Publications by authors named "Paola Papoff"

59 Publications

Assessing peak inspiratory flow for initial HFNC flow setting: the end point or a first step towards a new approach?

J Pediatr 2021 Mar 22. Epub 2021 Mar 22.

Medical Engineering Laboratory, Department of Civil Engineering and Computer Science Engineering, University of Rome "Tor Vergata", Rome, Italy.

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http://dx.doi.org/10.1016/j.jpeds.2021.03.030DOI Listing
March 2021

Floating Bone Phenomenon in Pierre Robin Sequence.

J Craniofac Surg 2020 Sep;31(6):1699-1704

Maxillo-Facial Surgery Department.

After a failed mandibular osteodistraction, the wrong positioned mandible of a few patients with Pierre Robin sequence returned in the most functional position and regained a proper symmetry, without external intervention. The study aims to explain this self-adjustment and introduce the floating bone phenomenon.The inclusion criteria were severe micrognathia, Fast and Early Mandibular Distraction Osteogenesis protocol, postoperative mandibular wrong positioning, presurgery, immediate postsurgery, and long-term computed tomography scan. Five patients were included. The considered parameters were the distance between mandibular dental centerline and midsagittal facial axis, the rotation of the mandibular body, the magnitude of elongation, and the lowering of the mandibular body.Three patients went from a decentralization >4 mm in the activation phase to a normalization of the said value in the follow-up. In the same period, the interincisal point of 2 patients moved respectively from 0.5 mm on the left and 0.8 mm on the right to 1.2 mm and 1.6 mm on the right, respectively. The rotation of the mandibular body was meanly 25.6° among all patients. The mean value of the distraction was 14.1 mm. A difference of about 4.4 mm between the left and the right side was measured. The lowering of the mandible varied between 2.8 and 12.6 mm.All patients improved their symmetry. Four of them improved in all the measured parameters, while 1 patient presented a worsening in the decentralization of the interincisal point.The floating bone phenomenon could break new grounds in the management of patients with Pierre Robin sequence.
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http://dx.doi.org/10.1097/SCS.0000000000006405DOI Listing
September 2020

Early Post-cooling Brain Magnetic Resonance for the Prediction of Neurodevelopmental Outcome in Newborns with Hypoxic-Ischemic Encephalopathy.

J Pediatr Neurosci 2019 Oct-Dec;14(4):191-202. Epub 2019 Dec 3.

Pediatric Intensive Care Unit, Department of Pediatrics, Child Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.

Aim And Objectives: This study aimed to evaluate the predictive role of early post-cooling brain magnetic resonance for developmental outcome in newborns with hypoxic-ischemic encephalopathy.

Materials And Methods: A retrospective cohort study was performed on 29 consecutive patients through magnetic resonance evaluation (visual analysis of the images and scoring of the detected lesions; mean diffusivity of semioval centre and lenticular nuclei; and area under the curve of basal ganglia -acetylaspartate at proton magnetic resonance spectroscopic imaging) and Griffiths Mental Development Scales-third edition at 12 and 24 months.

Results: Brain magnetic resonance was performed at a mean age of 5.7 ± 3.7 days. Newborns with no/minor magnetic resonance abnormalities had a better developmental outcome than patients with moderate or severe lesions. Structural and spectroscopic abnormalities in basal ganglia resulted in the most significant predictors for an unfavorable outcome.

Conclusion: Normal magnetic resonance in early post-cooling phases is strongly associated with a favorable developmental outcome.
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http://dx.doi.org/10.4103/jpn.JPN_25_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935984PMC
December 2019

Increased T-helper Cell 2 Response in Infants With Respiratory Syncytial Virus Bronchiolitis Hospitalized Outside Epidemic Peak.

Pediatr Infect Dis J 2020 01;39(1):61-67

From the Department of Pediatrics, Sapienza University of Rome, Rome, Italy.

Aim: To test the hypothesis that the balance of type-1/type-2 immune response differs between infants hospitalized with respiratory syncytial virus (RSV) bronchiolitis during the peak months and those during the nonpeak months.

Methods: We prospectively enrolled 90 unrelated full-term previously healthy infants hospitalized during the first year of life for RSV sole bronchiolitis over 2 epidemics (November 2016 to April 2017 and October 2017 to April 2018). We stratified infants as follows: hospitalized during the peak months (n: 71) and during the nonpeak months (n: 19). The frequencies of CD4+ producing interferon (IFN)-γ and interleukin (IL)-4 and of CD8+ producing IFN-γ T cells were measured by flow cytometry from infant peripheral whole blood. The T-helper cell (Th2) polarization index was calculated as the ratio between CD4+ T cells producing IL-4 and CD4+ T cells producing IFN-γ.

