Score 0 1. Median levels (at timepoint 12 month) of pts with mucosal healing and pts with mucosal activity were 5 mg/g vs 37 mg/g for FLA (p = 0.09), 0.2 mg/dl vs 0.1 mg/dl for CRP (p = 0.882) and 5.9 vs 6.0/nl for WBC (p = 0.787), respectively. Of pts in sustained remission, 41 did not show any signs of acute histological activity (Riley Score). Median levels (at timepoint 12 month) of pts without signs and with signs of histological activity were 4.6 mg/g vs 14.4 mg/g for FLA (p = 0.198), 0.2 mg/dl vs 0.1 mg/dl for CRP (p = 0.948) and 6.0 vs 6.0/nl for WBC (p = 0.759), respectively. FLA was the only biomarker to show a median level above cutoff for active disease defined by endoscopy as well as histology for pts in sustained clinical remission. Conclusions: Our results confirm that fecal lactoferrin is a useful biomarker for identifying active UC and for determining patients that achieve mucosal healing.

Current Opinion in Pediatrics, 1995

Inflammatory Bowel Diseases

Background Scarce data have investigated the association between pediatric inflammatory bowel dis... more Background Scarce data have investigated the association between pediatric inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE). We, therefore, aimed to describe the epidemiology and the possible peculiar phenotype and natural history of such an association. Methods Case-control study is based on the Italian Society for Pediatric Gastroenterology (SIGENP) national registry. All children with a combined diagnosis of IBD and EoE were included. The overall prevalence and incidence in 2 periods, 2009 to 2015, and 2016 to 2021, were calculated. Cases were matched with IBD only and EoE only patients in a 1:3:3 ratio. Phenotype and outcomes (courses of steroids, risk of complications, surgery, treatment escalation, and hospitalization) were compared between groups. Results Eleven patients (age 11.2 ± 2.8 years, Males 91%) with EoE-IBD out of 3090 patients with IBD were identified, resulting in an overall prevalence of 0.35% and an incidence of 0.18% for 2009 to 2015 and 0.45...

Nutrients

Scurvy is a well-known clinical condition caused by vitamin C deficiency. Although considered a r... more Scurvy is a well-known clinical condition caused by vitamin C deficiency. Although considered a rare disease in high-income countries, it has been recently increasingly reported in children, especially in those with abnormal dietary habits, mental or physical disabilities. We performed an extensive review of the literature analyzing studies published in the last 20 years focusing on clinical features, differential diagnosis and diagnostic delay. Fifteen articles were selected, collectively reporting a total of 166 children. Because of the wide clinical spectrum (musculoskeletal complaints and/or mucocutaneous lesions or systemic symptoms), scurvy can mimic several conditions, including autoimmune diseases, infections, and neoplasia. In addition, frequent findings such as normal nutritional status, anemia or elevated inflammatory markers may guide clinicians towards the abovementioned misdiagnoses. Scurvy should be considered in patients presenting with musculoskeletal complaints, no...

Nutrients

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Clinica Dietologica, Aug 10, 1991

The human gut ‘‘metagenome’’ is a complex consortium of trillions of microbes, whose collective g... more The human gut ‘‘metagenome’’ is a complex consortium of trillions of microbes, whose collective genomes contain at least 100 times as many genes as our own eukaryote genome. This essential ‘‘organ’’ provides the host with enhanced metabolic capabilities, protection against pathogens, education of the immune system, and modulation of gastrointestinal development. Historically, the microbial ecosystem of the digestive tract was specific for a geographic area, as much as the flora and fauna of an ecosystem are geographically distinct. A clear example of this richness and diversity is that currently in Africa, the microbial composition is very different from that described in the Western world. Globalization of the microbial population of our digestive tracts is due to industrialization and standardization of food chain products that homogenize the microorganisms we ingest. We describe how this relative homogeneity of the microbial composition of Europeans and North Americans could be related to globalization rather than a transcendent tendency of humans to select the same bacteria worldwid

