Breath Prints for Diagnosing Asthma in Children.

Electronic nose (e-nose) is a new technology applied for the identification of volatile organic compounds (VOC) in breath air. Measuring VOC in exhaled breath can adequately identify airway inflammation, especially in asthma. Its noninvasive character makes e-nose an attractive technology applicable in pediatrics. We hypothesized that an electronic nose could discriminate the breath prints of patients with asthma from controls. A cross-sectional study was conducted and included 35 pediatric patients. Eleven cases and seven controls formed the two training models (models A and B). Another nine cases and eight controls formed the external validation group. Exhaled breath samples were analyzed using Cyranose 320, Smith Detections, Pasadena, CA, USA. The discriminative ability of breath prints was investigated by principal component analysis (PCA) and canonical discriminative analysis (CDA). Cross-validation accuracy (CVA) was calculated. For the external validation step, accuracy, sensitivity and specificity were calculated. Duplicate sampling of exhaled breath was obtained for ten patients. E-nose was able to discriminate between the controls and asthmatic patient group with a CVA of 63.63% and an M-distance of 3.13 for model A and a CVA of 90% and an M-distance of 5.55 for model B in the internal validation step. In the second step of external validation, accuracy, sensitivity and specificity were 64%, 77% and 50%, respectively, for model A, and 58%, 66% and 50%, respectively, for model B. Between paired breath sample fingerprints, there were no significant differences. An electronic nose can discriminate pediatric patients with asthma from controls, but the accuracy obtained in the external validation was lower than the CVA obtained in the internal validation step.

Mechanical Properties of Orthodontic Cements and Their Behavior in Acidic Environments.

The present research is focused on three different classes of orthodontic cements: resin composites (e.g., BracePaste); resin-modified glass ionomer RMGIC (e.g., Fuji Ortho) and resin cement (e.g., Transbond). Their mechanical properties such as compressive strength, diametral tensile strength and flexural strength were correlated with the samples' microstructures, liquid absorption, and solubility in liquid. The results show that the best compressive (100 MPa) and flexural strength (75 Mpa) was obtained by BracePaste and the best diametral tensile strength was obtained by Transbond (230 MPa). The lowestvalues were obtained by Fuji Ortho RMGIC. The elastic modulus is relatively high around 14 GPa for BracePaste, and Fuji Ortho and Transbond have only 7 GPa. The samples were also subjected to artificial saliva and tested in different acidic environments such as Coca-Cola and Red Bull. Their absorption and solubility were investigated at different times ranging from 1 day to 21 days. Fuji Ortho presents the highest liquid absorption followed by Transbond, the artificial saliva has the best absorption and Red Bull has the lowest absorption. The best resistance to the liquids was obtained by BracePaste in all environments. Coca-Cola presents values four times greater than the ones observed for artificial saliva. Solubility tests show that BracePaste is more soluble in artificial saliva, and Fuji Ortho and Transbond are more soluble in Red Bull and Coca-Cola. Scanning electron microscopy (SEM) images evidenced a compact structure for BracePaste in all environments sustaining the lower liquid absorption values. Fuji Ortho and Transbond present a fissure network allowing the liquid to carry out in-depth penetration of materials. SEM observations are in good agreement with the atomic force microscopy (AFM) results. The surface roughness decreases with the acidity increasing for BracePaste meanwhile it increases with the acidity for Fuji Ortho and Transbond. In conclusion: BracePaste is recommended for long-term orthodontic treatment for patients who regularly consume acidic beverages, Fuji Ortho is recommended for short-term orthodontic treatment for patients who regularly consume acidic beverages and Transbond is recommended for orthodontic treatment over an average time period for patients who do not regularly consume acidic beverages.

The value of abdominal ultrasonography compared to colonoscopy and faecal calprotectin in following up paediatric patients with ulcerative colitis.