Results: Infants hospitalized during nonpeak months were significantly less frequently breast-fed, had a higher eosinophils count, a significantly higher percentage of CD4+ T cells producing IL-4 and higher Th2 polarization index than infants hospitalized during the peak months.

Conclusions: We elucidated the presence of different endotypes in infants with RSV sole bronchiolitis. Previously healthy full-term infants hospitalized during the nonpeak months seem to be more likely those with a possible predisposition to atopy.
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http://dx.doi.org/10.1097/INF.0000000000002505DOI Listing
January 2020

Bevacizumab-containing regimen in relapsed/progressed brain tumors: a single-institution experience.

Childs Nerv Syst 2019 06 21;35(6):1007-1012. Epub 2019 Mar 21.

Department of Radiology Emergency, "Sapienza" University, Rome, Italy.

Aim: The aim of the study is to assess tumor response, treatment-related toxicities, progression-free survival (PFS), and overall survival (OS) in patients with relapsed/refractory brain tumors treated with bevacizumab-containing regimen.

Methods: Patients that had received I and II line treatments with or without megatherapy were included. Doses and schedule were as follows: bevacizumab (BVZ) 10 mg/kg i.v. with irinotecan (IRI) 150 mg/m i.v. every 2 weeks ± temozolamide (TMZ) 200 mg/m p.o. daily for 5 days every 4 weeks. TMZ was omitted in heavily pretreated cases.

Results: Between 2013 and 2018, 12 patients (3F/9M), median age 161 months (range 66-348), affected with medulloblastoma (n 7), or low-grade glioma (n 2), or high-grade glioma (n 3), received BVZ/IRI association (median courses 20, range 4-67); 3 of them continued single-agent BVZ (median courses 23, range 8-39). TMZ (median courses 8, range 2-26) was administered in eight patients and then stopped in three of them because of myelotoxicity or lack of compliance. Treatment was well tolerated. After 3 months, two complete responses, two partial responses, seven stable diseases, and one progressive disease were observed. Nine cases experienced an improvement in neurological symptoms. Median time to progression was 11 months (95% confidence interval, 4-18 months). Six-month and 2-year PFS were 75% and 42%, respectively. The OS is 33%; interestingly, two cases (one medulloblastoma and one high-grade glioma) are progression-free off-therapy since 30 and 48 months, respectively.

Conclusions: BVZ/IRI association ± TMZ showed encouraging therapeutic activity and low toxicity in this series of relapsed/refractory brain tumors.
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http://dx.doi.org/10.1007/s00381-019-04117-zDOI Listing
June 2019

A 12-Week Maintenance Therapy with a New Prepared Viscous Budesonide in Pediatric Eosinophilic Esophagitis.

Dig Dis Sci 2019 06 19;64(6):1571-1578. Epub 2019 Jan 19.

Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.

Background: A new prepared oral viscous budesonide (PVB) has been effective in inducing clinical and histological remission in pediatric eosinophilic esophagitis (EoE).

Aims: To evaluate the efficacy of a 12-week maintenance therapy on clinical, endoscopic, and histological remission using half of the dose used in the induction therapy.

Methods: We prospectively enrolled pediatric patients with active EoE. After 12 weeks of induction therapy with PVB (< 150 cm: 2 mg/day; ≥ 150 cm: 4 mg/day) patients received a maintenance dose of half of the dose used in the induction therapy (1 mg or 2 mg) for another 12 weeks. A 12-week follow-up was then performed in all patients after the end of therapy. Endoscopy was performed at weeks 0, 12, 24, and 36. Symptoms, endoscopy, and histology scores were also calculated. Serum cortisol was evaluated during the treatment period.

Results: We enrolled 20 children (15 males; median age 10 years; range 4-17). After the 12-week induction therapy 18 patients (90%) were in remission, with a significant decrease in the median peak of eosinophil count/HPF as well as a marked reduction in clinical, endoscopic, and histological scores (p < 0.01). At the end of the maintenance therapy (week 24), 17 patients (85%) were still in remission, while there were only 9 at week 36 (45%). No significant changes in cortisol levels were observed during the study period.

Conclusions: The 12-week maintenance treatment with the half the dose of PVB was effective in sustaining remission at week 24; however, no reduction in the rate of relapse after suspension of treatment occurred.
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http://dx.doi.org/10.1007/s10620-018-5449-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522447PMC
June 2019

A Treat to Target Strategy Using Panenteric Capsule Endoscopy in Pediatric Patients With Crohn's Disease.

Clin Gastroenterol Hepatol 2019 09 13;17(10):2060-2067.e1. Epub 2018 Oct 13.

Children's Centre for Digestive Health Care, Atlanta, Georgia.

