Publications by authors named "Dario Prais"

51 Publications

Low flow intermittent bronchoscopic oxygen insufflation to identify occult tracheo-esophageal fistulas.

Respir Med 2021 Jul 24;186:106544. Epub 2021 Jul 24.

Pulmonary Institute, Schneider Children's Medical Center, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.

Background: Esophageal atresia and tracheo-esophageal fistula (TEF), a well described congenital anomaly of the aero-digestive tract, commonly presents with inability to swallow and feed immediately after birth. However, diagnosis of recurrent or isolated TEF can be challenging and requires a combination of endoscopic and contrast studies. We describe a hitherto unreported technique of low flow intermittent oxygen insufflation into the suspicious tract and examine its safety and diagnostic yield for identification of occult TEF.

Methods: A retrospective single center cohort study, analyzing case notes of patients with TEF who underwent bronchoscopic oxygen insufflation for suspected recurrent or isolated TEF between 2006 and 2019 at a tertiary pediatric hospital.

Results: One-hundred and seven patients with TEF underwent 142 bronchoscopies during the study period. Of these, 22 patients underwent 28 bronchoscopies with oxygen insufflation. Twelve (43%) open fistulas were identified; of these, 9 (75%) were found using oxygen insufflation, revealing the fistula in 4/9 (44%) cases that had not been apparent using simple bronchoscopic visualization alone. One fistula was missed with multiple investigations, including bronchography and found only using oxygen insufflation. No complications were encountered.

Conclusions: Recurrent or isolated TEF may be missed using ordinary flexible bronchoscopy and imaging studies. Low flow oxygen insufflation can be applied safely and may detect otherwise occult TEF.
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http://dx.doi.org/10.1016/j.rmed.2021.106544DOI Listing
July 2021

Effects of Wearing Facemasks During Brisk Walks: A COVID-19 Dilemma.

J Am Board Fam Med 2021 Jul-Aug;34(4):798-801

From the Pulmonary Institute, Schneider Children's Medical Center of Israel, Petach Tikva, Israel (OB-O, YG, PS, HL, GS, ES, DP, MM-Z); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (PS, HL, DP, MM-Z); The Department of Nursing, Ariel University, Ariel, Israel (YG).

Background: During the Coronavirus disease 2019 (COVID-19) pandemic, wearing facemasks became obligatory worldwide.

Objectives: The objective of this study was to evaluate the effects of facemasks on gas exchange.

Methods: Healthy adults were assessed at rest and during slow and brisk 5-minute walks, with and without masks. We monitored O saturation, end-tidal carbon dioxide (EtCO), and heart and respiratory rates. Participants graded their subjective difficulty and completed individual sensations questionnaires.

Results: Twenty-one participants with a median age of 38 years (range, 29-57 years) were recruited. At rest, all vital signs remained normal, without and with masks. However, during slow and brisk walks, EtCO increased; the rise was significantly higher while wearing masks: slow walk, mean EtCO (mmHg) change +4.5 ± 2.4 versus +2.9 ± 2.3, = .004; brisk walk EtCO change +8.4 ± 3.0 versus +6.2 ± 4.0, = .009, with and without masks, respectively. Wearing masks was also associated with higher proportions of participant hypercarbia (EtCO range, 46-49 mmHg) compared with walking without masks, though this was only partially significant. Mean O-saturation remained stable (98%) while walking without masks but decreased by 1.2 % ± 2.2 while walking briskly with a mask ( = .01). Mild desaturation (O range, 93% to 96%) was noted during brisk walks among 43% of participants with masks, compared with only 14% without masks ( = .08). Borg's scale significantly increased while walking with a mask, for both slow and brisk walks ( < .001). Sensations of difficulty breathing and shortness of breath were more common while walking with masks.

Conclusion: While important to prevent viral spread, wearing facemasks during brisk 5-minute walks might be associated with mild hypercarbia and desaturation. The clinical significance of these minor gas exchange abnormalities is unclear and should be further investigated.
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http://dx.doi.org/10.3122/jabfm.2021.04.200559DOI Listing
October 2020

COVID-19 in advanced Duchenne/Becker muscular dystrophy patients.

Neuromuscul Disord 2021 Apr 6. Epub 2021 Apr 6.

Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel; Department of Pediatrics B, Schneider Children's Medical Center, Petah-Tikva, Israel; Pediatric Infectious Disease Unit, Schneider Children's Medical Center.

Duchenne muscular dystrophy (DMD) is the most common childhood muscular dystrophy. As a result of progressive muscle weakness, pulmonary function decreases during the second decade of life and lung disease contributes significantly to morbidity and mortality in these patients. Corticosteroids are the current standard of care for patients with DMD, despite known adverse effects such as obesity and immunosuppression. Over the past year (2020), the novel coronavirus (COVID-19/SARS-CoV2) outbreak has caused a global pandemic. Restrictive lung disease due to low lung volumes, chronic immunosuppressive treatment with corticosteroids, and obesity are potential risk factors that may contribute to a more severe course of the disease. Out of 116 Duchenne/Becker muscular dystrophy patients treated in our tertiary neuromuscular center, six patients with DMD and one with advanced Becker muscular dystrophy were found to be positive for COVID-19 infection. Two of the DMD patients were admitted for hospitalization, of whom one was dependent on daily nocturnal non-invasive ventilation. All patients recovered without complications despite obesity, steroid treatment and severe restrictive lung disease.
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http://dx.doi.org/10.1016/j.nmd.2021.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021445PMC
April 2021

Risk factors for respiratory syncytial virus bronchiolitis hospitalizations in children with chronic diseases.

Pediatr Pulmonol 2021 Jul 7;56(7):2204-2211. Epub 2021 May 7.

Pediatric Pulmonology Institute, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Background: Respiratory syncytial virus (RSV) bronchiolitis is the most common lower respiratory tract disorder causing hospitalization in infants. Due to decreased hospitalization rates of premature infants following Palivizumab immune prophylaxis, the proportion of infants with chronic diseases not eligible for Palivizumab has increased.

Aim: To characterize infants hospitalized during 2014-2018 with RSV bronchiolitis, to compare between those with and without chronic conditions, and to identify risk factors for severe disease.

Methods: This retrospective study analyzed demographic and clinical data of patients younger than 2 years admitted with bronchiolitis during four consecutive RSV seasons.