AIM: To evaluate the value of abdominal ultrasonography (US) in the follow-up of paediatric patients with ulcerative colitis (UC) compared to faecal calprotectin (FC) and colonoscopy. MATERIAL AND METHOD: In this retrospective study we enrolled 30 paediatric patients previously diagnosed with UC, examined by abdominal US and colonoscopy within the same week. FC was also determined during the same week. Disease activity was established using the paediatric ulcerative colitis activity index (PUCAI). The global endoscopic activity was evaluated using the Mayo endoscopic subscore. RESULTS: Endos-copy revealed pathological findings of active disease in 27 out of 30 patients; 3 patients were in endoscopic remission. Only 18 of them had clinical active disease (PUCAI >10), [sensitivity (Se) 66.7% and specificity (Sp) 33% of PUCAI in detecting endoscopic active disease). Twenty-three (76.7%) patients had FC >250 mcg/g, but in 2 of these cases the colonoscopy was normal (Se 77.8% and Sp 33.3% in detecting active disease). At US examination, pathological findings (increased bowel wall thickness, hypervascularity, lymphadenopathies, and/or mesenteric inflammatory fat) were found in 27 patients (90%), all with endoscopic active disease (agreement US - colonoscopy, at patient level, k=1.0, p<0.001, Se 100% and Sp 100%). At seg-ment level (totally 180 bowel segments examined by US), the overall agreement between US and colonoscopy was k=0.767, p<0.001, Se 86.5%, Sp 90.1%. Of the 27 patients with US pathological findings in any of colonic segments, 23 had FC >250 mcg/g (85.1%). The inter-observer agreement for the US measurements had an overall ICC of 0.926 with p<0.001. CONCLUSION: Abdominal US findings demonstrate a good to excellent concordance with endoscopic examination and are correlated with elevated FC levels. Therefore, US appears as an accurate technique in assessing activity in patients with UC and might replace colonoscopic evaluation for the follow-up.

B cell-activating factor (BAFF) in children with inflammatory bowel disease.

BACKGROUND: Assessing the inflammation is important in the follow-up of paediatric patients with inflammatory bowel disease (IBD). We aim to evaluate the value of B cell-activating factor (BAFF) in paediatric IBD as a potential biomarker for follow-up. METHOD: We determined BAFF in serum and faeces and faecal calprotectin (CP) in 32 IBD children-16 Crohn's disease (CD) and 16 ulcerative colitis (UC). Twenty-six healthy children and 10 children with irritable bowel syndrome (IBS) were included as controls. RESULTS: No differences were found in serum BAFF between IBD, IBS, and healthy group: 1037.35, 990.9 and 979.8 pg/ml, respectively, all p > 0.05, but faecal BAFF was higher in the IBD group: 15.1, 8.5 and 8.2 pg/ml, respectively, p < 0.05, and higher in the UC group (55.975 pg/ml) compared to the CD group (10.95 pg/ml), p = 0.015. Splitting the IBD group in relation to the CP level, the serum BAFF had no significantly different values between the subgroups, but the faecal BAFF was significantly higher in the >250 µg/g subgroup. Cut-off values of BAFF were calculated. CONCLUSION: Faecal BAFF is a promising marker for monitoring the children with IBD, higher levels of BAFF being correlated with high CP. IMPACT: Faecal BAFF is a promising marker in monitoring the children with IBD, higher levels of BAFF being correlated with high faecal calprotectin. To our knowledge, this is the first paediatric study concerning BAFF evaluation in IBD. Faecal BAFF levels could be considered a potential non-invasive marker in monitoring IBD activity in paediatric population with clinically mild or inactive disease.

Suboptimal Serum 25-Hydroxy-Vitamin D Is Associated with a History of Recent Disease Exacerbation in Pediatric Patients with Bronchial Asthma or Asthma-Suggestive Recurrent Wheezing.

Even though vitamin D is widely acknowledged as having a potential immunomodulatory role in asthma, its exact beneficial mechanisms are yet to be clarified. An optimal serum 25-hydroxy-vitamin D (25-OH-VitD) level in pediatric asthma patients might not rely solely on the effect of dose-dependent vitamin D3 intake, but might also be influenced by factors related to insufficient asthma control. We aimed to survey the prevalence of serum 25-OH-VitD deficiency and analyze whether suboptimal levels were associated with asthma severity factors. The current cross-sectional study enrolled 131 pediatric asthma or asthma-suggestive recurrent wheezing patients, for whom serum 25-OH-VitD, IgE, and eosinophil count were assessed. The prevalence of suboptimal serum 25-OH-VitD was 58.8%. A suboptimal vitamin D status was associated with asthma exacerbation in the previous month (p = 0.02). Even under seasonal oral vitamin D3 supplementation, patients with a positive history of asthma attack in the previous four weeks presented significantly lower serum 25-OH-VitD concentrations, compared to their peers with no disease exacerbation. In conclusion, sequential measurements of serum 25-OH-VitD might prove useful for future studies evaluating the dynamic changes in vitamin D3 status in regard to asthma, especially in symptomatic patients.

