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The occurrence of thrombotic events in adult patients with inflammatory bowel disease (IBD) is linked to multiple interactions between hereditary and acquired risk factors. There are few published data concerning children with iBD. The aim of this study was to investigate the presence of thromboembolic risk factors also in children with iBD.We enrolled three groups of children: one with Crohn disease (cD), one with ulcerative colitis (Uc), and a control group of healthy subjects. For all the participants the potential thromboembolic risk was evaluated clinically and with laboratory tests.We studied: 30 children (25.6%) with CD, 28 (23.9%) with UC, and 59 (50.4%) healthy control subjects. Regarding Pediatric Crohn Disease Activity Index, no significant differences between thromboembolic risk factors and disease activity were detected. Instead, in the patients with UC, stratified with the Pediatric Ulcerative Colitis Activity Index, there was a statistically significant difference in serum fibrinogen levels between patients with mild and moderate/severe disease [3.8 (3.2-4.5) g/L vs 5.7 (4.8-6.2) g/L, P 0.0032]. serum homocysteine levels were lower in healthy controls than in CD (P = 0.176) and UC (P = 0.026). An increased level ofhomocysteine in UC with a homozygous mutation in the methylene tetrahydrofolate reductase C677T gene was also observed.Our study showed that children with IBD have clinical features, acquired and congenital factors that can increase thrombotic risk, similarly to adults.

The COVID-19 pandemic could be a threat for the health status of children with a chronic condition. The present study aimed to explore parents’ and children’s psychological adjustment during the current pandemic, pursuing a triple objective: to compare the psychological adjustment of parents of children with pediatric rheumatic diseases (PRDs) and parents of healthy children; to analyze children’s psychological symptoms (emotional problems and hyperactivity) before and during the COVID-19 pandemic, and with or without a PRDs diagnosis; to explore the associations of children’s emotional problems and hyperactivity with parents’ psychological adjustment, parent–child interactions and belonging or not to families with PRDs. This cross-sectional study involved 56 parents of children with PRDs and 53 parents of healthy children. Self-report questionnaires about parents’ depression, anxiety, parenting stress, and children’s emotional symptoms and hyperactivity-inattention were administered. No differences were detected on psychological adjustment between parents of children with PRDs and parents of healthy children. Parents of children with PRDs reported statistically significant higher levels of children’s emotional problems and hyperactivity before the pandemic, compared to parents of healthy children; during COVID-19 pandemic, emotional symptoms increased for both groups, while hyperactivity-inattention symptoms increased only in the group of healthy children. Children’s emotional difficulties were associated with higher levels of parental anxiety, worse parent–child interaction and having PRDs; children’s hyperactivity symptoms were related to parent–child difficult interaction and higher levels of parental depression. Findings suggest the importance to target the children in relation to their parents, when approaching the psychological aspects of PRDs.

Background: actual literature suggests that children of methylmalonic acidemia patients are mostly healthy, but data are only partial, especially regarding long-term outcome. Therefore, our aim was to evaluate the possible long-term neurological effects of fetal exposure to high levels of methylmalonic acid in a child of a renal transplant recipient. Methods: we retrospectively evaluated the clinical and neurological records of a girl whose mother is a kidney transplant recipient affected by methylmalonic acidemia. Subsequently, we compared our results with the ones already published. Results: the girl’s weight and stature were within the normal range in the first years of life but, starting from 4 years of age, she became progressively overweight. Regarding the neurodevelopment aspects, for the first time we performed a complete and seriated neuropsychological evaluation, highlighting a mild but significant weakness in the verbal domain, with a worsening trend at three-year revaluation. Conclusions: since children of MMA patients are exposed to methylmalonic acid, the efforts of the physicians caring for these children should be directed on careful evaluation of growth, prevention of obesity and regular neurological examination together with structured neuropsychological tests to achieve a better insight in possible complications of pregnancy in patients suffering from this condition.

Background: IBD management has been significantly affected during the COVID-19 lockdown with potential clinical issues. Aims: The aim of this study was to analyse the impact of COVID-19 pandemic on the Italian paediatric IBD cohort. Methods: This was a multicentre, retrospective, cohort investigation including 21 different Italian IBD referral centres. An electronic data collection was performed among the participating centres including: clinical characteristics of IBD patients, number of COVID-19 cases and clinical outcomes, disease management during the lockdown and the previous 9 weeks. Results: 2291 children affected by IBD were enrolled. We experienced a significant reduction of the hospital admissions [604/2291 (26.3%) vs 1281/2291 (55.9%); p < 0.001]. More specifically, we observed a reduction 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.