Results: Of 1124 hospitalizations due to RSV bronchiolitis, 244 (22%) were in infants with chronic diseases. Although 20/1124 qualified for RSV prophylaxis, only eight received immune prophylaxis. Compared to otherwise healthy infants, children with chronic diseases had longer hospitalizations, median 4.8 days (interquartile range [IQR]: 3.4-8.3) versus 3.7 days (IQR: 2.7-5.1), p < .001; and higher pediatric intensive care unit (PICU) and readmission rates (9% vs. 4.5%, p = .007% and 3% vs. 1%, p = .055, respectively). Children with Down's syndrome comprised 2% of all hospitalizations, but 8% of PICU admissions; their median length of hospitalization was 10.7 days (IQR: 6.6-17.6). Respiratory tract malformations were present in 2% of hospitalizations, and comprised 4% of PICU admissions.

Conclusion: Among infants admitted with RSV bronchiolitis, those with chronic diseases had longer hospitalizations and higher rates of transfer to the PICU. Children with multiple comorbidities, and especially those with Down's syndrome, are at particularly high risk for severe hospitalization and may benefit from RSV immune prophylaxis.
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http://dx.doi.org/10.1002/ppul.25435DOI Listing
July 2021

Diagnostic value of sputum cultures in children under 2 years of age with chronic suppurative lung diseases.

Pediatr Pulmonol 2020 12 12;55(12):3421-3428. Epub 2020 Oct 12.

Graub CF Center Pulmonary Institute, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Background: Acquiring sputum cultures from infants is considered challenging. We describe their yield in infants with cystic fibrosis (CF) and other chronic suppurative lung diseases (CSLDs).

Methods: Retrospective medical record review over a 4-year period, for infants aged 0-2 years with ≥2 airway bacterial cultures acquired by deep suction or induced sputum ≥4 weeks apart. Data included demographics, culture results, and clinical status.

Results: A total of 98 infants (16 CF) were evaluated and 534 sputum cultures acquired, 201 in CF and 333 in CSLD. There were 12 (2-23), median (range) cultures/CF infant, and 3 (2-21)/CSLD infant. Age at first culture was 3.8 (1-19.5) months for CF and 10.4 (0.5-22) months for CSLD; p = .016. In total, 360 cultures (67%) were positive for any bacteria, with 170/234 (73%) positive during exacerbations, compared with 190/300 (63%) during routine visits; p = .05. More infants with CF than CSLD had cultures positive for Staphylococcus aureus (SA; 75% vs. 34%; p = .004) throughout the period. Pseudomonas aeruginosa (PA) was common in both CF and CSLD (56% and 44%, respectively; p = .42) and increased over time for CF but was high throughout for CSLD. The number of hospital days before PA acquisition was 6 (10.2) for CF and 28.8 (38.7) for CSLD (p = .003). No CF but 6/82 (7%) CSLD infants had chronic PA (p = .56).

Conclusions: Sputum cultures showed that infection, in particular PA, is common in CF and CSLD whereas SA is more common in CF. Prospective studies are warranted to elucidate the role of active surveillance in guiding antibiotic therapy.
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http://dx.doi.org/10.1002/ppul.25103DOI Listing
December 2020

Topical Propranolol Improves Epistaxis Control in Hereditary Hemorrhagic Telangiectasia (HHT): A Randomized Double-Blind Placebo-Controlled Trial.

J Clin Med 2020 Sep 28;9(10). Epub 2020 Sep 28.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

Epistaxis is a common debilitating manifestation in hereditary hemorrhagic telangiectasia (HHT), due to mucocutaneous telangiectases. The epistaxis can be difficult to control despite available treatments. Dysregulated angiogenesis has been shown to be associated with telangiectases formation. Topical propranolol has demonstrated antiangiogenic properties. We performed a two-phase study, i.e., a double-blind placebo-controlled phase, followed by an open-label phase. The aim of the study was assessment of safety and efficacy of nasal propranolol gel in HHT-related epistaxis. Twenty participants with moderate-severe HHT-related epistaxis were randomized to eight weeks of propranolol gel 1.5%, or placebo 0.5 cc, applied to each nostril twice daily; and continued propranolol for eight weeks in an open-label study. For the propranolol group, the epistaxis severity score (ESS) improved significantly (-2.03 ± 1.7 as compared with -0.35 ± 0.68 for the placebo group, = 0.009); hemoglobin levels improved significantly (10.5 ± 2.6 to 11.4 ± 2.02 g/dL, = 0.009); and intravenous iron and blood transfusion requirement decreased. The change in nasal endoscopy findings was not significant. During the open-label period, the ESS score improved significantly in the former placebo group (-1.99 ± 1.41, = 0.005). The most common adverse event was nasal mucosa burning sensation. No cardiovascular events were reported. Our results suggest that topical propranolol gel is safe and effective in HHT-related epistaxis.
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http://dx.doi.org/10.3390/jcm9103130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601781PMC
September 2020

Palivizumab Following Extremely Premature Birth Does Not Affect Pulmonary Outcomes in Adolescence.

Chest 2020 08 13;158(2):660-669. Epub 2020 Apr 13.

Pulmonary Institute, Schneider Children's Medical Center of Israel, Petah Tikva; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv. Electronic address:

Background: Prematurity is a risk factor for impaired lung function. We sought to assess the long-term effect of palivizumab immunization and extreme prematurity (<29 weeks gestation) on respiratory symptoms and pulmonary function in adolescence.

Research Question: What is the long-term effect of palivizumab immunization and extreme prematurity (<29 weeks) on respiratory symptoms and pulmonary function in adolescence?

Study Design And Methods: We examined survivors of extreme prematurity (<29 weeks gestation) at 13 to 18 years of age (study group). Study group babies who were born immediately before palivizumab immunization (nonpalivizumab group [NPG]) were compared with those babies who were born just after implementation (PG) and with a control group. For study group patients, lung function in adolescence was further compared longitudinally with that at primary school age.