Background & Aims: Pan-enteric capsule endoscopy (PCE) is effective for assessment of small intestinal and colonic Crohn's disease (CD) in pediatric patients. We aimed to determine whether PCE can be used to monitor mucosal healing and deep remission, in a treat to target strategy for pediatric patients with CD.

Methods: We performed a prospective study of 48 children with a diagnosis of CD at a tertiary care pediatric gastroenterology unit; 46 patients were included in the final analysis. Biomarker, imaging, and PCE analyses were performed at baseline and after 24 and 52 weeks. Small bowel and colonic mucosal healing were defined by Lewis scores <135 and simple endoscopic score for CD ≤1, respectively. Clinical remission was defined as defined as a pediatric CD activity index score <10 and biomarker-based remission based on normal levels of biomarkers; deep remission was defined as a combination of clinical remission, biomarker-based remission, and mucosal healing. Treatments were adjusted based on findings from PCE (imaging was considered only for patients with negative findings from PCE). Therapies were introduced, optimized, switched, or combined at the discretion of treating clinicians. The primary outcome was the ability of PCE to assess mucosal healing and deep remission at 3 timepoints and to guide a treat to target strategy.

Results: PCE detected inflammation in 34 patients (71%) at baseline, 22 patients (46%) at week 24, and 18 patients (39%) at week 52 (P for comparison among timepoints <.05). Findings from PCE led to a change in therapy for 34 patients (71%) at baseline and 11 patients (23%) at 24 weeks, whereas only 2 patients with negative results from PCE (4%) changed therapies based on findings from imaging. When the treat to target strategy was applied, proportions of patients with mucosal healing and deep remission increased from 21% at baseline, to 54% at week 24, to 58% at week 52 (P for comparison among timepoints <.05); 2 patients (4%) did not respond to treatment.

Conclusion: In a prospective study of 48 children with CD, we found a treat to target strategy, based on findings from PCE, to significantly increase the proportions of patients with mucosal healing and deep remission.

Clinical Trial: gov no: NCT03161886.
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http://dx.doi.org/10.1016/j.cgh.2018.10.015DOI Listing
September 2019

Combined multichannel intraluminal impedance and pH monitoring is helpful in managing children with suspected gastro-oesophageal reflux disease.

Dig Liver Dis 2018 Sep 5;50(9):910-915. Epub 2018 Apr 5.

Department of Paediatrics, Sapienza University of Rome, Rome, Italy. Electronic address:

Background: Gastro-oesophageal reflux is very common in the paediatric age group. There is no single and reliable test to distinguish between physiologic and pathological gastro-oesophageal reflux, and this lack of clear distinction between disease and normal can have a negative impact on the management of children.

Aims: To evaluate the usefulness of 24-h oesophageal pH-impedance study in infants and children with suspected gastro-oesophageal reflux disease.

Methods: Patients were classified by age groups (A-C) and reflux-related symptoms (typical and atypical). All underwent pH-impedance study. If the latter suggested an abnormal reflux, patients received therapy in accordance with NASPGHAN/ESPGHAN recommendations, while those with normal study had an additional diagnostic work-up. The efficacy of therapy was evaluated with a specific standardized questionnaire for different ages.

Results: The study was abnormal in 203/428 patients (47%) while normal in 225/428 (53%). Of those with abnormal study, 109 exhibited typical symptoms (54%), and 94 atypical (46%). The great majority of the patients with abnormal study were responsive to medical anti-reflux therapy.

Conclusions: We confirm the utility of prolonged oesophageal pH-impedance study in detecting gastro-oesophageal reflux disease in children and in guiding therapy. Performing oesophageal pH-impedance monitoring in children with suspected gastro-oesophageal reflux disease is helpful to establish the diagnosis and avoid unnecessary therapy.
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http://dx.doi.org/10.1016/j.dld.2018.03.031DOI Listing
September 2018

A flow-leak correction algorithm for pneumotachographic work-of-breathing measurement during high-flow nasal cannula oxygen therapy.

Med Eng Phys 2018 04 2;54:32-43. Epub 2018 Mar 2.

Pediatric Intensive Care Unit, Department of Pediatrics, Umberto I Policlinico, Sapienza University of Rome, Rome, Italy. Electronic address:

Measuring work of breathing (WOB) is an intricate task during high-flow nasal cannula (HFNC) therapy because the continuous unidirectional flow toward the patient makes pneumotachography technically difficult to use. We implemented a new method for measuring WOB based on a differential pneumotachography (DP) system, equipped with one pneumotachograph inserted in the HFNC circuit and another connected to a monitoring facemask, combined with a leak correction algorithm (LCA) that corrects flow measurement errors arising from leakage around the monitoring facemask. To test this system, we used a mechanical lung model that provided data to compare LCA-corrected respiratory flow, volume and time values with effective values obtained with a third pneumotachograph used instead of the LCA to measure mask flow leaks directly. Effective and corrected volume and time data showed high agreement (Bland-Altman plots) even at the highest leak. Studies on two healthy adult volunteers confirmed that corrected respiratory flow combined with esophageal pressure measurements can accurately determine WOB (relative error < 1%). We conclude that during HFNC therapy, a DP system combined with a facemask and an algorithm that corrects errors due to flow leakages allows pneumotachography to measure reliably the respiratory flow and volume data needed for calculating WOB.
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http://dx.doi.org/10.1016/j.medengphy.2018.02.004DOI Listing
April 2018

Intentional tracheoesophageal fistula cannulation for gastric decompression in type C esophageal atresia.

Paediatr Anaesth 2018 04 26;28(4):367-369. Epub 2018 Feb 26.

Department of Pediatrics, Division of Pediatric Surgery, Sapienza University, Rome, Italy.

We describe a nonsurgical technique for managing gastric distention in infants with type C esophageal atresia, involving intubating the trachea with an umbilical catheter and entering the stomach through the fistula as soon as a flexible bronchoscope found its wide-open orifice. This technique might have a special role when gastric distention precedes other commonly used preventive measures.
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http://dx.doi.org/10.1111/pan.13351DOI Listing
April 2018

Acute bronchiolitis: Influence of viral co-infection in infants hospitalized over 12 consecutive epidemic seasons.

J Med Virol 2018 04 11;90(4):631-638. Epub 2017 Dec 11.

Department of Paediatrics, "Sapienza" University of Rome, Rome, Italy.

Bronchiolitis is the first lower respiratory tract viral infection manifesting in infants younger than 12 months of age. Our aim was to evaluate clinical and serological differences in infants with bronchiolitis from a single or from multiple viruses. Our secondary aim was to investigate differences in recurrent wheezing episodes after 12-24-36 months of follow-up. We reviewed the clinical records for 486 full-term infants hospitalized for bronchiolitis with at least one virus detected in the nasopharyngeal aspirate. In 431 (88.7%) patients one virus was detected and in 55 (11.3%) infants more than one virus was found. No differences were observed in the length of hospitalization, clinical severity score, O supplementation or admission to the intensive care unit. Single virus was associated with higher serum C-reactive protein (C-RP) than infants with multiple viruses and higher blood neutrophil counts. Respiratory syncytial virus (RSV) was the most frequently detected virus. RSV alone was associated with higher C-RP (P = 0.007), compared to RSV coinfection. Infants with human rhinovirus (hRV) alone had higher white blood cell counts, higher blood neutrophils, and higher serum C-RP levels than hRV co-infection (P = 0.029, P = 0.008, P = 0.008). RSV + hRV, the most frequent co-infection, was associated with lower neutrophil count and lower C-RP levels (P = 0.008, P = 0.016) and less fever (P = 0.012), when comparing RSV versus hRV versus RSV + hRV. No differences were found in the frequency of recurrent wheezing between single versus multiple viruses after bronchiolitis. Our findings suggest that in infants with bronchiolitis multiple viral co-infections can occur, without influence in the clinical severity of the disease. Infants with co-infection seems to mount a lower inflammatory response.
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http://dx.doi.org/10.1002/jmv.24994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166564PMC
April 2018

Modifiable risk factors associated with bronchiolitis.

Ther Adv Respir Dis 2017 10 16;11(10):393-401. Epub 2017 Aug 16.

Department of Pediatrics, 'Sapienza' University of Rome, V.le Regina Elena 324, 00161, Rome, Italy.

Background: We sought to clarify possibly modifiable risk factors related to pollution responsible for acute bronchiolitis in hospitalized infants.

Methods: For this observational study, we recruited 213 consecutive infants with bronchiolitis (cases: median age: 2 months; age range: 0.5-12 months; boys: 55.4%) and 213 children aged <3 years (controls: median age: 12 months; age range: 0.5-36 months; boys: 54.5%) with a negative medical history for lower respiratory tract diseases hospitalized at 'Sapienza' University Rome and IRCCS Bambino Gesù Hospital. Infants' parents completed a standardized 53-item questionnaire seeking information on social-demographic and clinical characteristics, indoor pollution, eating habits and outdoor air pollution. Multivariate logistic regression analyses were run to assess the independent effect of risk factors, accounting for confounders and effect modifiers.