Objectives To perform a comprehensive clinic, laboratory, and instrumental evaluation of children affected by coronavirus disease (COVID‐19). Methods Children with a positive result of nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) underwent laboratory tests, anal and conjunctival swab, electrocardiography, lung, abdomen, and cardiac ultrasound. Twenty‐four‐hour ambulatory blood pressure monitoring was performed if abnormal basal blood pressure. Patients were followed‐up for 6 months. Results Three hundred and sixteen children were evaluated; 15 were finally included. Confirmed family member SARS‐CoV‐2 infection was present in all. Twenty‐seven percent were asymptomatic. Anal and conjunctival swabs tests resulted negative in all. Patients with lower body mass index (BMI) presented significantly higher viral loads. Main laboratory abnormalities were: lactate dehydrogenase increasing (73%), low vitamin D levels (87%), hematuria (33%), proteinuria (26%), renal hyperfiltration (33%), and hypofiltration (13%). Two of the patients with hyperfiltration exhibited high blood pressure levels at diagnosis, and persistence of prehypertension at 6‐month follow‐up. No abnormalities were seen at ultrasound, excepting for one patient who exhibited B‐lines at lung sonography. Immunoglobulin G seroconversion was observed in all at 1‐month. Conclusions Our study confirm that intra‐family transmission is important. The significant higher viral loads recorded among patients with lower BMI, together with low vitamin D levels, support the impact of nutritional status on immune system. Renal involvement is frequent even among children with mild COVID‐19, therefore prompt evaluation and identification of patients with reduced renal function reserve would allow a better stratification and management of patients. Seroconversion occurs also in asymptomatic children, with no differences in antibodies titer according to age, sex and clinical manifestations.

This cohort study examines whether the use of surgical face masks among children was associated with changes in respiratory function or signs of respiratory distress., Key Points Question Are surgical masks associated with episodes of oxygen desaturation or respiratory distress among children? Findings In this cohort study of 47 infants and young children in Italy, wearing surgical face masks for 30 minutes was not associated with changes in respiratory parameters or clinical signs of respiratory distress. Meaning These findings suggest that the use of surgical masks among children may be promoted during the coronavirus disease 2019 pandemic, especially in view of the reopening of schools., Importance Face masks have been associated with effective prevention of diffusion of viruses via droplets. However, the use of face masks among children, especially those aged younger than 3 years, is debated, and the US Centers for Disease Control and American Academy of Physicians recommend the use of face mask only among individuals aged 3 years or older. Objective To examine whether the use of surgical facial masks among children is associated with episodes of oxygen desaturation or respiratory distress. Design, Setting, and Participants This cohort study was conducted from May through June 2020 in a secondary-level hospital pediatric unit in Italy. Included participants were 47 healthy children divided by age (ie, group A, aged ≤24 months, and group B, aged >24 months to ≤144 months). Data were analyzed from May through June 2020. Interventions All participants were monitored every 15 minutes for changes in respiratory parameters for the first 30 minutes while not wearing a surgical face mask and for the next 30 minutes while wearing a face mask. Children aged 24 months and older then participated in a walking test for 12 minutes. Main Outcomes and Measures Changes in respiratory parameters during the use of surgical masks were evaluated. Results Among 47 children, 22 children (46.8%) were aged 24 months or younger (ie, group A), with 11 boys (50.0%) and median (interquartile range [IQR]) age 12.5 (10.0-17.5) months, and 25 children (53.2%) were aged older than 24 months to 144 months or younger, with 13 boys (52.0%) and median (IQR) age 100.0 (72.0-120.0) months. During the first 60 minutes of evaluation in the 2 groups, there was no significant change in group A in median (IQR) partial pressure of end-tidal carbon dioxide (Petco2; 33.0 [32.0-34.0] mm Hg; P for Kruskal Wallis = .59), oxygen saturation (Sao2; 98.0% [97.0%-99.0%]; P for Kruskal Wallis = .61), pulse rate (PR; 130.0 [115.0-140.0] pulsations/min; P for Kruskal Wallis = .99), or respiratory rate (RR; 30.0 [28.0-33.0] breaths/min; P for Kruskal Wallis = .69) or for group B in median (IQR) Petco2 (36.0 [34.0-38.0] mm Hg; P for Kruskal Wallis = .97), Sao2 (98.0% [97.0%-98.0%]; P for Kruskal Wallis = .52), PR (96.0 [84.0-104.5] pulsations/min; P for Kruskal Wallis test = .48), or RR (22.0 [20.0-25.0] breaths/min; P for Kruskal Wallis = .55). After the group B walking test, compared with before the walking test, there was a significant increase in median (IQR) PR (96.0 [84.0-104.5] pulsations/min vs 105.0 [100.0-115.0] pulsations/min; P