Results: Sixty-four adolescents aged 15.76 ± 1.52 years were included: 46 in the study group (17 PG and 29 NPG) and 18 in the control group. For the study group, wheezing episodes, inhaler use, and hospitalizations were uncommon. For the study group compared with the control group, FEV percent predicted was 82.60% ± 13.54% vs 105.83% ± 13.12% (P < .001), and the lung clearance index was 7.67 ± 1.02 vs 7.46 ± 0.70 (P = .48), respectively. Study group adolescents with bronchopulmonary dysplasia had a higher lung clearance index than did adolescents with no bronchopulmonary dysplasia (7.94 ± 1.11 vs 7.20 ± 0.60; P = .002). PG and NPG adolescents were not significantly different. Comparing the study group in adolescence with primary school age, we found improvement in mean FEV percent predicted bronchodilator response (0.37% ± 9.98% vs 5.67% ± 9.87%; P = .036) and mean provocative concentration causing 20% decline in FEV (12.16 ± 4.71 mg/mL vs 4.14 ± 4.51 mg/mL, respectively; P < .001).

Interpretation: Palivizumab did not provide any discernable long-term protective effect. Nevertheless, adolescent survivors of extreme prematurity showed good clinical and physiologic outcomes, except for mildly raised lung clearance index in patients with bronchopulmonary dysplasia. Airway hyperreactivity detected at primary school age, decreased by adolescence.
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http://dx.doi.org/10.1016/j.chest.2020.02.075DOI Listing
August 2020

Validation of a computerized scoring system for foreign body aspiration: An observational study.

Pediatr Pulmonol 2020 03 7;55(3):690-696. Epub 2020 Jan 7.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objective: The diagnosis of foreign body aspiration (FBA) is challenging. In a previous study, we developed a computerized scoring system (CSS) to support decision-making. In the present study, we aimed to validate it on a further cohort.

Study Design: In this observational study, 100 children referred to the emergency department of a tertiary pediatric hospital for suspected FBA and treated according to standard protocol, were assigned a probability score using the CSS, between 0 and 1 (0, very low probability; 1, very high). The diagnosis of FBA was based on bronchoscopy, and if discharged without bronchoscopy, determined via telephone questionnaire, 4 to 6 months after discharge, supplemented by clinical re-evaluation and bronchoscopy, if respiratory symptoms persisted.

Results: Thirty-five out of 100 children (35%) underwent bronchoscopy with 12 of 35 (34%) positive for FBA. Sixty-five patients were discharged without bronchoscopy and completed a telephone questionnaire. Seven patients required clinical re-evaluation for persistent respiratory symptoms, in two out of them, additional bronchoscopies were performed and were negative. The CSS median probability score was 0.94 in patients with FBA, as compared to 0.73 in patients without FBA (P = .007). The CSS area under the receiver operating curve was 0.74. At a probability score threshold of 0.6, the sensitivity and specificity were 100% and 41%, respectively.

Conclusion: The present validation study suggests a high sensitivity of the CSS for the identification of FBA in children. We suggest that it might aid decision-making with regard to the need for bronchoscopy in children presenting to the emergency room.
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http://dx.doi.org/10.1002/ppul.24632DOI Listing
March 2020

VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles.

N Engl J Med 2018 10 18;379(17):1599-1611. Epub 2018 Oct 18.

From Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).

Background: The next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector VX-659, in triple combination with tezacaftor and ivacaftor (VX-659-tezacaftor-ivacaftor), was developed to restore the function of Phe508del CFTR protein in patients with cystic fibrosis.

Methods: We evaluated the effects of VX-659-tezacaftor-ivacaftor on the processing, trafficking, and function of Phe508del CFTR protein using human bronchial epithelial cells. A range of oral VX-659-tezacaftor-ivacaftor doses in triple combination were then evaluated in randomized, controlled, double-blind, multicenter trials involving patients with cystic fibrosis who were heterozygous for the Phe508del CFTR mutation and a minimal-function CFTR mutation (Phe508del-MF genotypes) or homozygous for the Phe508del CFTR mutation (Phe508del-Phe508del genotype). The primary end points were safety and the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV).

Results: VX-659-tezacaftor-ivacaftor significantly improved the processing and trafficking of Phe508del CFTR protein as well as chloride transport in vitro. In patients, VX-659-tezacaftor-ivacaftor had an acceptable safety and side-effect profile. Most adverse events were mild or moderate. VX-659-tezacaftor-ivacaftor resulted in significant mean increases in the percentage of predicted FEV through day 29 (P<0.001) of up to 13.3 points in patients with Phe508del-MF genotypes; in patients with the Phe508del-Phe508del genotype already receiving tezacaftor-ivacaftor, adding VX-659 resulted in a further 9.7-point increase in the percentage of predicted FEV. The sweat chloride concentrations and scores on the respiratory domain of the Cystic Fibrosis Questionnaire-Revised improved in both patient populations.

Conclusions: Robust in vitro activity of VX-659-tezacaftor-ivacaftor targeting Phe508del CFTR protein translated into improvements for patients with Phe508del-MF or Phe508del-Phe508del genotypes. VX-659 triple-combination regimens have the potential to treat the underlying cause of disease in approximately 90% of patients with cystic fibrosis. (Funded by Vertex Pharmaceuticals; VX16-659-101 and VX16-659-001 ClinicalTrials.gov numbers, NCT03224351 and NCT03029455 .).
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http://dx.doi.org/10.1056/NEJMoa1807119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277022PMC
October 2018

Inspiromatic-safety and efficacy study of a new generation dry powder inhaler in asthmatic children.

Pediatr Pulmonol 2018 10 15;53(10):1348-1355. Epub 2018 Jun 15.

Pulmonary Institute, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

Background: Dry powder inhalers (DPI) are effective but forceful inhalation required to fluidize the powder may be difficult for children and patients with airway disease. Inspiromatic is a new generation active DPI that actively suspends drugs in synchrony with inhalation. We evaluated safety and efficacy of Formoterol delivery via Inspiromatic, compared to Aerolizer, a conventional DPI, in pediatric asthmatic subjects.

Methods: A phase I/II, randomized, single-center, double-blind, double-dummy, placebo-controlled, cross-over study. Subjects aged 8-18 years with FEV 40-80% predicted were included. Patients were randomized to inhale Formoterol via the Inspiromatic, immediately followed by the placebo via the Aerolizer or vice versa, in a double-blind fashion. Spirometry, blood pressure, and heart rate were measured at baseline and 15, 30, and 60 min after drug administration. Capsule emptying, comfort of use, confidence in efficacy, and patient satisfaction were assessed. At a subsequent visit, three months later, patients inhaled the active drug via the other DPI.

