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There are no recent data on primary ciliary dyskinesia (PCD) distribution, diagnosis and treatment in Italy.A descriptive study based on a survey questionnaire. It consisted of three sections (patients, diagnosis and treatment), and sent to all the Italian PCD Centers.questionnaires obtained from 20/22 centers in 12/20 regions showed that the total number of PCD patients treated at the participating centers was of 416. Out of all centers, 55% follow20 patients, 2 centers have40 patients, and 75% follow both pediatric and adults. Age at diagnosis was between 4 and 8 years in 45% of the centers,3 years in 3 centers. Nasal nitric oxide, transmission electron microscopy and ciliary high-speed video microscopy are performed in 75, 90 and 40% of centers, respectively. Immunofluorescence is available in 5 centers. Genetic analysis is offered in 55% of the centers, and in 7 centers50% of the patients have a known genetic profile. Patients treated at all centers receive inhaled saline solutions, corticosteroids and chest physiotherapy. Prophylactic antibiotics and mucolytics are prescribed in 95 and 50% of the centers, respectively. Pseudomonas infection is treated with oral or inhaled antibiotics.Many Italian centers care for a small number of pediatric and adult patients, and diagnosis is often delayed. We found a great variability in the available diagnostic procedures, as well in the prescribed therapies. Our study will help to uniform diagnostic algorithm and share treatments protocols for PCD in Italy and allowed to set specific national goals. This article is protected by copyright. All rights reserved.

Aim To explore the cardio-pulmonary function of children returning to play sports after mild or asymptomatic SARS-CoV-2 infection. Methods This is a consecutive case series conducted at the Institute for Maternal and Child Health, Trieste, Italy. Paediatric patients who accessed the Institute for cardiologic and pneumological evaluation before the return-to-play competitive sports were recruited, according to the Italian Sports Medical Federation recommendations. Echocardiogram, electrocardiogram, treadmill ECG test and pulmonary function tests were performed. Results One hundred and thirty-two patients (aged 8-17 years old, mean age 12.8 ± 2.5) were recruited. Among these, 127 children were considered for the final analysis (49.6% females). Out of 127, 84 (66.1%) had a mild symptomatic form of SARS-CoV-2 infection, while 43 (33.9%) were asymptomatic. The main referred symptoms were fever (n = 37, 44%), asthenia (n = 14, 16.7%), rhinitis (n = 16, 19%), ageusia (n = 19, 22.6%), anosmia (n = 24, 28.6%), sore throat (n = 3, 3.6%), cough (n = 9, 10.7%), arthralgia-myalgia (n = 11, 13.1%), headache (n = 23, 27.4%) and gastrointestinal symptoms (n = 7, 8.3%). No child presented evidence of cardio-pulmonary function impairment after an average time of 77.3 days (SD 35) from SARS-CoV-2 swab positivity and a median of 68 days (IQ1 52, IQ3 92.5). Conclusion This preliminary study suggests that, in the absence of specific symptoms, the diagnostic yield of cardio-pulmonary tests before returning to play sports may be very low.

The paper reports the case of a 20-year-old boy suffering from Duchenne muscular dystrophy. During his usual pneumology check-up he reported that he had cough with blood traces (not responsive to antibiotic therapy), palpitations, oppressive and retrosternal pain. Therefore, a chest X-ray was performed. Different diagnostic hypotheses and treatment options are discussed.