Digestive and Liver Disease, 2020

duction of hospitalizations for new diagnosis (from n = 44 to n = 27) and endoscopic re-evaluatio... more duction of hospitalizations for new diagnosis (from n = 44 to n = 27) and endoscopic re-evaluations (from n = 46 to n = 8). Hospitalization for relapses and surgical procedures remained substantially unchanged. Biologic infusions did not significantly vary [393/2291 (17.1%) vs 368/2291 (16%); p = 0.3]. Telemedicine services for children with IBD were activated in 52.3% of the centres. In 42/2291(1.8%) children immunosuppressive therapies were adapted due to the concurrent COVID-19 pandemic. Conclusion: Due to the several limitations of the lockdown, cares for children with IBD have been kept to minimal standards, giving priorities to the urgencies and to biologics' infusions and implementing telemedicine services.

International Journal of Rheumatic Diseases, 2020

Pediatric rheumatic diseases are often characterized by an evolving phenotype, resulting in diagn... more Pediatric rheumatic diseases are often characterized by an evolving phenotype, resulting in diagnostic dilemma for physicians involved in their management. Although several classification criteria are used in childhood to uniform patients' diagnoses, several conditions share similar clinical features and therefore their classifications may overlap or be ambiguous. This is particularly paradigmatic for the classification of juvenile spondyloarthritis (JSpA), as the currently available criteria do not encompass their complexity. The differential diagnosis of sacroiliitis is often challenging for clinicians and requires considering several conditions, which include infective, neoplastic and rheumatic diseases. We report the case of a 13-year-old boy with an evolving clinical phenotype; its progression shows the wide differential diagnosis required in pediatric rheumatic diseases and emphasizes the issues of the actual classification system.

Journal of Translational Autoimmunity, 2020

Investigation of the fungal communities in animal models of Inflammatory Bowel Diseases (IBD) sho... more Investigation of the fungal communities in animal models of Inflammatory Bowel Diseases (IBD) showed a controversial role of Saccharomyces cerevisiae and Candida spp. In health and disease. These conflicting observations could be ascribed to immunogenic differences among co-specific strains. To assess the relevance of intrastrains differences on yeast immunogenicity and impact on the microbiota, we screened S. cerevisiae and Candida spp. Strains isolated from fecal samples of IBD patients. We compared the cytokine profiles, obtained upon stimulation of Peripheral Blood Mononuclear Cells (PBMCs) and Dendritic Cells with different yeast strains, and evaluated the relationship between strain's cell wall sugar amount and immune response. Moreover, the gut microbiota composition was explored in relation to fungal isolation from fecal samples by metabarcoding analysis. The comparison of cytokine profiles showed strain dependent rather than species-dependent differences in immune responses. Differences in immunogenicity correlated with the cell wall composition of S. cerevisiae intestinal strains. Stimulation of human healthy PBMCs with different strains showed a pro-inflammatory IL-6 response counterbalanced by IL-10 production. Interestingly, Crohn's (CD) patients responded differently to "self" and "non-self" strains, eliciting pure Th1 or Th17 cytokine patterns. The differences observed in vitro were recapitulated in vivo, where different strains contributed in dramatically different ways to local epithelial activity and to the inflammation of wild type and Interleukin-deficient mice. Furthermore, we observed that the gut microbiota profiles significantly differentiated according to the presence of Saccharomyces or Candida spp. or the absence of fungal isolates in fecal samples. Our results show the importance to deepen metagenomics and immunophenotyping analyses to the strain level, to elucidate the role of fungal and bacterial communities in health and disease.

