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Pulmonary renal syndrome in a child with coexistence of anti-neutrophil cytoplasmic antibodies and anti-glomerular basement membrane disease: case report and literature review

BackgroundPulmonary renal syndrome (PRS), denoting the presence of diffuse alveolar hemorrhage and glomerulonephritis as manifestations of systemic autoimmune disease, is very rare in childhood. The coexistence of circulating anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) disease in children affected by this syndrome is exceptional, with unfavorable outcome in five out of seven patients reported to date. We describe a child with PRS associated with both circulating anti-myeloperoxidase (anti-MPO) ANCA and anti-GBM disease on renal biopsy who was successfully treated with immunosuppressive therapy.Case presentationA 10-year old girl presented with fever, fatigue, malaise, and pallor followed by hemoptysis and severe anemia. Diffuse alveolar hemorrhage was revealed on fiberoptic bronchoscopy. Renal findings consisted of microscopic hematuria, moderate proteinuria, and anti-GBM disease on renal biopsy. ANCA with anti-MPO specificity were present whereas anti-GBM antibodies were on borderline for positivity. Methyl-prednisolone pulses followed by prednisone led to cessation of hemoptysis, marked improvement of lung fuction, and normal finding on chest x-ray within 10 days. An immunosuppressive regimen was then given consisting of prednisone daily for 4 weeks with subsequent taper on alternate day, i.v. cyclophosphamide pulses monthly for 6 doses, followed by mycophenolate mofetil that resulted in normal lung function tests, hemoglobin concentration, and anti-MPO level within four subsequent weeks. During 10-months of follow-up she remained well, her blood pressure and renal function tests were normal, and proteinuria and hematuria gradually resolved.ConclusionWe report a child with an exceptionally rare coexistence of circulating ANCA and anti-GBM disease manifesting as PRS in whom renal disease was not the prominent part of clinical presentation, contrary to other reported pediatric patients. A review of literature on disease with double positive antibodies is also presented. Evaluation of a patient with PRS should include testing for presence of different antibodies. An early diagnosis and rapid institution of aggressive immunosuppressive therapy can induce remission and preserve renal function. Renal prognosis depends on the extent of kidney injury at diagnosis and appropriate treatment.

Home mechanical ventilation in children is feasible in developing countries

Background:  The results of many national surveys on pediatric home mechanical ventilation (HMV) in developed countries have been presented elsewhere, but data from developing countries with low national incomes are scarce.

Static Hyperinflation Is Associated With Decreased Peak Exercise Performance in Children With Cystic Fibrosis

BACKGROUND: We evaluated the exercise capacity of children with cystic fibrosis to determine whether ventilatory limitation associated with static hyperinflation is related with decreased exercise capacity, thus predisposing these children to arterial hypoxemia during progressive exercise. METHODS: Thirty-seven children, ages 8–17 years, underwent spirometry, body plethysmography, and cardiopulmonary exercise testing after arterial catheter placement. According to the ratio of residual volume to total lung capacity (RV/TLC), the subjects were categorized as either with (RV/TLC > 30%) or without static hyperinflation (RV/TLC < 30%). RESULTS: Children with static hyperinflation showed lower values of maximum load per kilogram (% predicted) (P = .01), which was aggravated by ventilatory limitation (FEV1 < 80% of predicted, peak oxygen consumption [% predicted] < 85%, and breathing reserve index > 0.7). Subjects with ventilatory limitation had significantly lower oxygen saturation (P = .04) and hypoxemia (P = .03) than did subjects without ventilatory limitation. CONCLUSIONS: In children with cystic fibrosis, static hyperinflation and ventilatory limitation are associated with decrease in exercise performance, oxygen saturation, and PaO2 during maximum cardiopulmonary exercise testing. All children with cystic fibrosis who exhibit static hyperinflation and ventilatory limitation may require SaO2 monitoring during progressive exercise.

Successful treatment of hodgkin lymphoma in nijmegen breakage syndrome.