Objective To assess whether use of an N95 mask by children is associated with episodes of desaturation or respiratory distress. Study design Twenty-two healthy children were assigned at random to 1 of 2 groups: one group wearing N95 masks without an exhalation valve and the other group wearing N95 masks with an exhalation valve. We tracked changes in partial pressure of end-tidal carbon dioxide (PETCO2), oxygen saturation, pulse rate, and respiratory rate over 72 minutes of mask use. All subjects were monitored every 15 minutes, the first 30 minutes while not wearing a mask and the next 30 minutes while wearing a mask. They then performed a 12-minute walking test. Results The children did not experience a statistically significant change in oxygen saturation or pulse rate during the study. There were significant increases in respiratory rate and PETCO2 in the children wearing an N95 mask without an exhalation valve, whereas these increases were seen in the children wearing a mask with an exhalation valve only after the walking test. Conclusions The use of an N95 mask could potentially cause breathing difficulties in children if the mask does not have an exhalation valve, particularly during a physical activity. We believe that wearing a surgical mask may be more appropriate for children.

In response to the current COVID-19 pandemic, universal face masking represents one of the most important strategies to limit the spread of infection. However, their use in children is still highly debated (Esposito and Principi, 2020; Esposito et al., 2020) and there are few data (Lubrano et al., 2021a, 2021b) describing their possible effects on respiratory function in children. A dataset in this paper presents a comparison of the data related to the effects on respiratory function of children wearing a filtering facepiece 2 (N95 mask) with or without exhalation valve. 22 healthy children were randomly assigned to two groups, both groups wearing an N95 mask: one without an exhalation valve (group A), another with an exhalation valve (group B). Children were subjected to a 72 min test: the first 30 min without mask, then 30 min wearing face mask while practiced their usual play activity; finally, 12 min, with face mask in place, while they walked as in a walking test. They were monitored through to microstream capnography system (Rad-97TM with Nomo-Line Capnography, Masimo, Irvine, CA, USA) to log oxygen saturation (SpO2) and respiratory rate (RR). We use the Wilcoxon test to analyzed the differences between the parameters recorded during the study in group A and B. Data analysis was performed using JMP14.3.0 program for Mac by SAS Institute inc.

Since the outbreak of SARS-CoV-2 among the population has occurred quite recently, there is a lack of evidence on the long-term duration of antibody response, especially in children. It is therefore crucial to clarify this aspect, considering its implications in the development of successful surveillance strategies, therapies, and vaccinations. The aim of this study was to assess the antibody response in a children group after SARS-CoV-2 infection, and to compare it with that of their parents affected by SARS-CoV-2 infection. We enrolled 12 children and their parents, both groups being affected by COVID-19 in April 2020. In the children’s group, we collected real-time RT-PCR cycle threshold (Ct) values and gene characterization of first nasal-throat swab at the time of diagnosis (T0); 30 days after the diagnosis (T30), we performed blood tests to detect anti-SARS-CoV-2 IgM and IgG. Finally, 180 days after the diagnosis (T180), we measured anti-SARS-CoV-2 IgG in both children and parents. In children, antibody levels declined significantly at 180 days (T180) after first measurement (T30). There were no significant differences in IgG level related to age, sex, and clinical manifestations. We found a significant correlation between IgG titers at T30 and Ct value of gene N. Children showed a lower level of antibodies against SARS-CoV-2 at T180 compared to their parents.Conclusion: Antibody responses in children waned 180 days after SARS-CoV-2 infection, and at the same time, their parents showed a different antibody response to the virus. These results highlight that serological tests should be used with caution in surveillance strategies among the general population. What is known:• Currently is not known how long antibody response will be maintained or if it protects from reinfection.• Recent reports in adults suggest that antibodies to SARS-CoV-2 declined several months after infection, but data are missing in pediatric age. What is new:• We showed that antibody responses to SARS-CoV-2 wane several months after infection also in children with quantitative differences in antibody levels between children and adults.• In this context, serological tests should be used with caution in surveillance strategies.