Results: In the 213 hospitalized infants the questionnaire identified the following risk factors for acute bronchiolitis: breastfeeding ⩾3 months (OR: 2.1, 95% confidence interval [CI]: 1.2-3.6), presence of older siblings (OR: 2.8, 95% CI: 1.7-4.7), ⩾4 cohabitants (OR: 1.5, 95% CI: 1.1-2.1), and using seed oil for cooking (OR: 1.7, 95% CI: 1.2-2.6). Having renovated their home in the past 12 months and concurrently being exposed daily to smoking, involving more than 11 cigarettes and two or more smoking cohabitants, were more frequent factors in cases than in controls ( p = 0.021 and 0.05), whereas self-estimated proximity to road and traffic was similar in the two groups.

Conclusions: We identified several risk factors for acute bronchiolitis related to indoor and outdoor pollution, including inhaling cooking oil fumes. Having this information would help public health authorities draw up effective preventive measures - for example, teach mothers to avoid handling their child when they have a cold and eliminate exposure to second-hand tobacco smoke.
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http://dx.doi.org/10.1177/1753465817725722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933664PMC
October 2017

Respiratory syncytial virus bronchiolitis, weather conditions and air pollution in an Italian urban area: An observational study.

Environ Res 2017 10 3;158:188-193. Epub 2017 Jul 3.

Department of Pediatrics and Infantile Neuropsychiatry, "Sapienza" University, Rome, Italy. Electronic address:

Background: In this study we sought to evaluate the association between viral bronchiolitis, weather conditions, and air pollution in an urban area in Italy.

Methods: We included infants hospitalized for acute bronchiolitis from 2004 to 2014. All infants underwent a nasal washing for virus detection. A regional agency network collected meteorological data (mean temperature, relative humidity and wind velocity) and the following air pollutants: sulfur dioxide, nitrogen oxide, carbon monoxide, ozone, benzene and suspended particulate matter measuring less than 10µm (PM) and less than 2.5µm (PM) in aerodynamic diameter. We obtained mean weekly concentration data for the day of admission, from the urban background monitoring sites nearest to each child's home address. Overdispersed Poisson regression model was fitted and adjusted for seasonality of the respiratory syncytial virus (RSV) infection, to evaluate the impact of individual characteristics and environmental factors on the probability of a being positive RSV.

Results: Of the 723 nasal washings from the infants enrolled, 266 (68%) contained RSV, 63 (16.1%) rhinovirus, 26 (6.6%) human bocavirus, 20 (5.1%) human metapneumovirus, and 16 (2.2%) other viruses. The number of RSV-positive infants correlated negatively with temperature (p < 0.001), and positively with relative humidity (p < 0.001). Air pollutant concentrations differed significantly during the peak RSV months and the other months. Benzene concentration was independently associated with RSV incidence (p = 0.0124).

Conclusions: Seasonal weather conditions and concentration of air pollutants seem to influence RSV-related bronchiolitis epidemics in an Italian urban area.
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http://dx.doi.org/10.1016/j.envres.2017.06.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125886PMC
October 2017

Reply to "Post-surgical mutism and catatonia".

Acta Neurochir (Wien) 2017 07 8;159(7):1255-1256. Epub 2017 Apr 8.

Pediatric oncology division, Department of Pediatrics, Umberto I Hospital, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1007/s00701-017-3173-5DOI Listing
July 2017

Rhinovirus species/genotypes and interferon-λ: subtypes, receptor and polymorphisms - missing pieces of the puzzle of childhood asthma?

Eur Respir J 2017 03 29;49(3). Epub 2017 Mar 29.

Dept of Molecular Medicine, Laboratory of Virology affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Sapienza University, Rome, Italy.

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http://dx.doi.org/10.1183/13993003.00060-2017DOI Listing
March 2017

Three-dimensional airways volumetric analysis before and after fast and early mandibular osteodistraction.

J Craniomaxillofac Surg 2017 Mar 18;45(3):377-380. Epub 2016 Dec 18.

Dipartimento di Scienze Odontostomatologiche e Maxillo Facciale (Head: Prof. Ersilia Barbato), "Sapienza" Università di Roma, Italy.

Purpose: Newborns with Pierre Robin sequence (PRS) and syndromic micrognathia show microgenia and glossoptosis, which cause reduction of the airway and breathing difficulty from birth. Our goal is to analyze quantitative and qualitative volumetric changes before and after fast and early mandibular osteodistraction (FEMOD) and to compare radiological data.

Methods: The sample was composed of 4 patients, who satisfied inclusion criteria for completeness of data. Computed tomography pre- and post-operation were performed, then a volumetric assessment was made with Dolphin Imaging. Polysomnography was performed before and after FEMOD.

Results: Pre- and post-operative CT scan data were compared. The analysis of all three sections showed a significant increase of volumetric parameters. The retroglossal volume average increase was 346%, and the retropalatal volume average increase was 169%. These data matched the improvement recorded by polysomnography.