Journal of Crohn's and Colitis, 2019

IntroductionThe ability to predict risk for poor outcomes in Crohn’s disease [CD] would enable ea... more IntroductionThe ability to predict risk for poor outcomes in Crohn’s disease [CD] would enable early treatment intensification. We aimed to identify children with CD with complications at baseline and throughout the study period who are at risk for surgery 2 years from diagnosis.MethodsNewly diagnosed children with CD were enrolled into a prospective, multicentre inception cohort. Disease characteristics and serological markers were obtained at baseline and week 12 thereafter. Outcome data including disease activity, therapies, complications and need for surgery were collected until the end of 104 weeks. A chi-square automatic interaction detection [CHAID] algorithm was used to develop a prediction model for early surgery.ResultsOf 285 children enrolled, 31 [10.9%] required surgery within 2 years. Multivariate analysis identified stricturing disease at baseline (odds ratio [OR] 5.26, 95% confidence interval [CI] 2.02–13.67 [p = 0.001]), and Paediatric Crohn’s Disease Activity Index ...

Italian Journal of Pediatrics

The aim of our study was to better define the clinical pattern of diencephalic syndrome, a rare b... more The aim of our study was to better define the clinical pattern of diencephalic syndrome, a rare but potentially lethal cause of failure to thrive in infancy. Poor weight gain or weight loss, the characteristic presenting feature, often firstly attributed to gastrointestinal or endocrinological or genetic diseases, is secondary to a malfunctioning hypothalamus, caused by a diencephalic tumor. Due to its unexpected clinical onset, diagnostic delay and misdiagnosis are common. We described a case series of 3 children with diencephalic syndrome admitted at our Hospital, over a 5-year period. Furthermore, a narrative review on all pediatric cases published in the last seventy years was performed. Clinical pattern, timing to diagnosis, neuroimaging, management, and outcome were analyzed. Our three cases are singularly described in all clinical and diagnostic findings. Overall, 100 children were selected; all these cases as well as our children presented with failure to thrive: 96% had bod...

Inflammatory Bowel Diseases, 2021

BackgroundThe aim of the present study was to investigate outcomes of anti-TNF-alpha (ATA) withdr... more BackgroundThe aim of the present study was to investigate outcomes of anti-TNF-alpha (ATA) withdrawal in selected pediatric patients with inflammatory bowel disease who achieved clinical remission and mucosal and histological healing (MH and HH).MethodsA retrospective analysis was performed on children and adolescents affected by Crohn disease (CD) and ulcerative colitis (UC) who were followed up at 2 tertiary referral centers from 2008 through 2018. The main outcome measure was clinical relapse rates after ATA withdrawal.ResultsOne hundred seventy patients received scheduled ATA treatment; 78 patients with CD and 56 patients with UC underwent endoscopic reassessment. We found that MH was achieved by 32 patients with CD (41%) and 30 patients with UC (53.6%); 26 patients with CD (33.3%) and 22 patients with UC (39.3%) achieved HH. The ATA treatment was suspended in 45 patients, 24 affected by CD and 21 by UC, who all achieved concurrently complete MH (Simplified Endoscopic Score for ...

Digestive and Liver Disease, 2021

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Journal of Pediatric Gastroenterology & Nutrition, 2021

Objectives: Adult studies suggest that patients with isolated colonic Crohn disease (L2 CD) exhib... more Objectives: Adult studies suggest that patients with isolated colonic Crohn disease (L2 CD) exhibit unique characteristics differentiating them from patients with ileo-caecal (L1) CD and ulcerative colitis (UC). We aimed to characterize clinical features and outcomes of paediatric patients with L2. Methods: Retrospective data was collected through the Porto Inflammatory Bowel Disease group of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) on Paediatric patients with L2, L1 or UC at different time-points. Outcome measures included time to first flare, hospital admissions, initiation of anti-tumor necrosis factor-alpha (TNFα) drug, stricture and surgery. Results: Three hundred patients were included: 102 L1, 94 L2 and 104 UC. Rates of hematochezia at presentation were 14.7%, 44.7% and 95.2%, while rates of fever were 12.7%, 26.6% and 2.9%, for patients with L1, L2 and UC, respectively (P < 0.001 for all comparisons). Skip lesions were identi...