Low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet in children.

Irritable bowel syndrome (IBS) is a lifelong condition with a high prevalence among children and adults. As the diet is a frequent factor that triggers the symptoms, it has been assumed that by avoiding the consumption of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP), the symptoms might be improved. Therefore, in the past decade, low FODMAP diet has been intensively investigated in the management of IBS. The capacity of FODMAPs to trigger the symptoms in patients with IBS was related to the stimulation of mechanoreceptors in the small and large intestine. This stimulation appears as a response to a combination of increased luminal water (the osmotic effect) and the release of gases (carbon dioxide and hydrogen) due to the fermentation of oligosaccharides and malabsorption of fructose, lactose and polyols. Numerous studies have been published regarding the efficacy of a low FODMAP diet compared to a traditional diet in releasing the IBS symptoms in adults, but there are only a few studies in the juvenile population. The aim of this review is to analyze the current data on both low FODMAP diet in children with IBS and the effects on their nutritional status and physiological development, given the fact that it is a restrictive diet.

The role of novel atherosclerosis markers in peripheral artery disease: is there a gender difference?

Peripheral arterial disease (PAD) represents a major public health problem due to its high and increasing prevalence, worldwide distribution, and significant morbidity and mortality rate. Female gender is a risk factor for PAD globally and especially in low-income countries. In this review, we summarise the present knowledge regarding the role of novel atherosclerosis markers in the development of PAD in women. We discuss inflammatory markers, cytokines, cellular adhesion molecules, markers of oxidative stress and other circulating markers, and their role in the prediction of presence, severity and complications of PAD, with particular emphasis on gender. Although many PAD biomarkers are indicative of PAD in both males and females, some are strongly correlated with the disease in females. These gender differences could be useful for the early identification and management of PAD in women.

Antibiotic treatment in childhood community-acquired pneumonia - clinical practice versus guidelines: results from two university hospitals.

BACKGROUND AND AIMS: Community-acquired pneumonia (CAP) is a both common and serious childhood infection. Antibiotic treatment guidelines help to reduce inadequate antibiotics prescriptions. METHODS: We conducted a retrospective study at the Clinical Emergency Hospital for Children, 3rd Pediatric Clinic, Cluj-Napoca and Dr. Gavril Curteanu Clinical City Hospital, in Oradea. All patients discharged with a diagnosis of CAP between December 1, 2014 and February 28, 2015, were included in the study. RESULTS: There were 146 cases discharged with pneumonia in Cluj-Napoca center (mean age 4 years; range: 1 month - 16 years), and 212 cases in Oradea center (mean age 0.9 years; range: 2 weeks - 8 years). All cases were analyzed. The analysis made in Clinical Emergency Hospital for Children, 3rd Pediatric Clinic, Cluj-Napoca, showed that the antibiotics used in children hospitalized with community-acquired CAP are cefuroxime (43%), ceftriaxone (23%), macrolides (16%), ampicillin in association with an aminoglycoside (6%) and other antibiotics. The same antibiotics were used in Dr. Gavril Curteanu Clinical City Hospital of Oradea, where ampicillin in association with aminoglycoside was utilized in younger children (mean age 1.3 years), while ceftriaxone in older children (5.7 years) and children with high inflammation markers (ESR, CRP). From 11 pleurisy cases, 9 received cefuroxime or ceftriaxone. CONCLUSIONS: There was a wide variability in CAP antibiotic treatment across university hospitals, regarding antibiotic choice and dosing. Antibiotic selection was not always related to the clinical and laboratory characteristics of the patient. The national guideline was not followed, especially in children aged one to three months.