Cystic Fibrosis (CF), one of the most common lethal genetic diseases in people of Caucasian origin, causes a severe increase of mucus viscosity (due to water loss) in many organs, mainly the airways. As a consequence, increased viscosity impairs muco-ciliary clearance determining sputum (pathological mucus) stagnation, thus promoting bacterial lung infections. In the case of drugs administered by inhalation (usually, mucolytics, anti-inflammatory and antibiotics), the structure of the Airway Surface Liquid (ASL) lining the walls of the bronchial tree requires an in-depth understanding in order to improve the efficacy of the drugs. Indeed, ASL is composed by a thin inner water-like serous fluid named periciliary layer, where cells cilia beat, and by a thicker outer non-Newtonian viscoelastic fluid representing the Mucus Layer (ML). In particular, ML, is a heterogeneous medium made up of mainly physical cross-linked polymeric regions, embedded in a less viscous water-like fluid. Although drug transport inside ASL can depend on different factors, drug diffusion is one of the most important. Thus, the estimation of the drug diffusion coefficient (D) is a key factor: at this purpose the Lustig-Peppas model for not swelling systems represents an effective tool. Indeed, this model refers to both the network mesh size and the volume fraction of the solid (polymeric) network permeating the ML. Interestingly, based on the Flory, Chui and Schurz theories, it is possible to express D directly as a function of the ML shear modulus (G). Thus, assuming that ASL rheological properties are similar to those of sputum, it is possible evaluating D and the kinetics of drug penetration inside ASL. Therefore, this work provided to measure CF sputum G by fitting the generalized Maxwell model to frequency sweep data, to evaluate D and to simulate drug diffusion through the ASL layer by means of Fick's equation

The shear modulus G of the sputum obtained by expectoration from cystic fibrosis patients is fundamental to determine the mesh size of the polymeric network pervading the sputum, a parameter related to lung functionality. The Akaike criterion revealed that in 55.2 % of the examined samples, the best approach (among those considered) to determine G relied on the mechanical spectrum fitting by the generalised Maxwell model with relaxation times scaled by a factor 10. Thus, this approach was adopted to evaluate the mesh size distribution combining G knowledge with the determination of the average magnetic relaxation time (T2m) of sputum. As G and T2m determination can be negatively affected by sputum contamination by saliva, whose presence increases T2m and depresses G, we developed a proper “decontamination” procedure to obtain more reliable T2m and G estimations (necessary in 21 % of the samples). This procedure allowed to strengthen the T2m correlation with lung functionality evaluated by FEV1 (normalised air volume emitted in the first second during a spirometry test). This work is licensed under a Creative Commons Attribution 4.0 International License.

As bioactive small proteins with antimicrobial and immunomodulatory activities that are naturally produced by all living organisms, antimicrobial peptides (AMPs) have a marked potential as next-generation antibiotics. However, their development as antibacterial agents is limited by low stability and cytotoxicity. D-BMAP18, a membrane-permeabilizing antimicrobial peptide composed of D-amino acids, has shown good antibacterial and anti-inflammatory activities but also a non-negligible cytotoxicity against eukaryotic cell lines. In this study, a prodrug has been developed that extends the peptide with a negatively charged, inactivating sequence containing the cleavage site for neutrophil elastase (NE). The ultimate goal was to allow the activation of D-BMAP18 by endogenous elastase only at the site of infection/inflammation, enabling a slow and targeted release of the pharmacologically active peptide. In vitro activation of Pro-D-BMAP18 was confirmed using purified NE. Its antimicrobial and cytotoxic activities were tested in the presence and absence of elastase and compared to those of the parental form. The prodrug had minimal activity in the absence of elastase, while its proteolysis product retained an appreciable antimicrobial activity but lower cytotoxicity. Moreover, Pro-D-BMAP18 was found to be correctly converted to D-BMAP18 in the presence of CF sputum as a model of the lung environment and showed good antimicrobial activity under these conditions.