Paediatric rheumatology, 2019

Background: Autoinflammatory diseases (AID) are a group of hereditary diseases characterised by i... more Background: Autoinflammatory diseases (AID) are a group of hereditary diseases characterised by inflammation periods accompanied with clinical findings such as fever, skin rash, lymphadenopathy, abdominal pain, musculoskeletal symptoms, and with sign of inflammation in the blood. Each disease has own typical clinical findings and they are associated with mutations in specific genes such as in MEFV gene in familial Mediterranean fever (FMF), MVK gene in hyperimmunglobulin D syndrome (HIDS), TNFRSF1A gene in tumor necrosis factor-alpha receptor associated periodic fever syndrome (TRAPS) and NLRP3 gene in cryopyrin associated periodic fever syndrome (CAPS) (1,2). Also in some patients with periodic fever syndrome (PFS), clinical signs of these diseases can be seen but no mutation can be detected in the related genes (3,4). There are also patients exhibit the incomplete phenotype of a disease or overlap signs of more than one AID. The diagnosis of these undifferentiated patients have difficult and may not be possible by a single target gene analysis (5). Screening of the periodic fever syndrome (PFS) panel including various AID genes may be beneficial to define the atypical cases. Molecular genetics has an important role for lead to diagnosis in these patients. Objectives: The aim of this study was to investigate the genotypic diagnosis in patients with non-characteristic PFS findings for any AID. Methods: This is a prospective study and conducted between June 2016 and December 2018. Next-generation sequencing (NGS) analysis was performed by using "Fever and AutoInflammatory Syndrome panel: Panel by Sophia Genetics" including 8 genes (MEFV, MVK, NLRP3, NLRP12, TNFRSF1A, TNFRSF11A, LPIN2 and PSTPIP1) in 30 patients with undifferentiated PFS. Clinical features and genetic results were evaluated together and final diagnoses were determined. Results: Thirty patients included in the study did not have typical clinical features for any of the eight monogenic diseases in the PFS panel. In the result of the genetic screening; disease-causing mutation was found in MEFV gene in 12 patient, in NLRP3 gene in four patient, in NLRP12 gene in two patient and in MVK gene in one patient. Also, genetic variants of uncertain significance (VUS) in different genes were shown in five patient. No mutation was detected in remaining six patient. The final diagnosis was made by both phenotypic and genotypic data. 12 patients were diagnosed with FMF, four were FCAS, two were FCAS2, one was TRAPS and one was HIDS. Patients with negative genetic screening or had mutation as VUS, were followed as undifferentiated PFS. Conclusion: Autoinflammatory diseases may not always be appear with typical clinical findings of related disease. In such patients, target gene sequencing and detection of underlying disease can be challenging. Our study has shown that the NGS analysis may help to determined the diagnosis in patients with non-characteristic PFS findings for any AID.

Inflammatory bowel diseases, Oct 16, 2017

Thalidomide is an effective therapy in children with inflammatory bowel disease refractory to sta... more Thalidomide is an effective therapy in children with inflammatory bowel disease refractory to standard treatments, but thalidomide-induced peripheral neuropathy (TiPN) limits its long-term use. We aimed to investigate the risk factors and the outcome of TiPN in children with inflammatory bowel disease. Within a retrospective multicenter cohort study, we evaluated prevalence and evolution of TiPN. Clinical data and candidate genetic profiles of patients with and without TiPN were compared with detect predisposing factors. One hundred forty-two patients were identified. TiPN was found in 72.5% of patients (38.7% clinical and instrumental alterations, 26.8% exclusive electrophysiological anomalies, and 7.0% exclusive neurological symptoms). Median TiPN-free period of treatment was 16.5 months; percentage of TiPN-free patients was 70.0% and 35.6% at 12 and 24 months of treatment, respectively. The risk of TiPN increased depending on the mean daily dose (50-99 mg/d adjusted hazard ratio ...