Echocardiography as the first diagnostic clue to rapidly progressive systemic AL amyloidosis associated with multiple site thrombosis. A case report.

AL-amyloidosis is a rare, but complex disease, with a severe prognosis, cardiac involvement being found in half of the patients. The rapid increase of the LV wall thickness predicts an unfavorable evolution. We report the case of a 63-year-old man diagnosed with AL-amyloidosis, with cardiac involvement, associated with multiple site thrombosis.  Specific echocardiographic methods like tissue Doppler imaging and speckle tracking provided crucial diagnostic and prognostic information.

Performance of lung ultrasonography for the diagnosis of communityacquired pneumonia in hospitalized children.

AIMS: The objective of the study was to assess the performance of lung ultrasonography (LUS) as compared to chest radiography and the clinical criteria for the diagnosis of pneumonia in children. MATERIALS AND METHODS: This was a retrospective study in which data were collected from medical files of 81 children admitted with a clinical suspicion of pneumonia in which both an LUS and a chest radiograph during the hospitalization were performed. Reference standard used for the diagnosis of pneumonia were chest radiographs (consolidation, parenchymal infiltrates, and interstitial infiltrate) and clinical criteria. LUSfindings were reported as normal, parenchymal consolidations and pleural effusions. RESULTS: Radiological pneumonia was reported in 72 of the 81 patients (88.9%). LUS identified parenchymal consolidations in 62 cases. LUS correctly identified radiological pneumonia with a sensitivity of 79.2% and a specificity of 44.4%. The positive predictive value (PPV) was 91.9% and the negative predictive value (NPV) was 21.0%. When clinical criteria were used as reference standard, the sensitivity, specificity, PPV and NPV of correctly identifying clinical pneumonia cases by LUS (only consolidations) were 80.0%, 66.7%, 96.8% and 21.0%. When indicative for the presence of pneumonia either the ultrasound consolidation or the ultrasound detected pleural effusion were considered when the sensitivity, PPV and NPV increased to 96.0% (95%CI: 88.8-99.2), 97.3% (95%CI: 92.0-99.1), and 57.1% (95%CI: 27.7-82.2), respectively. CONCLUSIONS: In our opinion, our findings together withprevious ones available in the literature recommend LUS as a valuable investigation for the diagnosis of community-acquiredpneumonia in children.

Fatal hypersensitivity pneumonitis after chemical occupational exposure.

Hypersensitivity pneumonitis (HP; extrinsic allergic alveolitis) is a rare non-immunoglobulin E (IgE)-mediated inflammatory lung disease caused by inhalation exposure (occupational, recreational or ordinary home exposure). A 36-year-old female patient, without significant medical history, is referred to an outpatient pulmonology clinic for dry cough, shortness of breath, fever, fatigue and weight loss. Chest high-resolution computed tomography (HRCT) was performed, and significant lung fibrosis (especially centrilobular and interlobular in bilateral "thick lines"), traction bronchiectasis and alveolitis in both superior lobes are described. Lung function tests showed severe restrictive dysfunction. Transfer factor of the lung for carbon monoxide (TLCO) being very low, the flexible bronchoscopy was contraindicated. Surgical lung biopsy was performed. Histopathological examination showed characteristic lesions of chronic bilateral hypersensitivity pneumonitis. The patient died four days after the surgical intervention due to post-operative complications. Exposure to various chemical substances can form bonds with human proteins molecules and induce an exaggerated immune response in susceptible individuals. A high index of suspicion of occupational exposure can determine an early diagnosis with a better outcome.

Autoimmune hepatitis with sclerosing cholangitis in a patient with thiopurine methyltransferase deficiency: case presentation.

The association between two autoimmune diseases is known in the literature as overlap syndrome. We present the case of an 18-year-old boy, diagnosed at the age of 13 with an overlap syndrome between type I autoimmune hepatitis and sclerosing cholangitis. The response to immunosuppressant therapy was hampered by azathioprine-induced toxicity causing severe pancytopenia, as a result of thiopurine methyltransferase enzyme genetic deficiency. Treatment was replaced by mycophenolate mofetil. Although the relapse rate was reduced, the disease progressed to cirrhosis. Specific features of this case were the overlap syndrome, young age of onset, especially for sclerosing cholangitis, azathioprine toxicity that influenced the prognosis and the treatment problems regarding the use and efficiency of alternative immunosuppressant agents in pediatric patients.