PURPOSE To develop a novel approach to monitor lung ventilation/inflammation in cystic fibrosis (CF) patients. Lung assessment in CF patients is relevant given that most patients succumb to respiratory failure. Respiratory functional tests (forced expiratory volume in the first second; FEV1 ) and inflammatory markers are used to test pulmonary ventilation/inflammation, respectively. However, FEV1 is effort dependent and might be uncomfortable for CF patients. Furthermore, inflammatory marker detection is costly and not rapid. To overcome these limitations, we propose the measurement, by means of low field nuclear magnetic resonance, of the spin-spin relaxation time (T2m ) of water hydrogens present in CF patient sputum. In CF sputum, different biological components are pathologically increased and inversely related to lung functionality. Moreover, we showed that these components alter in a dose-dependent manner the T2m in synthetic CF sputum. METHODS Sputum samples were obtained from 42 CF subjects by voluntary expectoration; FEV1 , C-reactive protein (CRP), blood neutrophil counts together with cytokine (tumor necrosis factor alpha [TNFα], interleukin [IL]-1β, IL-4, and vascular endothelial growth factor) quantifications were then evaluated. RESULTS In sputum samples, we observe that T2m directly correlates (rFEV1 = 0.44; P < 10-4 ; 169 samples) with FEV1 . Moreover, T2m inversely correlates with the circulating inflammation markers CRP/neutrophil number (rCRP = -0.44, P < 10-4 ; rNC = -0.37, P < 2 * 10-4 ; 103 and 86 samples, respectively) and with the sputum inflammatory cytokines TNFα/IL-β1 (rTNFα = -0.72, P < 10-4 ; rIL-1β = -0.685, P < 10-4 ; 27 samples). T2m variations also correspond to FEV1 values over time in defined patients. CONCLUSION These findings, together with the fast, reliable, and simple determination of T2m , make our approach a novel tool potentially usable in the real world of CF patients.

SETTING: Early diagnosis of latent tuberculous infection (LTBI) should be pursued in healthcare workers (HCWs). While HCWs in hospitals are screened for LTBI, HCWs in outpatient settings are usually not. In 2017, in Italy, a tuberculosis (TB) infected paediatrician working in an outpatient vaccination service infected 15 adults and nine children. The investigation involved 2490 children and 151 adults. Among children, nine were tuberculin skin test-positive, and four developed active TB. Among 123 adult contacts with longer exposure, seven were interferon-gamma release assay (IGRA) positive and none had active TB. Among 28 close contacts, eight had a positive IGRA, and three had pulmonary TB. The total outbreak cost €1 017 903.OBJECTIVE: To compare the outbreak cost with those of potential screening programme strategies.RESULTS: Regular screening of paediatric outpatient HCWs would have cost between €2592 and €11 373. Extending the screening to all outpatient HCWs (caring for adults and children) would have cost between €66 384 and €155 043. Investigating only close contacts would have cost €42 857.CONCLUSION: Each of these screening strategies would have been cost-effective compared with the outbreak investigation occurring in real life with a cut-off of 474 for the maximum number of tested outpatient HCWs needed for the screening strategy to be cost-saving.

A healthy 5-year-old boy presented with a 10-day history of painless, swollen and hyperaemic eyelids without conjunctival injection or fever. Baseline blood tests including inflammatory markers were unremarkable except for mild raised levels of erytrocyte sedimentation rate (38 mm/hour). Physical examination was totally negative with no sign of sinusitis. During the recovery, 3 days after the admission, an orthoptic evaluation showed bilateral upper eyelid ptosis (figure 1) and painful extrinsic ocular movements, with a restriction of upgaze in both eyes. Biomicroscopy showed conjunctival hyperaemia and chemosis; fundus oculi was normal. Figure 1 Bilateral upper painless swollen and hyperaemic eyelids with associated ptosis. Which of the following do you think is the most likely diagnosis in this patients? 1. Orbital cellulitis . 2. Orbital myositis. 3. Thyroid orbitopathy. 4. Myasthenia gravis. Which is the next diagnostic step to confirm the clinical hypothesis? 1. Orbital biopsy. 2. CT. 3. MRI. 4. Visual …