Conclusions: The data confirm FEMOD as an efficient treatment to improve airways and breathing problem in patients affected by Pierre Robin sequence and syndromic micrognathia. The three-dimensional volume rendering could be a useful method to evaluate and quantify the increase in airways volume.
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http://dx.doi.org/10.1016/j.jcms.2016.12.007DOI Listing
March 2017

Sudden benzodiazepine-induced resolution of post-operative pediatric cerebellar mutism syndrome: a clinical-SPECT study.

Acta Neurochir (Wien) 2017 03 3;159(3):475-479. Epub 2017 Jan 3.

Pediatric Oncology Division, Department of Pediatrics and Child Neuropsychiatry, Umberto I Hospital, Sapienza University of Rome, Rome, Italy.

Post-operative pediatric cerebellar mutism syndrome (PPCMS) is a clinical syndrome arising from cerebellar injury and characterized by absence of speech and other possible symptoms and signs. Rare reports described some benefit after administration of dopamine agonist therapy, but no treatment has proven efficacy. In this paper, we report on the dramatic, sudden resolution of PPCMS induced by midazolam administration in a boy who underwent posterior fossa surgery for choroid plexus papilloma of the fourth ventricle. In addition to clinical improvement, post-midazolam single-photon emission computed tomography also demonstrated amelioration of brain perfusion.
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http://dx.doi.org/10.1007/s00701-016-3059-yDOI Listing
March 2017

Risk Factors for Virus-induced Acute Respiratory Tract Infections in Children Younger Than 3 Years and Recurrent Wheezing at 36 Months Follow-Up After Discharge.

Pediatr Infect Dis J 2017 02;36(2):179-183

From the *Department of Pediatrics and Infantile Neuropsychiatry, and †Department of Molecular Medicine, "Sapienza" University Rome, Rome, Italy.

Background: We sought to know more about how 14 common respiratory viruses manifest clinically, and to identify risk factors for specific virus-induced acute respiratory tract infections (ARTIs) in children younger than 3 years old and for wheezing at 36-month follow-up.

Methods: We retrospectively studied the clinical records for 273 full-term children (median age, 2.9 months; range, 0.26-39; boys, 61.2%) hospitalized for ARTIs, whose nasopharyngeal specimen tested positive for a respiratory virus and 101 children with no history of respiratory diseases (median age, 8 months; range, 0.5-36.5; boys, 58.4%). At 12, 24 and 36 months after children's discharge, all parents were interviewed by telephone with a structured questionnaire on wheezing episodes.

Results: The most frequently detected viruses were respiratory syncytial virus in bronchiolitis, human rhinovirus in pneumonia and human bocavirus in wheezing. Multivariate analysis identified, as risk factors for virus-induced ARTIs, the presence of siblings [odds ratio (OR): 3.0 (95% confidence interval [CI]: 1.8-5.2)], smoking cohabitants (OR: 2.3 (95% CI: 2-4.2)] and breastfeeding lasting less than 3 months [OR: 0.5 (95% CI: 0.3-0.9)]. The major risk factor for respiratory syncytial virus-induced ARTIs was exposure to tobacco smoke [OR: 1.8 (95% CI: 1.1-3.2)]. Risk factors for human rhinovirus-induced ARTIs were attending day-care [OR: 5.0 (95% CI: 2.3-10.6)] and high eosinophil blood counts [OR: 2.6 (95% CI: 1.2-5.7)]. The leading risk factor for recurrent wheezing was exposure to tobacco smoke [OR: 2.5 (95% CI: 1.1-15.6)].

Conclusions: Each respiratory virus leads to a specific clinical manifestation. Avoiding exposing children to tobacco smoke might restrict viral spread from sick parents and siblings to younger children, prevent severe respiratory diseases, and possibly limit sequelae.
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http://dx.doi.org/10.1097/INF.0000000000001385DOI Listing
February 2017

Early Mandibular Distraction to Relieve Robin Severe Airway Obstruction in Two Siblings with Lymphedema-Distichiasis Syndrome.

J Maxillofac Oral Surg 2016 Sep 18;15(3):384-389. Epub 2015 Mar 18.

Department of Maxillofacial Surgery, Sapienza University of Rome, Rome, Italy.

Although micrognathia and cleft palate have been reported in patients with Lymphedema-distichiasis syndrome (LDS), the classic Robin sequence with glossoptosis and airway obstruction has not been previously described in patients with genetically confirmed LDS. Here we report on two female siblings with LDS confirmed by a mutation who presented at birth with severe airway obstruction related to Robin sequence. Respiratory obstruction was successfully managed by early distraction osteogenesis. Our report highlights the unusual occurrence of Robin sequence in LDS patients and advises distraction osteogenesis to resolve breathing problems in LDS patients who present with Robin related severe airway obstruction.
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http://dx.doi.org/10.1007/s12663-015-0774-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048309PMC
September 2016

A New Formulation of Oral Viscous Budesonide in Treating Paediatric Eosinophilic Oesophagitis: A Pilot Study.