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2, spreading in Italy during the first months of 2020, abruptly changed the way of practicing medicine in this country. As a consequence of the lockdown, the diagnostic and therapeutic management of paediatric chronic conditions, such as inflammatory bowel disease (IBD) has been affected. During the peak of COVID-19 pandemic, elective visits, endoscopies and infusions have been postponed, with potential clinical and psychological impact on disease course and a high likelihood of increasing waiting lists. While slowly moving back towards normality, clinicians need to recognize the best ways to care for patients with IBD, carefully avoiding risk factors for new potential epidemic outbreaks. In this uncertain scenario until the development and spread of COVID-19 vaccine, it is necessary to continue to operate with caution. Hereby we provide useful indications for a safer and gradual restarting of routine clinical activities after COVID-19 peak in Italy.

Objectives We aimed to identify early noninvasive predictors of clinical and endoscopic remission in children with Crohn disease (CD) under infliximab (IFX). Methods Prospective observational study conducted in children with moderate-to-severe CD starting IFX. All patients underwent weighted pediatric CD activity index (wPCDAI) assessment, C-reactive protein and fecal calprotectin (FC) at week 0, 14, and 48. Endoscopy was performed at 0 and 48 weeks. The primary outcome was to determine the ability of 14-week wPCDAI, C-reactive protein, and FC to predict 1-year steroid-free clinical remission and mucosal healing. As a secondary outcome we evaluated their concordance with Simple Endoscopic Score for CD (SES-CD) at week 48. Results Forty-one children were enrolled. At 1 year, 21 (51%) and 16 (39%) were in clinical and endoscopic remission. Only combined postinduction FC and wPCDAI were able to predict 1-year clinical and endoscopic remission (hazard ratio 4.81 [95% confidence interval 1.76-20.45], P = 0.05 and hazard ratio 5.51 [95% confidence interval 1.83-26.9], P = 0.03). One-year SES-CD moderately correlated with FC (r = 0.52; P = 0.001). The FC cut-off value for mucosal healing was 120.5 μg/g (area under the curve 0.863, 83% sensitivity, 75.5% specificity; P = 0.005). The concordance between wPCDAI and SES-CD was excellent and good for severe disease and remission (k 0.87 and 0.76). Conclusions Post induction FC combined with wPCDAI can predict 1-year clinical and endoscopic response to IFX in pediatric CD. FC shows a moderate correlation with SES-CD, whereas wPCDAI has a good concordance with endoscopic remission or severe disease, but not with mild and moderate disease.

Introduction: Growth failure in children is a frequent feature of childhood-onset Crohn’s disease (CD), and stunting can persist into adulthood. Growth is an important outcome by which to judge the effectiveness of therapies in children; currently available studies in CD children have focused on the short-term impact of treatments on growth, and there are limited data regarding the long-term effects of treatments upon growth.Areas covered: We designed the present article to review whether the first treatment performed in newly diagnosed CD children may have a role on the future growth course. We conducted a systematic literature search to identify relevant studies published on the PubMed database from January 2002 up to now. We found only six surveys that documented mid-term growth course in newly diagnosed CD patients.Expert commentary: In the last years there have been relevant advances in the clinical management of CD children; however, there is a lack of knowledge about the best strategy to re...

Background Gastro-oesophageal reflux is very common in the paediatric age group. There is no single and reliable test to distinguish between physiologic and pathological gastro-oesophageal reflux, and this lack of clear distinction between disease and normal can have a negative impact on the management of children. Aims To evaluate the usefulness of 24-h oesophageal pH-impedance study in infants and children with suspected gastro-oesophageal reflux disease. Methods Patients were classified by age groups (A–C) and reflux-related symptoms (typical and atypical). All underwent pH-impedance study. If the latter suggested an abnormal reflux, patients received therapy in accordance with NASPGHAN/ESPGHAN recommendations, while those with normal study had an additional diagnostic work-up. The efficacy of therapy was evaluated with a specific standardized questionnaire for different ages. Results The study was abnormal in 203/428 patients (47%) while normal in 225/428 (53%). Of those with abnormal study, 109 exhibited typical symptoms (54%), and 94 atypical (46%). The great majority of the patients with abnormal study were responsive to medical anti-reflux therapy. Conclusions We confirm the utility of prolonged oesophageal pH-impedance study in detecting gastro-oesophageal reflux disease in children and in guiding therapy. Performing oesophageal pH-impedance monitoring in children with suspected gastro-oesophageal reflux disease is helpful to establish the diagnosis and avoid unnecessary therapy.