Background As most cystic fibrosis (CF) patients progress to respiratory failure, lung functionality assessment is pivotal. We previously developed a test that indirectly monitors airways (inflammation/functional test) by measuring the spin-spin relaxation time (T2m) of the water hydrogens present in CF sputum. Here the T2m significance in the monitoring of CF lung disease was further investigated by studying the correlation of T2m with: 1) sputum viscoelasticity, 2) mucociliary clearability index (MCI)/cough clearability index (CCI) and 3) sputum average mesh-size. Methods Sputum samples from 25 consenting CF subjects were analyzed by rheology tests (elastic modulus G and zero shear viscosity η0) and Low Field Nuclear Magnetic (LF-NMR) resonance (T2m). MCI/CCI were calculated from the rheological parameters. The average mesh-size (ξ) of the sputum structure was then evaluated by rheology/LF-NMR, together with FEV1 for each patient. Results There was an inverse correlation between G and η0 versus T2m, indicating that a worsening of the lung condition (T2m-FEV1 drop) is paralleled by an increase in sputum viscoelasticity (G and η0) favoring mucus stasis/inflammation. A direct correlation was also observed between T2m and MCI/CCI, showing that T2m provides information as to airway mucus clearing. Moreover, there was a direct correlation between T2m and the average sputum mesh size (ξ). Conclusions We demonstrated a correlation between T2m (measured in CF patient's sputum) and the sputum viscoelasticity/average mesh-size and with MCI/CCI, parameters related to airway mucus clearing. Thus, the present data strengthen the potential of our test to provide indirect monitoring of airway disease course in CF patients as T2m depends on mucus solid concentration and nanostructure.

Hyper-concentrated and more viscous mucus presents in the lungs of patients suffering from cystic fibrosis (CF) provoke mucus stasis providing an optimal environment for bacterial growth. The sputum of CF patients has been subjected to rheological and low-field NMR investigation, providing information on i) the state of viscoelasticity (G0, h 0 ) and mucus hydration (T2avg), ii) possible correlations also with parameter of patients clinical status given by spirometry(FEV1) iii) the structure of the polymeric network in mucus. The absence of correlation among magnetic and mechanical-rheological relaxation notes that these phenomena are linked to different aspects of sputum. However, correlations exist among FEV1, T2av and rheological properties G0, h 0. Moreover, T2avg correlates with the mucociliary clearability index (MCI) and cough clearability index (CCI), two indices derived from the rheological characterization. The clinical condition of the patient can, therefore, be summarized by T2avg alone. Finally, information from the two characterizations make it possible to estimate the mesh size distribution of the polymeric network pervading sputum. This knowledge is very useful to better understand drugs penetration in mucus.

Purpose To describe the clinical course of COVID-19 in patients with cystic fibrosis (CF) and to identify risk factors for severe COVID-19. Methods We conducted a prospective study within the Italian CF Society. CF centers collected baseline and follow-up data of patients with virologically confirmed SARS-CoV-2 infection between March 2020 and June 2021. Odds ratios (ORs) for severe SARS-CoV-2 (as defined by hospital admission) were estimated by logistic regression models. Results The study included 236 patients with positive molecular test for SARS-CoV-2. Six patients died, 43 patients were admitted to hospital, 4 admitted to intensive care unit. Pancreatic insufficiency was associated with increased risk of severe COVID-19 (OR 4.04, 95% CI 1.52; 10.8). After adjusting for age and pancreatic insufficiency, forced expiratory volume in one second (FEVp)

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Mepolizumab, a monoclonal antibody blocking IL-5, is efficacious in the treatment of severe lung diseases sharing eosinophilic inflammation pattern. The paper describes two cases in which the drug was used with excellent results. The first involved a 14-year-old boy with obliterative bronchiolitis, the other an 11-year-old girl with non-atopic asthma. Both cases shared the eosinophilic phenotype of the disease, defined by an eosinophilic count in the peripheral blood equal to or greater than 2% (i.e. a baseline value of 150-200 cells/µl or 300 cells/µl during the previous year). Its use demonstrates clinical improvement in severe refractory asthma with eosinophilic phenotype and as off-label drug in obliterative bronchiolitis, leading to a decrease in the rate of exacerbations and enabling the reduction of corticosteroids as well as the resolution of structural anomalies, respectively.