Journal of pediatric gastroenterology and nutrition, Jan 3, 2015

Performing well designed and ethical trials in pediatric inflammatory bowel diseases (IBD) is a p... more Performing well designed and ethical trials in pediatric inflammatory bowel diseases (IBD) is a priority to support optimal therapy and to reduce the unacceptable long lag between adult and pediatric drug approval. Recently, clinical trials in children have been incorporating placebo arms into their protocols under conditions that created controversy. Therefore, four organizations (ESPGHAN, ECCO, the Canadian Children IBD Network and the global pediatric IBD network (PIBDnet)) jointly provide a statement on the role of placebo in pediatric IBD trials. Consensus was achieved by 94/100 (94%) voting committees' members that placebo should only be used if there is genuine equipoise between the active treatment and placebo. For example, this may be considered in trials of drugs with new mechanisms of action without existing adult data, especially when proven effective alternatives do not exist outside the trial. Placebo may also be used in situations where it is an 'add-on" ...

Journal of Pediatric Gastroenterology & Nutrition, 2012

Background and Aims: Pediatric ulcerative colitis (UC) shares many features with adult-onset dise... more Background and Aims: Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). Methods: A group of 27 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to ESPGHAN and ECCO members. A list of 23 predefined questions were addressed by working subgroups based on a SR of the literature. Results: A total of 40 formal recommendations and 68 practice points were endorsed with a consensus rate of at least 89% regarding initial evaluation, how to monitor disease activity, the role of endoscopic evaluation, medical and surgical therapy, timing and choice of each medication, the role of combined therapy, and when to stop medications. A management flowchart, based on the Pediatric Ulcerative Colitis Activity Index (PUCAI), is presented. Conclusions: These guidelines provide clinically useful points to guide the management of UC in children. Taken together, the recommendations offer a standardized protocol that allows effective, timely management and

Journal of Crohn's and Colitis, 2012

Poster presentations immunoassay and lab parameters (CRP and WBC), respectively. Sigmoidoscopy wi... more Poster presentations immunoassay and lab parameters (CRP and WBC), respectively. Sigmoidoscopy with histology was performed at baseline, in the event of an acute flare (CAI >4) or at the end of the 12 month period. Endoscopy score (Rachmilewitz) was used for defining mucosal healing. Absence of acute immune cell infiltration, crypt abscess, mucin depletion and breaches in the surface epithelium (Riley Score) was used for defining histological healing. Results: A total of 85 pts (male-female ratio 1:1; age range 20 to 75 years) were monitored for the complete 12-months. A total of 36 pts suffered a flare and 49 pts experienced sustained remission defined by CAI. Median FLA levels were 40 mg/g vs 5 mg/g (p < 0.0001), median CRP levels 0.6 mg/dl vs 0.1 mg/dl (p < 0.001) and median WBC levels 7.6 vs 6.0/nl (p = 0.01) for flare vs. remission, respectively. Of the pts in sustained remission, 44 achieved mucosal healing based on Endoscopy Score 0 1. Median levels (at timepoint 12 month) of pts with mucosal healing and pts with mucosal activity were 5 mg/g vs 37 mg/g for FLA (p = 0.09), 0.2 mg/dl vs 0.1 mg/dl for CRP (p = 0.882) and 5.9 vs 6.0/nl for WBC (p = 0.787), respectively. Of pts in sustained remission, 41 did not show any signs of acute histological activity (Riley Score). Median levels (at timepoint 12 month) of pts without signs and with signs of histological activity were 4.6 mg/g vs 14.4 mg/g for FLA (p = 0.198), 0.2 mg/dl vs 0.1 mg/dl for CRP (p = 0.948) and 6.0 vs 6.0/nl for WBC (p = 0.759), respectively. FLA was the only biomarker to show a median level above cutoff for active disease defined by endoscopy as well as histology for pts in sustained clinical remission. Conclusions: Our results confirm that fecal lactoferrin is a useful biomarker for identifying active UC and for determining patients that achieve mucosal healing.