Results: Twenty-nine patients, aged 12.6 (±2.3) years, mean (SD), completed the study. Baseline FEV was 69.1 (±6.7) % at visit one and 65.3 (±9) % at visit two. Maximal FEV increase was 16.6 (±7.1) % with Inspiromatic and 15.5 (±7.5) % with Aerolizer (P = 0.47). No differences in heart rate or blood pressure were observed; 24/28 capsules were emptied using the Inspiromatic and 19/28 with the Aerolizer (P = 0.5); 21/28 preferred the Inspiromatic and 7/28 the Aerolizer (P < 0.001). There were no adverse events.

Conclusions: Formoterol inhalation via the Inspiromatic is safe and as efficacious as with the Aerolizer. The device is well accepted by asthmatic subjects.
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http://dx.doi.org/10.1002/ppul.24077DOI Listing
October 2018

[DIAGNOSIS AND TREATMENT OF BRONCHIECTASIS: POSITION PAPER OF THE ISRAELI PULMONOLOGY SOCIETY AND THE ISRAELI PEDIATRIC PULMONOLOGY SOCIETY].

Harefuah 2018 Feb;157(2):117-121

Pulmonology Department, Meir Medical Center, Kfar Saba, Israel.

Introduction: Bronchiectasis is anatomically defined by irreversible distortion of the bronchi. Clinically, its manifestations are cough with sputum production and a predisposition to pulmonary infections. Unlike asthma and COPD, where ample clinical data are present regarding the course and effective treatment, knowledge of bronchiectasis has yet to evolve. Lately, bronchiectasis is gaining renewed attention among the medical community, with growing basic and clinical research-based data. In Israel, no registered treatments exist for bronchiectasis, which makes it difficult to treat these patients. This paper is a summary of the position of the Israeli Pulmonology Association and the Israeli Pediatric Pulmonology Association for diagnosis and treatment of bronchiectasis.
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February 2018

Successful Intravenous Immunoglobulin Treatment in Pediatric Severe DRESS Syndrome.

J Allergy Clin Immunol Pract 2018 Jul - Aug;6(4):1238-1242. Epub 2017 Dec 1.

Department of Pediatrics B, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, potentially life-threatening delayed drug-induced hypersensitivity reaction. The most frequently reported drugs causing DRESS are aromatic antiepileptic agents. Prompt withdrawal of the offending drug and administering systemic corticosteroids is the most widely accepted and used treatment. The treatment of severe DRESS not responsive to systemic corticosteroids is uncertain.

Objective: The objective of this study was to describe a case series of pediatric patients with DRESS who were treated successfully with intravenous immunoglobulins (IVIGs).

Methods: A retrospective review of all children hospitalized in a tertiary care children's hospital with severe DRESS syndrome who received IVIG in addition to offending drug withdrawal and systemic corticosteroids during 1999-2017 is performed.

Results: Seven severe DRESS patients (4 males, age: 9.5 ± 5.7 years) are described. The offending drugs were antiepileptics in all but one case. Clinical findings included fever, rash, lymphadenopathy, dyspnea, anasarca, and hepatic involvement. After IVIG treatment (total dosage: 1-2 g/kg), fever resolved within a median time of 1 (range, 0-5) day, rash disappeared after 6.3 ± 1.6 days, and liver enzymes substantially improved after 3.8 ± 1.6 days. Patients were discharged 6.1 ± 2.7 days after IVIG commencement. There was no mortality.

Conclusion: The addition of IVIG in DRESS syndrome resistant to regular drug withdrawal and systemic corticosteroid therapy may hasten disease recovery.
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http://dx.doi.org/10.1016/j.jaip.2017.10.016DOI Listing
October 2019

Lung transplantation in cystic fibrosis patients in Israel: The importance of ethnicity and nutritional status.

Clin Transplant 2017 Nov;31(11)

Rabin Medical Center, Pulmonary Institute, Petach Tiqva, Israel.

Objectives: To assess the characteristics that correlate with better outcomes after lung transplantation for patients with cystic fibrosis (CF).

Methods: We retrospectively reviewed the charts of all patients with CF who underwent lung transplantation between 1996 and 2014 at Rabin Medical Center, Israel.

Results: Fifty patients with CF underwent 55 lung transplantations. Eighteen patients (36%) died during the study period. Actuarial survival was 83%, 68%, 62%, and 39% at 1, 3, 5, and 10 years, respectively. Better survival correlated with: BMI at 6 months and 1 year after transplantation (P = .002 and P = .003, respectively), ischemic time of less than 300 minutes (P = .023), absence of liver disease (P = .012), and Jewish compared to Arab ethnicity (P = .007). Freedom from bronchiolitis obliterans syndrome (BOS) was 87%, 75%, and 72% at 1, 3, and 5 years, respectively. BOS was more common and appeared earlier in the Arab than in the Jewish population (P = .012, P = .007). Additionally, prolonged time free of BOS correlated with male gender (P = .039), older age (P < .001), absence of liver disease (P = .012), and higher BMI 1 year after transplantation (P < .001).

Conclusions: Clinically important determinants for survival include BMI pre- and 1-year post-transplantation and improved freedom from BOS. Arab ethnicity correlated with higher incidence and earlier onset of BOS compared to Jewish ethnicity in Israel.
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http://dx.doi.org/10.1111/ctr.13111DOI Listing
November 2017

Nationwide genetic analysis for molecularly unresolved cystic fibrosis patients in a multiethnic society: implications for preconception carrier screening.

Mol Genet Genomic Med 2017 May 19;5(3):223-236. Epub 2017 Feb 19.

Medical GeneticsBarzilai Medical CenterAshkelonIsrael.

Background: Preconception carrier screening for cystic fibrosis (CF) is usually performed using ethnically targeted panels of selected mutations. This has been recently challenged by the use of expanded, ethnically indifferent, pan-population panels. Israel is characterized by genetically heterogeneous populations carrying a wide range of CFTR mutations. To assess the potential of expanding the current Israeli preconception screening program, we sought the subset of molecularly unresolved CF patients listed in the Israeli CF data registry comprising ~650 patients.

Methods: An Israeli nationwide genotyping of 152 CF cases, representing 176 patients lacking molecular diagnosis, was conducted. Molecular analysis included Sanger sequencing for all exons and splice sites, multiplex ligation probe amplification (MLPA), and next-generation sequencing of the poly-T/TG tracts.