Most Cystic Fibrosis (CF) patients succumb to airway inflammation and pulmonary infections due to Pseudomonas aeruginosa. D-BMAP18, a membrane-permeabilizing antimicrobial peptide composed of D-amino acids, was evaluated as a possible antibacterial aimed to address this issue. The antipseudomonal activity of D-BMAP18 was tested in a pathophysiological context. The peptide displayed activity against CF isolates of Pseudomonas aeruginosa in the presence of CF sputum when combined with sodium chloride and DNase I. In combination with DNase I, D-BMAP18 discouraged the deposition of new biofilm and eradicated preformed biofilms of some P. aeruginosa strains. In addition, D-BMAP18 down regulated the production of TNF-&alpha, IL1-&beta, and TGF-&beta, in LPS-stimulated or IFN-&gamma, macrophages derived from THP-1 cells indicating an anti-inflammatory activity. The biocompatibility of D-BMAP18 was assessed using four different cell lines, showing that residual cell-specific cytotoxicity at bactericidal concentrations could be abolished by the presence of CF sputum. Overall, this study suggests that D-BMAP18 may be an interesting molecule as a starting point to develop a novel therapeutic agent to simultaneously contrast lung infections and inflammation in CF patients.

Aim - To evaluate the cardiopulmonary function in children returning to play sports after mild or asymptomatic SARS-CoV-2 infection. - Methods - This is a consecutive case series conducted at the Institute for Maternal and Child Health, Trieste, Italy. Paediatric patients who accessed the Institute for cardiologic and pneumological evaluation before the return to play competitive sports were recruited. According to the Italian Sports Medical Federation recommendations, echocardiogram, electrocardiogram, treadmill ECG test and pulmonary function tests were performed. - Results - 240 patients (aged 8-17 years old) were recruited. Among these, 233 children were considered for the final analysis. Out of 233, 147 (63.1%) had a mild symptomatic form of SARS-CoV-2 infection, while 86 (36.9%) were asymptomatic. The main referred symptoms were fever (n = 68, 46.3%), headache (n = 42, 28.6%), anosmia (n = 40, 27.2%), rhinitis (n = 34, 23.1%), ageusia (n = 32, 21.8%), cough (n = 22, 15%), asthenia (n = 21, 14.3%), arthralgia-myalgia (n = 20, 13.6%), sore throat (n = 14, 9.5%) and gastrointestinal symptoms (n = 9, 6.1%). No child presented evidence of cardiopulmonary function impairment after an average time of 76.1 days (SD 39.2) from SARS-CoV-2 swab positivity and a median of 68 days (IQ1 49, IQ3 98). - Conclusion - This study suggests that the diagnostic yield of cardiopulmonary tests before returning to play sports may be very low in the absence of specific symptoms.

Wandering spleen is a rare condition, typically not only due to embryological defects of the splenic ligaments, but also secondary to trauma and splenomegaly. The most common presentation is acute abdomen with a mobile abdominal mass or recurrent abdominal pain. However, the spleen may be temporary in its normal position, and patients could be asymptomatic. A familiarity, if present, strengthens the diagnostic suspect.Abdominal ultrasonography and computed tomography are the examination of choice, and the management is surgical.

