Search

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day–17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered.

Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered.Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. What is Known:• There is limited evidence on the clinical presentation and outcomes of children with COVID-19 in Europe, and almost no evidence on characteristics and risk factors of severe cases. What is New:• Among a case series of 130 children, mostly diagnosed at hospital level, and with a relatively high rate (26.2%) of comorbidities, about three-quarter had an asymptomatic or mild disease.• However, 57.7% were hospitalized, 11.5% needed some respiratory support, and 6.9% were treated in an intensive care unit.

OBJECTIVES: The Berlin definition of acute respiratory distress syndrome has introduced three classes of severity according to PaO2/FIO2 thresholds. The level of positive end-expiratory pressure applied may greatly affect PaO2/FIO2, thereby masking acute respiratory distress syndrome severity, which should reflect the underlying lung injury (lung edema and recruitability). We hypothesized that the assessment of acute respiratory distress syndrome severity at standardized low positive end-expiratory pressure may improve the association between the underlying lung injury, as detected by CT, and PaO2/FIO2-derived severity. DESIGN: Retrospective analysis. SETTING: Four university hospitals (Italy, Germany, and Chile). PATIENTS: One hundred forty-eight patients with acute lung injury or acute respiratory distress syndrome according to the American-European Consensus Conference criteria. INTERVENTIONS: Patients underwent a three-step ventilator protocol (at clinical, 5 cm H2O, or 15 cm H2O positive end-expiratory pressure). Whole-lung CT scans were obtained at 5 and 45 cm H2O airway pressure. MEASUREMENTS AND MAIN RESULTS: Nine patients did not fulfill acute respiratory distress syndrome criteria of the novel Berlin definition. Patients were then classified according to PaO2/FIO2 assessed at clinical, 5 cm H2O, or 15 cm H2O positive end-expiratory pressure. At clinical positive end-expiratory pressure (11 ± 3 cm H2O), patients with severe acute respiratory distress syndrome had a greater lung tissue weight and recruitability than patients with mild or moderate acute respiratory distress syndrome (p < 0.001). At 5 cm H2O, 54% of patients with mild acute respiratory distress syndrome at clinical positive end-expiratory pressure were reclassified to either moderate or severe acute respiratory distress syndrome. In these patients, lung recruitability and clinical positive end-expiratory pressure were higher than in patients who remained in the mild subgroup (p < 0.05). When patients were classified at 5 cm H2O, but not at clinical or 15 cm H2O, lung recruitability linearly increases with acute respiratory distress syndrome severity (5% [2-12%] vs 12% [7-18%] vs 23% [12-30%], respectively, p < 0.001). The potentially recruitable lung was the only CT-derived variable independently associated with ICU mortality (p = 0.007). CONCLUSIONS: The Berlin definition of acute respiratory distress syndrome assessed at 5 cm H2O allows a better evaluation of lung recruitability and edema than at higher positive end-expiratory pressure clinically set.

Chest computed tomography (CT) is a fundamental tool for the characterization of acute respiratory distress syndrome (ARDS). Its frequent use is, however, hindered by the associated radiation exposure. The aim of the present study was to evaluate, in patients with ARDS, the accuracy of quantitative and visual anatomical lung analysis performed on low-dose CT. We hypothesized that low-dose CT would provide accurate quantitative and visual anatomical results. Chest CT was performed in 45 ARDS patients in static conditions at set airway pressures of 45 and 15 or 45 and 5 cmH(2)O. During each pause, two consecutive scans were obtained at two different tube current-time products (mAs). In 24 patients 110 mAs was coupled with 60 mAs; in 21 patients 110 was coupled with 30 mAs. All other CT parameters were kept unaltered. Quantitative and visual anatomical results obtained at different mAs were compared via Bland-Altman analysis. Good agreements were observed between 110 and 60 mAs and between 110 and 30 mAs both for quantitative and visual anatomical results (all biases below 1.5 %). Estimated mean effective dose at 110, 60, and 30 mAs corresponded to 5.3 +/- A 1.6, 2.8 +/- A 0.8, and 1.4 +/- A 0.3 mSv, respectively. In patients with ARDS a reduction of mAs up to 30 (70 % effective dose reduction) can be achieved without significant effect on quantitative and visual anatomical results. Low-dose chest CT, with related quantitative and visual anatomical analysis, could be a valuable tool to characterize and potentially monitor lung disease in patients with ARDS

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.

N/A

RATIONALE: Unphysiologic strain (the ratio between tidal volume and functional residual capacity) and stress (the transpulmonary pressure) can cause ventilator-induced lung damage. OBJECTIVES: To identify a strain-stress threshold (if any) above which ventilator-induced lung damage can occur. METHODS: Twenty-nine healthy pigs were mechanically ventilated for 54 hours with a tidal volume producing a strain between 0.45 and 3.30. Ventilator-induced lung damage was defined as net increase in lung weight. MEASUREMENTS AND MAIN RESULTS: Initial lung weight and functional residual capacity were measured with computed tomography. Final lung weight was measured using a balance. After setting tidal volume, data collection included respiratory system mechanics, gas exchange and hemodynamics (every 6 h); cytokine levels in serum (every 12 h) and bronchoalveolar lavage fluid (end of the experiment); and blood laboratory examination (start and end of the experiment). Two clusters of animals could be clearly identified: animals that increased their lung weight (n = 14) and those that did not (n = 15). Tidal volume was 38 ± 9 ml/kg in the former and 22 ± 8 ml/kg in the latter group, corresponding to a strain of 2.16 ± 0.58 and 1.29 ± 0.57 and a stress of 13 ± 5 and 8 ± 3 cm H(2)O, respectively. Lung weight gain was associated with deterioration in respiratory system mechanics, gas exchange, and hemodynamics, pulmonary and systemic inflammation and multiple organ dysfunction. CONCLUSIONS: In healthy pigs, ventilator-induced lung damage develops only when a strain greater than 1.5-2 is reached or overcome. Because of differences in intrinsic lung properties, caution is warranted in translating these findings to humans

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)

Nephropathic cystinosis is a severe autosomal recessive inherited metabolic disease characterized by accumulation of free cystine in lysosomes. Cystinosis can lead to renal failure and multiorgan impairment. Only five cases of cystinosis with associated Bartter syndrome are reported in the literature, and no genetic evaluation has been reported. We describe two siblings with nephropathic cystinosis presenting with features of Bartter syndrome and their genetic pattern.