Myositis ossificans traumatica of the neck - a pediatric case.

Myositis ossificans circumscripta (MOC) is an extra-osseous non- neoplastic growth of a new bone. It occurs most commonly in the second and the third decade of life, while it is rare in children. The etiology of MOC is unknown and the quadriceps and brachials are the most affected. The occurrence of traumatic MOC in tissues of the neck is uncommon. We are presenting below a rare case of traumatic myositis ossificans occurring in sternocleidomastoid and trapezius muscles in a 17-year-old girl.

Immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted vaccine administered according to an alternative dosing schedule compared with the standard dosing schedule in healthy women aged 15 to 25 years: results from a randomized study.

BACKGROUND: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine is immunogenic, has a clinically acceptable safety profile, and prevents incident and persistent HPV-16/18 infection and cervical precancerous lesions. This study (NCT00552279) evaluated the vaccine when administered according to an alternative dosing schedule (0-1-12 months) compared with the standard dosing schedule (0-1-6 months). METHODS: The study was of randomized open design and was conducted at multiple centers in Europe. Healthy women aged 15 to 25 years were randomized (1:1) to receive HPV-16/18 vaccine according to the standard schedule at months 0, 1, and 6 (n = 401) or an alternative schedule at months 0, 1, and 12 (n = 403). HPV-16 and -18 antibodies were measured by enzyme-linked immunosorbent assay at months 0, 2, and 7 or 13 (depending on group); noninferiority evaluation was performed sequentially for seroconversion rates and geometric mean antibody titers. Primary analysis of immunogenicity was based on the according-to-protocol cohort. Vaccine safety and reactogenicity were assessed on the total vaccinated cohort. RESULTS: Predefined noninferiority criteria were met 1 month after the third vaccine dose when the HPV-16/18 vaccine was administered according to the 0-1-12 month schedule compared with the 0-1-6 month schedule in terms of seroconversion rates for HPV-16 (100% and 100%) and HPV-18 (99.7% and 100%) and geometric mean antibody titers for HPV-16 (11884.7 and 10311.9 ELISA units/mL) and HPV-18 (4501.3 and 3963.6 ELISA units/mL), respectively. The HPV-16/18 vaccine had a clinically acceptable safety profile when administered according to either schedule. CONCLUSIONS: The third dose of the HPV-16/18 vaccine can be administered any time between 6 and 12 months after the first dose, with adequate immunogenicity and a clinically acceptable safety profile.

The interrupter technique: feasibility in children in acute asthma.

BACKGROUND: Asthma exacerbation's severity is difficult to evaluate, as it is mainly assessed by clinical parameters. Evaluation of lung function during the acute asthma might provide an objective assessment on the severity of respiratory function impairment. OBJECTIVE: To determine feasibility of interrupter technique in evaluating respiratory resistance (Rocc) on children with acute asthmaMethods: The study included 30 children aged 3 to 14 years, diagnosed with asthma, during an exacerbation; severity of acute asthma has been assessed according to the GINA classification 2007, evaluating individual parameters like intercostals retractions, wheezing, air entry intensity, as well as their association in a clinical score. For every patient spirometry, peakflowmetry and the interrupter technique was applied for assessing respiratory function. The feasibility rate for each method was calculated and compared with the clinical parameters. RESULTS: Out of the 30 children examined, the feasibility rate during the attack was 90% for the interrupter technique, 47% for peakflowmetry and only 27% for spirometry. Fifty-three percent of the exacerbations were classified as mild, 30% of moderate intensity and the remaining 37% being classified as severe exacerbations. The baseline Rocc has been correlated with clinical parameters and the clinical severity score. Best correlations were recorded between baseline Rocc and respiratory rate (r=0.73, p<0.0001), Rocc and heart rate (r=0.5, p=0.0076) and Rocc and the clinical score (r= 0.78, p<0.0001). CONCLUSION: The study shows good feasibility of interrupter technique during asthma exacerbations, as well as strong correlation with clinical parameters assessing severity.