A 12-year-old girl was referred with a 7-month history of episodes of dyspnoea, stridor and a sense of chest constriction during physical exercise. These were self-limiting and never occurred at night. Physical examination was normal. An initial diagnosis of vocal cord dysfunction was made.Spirometry showed a plateau of forced expiratory flow, with a truncated aspect of the expiratory phase (figure 1). Six weeks later she described occasional dysphagia with solid foods. The barium swallow, performed only in anteroposterior projection, did not show oesophageal dilation. A bronchoscopy showed extrinsic compression of the middle lower third of the trachea and the right main bronchus. A chest CT scan was performed (figures 2 and 3).Figure 1The spirometry showed a truncated expiratory phase with a substantially decreased PEF, compared with FEV1: indicating central intrathoracic airway obstruction. FEF, forced expiratory flow; FEV1, forced expiratory volume in 1 s; FIF, forced inspiratory flow; FIV1, forced inspiratory volume in 1 s; FIVC, forced inspiratory vital capacity; FVC, forced vital capacity; PEF, peak expiratory flow; PIF, peak inspiratory flow.Figure 2Contrast enhanced CT axial section image showing right aortic arch (white arrow on the left) with aberrant subclavian artery (red arrow on the right) encircling the trachea and the oesophagus.Figure 3CT three-dimensional reconstruction arteriography posterior view showing right aortic arch (white arrow), diverticulum of Kommerell (white star) from which the left subclavian artery (red arrow) arose. D Ao, descending aorta.QuestionsWhat is your diagnosis?Persistent vocal cord dysfunctionAchalasiaVascular ringAsthmaWhat is the gold standard for diagnosis of VR?ECGChest radiographCT and/or MRIBronchoscopyHow should this patient be treated?Surgical correctionVideo-assisted thoracoscopyDecompression of the oesophagus with a nasogastric tubeInspiratory muscle training and ipratropium bromide inhalerWhat signs in the history pointed away from vocal cord dysfunction?Dysphagia with solid food was present.The episodes of dyspnoea and stridor never occurred at night.The episodes arose mainly on exertion.The episodes of dyspnoea and stridor were self-limiting.Answers can be found on page 2.

A 5-year-old boy presented with 2 days of fever and cough. On examination, he had mild dyspnoea and chest pain, with crackles and hypoventilation at the right lung base. Blood tests showed white blood cells of 39.1×109/L, neutrophils of 28.9×109/L, haemoglobin of 11.3 g/dL, platelets of 375×109/L, c-reactive protein of 28.7 mg/dL and erythrocyte sedimentation rate of 41 mm/hour. Chest X-ray confirmed a pulmonary consolidation in the right lower lobe (figure 1), with an associated pleural effusion. Bacterial pneumonia was diagnosed and intravenous ceftriaxone 100 mg/kg/ day was started. The following day, he developed palpebral oedema and his urine became tea-coloured. His blood pressure was 126/82 mm Hg (>99th percentile).1 Serum creatinine rose from 0.45 mg/dL to 1.09 mg/dL (39.8–93.4 µmol/L) and C3 was 9 mg/dL (normal range 90–180 mg/dL). Urinalysis revealed gross haematuria and 3+ proteinuria, with microscopy showing dysmorphic red blood cells with casts. Ultrasounds showed enlarged …

PURPOSE Development of a reliable, simple method to monitor lung condition in cystic fibrosis (CF) patients. Lung functionality assessment in CF patients is relevant, as most of them still die of respiratory failure. In lung mucus (sputum) of CF patients, components such as proteins, biopolymers, DNA, bacteria, and mucin are pathologically increased. As lung functionality is related to the amount of the pathological components in the sputum, their determination can help clinicians in monitoring lung condition and planning therapy. METHODS Low-field NMR was used to evaluate the variation of the relaxation time (T2m ) of the water hydrogens present in CF sputum in relation to the amounts of the pathological components. Low-field NMR was tested in artificial samples (mucin or alginates), then in conditional sputum (saliva from healthy volunteers, added by different amounts of the pathological components), and finally in 12 patients' sputums, in which T2m was correlated to a commonly used lung monitoring test (i.e., forced expiratory volume in the first second). RESULTS T2m significantly (P

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).