Nijmegen breakage syndrome (NBS) is a rare DNA repair disorder characterized by microcephaly, immunodeficiency, and predisposition to malignancy. We report on a 5-year-old patient with NBS who presented with nodular sclerosing type of Hodgkin disease stage IVB. Chemotherapy consisting of COPP/ABV regimen with reduction at 75% of full doses was employed. During this treatment, no major toxic or infectious complications were observed. Complete remission was achieved lasting now for 20 months. In DNA repair disorders, prognosis of Hodgkin disease is poor as opposed to excellent overall prognosis in general pediatric population. Better survival may be achieved both with adopted, disease-specific regimens, and individualized approach considering patients clinical condition. Also, better recognition and treatment of infections during chemotherapy may reduce early deaths in patients with DNA repair disorders.

Clinical characteristics of respiratory syncytial virus infection in neonates and young infants.

INTRODUCTION/AIM Infection with respiratory syncytial virus (RSV) occurs during the first year of life in 50% of children and 20%-40% of them have signs of lower respiratory tract infection (bronchiolitis or pneumonia). There is an increased risk for complicated course and death from RSV infection in premature infants, especially those with bronchopulmonary dysplasia (BPD) or congenital heart disease. The aim of our study was to analyze clinical characteristics of laboratory confirmed RSV infection in order to evaluate the need for preventive measures in neonates and young infants. METHODS The prospective study included children under age of 12 months admitted to our hospital in the period November 2008-March 2009 who were positive for RSV by enzyme immunoassay membrane test. The course of disease was assessed by clinical score and radiographic findings. RESULTS Infection with RSV was confirmed in 91 patients: 21 (23.0%) were under the age of 30 days, 37 (40.7%) were between 31-60 days, and 33 patients (36.3%) were older than 60 days (p > 0.05). The highest hospitalization rate was in January--33 patients (36.3%; p < 0.01). Disease severity score in these age groups (AG) were: 8.4 +/- 0.4 (AG 0-30 days); 9.0 +/- 0.3 (AG 31-60 days) and 8.3 +/- 0.3 (AG > 60 days), without statistically significant difference among the groups (p > 0.05). Clinical scores in patients with and without risk factors were 10.5 +/- 0.5 and 8.3 +/- 0.2, respectively (p < 0.01). Pathological radiographic findings were observed in 72 (79.1%) and complications (apnea, significant atelectasis, encephalopathy) occured in 15 (16.5%) patients. The average length of hospital stay in complicated and uncomplicated course of the disease was 9 days and 6 days, respectively (p < 0.01). Therapy in 85 (93.4%) patients included bronchodilators, while systemic glucocorticoids and oxygen therapy were used in 51 (56.0%) and 44 (48.4%) patients, respectively. Death occured in 2 (2.2%) patients, both from a high risk group (the patient with BPD and the other one with congenital heart disease and Down syndrome). CONCLUSION Infection with RSV in our settings showed marked seasonal characteristics with highest hospitalization rate in January. Although the course and outcome of the disease were favorable in the majority of our patients, the need for hospitalization and administration of therapy with possible side effects warrants that general measures for prevention of respiratory infections are followed especially in the first year of life. Severe disease and death are more probable in neonates and infants with risk factors. In these children passive immunisation with specific monoclonal antibody (e.g. palivizumab) during RSV season should be considered.

Surgical treatment of severe laryngomalacia: Six month follow up

Laryngomalacia (LM) is the most common congenital anomaly of larynx that causes stridor in children. We evaluated the efficacy of epiglottic suture and laser epiglottopexy for treatment of infants with severe LM.