Current Opinion in Pediatrics, 1995

Inflammatory Bowel Diseases

Background Scarce data have investigated the association between pediatric inflammatory bowel dis... more Background Scarce data have investigated the association between pediatric inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE). We, therefore, aimed to describe the epidemiology and the possible peculiar phenotype and natural history of such an association. Methods Case-control study is based on the Italian Society for Pediatric Gastroenterology (SIGENP) national registry. All children with a combined diagnosis of IBD and EoE were included. The overall prevalence and incidence in 2 periods, 2009 to 2015, and 2016 to 2021, were calculated. Cases were matched with IBD only and EoE only patients in a 1:3:3 ratio. Phenotype and outcomes (courses of steroids, risk of complications, surgery, treatment escalation, and hospitalization) were compared between groups. Results Eleven patients (age 11.2 ± 2.8 years, Males 91%) with EoE-IBD out of 3090 patients with IBD were identified, resulting in an overall prevalence of 0.35% and an incidence of 0.18% for 2009 to 2015 and 0.45...

Nutrients

Scurvy is a well-known clinical condition caused by vitamin C deficiency. Although considered a r... more Scurvy is a well-known clinical condition caused by vitamin C deficiency. Although considered a rare disease in high-income countries, it has been recently increasingly reported in children, especially in those with abnormal dietary habits, mental or physical disabilities. We performed an extensive review of the literature analyzing studies published in the last 20 years focusing on clinical features, differential diagnosis and diagnostic delay. Fifteen articles were selected, collectively reporting a total of 166 children. Because of the wide clinical spectrum (musculoskeletal complaints and/or mucocutaneous lesions or systemic symptoms), scurvy can mimic several conditions, including autoimmune diseases, infections, and neoplasia. In addition, frequent findings such as normal nutritional status, anemia or elevated inflammatory markers may guide clinicians towards the abovementioned misdiagnoses. Scurvy should be considered in patients presenting with musculoskeletal complaints, no...

Nutrients

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Clinica Dietologica, Aug 10, 1991

The human gut ‘‘metagenome’’ is a complex consortium of trillions of microbes, whose collective g... more The human gut ‘‘metagenome’’ is a complex consortium of trillions of microbes, whose collective genomes contain at least 100 times as many genes as our own eukaryote genome. This essential ‘‘organ’’ provides the host with enhanced metabolic capabilities, protection against pathogens, education of the immune system, and modulation of gastrointestinal development. Historically, the microbial ecosystem of the digestive tract was specific for a geographic area, as much as the flora and fauna of an ecosystem are geographically distinct. A clear example of this richness and diversity is that currently in Africa, the microbial composition is very different from that described in the Western world. Globalization of the microbial population of our digestive tracts is due to industrialization and standardization of food chain products that homogenize the microorganisms we ingest. We describe how this relative homogeneity of the microbial composition of Europeans and North Americans could be related to globalization rather than a transcendent tendency of humans to select the same bacteria worldwid

Digestive and Liver Disease, 2020

duction of hospitalizations for new diagnosis (from n = 44 to n = 27) and endoscopic re-evaluatio... more duction of hospitalizations for new diagnosis (from n = 44 to n = 27) and endoscopic re-evaluations (from n = 46 to n = 8). Hospitalization for relapses and surgical procedures remained substantially unchanged. Biologic infusions did not significantly vary [393/2291 (17.1%) vs 368/2291 (16%); p = 0.3]. Telemedicine services for children with IBD were activated in 52.3% of the centres. In 42/2291(1.8%) children immunosuppressive therapies were adapted due to the concurrent COVID-19 pandemic. Conclusion: Due to the several limitations of the lockdown, cares for children with IBD have been kept to minimal standards, giving priorities to the urgencies and to biologics' infusions and implementing telemedicine services.