Children under 5 years of age are at risk for tuberculosis after occasional contact with highly contagious patients http://ow.ly/RqAn30fKdGk

Journal of Pediatrics, The - In Press.Proof corrected by the author Available online since lundi 6 juin 2016

A 14-year-old girl presented to our paediatric department in May, 2012, with massive abdominal distension that had developed over the previous 2 years. She reported chronic abdominal discomfort, alternating diarrhoea and constipation, and two previous subocclusive episodes that had resolved with laxative therapy. Plain abdominal radiographs showed substantial large bowel distension and several air–fl uid levels. No air was evident in the rectum or anal canal (fi gure). She underwent surgery, and because no mechanical obstruction was observed a diverting ileostomy was done. Analysis of full-thickness large bowel and rectal biopsy samples obtained during surgery showed a decreased number of ganglion cells and acetylcho linesterase activity compatible with the diagnosis of hypo ganglionosis. In November, 2012, she had large bowel resection, ileorectal anastomosis, and ileostomy repositioning. The postoperative course was character ised by progressive intestinal recanalisation, although she had persistent watery stools with faecal sodium loss. The resulting electrolyte imbalance was corrected with partial parenteral nutrition. The patient was discharged 2 months after the procedure and continued parenteral nutrition at home. She had a gradual reduction of watery diarrhoea so we tapered the partial parenteral nutrition and weaning was possible after 12 months. At last follow-up in July, 2014, the patient reported no more episodes of abdominal distension. Hypoganglionosis is classed as a hypogenetic type of intestinal innervation disorder characterised by very low or absent acetylcholinesterase mucosal activity and a decreased number of ganglion cells within the myenteric and submucosal plexus of a variable intestinal segment. The most common presenting symptoms of hypoganglionosis are acute constipation, intestinal obstruction, and enterocolitis. The disorder thus resembles Hirschsprung’s disease, but clinical pre sentation might be subtle and misdiagnosed as chronic constipation. The median age at diagnosis is usually higher in patients with hypoganglionosis than Hirschsprung’s disease. Defi nitive diagnosis requires the analysis of full-thickness biopsy sample of the aff ected intestinal segment. The treatment is surgical, involving resection of the hypoganglionotic tract of the intestine.

Anti-transglutaminase antibodies are the diagnostic marker of celiac disease, and are considered to be synthesized only by intestinal B-lymphocytes. During an infectious disease, these antibodies are transiently detected in serum. We show that these infection-triggered antibodies may not originate in the intestinal mucosa and are not an indication of celiac disease.

BACKGROUND: In a randomized controlled trial, thalidomide has shown to be effective in refractory Crohn's disease in children. This pilot study aimed at evaluating thalidomide in refractory pediatric ulcerative colitis (UC). METHODS: Double-blind, placebo-controlled randomized clinical trial on thalidomide 1.5 to 2.5 mg/kg/day in children with active UC despite multiple immunosuppressive treatments. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks; all responders were followed up for a minimum of 52 weeks. RESULTS: Twenty-six children with refractory UC were randomized to thalidomide or placebo. Clinical remission at week 8 was achieved by significantly more children treated with thalidomide {10/12 (83.3%) versus 2/11 (18.8%); risk ratio, 4.5 (95% confidence interval [CI], 1.2-16.4); P = 0.005; number needed to treat, 1.5}. Of the nonresponders to placebo who were switched to thalidomide, 8 of 11 (72.7%) subsequently reached remission at week 8 (risk ratio, 4.0 [95% CI, 1.1-14.7]; number needed to treat, 2.45; P = 0.01). Clinical remission in the thalidomide group was 135.0 weeks (95% CI, 32-238), compared with 8.0 weeks (95% CI, 2.4-13.6) in the placebo group (P < 0.0001). Cumulative incidence of severe adverse events was 3.1 per 1000 patient-weeks. Peripheral neuropathy and amenorrhea were the most frequent adverse events. CONCLUSIONS: In this pilot randomized controlled trial on cases of UC refractory to immunosuppressive therapy, thalidomide compared with placebo resulted in improved clinical remission at 8 weeks of treatment and in longer term maintenance of remission. These findings require replication in larger clinical studies evaluating both thalidomide efficacy and safety.