J Pediatr Gastroenterol Nutr 2017 02;64(2):218-224

*Department of Paediatrics and Childhood Neuropsychiatry, Paediatric Gastroenterology and Liver Unit †Department of Paediatrics and Childhood Neuropsychiatry, PICU ‡Department of Radiological Sciences, Oncology, and Anatomical Pathology, Sapienza-University of Rome, Rome, Italy §Unit of Pediatric Gastroenterology, Integrated Pediatric Hospital, Centro Hospitalar de São João, Porto, Portugal.

Objectives: Oral viscous budesonide is a recent therapeutic option for eosinophilic oesophagitis (EoE) compared with dietary restriction and inhaled steroids. This single-centre, open-label, not blinded study aims to evaluate the efficacy and safety of a new, preprepared oral viscous budesonide suspension (PVB) in children and adolescents with EoE.

Methods: We treated 36 children with PVB (29 boys; median age 12 years) with EoE diagnosed according to European Society for Paediatric Gastroenterology Hepatology and Nutrition guidelines. Patients <150 and >150 cm height received 2 and 4 mg PVB daily, respectively, for 12 weeks. Upper gastrointestinal endoscopy was performed at baseline, after 12 weeks of therapy and 24 weeks after the end of therapy. Baseline and post-treatment scores were calculated for symptoms, endoscopy, and histology. Serum cortisol was performed at baseline, 12, and 36 weeks.

Results: At the end of PVB trial, endoscopy showed macroscopic remission in 32 patients (88.9%), whereas at histology median pre- and post-treatment peak eosinophil count/high power field (HPF) markedly decreased from 42.2 (range: 15-100) to 2.9 (range: 0-30); moreover, mean symptom and histology scores impressively improved compared with baseline (P < 0.01). At 24 weeks after the end of PVB therapy, endoscopy showed oesophageal relapse in 21 patients (58.3%), whereas 15 (41.7%) were still in remission. Seven children (19.4%) with positive multichannel intraluminal impedance-pH were treated also with proton pump inhibitors. No significant difference between pre-/post-treatment morning cortisol levels occurred.

Conclusions: The new PVB suspension presented in the present study is effective and safe for treating children with proven EoE. Larger placebo-controlled clinical trials would provide more information about dosing, efficacy, and long-term safety of this formulation, specifically designed for the oesophagus.
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http://dx.doi.org/10.1097/MPG.0000000000001281DOI Listing
February 2017

Synchronized Nasal Intermittent Positive Pressure Ventilation of the Newborn: Technical Issues and Clinical Results.

Neonatology 2016 3;109(4):359-65. Epub 2016 Jun 3.

Pediatric Emergency and Intensive Care, Department of Pediatrics, Policlinico x2018;Umberto I', Sapienza University of Rome, Rome, Italy.

Although mechanical ventilation via an endotracheal tube has undoubtedly led to improvement in neonatal survival in the last 40 years, the prolonged use of this technique may predispose the infant to development of many possible complications including bronchopulmonary dysplasia. Avoiding mechanical ventilation is thought to be a critical goal, and different modes of noninvasive respiratory support beyond nasal continuous positive airway pressure, such as nasal intermittent positive pressure ventilation and synchronized nasal intermittent positive pressure ventilation, are also available and may reduce intubation rate. Several trials have demonstrated that the newer modes of noninvasive ventilation are more effective than nasal continuous positive airway pressure in reducing extubation failure and may also be more helpful as modes of primary support to treat respiratory distress syndrome after surfactant and for treatment of apnea of prematurity. With synchronized noninvasive ventilation, these benefits are more consistent, and different modes of synchronization have been reported. Although flow-triggering is the most common mode of synchronization, this technique is not reliable for noninvasive ventilation in neonates because it is affected by variable leaks at the mouth and nose. This review discusses the mechanisms of action, benefits and limitations of noninvasive ventilation, describes the different modes of synchronization and analyzes the technical characteristics, properties and clinical results of a flow-sensor expressly developed for synchronized noninvasive ventilation.
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http://dx.doi.org/10.1159/000444898DOI Listing
November 2017

Bronchiolitis: Analysis of 10 consecutive epidemic seasons.

Pediatr Pulmonol 2016 12 26;51(12):1330-1335. Epub 2016 May 26.

Department of Pediatrics and Infantile Neuropsychiatry, "Sapienza" University of Rome, V.le Regina Elena 324, Rome 00161, Italy.