OBJECTIVES The aims of this study were to determine the presence of endothelial dysfunction by measuring aortic intima-media thickness (aIMT) and carotid intima-media thickness (cIMT) and to evaluate the role of traditional risk factors for premature atherosclerosis in children with inflammatory bowel disease (IBD). METHODS Thirty-four children with IBD (25 Crohn disease [CD] and 9 ulcerative colitis [UC]; mean age 11.1 years) and 27 healthy subjects matched for sex and age were enrolled. In all of the patients, demographic characteristics and risk factors for atherosclerosis (age, sex, body mass index, blood pressure, dyslipidemia, active and passive smoking, and family history for cardiovascular diseases), CD and UC clinical activity scores, and inflammatory markers were evaluated. aIMT and cIMT were measured by high-resolution B-mode ultrasound. RESULTS aIMT was significantly higher in patients than in controls (P

a b s t r a c t Background: Stricturing is the most common complicated phenotype in paediatric Crohn's disease, but only few studies have described its course, while data on the outcome of medical treatment are scanty. Aim: To retrospectively describes the course of paediatric stricturing Crohn's disease and assess clinical and imaging response to medical therapy. Patients and methods: Thirty-six patients with stricturing Crohn's disease were identified by our depart- ment database. Paediatric Crohn's disease activity index, need of surgery and magnetic resonance were evaluated as outcomes at 6, 12, 18 and 24 months after detection of stenosis. Results: Strictures were ileal, ileocolonic and colonic in 61%, 28% and 11% of patients. Thirteen (36%) had stricturing disease at the diagnosis of Crohn's disease, while 64% developed it at the follow-up. At baseline, 89% had medical treatment, while 11% surgery. At 6, 12, 18, and 24 months, 53%, 50%, 42%, and 35% had complete response to medical treatment, respectively. Overall, 44% were unresponsive to medical therapy and required surgery at the follow-up. Responders and non-responders significantly differed for inflammatory imaging findings at the stenosis detection. Conclusions: A stricturing phenotype is not uncommon at the diagnosis of Crohn's disease in children. Medical therapy seems poorly effective in avoiding intestinal resection. Magnetic resonance imaging is

Objectives To evaluate the usefulness of colonic ultrasonography (US) in assessing the extent and activity of disease in pediatric ulcerative colitis (UC) and to compare US findings with clinical and endoscopic features. Study design Consecutive pediatric patients (n = 60) with a diagnosis of UC and suspected disease flare-up were prospectively enrolled; of these, 50 patients were eligible for the study. All underwent clinical evaluation, bowel US with color Doppler examination and colonoscopy. Blind US was performed the day before endoscopy in all patients. The US assessed variables were bowel wall thickness >3 mm, bowel wall stratification, vascularity, presence of haustra coli, and enlarged mesenteric lymph nodes. Results The endoscopic extent of disease was independently confirmed in 47 patients by US that yielded a 90% concordance with endoscopy (95% CI 0.82-0.96). Multiple regression analysis showed that US measurements with an independent predictive value of severity at endoscopy were increased bowel wall thickness ( P P P = .031), and loss of stratification of the bowel wall ( P = .021). Each variable was assigned a value of 1 if present. The US score strongly correlated with clinical (r = 0.94) and endoscopic activity (r = 0.90) of disease ( P Conclusions Colonic US is a useful first line noninvasive tool to assess the extent and activity of disease in children with UC and to estimate the severity of a flare-up, prior to further invasive tests.