Results: We identified 54 different mutations, of which only 16 overlapped the 22 mutations included in the Israeli preconception screening program. A total of 29/54 (53.7%) mutations were already listed as CF causing by the CFTR2 database, and only 4/54 (7.4%) were novel. Molecular diagnosis was reached in 78/152 (51.3%) cases. Prenatal diagnosis of 24/78 (30.8%) cases could have been achieved by including all CFTR2-causing mutations in the Israeli panel.

Conclusions: Our data reveal an overwhelming hidden abundance of gene mutations suggesting that expanded preconception carrier screening might achieve higher preconception detection rates.
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http://dx.doi.org/10.1002/mgg3.278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441412PMC
May 2017

Real-life comparison of three general paediatric wards showed similar outcomes for children with bronchiolitis despite different treatment regimens.

Acta Paediatr 2017 Sep 9;106(9):1507-1511. Epub 2017 Jun 9.

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Aim: This study evaluated the effectiveness of three different treatments for bronchiolitis in a tertiary paediatric facility.

Methods: Patients with bronchiolitis who were younger than two years of age and were randomly allocated to three general wards at Schneider Children's Medical Center, Israel, after admission were included. Different treatment protocols in the wards were retrospectively compared.

Results: The study comprised 286 children. The clinical and laboratory parameters on admission were similar between the wards. In Ward C where nebulised hypertonic saline was infrequently administered (6.7%), the mean number of days with oxygen saturation under 92% and the meanlength of hospital stay (1.8 and 3.8 days) were significantly lower than Ward A (2.8 and 5.3 days) and Ward B, (2.9 and 4.7 days) where nebulised hypertonic saline was given more frequently (38.7%-74.7%). Multivariate analysis indicated that low saturation on admission, leukocytosis and use of nebulised hypertonic saline or adrenalin were independent predictors of a longer period of desaturation and hospital stay.

Conclusion: Different treatment protocols for bronchiolitis were used in three paediatric wards in this real-life study. No treatment regimen proved superior. Inhalations of hypertonic saline or adrenaline were associated with a longer hospital stay.
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http://dx.doi.org/10.1111/apa.13921DOI Listing
September 2017

Propranolol treatment for infantile hemangioma does not increase risk of childhood wheezing.

Pediatr Pulmonol 2017 08 7;52(8):1071-1075. Epub 2017 Mar 7.

Sackler School of Medicine, Tel Aviv University, Israel.

Objective: Propranolol is the treatment of choice for infantile hemangiomas requiring medical intervention. Although contraindicated in asthma, its bronchoconstrictive effect in infants and children has not been extensively studied. We aimed to assess the incidence of wheezing episodes in infants and children treated with propranolol for infantile hemangiomas.

Study Design: A retrospective case-control study.

Setting: a tertiary pediatric hospital.

Patients: All Children followed for infantile hemangioma between 2009 and 2014. Children followed conservatively served as control group and were matched 1:1 for gender and month of birth by random matching to children treated with propranolol.

Interventions: All respiratory episodes (asthma, wheezing, stridor, and pneumonia) and respiratory associated hospitalizations were recorded from hospital records, from the primary care physician visits records and pharmacy prescriptions. The main outcome measure was the incidence of respiratory episodes in the treatment and the control groups.

Results: A total of 1828 clinic visits were reviewed for 683 children. In addition, primary care physician visits records were available in 80% of them. Two hundred and sixteen children were treated with propranolol. Incidence of respiratory episodes and recurrent respiratory episodes was similar in the propranolol and control groups (8.3% vs 12%, P = 0.265; 3.7% vs 6.5%, P = 0.274, respectively). Time to first episode was similar in the treatment and control groups (5.03 ± 3.32 vs 4.45 ± 3.21 months, respectively, P = 0.09). Respiratory hospital admission rate was similar in both groups.

Conclusions: Propranolol treatment does not exacerbate wheezing episodes in infants and children.
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http://dx.doi.org/10.1002/ppul.23683DOI Listing
August 2017

Feasibility of multiple breath washout measurements in infants with bronchiolitis: A pilot study.

Pediatr Pulmonol 2017 06 21;52(6):763-770. Epub 2017 Feb 21.

Pulmonary Institute, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

Background: Lung clearance index (LCI) reflects ventilation inhomogeneity and is raised in obstructive airway disease. Feasibility of multiple breath washout (MBW) measurement during acute lung disease in infants is unknown. As a further measure of disease, exhaled nitric oxide (eNO) may paradoxically decrease in acute bronchiolitis. We hypothesized that MBW measurements were attainable in infants with bronchiolitis and that LCI was raised and eNO reduced, compared to normal controls.

Methods: Infants with acute bronchiolitis were tested with sulfur hexafluoride (SF ) MBW during hospitalization and compared to controls. Tidal breathing and eNO parameters were obtained. Measurements were performed during natural sleep.

Results: Twenty-nine infants with bronchiolitis aged 3.7 ± 2.3 months (mean ± SD) and 23 controls aged 4.2 ± 2.5 months (P = 0.07) were evaluated. Fifteen of 29 (52%) infants with bronchiolitis and 19/23 (83%) controls achieved ≥2 valid MBW measurements. Reasons for test failure included waking up during facemask application and an irregular respiratory pattern. LCI was 8.4 ± 0.8 in the study group and 7.3 ± 0.7 in controls (P < 0.001). ENO was 2.3 ± 2.7 ppb in the study group and 7.9 ± 6.9 ppb in controls (P = 0.004).

Conclusion: MBW measurements during natural sleep are feasible but technically challenging in infants with acute bronchiolitis. LCI is raised compared to healthy controls. Larger trials, possibly using sedation protocols and shortened washout periods, are required to corroborate these findings. LCI can potentially serve as an objective indicator of severity and could be considered as a biomarker for future interventional trials.
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http://dx.doi.org/10.1002/ppul.23674DOI Listing
June 2017

Primary ciliary dyskinesia in Israel: Prevalence, clinical features, current diagnosis and management practices.

Respir Med 2016 10 23;119:41-47. Epub 2016 Aug 23.

Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.

Background: Primary Ciliary Dyskinesia (PCD) is rare and its features in Israel have not been described.

Aims: to assess prevalence utilizing state-of-the-art diagnostic techniques, and describe clinical features, diagnostic and management practices in Israel.