Candida bloodstream infections in Serbia: First multicentre report of a national prospective observational survey in intensive care units

Candida bloodstream infections (BSI) are a significant cause of mortality in intensive care units (ICU), hereof the prospective 12‐months (2014‐2015) hospital‐ and laboratory‐based survey was performed at the Serbian National Reference Medical Mycology Laboratory (NRMML). Candida identification was done by a matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry and a susceptibility test, according to the Clinical and Laboratory Standards Institute methodology. Among nine centres (265 beds; 10 820 patient admissions), four neonatal/paediatric (NICU/PICUs) and five adult centres (ICUs) participated, representing 89 beds and 3446 patient admissions, 166 beds and 7347 patient admissions respectively. The NRMML received 43 isolates, 17 from NICU/PICUs and 26 from adult ICUs. C. albicans dominated highly in NICU/PICUs (~71%), whereas C. albicans and C. parapsilosis were equally distributed within adults (46%, each), both accounting for ~90% of received isolates. The resistance to itraconazole and flucytosine were 25% and 2.4% respectively. In addition, the 2 C. albicans were azole cross‐resistant (4.6%). The overall incidence of CandidaBSI was ~3.97 cases/1000 patient admissions (4.93 in NICU/PICU and 3.53 in adult ICU). The 30‐day mortality was ~37%, most associated with C. tropicalis and C. glabrataBSI. Data from this national survey may contribute to improving the Balkan and Mediterranean region epidemiology of CandidaBSI within ICUs.

Successful treatment of laryngomalacia and bilateral vocal cord paralysis with continuous positive airway pressure

INTRODUCTION Laryngomalacia is the most frequent congenital anomaly of airways, and it may cause obstructive sleep apneas. The associated vocal cord paralysis may aggravate the symptoms of upper airway obstruction. CASE REPORT In a 14 month old boy severe laryngomalacia and bilateral vocal cord paralysis were diagnosed by flexible bronchoscopy. A sleep study showed a severe obstructive sleep apnoea (OSA). The patient was ventilated at home via the face mask with non invasive mechanical ventilation (CPAP) for a year. The level of pressure had to be set at 7 cm H2O to correct desaturation with an improvement in mean SpO2. On the follow up bronchoscopic examination laryngomalatia was improved, vocal cord paralysis persisted and sleep study revealed significant improvement. DISCUSSION In the patient with severe laryngomalatia and bilateral vocal cord paralysis with OSA conservative treatment with CPAP was used instead of a surgical intervention. Non invasive ventilation was used every night, for at least 6 hours, without adverse events. Invasive measurement of transdiaphragmatic pressure is the best way of titrating of CPAP level. This case report suggests the efficacy of noninvasive titrating of CPAP level by the hemoglobin oxygen saturation trend measurement. CONCLUSION In case of severe laryngomalatia and associated vocal cord paralysis, followed by OSA non invasive ventilation by nasal CPAP represents an effective and safe alternative to surgery.

Late-Presenting Congenital Diaphragmatic Hernia in a Child with Tmem70 Deficiency.