We present 3 children affected by B. quintana infection treated at the IRCCS Burlo Garofolo of Trieste between March and April 2013. B. quintana infection is rare but it should be suspected in patients with fever and lymphadenopathy who do not respond to conventional antibiotic treatment. All patients had a complete recovery without sequelae or relapses.

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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 As many as 1.2 million people in Europe and more than half a million in the United States are estimated to have Crohn disease. Its incidence is increasing globally,1- 3 and its prevalence is particularly high in North America and Europe (319 to 322 per 100 000 persons).2 About 25% of people with Crohn disease develop symptoms as children, and these cases are generally more severe than adult-onset cases. Resistance or intolerance to therapy is common in children with Crohn disease, with up to approximately 18% of cases requiring surgery within 5 years from disease onset. If not adequately treated, children with Crohn disease may have permanent impairments (eg, growth failure, osteoporosis, delayed sexual development, psychological disorders, failure to achieve full educational and career potential).4- 8 Few randomized trials have evaluated the efficacy and safety of second- and third-line drugs (ie, after failure of steroids or enteral nutrition) in children with Crohn disease.9- 13 Thalidomide is a small molecule with anti�tumor necrosis factor ?, immunomodulatory, and antiangiogenic properties.14,15 It has been used since the 1960s to treat patients with erythema nodosum leprosum (an immunologic complication of leprosy) and, more recently, several other inflammatory diseases of the skin and mucous membranes (aphthous stomatitis, Behcet syndrome, mouth and esophageal ulcers in human immunodeficiency virus, mucocutaneous graft-vs-host disease, and cutaneous manifestations of systemic lupus erythematosus).14,15 Observational studies on thalidomide in patients with Crohn disease have reported encouraging results, with remission rates ranging from 40% to 70%.14,15 We evaluated the efficacy and adverse effects of thalidomide in inducing clinical remission in children and adolescents with refractory Crohn disease in a multicenter, double-blind, placebo-controlled, randomized controlled trial.

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Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.

Background: Several studies suggest an increased risk of venous and arterial thromboembolism (TE) in adults with inflammatory bowel disease (IBD) compared to the general population. We performed a systematic review of studies on incidence and characteristic of TE in children with IBD. Methods: We searched Medline, LILACS, EMBASE, POPLINE, CINHAL, and reference lists of identified articles, without language restrictions, in August 2010. Results: Population studies suggest that there is an increased risk of TE in children with IBD compared to controls. TE occurred in children with IBD in all age ranges, mostly (82.8%) during active disease, and more frequently in children with ulcerative colitis (odds ratio [OR] 3.7, 95% confidence interval [CI] 1.8–7.6). At least one specific risk factor for TE was recognized in 50% of cases; two risk factors were present in 24%. Out of 92 published cases of TE in children with IBD, 54.3% occurred in cerebral site, 26% in the limbs, 13% in the abdominal vessels, and the remaining in the retina and lungs. After a first episode of TE, an early recurrence was observed in 11.4% of children, a late recurrence in 10%. A number of different therapeutic schemes were used. Overall mortality was 5.7% and was mostly associated with cerebral TE. Conclusions: Population studies are needed to clarify the risk of TE in children with IBD, the relative weight of other risk factors, the characteristics of the events, and to define guidelines of therapy and prophylaxis. (Inflamm Bowel Dis 2010)

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No abstract available

A 15-year-old male presented with persistent and asymptomatic enlargement of the proximal interphalangeal (PIP) joints of both hands. X-ray and ultrasound demonstrated soft tissue swelling with no bony or articular damage. Histological examination showed increased dermal deposition of collagen fibers. A diagnosis of pachydermodactyly was given. A 15-year-old male presented with a 2-year history of persistent enlargement of the proximal interphalangeal (PIP) …