Methods: A national multicenter study from 2012 to 2013 recruited patients diagnosed or suspected of having PCD. Diagnosis was verified using: nasal Nitric Oxide (nNO); High-speed Video Microscope Analysis (HVMA); Transmission Electron Microscopy (TEM) of cilia; Immuno-fluorescence staining (IF) for ciliary proteins, and genetic analysis.

Results: Of the 203 patients recruited from 14 pediatric centers, 150 had a PCD diagnosis verified. Median age was 15.05y, with range 0.15-60.5y. PCD prevalence was 1:54,000 for the general population and 1:25,000 in children (5-14 y). For the non-Jewish (mainly Druze and Arab Moslem) compared to Jewish populations, prevalence was 1:16,500 and 1:139,000 respectively (p < 0.0001) and parental consanguinity was 85.4% and 21.9% respectively (p < 0.0001). Clinical features included bronchiectasis (88%), rhinitis (81%), recurrent pneumonia (78%), recurrent otitis (62%), neonatal pneumonia (60%) and situs inversus (42%). Prior diagnostic practices varied widely between centers with TEM assessed in 55% and abnormal in 61% of these. Management included antibiotics and airway clearance. Diagnostic verification revealed for 150 PCD patients: 81% nNO<233 ppb, 62% abnormal HVMA, 51% diagnostic TEM, 58% diagnostic IF and, 57% genetic diagnosis.

Conclusions: PCD in Israel is rare, with comprehensive diagnostic tests showing prevalence in children similar to Europe. Prevalence was higher in non-Jews, associated with parental consanguinity. Diagnostic and management practices vary. Referral centers providing comprehensive diagnostic and care capabilities should be established.
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http://dx.doi.org/10.1016/j.rmed.2016.08.015DOI Listing
October 2016

Pseudomonas aeruginosa identified as a key pathogen in hospitalised children with aspiration pneumonia and a high aspiration risk.

Acta Paediatr 2016 Dec 12;105(12):e588-e592. Epub 2016 Aug 12.

Department of Pediarics B&C, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Aim: Data on the causative pathogens and optimal empirical therapy of aspiration pneumonia in children are limited. This study sought to describe the bacteriology of aspiration pneumonia in hospitalised children with a high aspiration risk.

Methods: Respiratory tract specimens were prospectively collected using the induced sputum technique from children with a high aspiration risk who were hospitalised for aspiration pneumonia in a tertiary paediatric medical centre from 2009 to 2014. Clinical, microbiological and treatment data were recorded and analysed for each admission.

Results: The cohort comprised 50 children with 235 hospital admissions. Of the 183 respiratory tract cultures performed, 110 were positive for bacteria, with 169 isolates, mostly Gram-negative. The most common Gram-negative pathogen was Pseudomonas aeruginosa. If patients had Pseudomonas aeruginosa isolation, the risk of them having the pathogen again was 81%. The multivariate analysis showed that the use of antibiotic prophylaxis and number of hospitalisations were significantly associated with Pseudomonas aeruginosa isolation.

Conclusion: Gram-negative bacilli, especially Pseudomonas aeruginosa, were the major causative agents of paediatric aspiration pneumonia in our study. Empiric antipseudomonas treatment should be considered, particularly in patients who are receiving antibiotic prophylaxis, have experienced recurrent hospitalisations or with previous respiratory cultures that showed Pseudomonas aeruginosa isolation.
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http://dx.doi.org/10.1111/apa.13523DOI Listing
December 2016

Clinical Impact of β-Lactamase-producing Enterobacteriaceae in Sputum of Cystic Fibrosis Patients.

Pediatr Infect Dis J 2016 Feb;35(2):216-9

From the *Graub CF Center, Pulmonary Institute, Schneider Children's Medical Center of Israel, Petah Tikva, Israel; †Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel; ‡Clalit Health Services, Sharon Shomron District, Israel; §Microbiology Laboratory, Rabin Medical Center, Petach Tikva, Israel; ¶Pediatrics A Department, and ‖Infectious Diseases Unit, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

This case series describes 18 cystic fibrosis (CF) patients of a 135-patient CF center cohort with extended spectrum β-lactamase-producing Enterobacteriaceae, from 2003 to 2012. Four had chronic infection. Prevalence increased annually from 0 to 6.35%. Risk factors compared with the 2010 CF center cohort included continuous inhaled antibiotics (P = 0.014) and courses of intravenous antibiotics during the year before first isolation (P = 0.009). Hospitalization rates were 1.05/year and 0.47/year preinfection and postinfection, respectively (P = 0.02). Slope of forced expiratory volume at 1 second% predicted remained unchanged during 12 months.
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http://dx.doi.org/10.1097/INF.0000000000000972DOI Listing
February 2016

The impact of a national population carrier screening program on cystic fibrosis birth rate and age at diagnosis: Implications for newborn screening.

J Cyst Fibros 2016 07 16;15(4):460-6. Epub 2015 Sep 16.

Kathy and Lee Graub Cystic Fibrosis Center, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Background: Population carrier screening (PCS) has been available in Israel since 1999 and universally subsidized since 2008. We sought to evaluate its impact.

Methods: A retrospective review of governmental databanks, the national CF registry and CF centers.

Results: CF rate per 100,000 live births has decreased from 14.5 in 1990 to 6 in 2011. From 2004-2011 there were 95 CF births: 22 utilized PCS; 68 (72%) had 2 known CFTR mutations; 37% were pancreatic sufficient. At diagnosis, age was 6 (0-98) months; 53/95 had respiratory symptoms, 41/95 failure to thrive and 19/95 pseudomonas. Thirty-four (36%) were Arabs and 19 (20%) orthodox Jews, compared to 20% and 8% respectively, in the general population.

Conclusions: PCS markedly reduced CF birth rates with a shift towards milder mutations, but was often avoided for cultural reasons. As children regularly have significant disease at diagnosis, we suggest a balanced approach, utilizing both PCS and newborn screening.
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http://dx.doi.org/10.1016/j.jcf.2015.08.007DOI Listing
July 2016

Short- and Long-term Pulmonary Outcome of Palivizumab in Children Born Extremely Prematurely.

Chest 2016 Mar 5;149(3):801-8. Epub 2016 Jan 5.

Pulmonary Institute, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Palivizumab reduces the severity of respiratory syncytial virus infection in premature infants, but whether there is a protective effect beyond the preschool age is unknown. This study sought to assess the short- and long-term effects of palivizumab immunization on respiratory morbidity and pulmonary function at school age in children born extremely prematurely.