Transmembrane protein 70 (TMEM70) deficiency has been delineated as a distinct mitochondrial disease less than a decade ago (Cízková et al. 2008). Hallmarks of the disease include hypotonia, developmental delay, hypertrophic cardiomyopathy (HCM), facial dysmorphism, microcephaly, hypospadia, lactic acidosis and 3-methylglutaconic aciduria (3MGA). Although there is no curative treatment, proper management of hyperammonemic metabolic crises seems to be crucial for the prognosis of these patients. Characteristic facial features with high forehead, downslanting palpebral fissures, curved eyebrows, prominent nasal bridge, low-set ears, thin lips, microretrognathia and ptosis have been described in two-thirds of patients. The disease is panethnic but particularly common in the Roma population with prevalent c.317-2 A > G mutation (Spiegel et al. 2011, Magner et al. 2015). Congenital malformations in patients with TMEM70 deficiency include heart defects (36%) with valve defects and aortic coarctation, hypospadia (50% of affected boys), umbilical and inguinal hernias (approximately one-third of cases), syndactyly between the second and third finger, congenital cataract, and agenesis or hypoplasia of corpus callosum (Spiegel et al. 2011, Magner et al. 2015). Congenital diaphragmatic hernia (CDH) has been described only in one patient with this disease, so far (Catteruccia et al. 2014). We report herein the second case of unique association of TMEM70 deficiency and CDH. Severe lactic acidosis and HCM were noted in a boy of Roma ethnicity in the neonatal period. Microcephaly, hypotonia and dysmorphic facial features (synophris, curved eyebrows, anteverted nostrils, low set ears, microretrognathia), but no hypospadia, were observed later in infancy. Chest radiograph made at the age of one year did not show presence of diaphragmatic hernia. At the age of 3.5 years, the boy was admitted to hospital due to vomiting and somnolence. Physical exam revealed tachycardia, tachypnoea and decreased breathing sounds on the left side of the chest. Chest radiograph showed hydroaeric levels at the left thoracic side (Fig. 1A). Upper gastrointestinal series with small bowel follow-through showed normally positioned esophagus and stomach, whereas duodenum ascended towards the left part of the chest cavity, which was filled with intestinal loops (Fig. 1B). Posterolateral left Bochdalek hernia with defect diameter of 5 cm and hernial sac protruding to the chest cavity was visualized during surgical intervention. The whole jejunum and ileum, including the ileocecal valve, was herniated. After repositioning of the abdominal organs, plastic of diaphragm and Ladd procedure followed. Twelve months later, the boy succumbed to severe metabolic crisis with lactic acidemia but absent 3MGA. Unfortunately, ammonia level was not measured at the time. Post-mortem mutation analysis of TMEM70 in the patient’s DNA sample documented homozygous mutation c.3172 A > G. Associated congenital anomalies are found in 8.6% of patients with late presenting CDH, cardiac anomalies being the most frequent (Bagłaj 2004). In dual-hit hypothesis of CDH evolution, a primary bilateral lung hypoplasia results from combined genetic and external factors, while the second hit affects only the left lung by pressure of intrathoracic bowels (Keijzer et al. 2000). Although the lung hypoplasia was described in one patient with TMEM70 (Spiegel et al. 2011), there was no proof of hypoplastic lungs in our patient or in the patient reported by Catterucia et al. (2014). Hypoplastic lungs may cause the persistent pulmonary hypertension in newborn (PPHN), which is frequently observed in children with TMEM70 (>50%). However, this finding has probably no relation to the reported CDH (Catteruccia et al. 2014). The second case, reported herein, further supports the association between TMEM70 deficiency and CDH, which might help to diagnose this rare but treatable disorder.

112 Analysis of long-term use of liposomal amikacin for inhalation (LAI) in patients with cystic fibrosis (CF) who have chronic infection from Pseudomonas aeruginosa

Objective Interim analysis to evaluate safety, tolerability, and efficacy of LAI, a novel amikacin formulation, in CF patients with chronic P aeruginosa infection previously treated with LAI or tobramycin inhalation solution (TIS). Methods In the CLEAR-108 trial, patients were randomized 1:1 to 3 treatment cycles (28 days on/28 days off) of LAI 590 mg QD or TIS 300 mg BID via nebulizer, and stratified by age and forced expiratory volume in 1 second (FEV 1 ). Eligible patients completing the CLEAR-108 trial enrolled in CLEAR-110 for up to 12 treatment cycles of LAI 590 mg QD via nebulizer. Results Of 266 patients who completed CLEAR-108, 206 (92 LAI; 114 TIS) enrolled in CLEAR-110 and received at least 1 dose of LAI 590 mg QD. At this data cut, 149 patients had completed ≥1 year (6 cycles) of LAI treatment in CLEAR-110. At the end of the 6th off-treatment cycle, FEV 1 continued to improve above baseline; relative mean change was 1.11% and 3.39% in patients on prior TIS and LAI, respectively. P aeruginosa sputum density reductions were similar regardless of prior treatment. 84.5% of patients on LAI had ≥1 TEAE (mild, 23.8%; moderate, 49.0%). As in CLEAR-108, most AEs were respiratory: the highest frequency occurred in Cycle 1 for patients in CLEAR-110 from the TIS arm (Cycles 1, 6: 21.1%, 8.6%). In the LAI arm, respiratory AEs were 7.6% and 8.9% for Cycles 1 and 6. A complete 2-year data set is expected in 2015. Conclusion LAI provides sustained pulmonary function improvement in CF patients infected with P aeruginosa. LAI has stable safety/tolerability with prolonged exposure. Data from ongoing analyses will deepen understanding of factors impacting patient response.