International Journal of Rheumatic Diseases, 2020

Pediatric rheumatic diseases are often characterized by an evolving phenotype, resulting in diagn... more Pediatric rheumatic diseases are often characterized by an evolving phenotype, resulting in diagnostic dilemma for physicians involved in their management. Although several classification criteria are used in childhood to uniform patients' diagnoses, several conditions share similar clinical features and therefore their classifications may overlap or be ambiguous. This is particularly paradigmatic for the classification of juvenile spondyloarthritis (JSpA), as the currently available criteria do not encompass their complexity. The differential diagnosis of sacroiliitis is often challenging for clinicians and requires considering several conditions, which include infective, neoplastic and rheumatic diseases. We report the case of a 13-year-old boy with an evolving clinical phenotype; its progression shows the wide differential diagnosis required in pediatric rheumatic diseases and emphasizes the issues of the actual classification system.

Journal of Translational Autoimmunity, 2020

Investigation of the fungal communities in animal models of Inflammatory Bowel Diseases (IBD) sho... more Investigation of the fungal communities in animal models of Inflammatory Bowel Diseases (IBD) showed a controversial role of Saccharomyces cerevisiae and Candida spp. In health and disease. These conflicting observations could be ascribed to immunogenic differences among co-specific strains. To assess the relevance of intrastrains differences on yeast immunogenicity and impact on the microbiota, we screened S. cerevisiae and Candida spp. Strains isolated from fecal samples of IBD patients. We compared the cytokine profiles, obtained upon stimulation of Peripheral Blood Mononuclear Cells (PBMCs) and Dendritic Cells with different yeast strains, and evaluated the relationship between strain's cell wall sugar amount and immune response. Moreover, the gut microbiota composition was explored in relation to fungal isolation from fecal samples by metabarcoding analysis. The comparison of cytokine profiles showed strain dependent rather than species-dependent differences in immune responses. Differences in immunogenicity correlated with the cell wall composition of S. cerevisiae intestinal strains. Stimulation of human healthy PBMCs with different strains showed a pro-inflammatory IL-6 response counterbalanced by IL-10 production. Interestingly, Crohn's (CD) patients responded differently to "self" and "non-self" strains, eliciting pure Th1 or Th17 cytokine patterns. The differences observed in vitro were recapitulated in vivo, where different strains contributed in dramatically different ways to local epithelial activity and to the inflammation of wild type and Interleukin-deficient mice. Furthermore, we observed that the gut microbiota profiles significantly differentiated according to the presence of Saccharomyces or Candida spp. or the absence of fungal isolates in fecal samples. Our results show the importance to deepen metagenomics and immunophenotyping analyses to the strain level, to elucidate the role of fungal and bacterial communities in health and disease.

Journal of Crohn's and Colitis, 2019

IntroductionThe ability to predict risk for poor outcomes in Crohn’s disease [CD] would enable ea... more IntroductionThe ability to predict risk for poor outcomes in Crohn’s disease [CD] would enable early treatment intensification. We aimed to identify children with CD with complications at baseline and throughout the study period who are at risk for surgery 2 years from diagnosis.MethodsNewly diagnosed children with CD were enrolled into a prospective, multicentre inception cohort. Disease characteristics and serological markers were obtained at baseline and week 12 thereafter. Outcome data including disease activity, therapies, complications and need for surgery were collected until the end of 104 weeks. A chi-square automatic interaction detection [CHAID] algorithm was used to develop a prediction model for early surgery.ResultsOf 285 children enrolled, 31 [10.9%] required surgery within 2 years. Multivariate analysis identified stricturing disease at baseline (odds ratio [OR] 5.26, 95% confidence interval [CI] 2.02–13.67 [p = 0.001]), and Paediatric Crohn’s Disease Activity Index ...