Methods: Infants born before 29 weeks' gestation in 2000 to 2003 were assessed at school age by parental questionnaire, hospital chart review, and lung function tests. Children born immediately before the introduction of routine palivizumab prophylaxis were compared with age-matched children who received palivizumab prophylaxis during the first respiratory syncytial virus season.

Results: Sixty-three children with a mean age 8.9 years were included: 30 had received palivizumab and 33 had not (control subjects). The groups were similar in terms of gestational age, birth weight, need for mechanical ventilation, and oxygen supplementation. Fifty-three percent of the palivizumab group, compared with 39% of the control group, had bronchopulmonary dysplasia (P = .14). Wheezing occurred in the first 2 years of life in 27% of the palivizumab group and in 70% of control subjects (P = .008); respective hospitalization rates were 33% and 70% (P = .001). At school age, rates of hyperresponsiveness (provocative concentration leading to a 20% fall in FEV1 < 1 mg/mL) were 33% and 48%, respectively (P = .38). Spirometry, lung volumes, diffusion, and exhaled nitric oxide were within normal limits, with no significant differences between groups.

Conclusion: Palivizumab prophylaxis was associated with reduced wheezing episodes and hospitalizations during the first 2 years of life in children born extremely prematurely. However, it did not affect pulmonary outcome at school age.
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http://dx.doi.org/10.1378/chest.15-0328DOI Listing
March 2016

The Spectrum of Nocardia Lung Disease in Cystic Fibrosis.

Pediatr Infect Dis J 2015 Aug;34(8):909-11

From the *The Kathy and Lee Graub Cystic Fibrosis Center, Pulmonary Institute, Schneider Children's Medical Center of Israel, Petah Tikva, Israel; †Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and ‡Pediatric Pulmonology Unit, Meyer Children's Hospital, Rambam Medical Center, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

We reviewed all cases of Nocardia infection in cystic fibrosis patients at 2 centers. Eight of 200 patients had Nocardia in sputum. Four developed severe lung disease, including 3 with associated allergic bronchopulmonary aspergillosis; 4 remained clinically stable. Nocardia is often associated with significant lung disease in cystic fibrosis, possibly associated with allergic bronchopulmonary aspergillosis or steroids.
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http://dx.doi.org/10.1097/INF.0000000000000759DOI Listing
August 2015

Increasing nontuberculous mycobacteria infection in cystic fibrosis.

J Cyst Fibros 2015 Jan 7;14(1):53-62. Epub 2014 Jun 7.

Graub CF Center, Pulmonary Institute, Schneider Children's Medical Center of Israel, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel Aviv, Israel. Electronic address:

Background: Nontuberculous mycobacteria (NTM) are emerging infections in the CF population.

Aims: To assess NTM infection prevalence and associated features in our CF clinic population.

Methods: Patient records, 2002-2011, were reviewed for NTM infection. FEV1, pancreatic function, sputum microbiology, and serum cytokines were compared in patients with and without NTM infection.

Results: Incidence rate of NTM infection increased from 0 in 2002 to 8.7% in 2011 (p<0.001). NTM infection prevalence increased 3-fold from 5% (4/79) in 2003 to 14.5% (16/110) in 2011 (p=0.05). Prevalence of chronic NTM lung disease has decreased somewhat since a peak in 2009, with institution of aggressive triple therapy. Of NTM-infected compared to uninfected patients, 88.2% vs. 60.3% had a known 'severe' CFTR genotype (p=0.04), 88.2% vs. 58.9% were pancreatic insufficient (p=0.02); 70.6% vs. 43.8% had chronic Pseudomonas aeruginosa (p=0.06); 75% vs. 32% had Aspergillus infection (p=0.007) and 23.5% vs 2.7% had allergic bronchopulmonary aspergillosis (p=0.01). Patients infected with Mycobacterium abscessus had increased TGF-β, TNF-α, IL-1β, IL-2, IL-4 and IL-5 levels (p<0.05). There was no difference in cytokine levels for all NTM infected compared to uninfected patients. M. abscessus comprised 46% of all NTM infections. Comparing M. abscessus versus other NTM, duration was 10.5 (1-118) months versus 1 (1-70) month, median (range) (p=0.004); lung disease occurred in 69% versus 17% (p=0.0004), with sputum conversion in 4/11 versus 5/6, respectively (NS).

Conclusions: NTM incidence and prevalence have increased dramatically in our CF clinic, associated with a severe CF genotype and phenotype. M. abscessus, the most prevalent NTM, caused prolonged infection despite therapy. There has been some decrease in the prevalence of NTM lung disease since 2009.
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http://dx.doi.org/10.1016/j.jcf.2014.05.008DOI Listing
January 2015

Effectiveness of long-term routine pulmonary function surveillance following pediatric hematopoietic stem cell transplantation.

Pediatr Pulmonol 2014 Nov 4;49(11):1124-32. Epub 2013 Nov 4.

Pulmonary Institute, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Introduction: Pulmonary complications following hematopoietic stem cell transplantation (HSCT) are common and often subclinical. Thus, periodic pulmonary function testing (PFT) is mandatory. This study sought to evaluate the effectiveness of long-term PFT surveillance for children undergoing HSCT and identify potential risk factors.

Methods: We reviewed long-term PFT for HSCT patients at a tertiary pediatric center. Inclusion criteria were PFT prior to and at least once following HSCT.

Results: Fifty-seven patients performed 202 spirometry and 193 plethysmographic maneuvers; 41 were tested during the first year after HSCT, but only 29 were evaluated consistently long term (2-12 years). FVC and FEV(1) decreased gradually suggesting a restrictive ventilatory defect: FVC % predicted [mean ± SD] dropped from 91 ± 14% to 85 ± 17% after 0-24 months and 80 ± 19% beyond 2 years (P = 0.01) whereas FEV(1) dropped from 95 ± 16% to 88 ± 19% and 82 ± 20%, respectively (P = 0.002). A slight reduction in TLC was observed. Those undergoing allogeneic HSCT had a greater decline in FVC (P = 0.025) and FEV(1) (P = 0.025) as did those conditioned with radiation, regarding both FVC (P = 0.003) and FEV(1) (P = 0.002). Decline occurred earlier (≤2 years) after chemotherapy compared with radiation. Seven children had severe irreversible obstruction at >2 years despite therapeutic intervention.