Objective The antitumor necrosis factor α (TNFα) antibodies infliximab and adalimumab are effective in inducing and maintaining remission in pediatric patients with Crohn disease (CD). The aim of the study was to evaluate the long-term efficacy and safety of biological therapy in pediatric patients with CD followed at a referral center. Methods This work is a retrospective observational study enrolling patients with CD treated with infliximab or adalimumab beyond the induction protocol. The patients' data were collected from the unit's IBD database (maximum follow-up evaluation after 36 months of treatment). The efficacy was evaluated by the Pediatric Crohn Disease Activity Index score and by analysis of the cumulative probability of continuing therapy; the safety was assessed in terms of adverse events. Results We enrolled 78 patients; the mean therapy duration was 27.2 ± 16.7 months, and the mean age at enrollment was 15 ± 3.1 years. The Kaplan-Meier analysis showed a cumulative probability of continuing therapy of 81%, 54%, and 33% at 1, 2, and 3 years, respectively, from the introduction of therapy. No association between the patients' baseline characteristics and the long-term outcome was found. The evaluation of the concomitant therapy with immunomodulators and anti-TNFα therapy versus anti-TNFα alone did not show a different outcome. No serious adverse events were recorded. Conclusions The study indicates that biological therapy is effective and safe in pediatric patients with CD in a longer follow-up period. The response to treatment was not influenced by the patients' baseline characteristics or by the immunomodulator association.

Background: Magnetic resonance imaging (MRI) is considered the gold-standard to evaluate SB in pediatric Crohn’s disease (CD). However, MRI is expensive, requires a strong compliance and a considerable amount of oral contrast to distend intestinal lumen. Small intestine contrast ultrasonography (SICUS) is non-invasive, low cost and generally well tolerated by patients. Objectives: To compare the diagnostic accuracy of SICUS and MRI in detecting presence, site and extension of SB disease and in assessing strictures in pediatric CD. Methods: Pediatric pts with suspected or known CD were prospectively enrolled. All underwent SICUS, MRI and ileocolonoscopy, performed by blind different operators. The SB was subdivided into: jejunum, ileum, terminal ileum (TI). The statistic concordance (k) between the two techniques was calculated. For the TI sensitivity (SE) and specificity (SP) were also assessed, with endoscopy as reference standard. The one-way ANOVA was used to compare the disease extension (cm) in the different segments. Results:66 consecutive patientswere included. The overall k for the presence of lesions was=0.94 (ES 0.06; 95%CI 0.8–1. The k for segments was 0.67 (jejunum), 0.91 (ileum) and 0.91 (TI). SE and SP (%) of SICUS andMRI for TI lesions were 98, 100 and 93, 92, respectively. There was no difference (p ns) in the evaluation of disease extension between the two techniques. The k for SB strictures was 0.62. SE and SP (%) of SICUS andMRI for TI strictures were 100, 100 and 92, 87, respectively. MRI provided 7 false positive results. Conclusions: The diagnostic performance of SICUS is comparable to that ofMRI. SICUSmight represent afirst-line tool in pediatric CD, able to reduce costs and to post-pone or even avoid more invasive investigations.

Background:High mobility group box-1 (HMGB1) is a DNA-binding protein that is released from injured cells during inflammation. Advances in targeting HMGB1 represent a major challenge to improve the treatment of acute/chronic inflammation.Aim:This study is aimed at verifying whether the inhibition of HMGB1 through dipotassium glycyrrhizate (DPG) is a good strategy to reduce intestinal inflammation.Methods:Human colon adenocarcinoma cell line, HT29, human epithelial colorectal adenocarcinoma, Caco2, and murine macrophage cell line, RAW 264.7, were cultured to investigate the effect of DPG on the secretion of HMGB1. Acute colitis was induced in C57BL/6 mice through administration of 3% dextran sodium sulphate (DSS); a combined treatment with DSS and 3 or 8 mg/kg/day DPG was used to investigate the effects of DPG on intestinal inflammation. Animals were euthanized at seventh day and colonic samples underwent molecular and histological analyses.Results:DPG significantly reduces in vitro the release of HMGB1 in the extracellular matrix as well as expression levels of pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6, by inhibiting HMGB1. Moreover, DPG significantly decreases the severity of DSS-induced colitis in mice. Murine colonic samples show decreased mRNA levels of pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6, as well as HMGB1 receptors, RAGE and TLR4. Finally, HMGB1, abundantly present in the feces of mice with DSS-induced colitis, is strongly reduced by DPG.Conclusions:HMGB1 is an early pro-inflammatory cytokine and an active protagonist of mucosal gut inflammation. DPG exerts inhibitory effects against HMGB1 activity, significantly reducing intestinal inflammation. Thus, we reason that DPG could represent an innovative tool for the management of human intestinal inflammation. © 2013 Vitali et al.