Conclusions: Most survivors of childhood HSCT maintain almost normal pulmonary function although mild restrictive lung disease may develop, particularly following allogeneic HSCT and conditioning with radiation. Severe airways obstruction developed in a small minority. The surveillance protocol for PFT needs to be followed more stringently to enable intervention possibly before early subclinical changes progress and become irreversible.
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http://dx.doi.org/10.1002/ppul.22944DOI Listing
November 2014

[Prevalence of H1N1 A influenza virus infection among hospitalized patients with bronchiolitis twelve months old and younger].

Harefuah 2012 Aug;151(8):469-71, 497

Schneider Childrens Medical Center of Israel, Petach Tikvah, Israel.

Background: Many pathogens have been reported to ause bronchiolitis during the winter season including he respiratory syncytial virus (RSV), influenza, oetapneumovirus, etc. The last H1N1 A influenza pandemic ccurred during the respiratory syncytial virus (RSV) eason. The role of the pandemic influenza strain as a ause of bronchiolitis was not documented.

Objective: Assessment of the prevalence of co-infections of RSV and H1N1 influenza virus among children aged 12 months and younger, hospitalized with bronchiolitis.

Methods: A retrospective study design was used. Clinical data on 93 infants, 12 months old and younger, hospitalized for bronchiolitis, were retrospectively collected, including test results for RSV and H1N1 A influenza infection.

Results: Sixty-six out of the 90 (73.3 %) patients tested were positive for RSV; 2 out of the 81 patients tested (2.5%) were positive for H1N1 influenza. No patient was positive for both.

Conclusions: The results of the present study clearly show that in infants younger than one year of age, who suffer from upper and lower respiratory tract infection (bronchiolitis), the main pathogen is RSV (also appeared in the middle of he H1N1 A influenza pandemic last winter). We conclude that the H1N1 A influenza infection is uncommon in infants hospitalized with bronchiolitis during the winter season.
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August 2012

Severe Bordetella pertussis infection associated with hemolytic uremic syndrome.

Isr Med Assoc J 2012 Jul;14(7):456-8

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petah Tikva, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.

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July 2012

Severe abdominal pain as a presenting symptom of probable catastrophic antiphospholipid syndrome.

Pediatrics 2012 Jul 18;130(1):e230-5. Epub 2012 Jun 18.

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petah-Tikva, Israel.

Catastrophic antiphospholipid syndrome (APS) in pediatric medicine is rare. We report 3 adolescents who presented with acute onset of severe abdominal pain as the first manifestation of probable catastrophic APS. The 3 patients, 2 male patients and 1 female patient were 14 to 18 years old. One had been diagnosed with systemic lupus erythematosus in the past, but the other 2 had no previous relevant medical history. All presented with excruciating abdominal pain without additional symptoms. Physical examination was noncontributory. Laboratory results were remarkable for high inflammatory markers. Abdominal ultrasonography was normal, and abdominal computed tomography scan showed nonspecific findings of liver infiltration. Only computed tomography angiography revealed evidence of extensive multiorgan thrombosis. All patients had elevated titers of antiphospholipid antibodies. The patients were treated with full heparinization, high-dose steroids, and intravenous immunoglobulin with a resolution of symptoms. One patient was resistant to the treatment and was treated with rituximab. In conclusion, severe acute abdominal pain can be the first manifestation of a thromboembolic event owing to catastrophic APS even in previously healthy adolescents. Diagnosis requires a high index of suspicion with prompt evaluation and treatment to prevent severe morbidity and mortality.
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http://dx.doi.org/10.1542/peds.2011-1694DOI Listing
July 2012

Encouraging pulmonary outcome for surviving, neurologically intact, extremely premature infants in the postsurfactant era.

Chest 2012 Sep;142(3):725-733

Pulmonary Institute, Schneider Children's Medical Center of Israel, Petah Tikva; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Objective: The aim of this study was to determine the long-term pulmonary outcome of extreme prematurity at a single tertiary-care center from 1997 to 2001 in the postsurfactant era.

Methods: We assessed symptoms, exhaled nitric oxide, spirometry, methacholine challenge (provocative concentration of methacholine required to decrease FEV₁ by 20% [PC(20)]), lung volumes, diffusion, and cardiopulmonary exercise tolerance.

Results: Of 279 infants born, 192 survived to discharge, and 79 of these developed bronchopulmonary dysplasia (BPD) (65 mild, 12 moderate, two severe). We studied a subgroup of 53 neurologically intact preterm subjects aged 10 ± 1.5 years (28 with BPD [born, 26.2 ± 1.4 weeks; birth weight, 821 ± 164 g] and 25 without BPD [born, 27.2 ± 1 weeks; birth weight, 1,050 ± 181 g]) and compared them with 23 term control subjects. Of the BPD cases, 21 were mild, seven were moderate, and none was severe; 77.4% of subjects received antenatal steroids, and 83% received postnatal surfactant. Sixty percent of the preterm subjects wheezed at age < 2 years compared with 13% of the control subjects (P < .001), but only 13% wheezed in the past year compared with 0% of control subjects (not significant). For preterm and control subjects, respectively (mean ± SD), FEV₁ % predicted was 85% ± 10% and 94% ± 10% (P < .001), with limited reversibility; residual volume/total lung capacity was 29.3% ± 5.5% and 25% ± 8% (P < .05); diffusing capacity/alveolar volume was 89.6% ± 9.2% and 97% ± 10% (P < .005); and PC(20) was 6.5 ± 5.8 mg/mL and 11.7 ± 5.5 mg/mL (P < .001). PC(20) was < 4 mg/mL in 49% of preterm subjects despite normal exhaled nitric oxide. Most measurements were similar in premature subjects with and without BPD. Peak oxygen consumption and breathing reserve were normal, but % predicted maximal load (measured in Watts) was 69% ± 15% for subjects with BPD compared with 88% ± 23% for subjects without and 86% ± 20% for control subjects (P < .01).

Conclusions: Pulmonary outcome was encouraging at mid-childhood for neurologically intact survivors in the postsurfactant era. Despite mechanical ventilation and oxygen therapy, most had no or mild BPD. Changes found probably reflect the hypoplastic lungs of prematurity.
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http://dx.doi.org/10.1378/chest.11-1562DOI Listing
September 2012
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