Bronchiolitis is the leading cause of hospitalization in infants under 12 months. Our aims were to analyze epidemiological characteristics of infants with bronchiolitis over 10 consecutive seasons and to evaluate whether there are any clinical differences between infants hospitalized for bronchiolitis during epidemic peak months and infants in non-peak months. We enrolled consecutive enrolled 723 previously healthy term infants hospitalized at the Paediatric Emergency Department, "Sapienza" University of Rome over the period 2004-2014. Fourteen respiratory viruses were detected from nasopharyngeal aspirates by molecular methods. Clinical and demographic data were extracted from clinical charts. Viruses were detected in 351 infants (48.5%): RSV in 234 (32.4%), RV in 44 (6.1%), hBoV in 11 (1.5%), hMPV in 12 (1.6%), co-infections in 39 (5.4%), and other viruses in 11 (1.5%). Analyzing the 10 epidemic seasons, we found higher incidence for bronchiolitis every 4 years with a peak during the months December-January. Infants hospitalized during peak months had lower family history for asthma (P = 0.003), more smoking mothers during pregnancy (P = 0.036), were slightly higher breastfed (0.056), had lower number of blood eosinophils (P = 0.015) and had a higher clinical severity score (P = 0.017). RSV was detected mostly during peak months, while RV was equally distributed during the seasons. We found some variations in bronchiolitis incidence during epidemics, and discriminative characteristics in infants hospitalized for bronchiolitis during peak months and in non-peak months, that might reflect two different populations of children. Pediatr Pulmonol. 2016;51:1330-1335. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ppul.23476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167938PMC
December 2016

The role of vancomycin in addition with colistin and meropenem against colistin-sensitive multidrug resistant Acinetobacter baumannii causing severe infections in a Paediatric Intensive Care Unit.

BMC Infect Dis 2015 Sep 30;15:393. Epub 2015 Sep 30.

Department of Public Health and Infectious Diseases, University of Rome "Sapienza", Viale del Policlinico 155, Rome, Italy.

Background: Acinetobacter baumannii has been associated with high morbidity and mortality rates, even in pediatric patients. Therapeutic options are limited, especially when the strain is multidrug resistant.

Methods: Clinical and microbiological analyses of 4 cases of systemic infections caused by multi drug resistant A. baumannii treated with colistin/vancomycin combination at a Pediatric Intensive Care Unit were performed in order to explore the potential synergistic activity of colistin plus vancomycin. All the patients were treated with colistin, meropenem and vancomycin.

Results: Four severe infections due to MDR A. baumannii were observed. All patients treated with colistin/vancomycin combination had a positive outcome with no infection relapses. Most importantly, no significant adverse events related to the simultaneous administration of COL plus VAN were observed. In our in-vitro experiments, the synergistic effect of the combination COL plus VAN showed an early bactericidal activity even at VAN concentration of 16 mg/L, which reflects the serum trough concentrations obtained in patients.

Discussion: An antimicrobial strategy based on the activity of colistin plus vancomycin was in-vitro and in-vivo effective in life-threatening infections caused by multidrug-resistant A. baumannii in a Pediatric Intensive Care Unit, in the absence of adverse effects. Colistin plus vancomycin were highly synergic and bactericidal against carbapenem-resistant, colistin sensitive A. baumannii whereas the addition of meropenem did not enhance the in-vitro activity of colistin plus vancomycin.

Conclusions: Our results confirm existing data on the potential synergistic activity of a therapeutic strategy including colistin plus vancomycin and provide important new clinical information for its potential use as a therapeutic option against MDR A. baumannii infections, especially in the pediatric population.
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http://dx.doi.org/10.1186/s12879-015-1133-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589198PMC
September 2015

Colon capsule endoscopy compared with other modalities in the evaluation of pediatric Crohn's disease of the small bowel and colon.

Gastrointest Endosc 2016 May 9;83(5):975-83. Epub 2015 Sep 9.

Children's Center for Digestive Health Care, Atlanta, Georgia, USA.

Background And Aims: Data on colon capsule endoscopy (CCE) in evaluating the small bowel and colon concurrently are rare. This study aimed to evaluate the accuracy of CCE in assessing disease activity of the small bowel and colon in pediatric Crohn's disease (CD) by comparison with magnetic resonance enterography (MRE), small-intestine contrast US (SICUS), and ileocolonoscopy.

Methods: We prospectively enrolled 40 consecutive patients (22 male, 18 female, mean age 13.1 ± 3.1 years) with CD of the small bowel and colon. All underwent SICUS, MRE, CCE, and ileocolonoscopy sequentially over 5 days. All investigators were blinded to patient history and test results. Patients were classified as active or inactive for the small bowel and the colon according to specific criteria for each tool (simple endoscopic score for CD, Lewis score, US and magnetic resonance parameters of activity). For colon mucosa evaluation, ileocolonoscopy was the comparator. For the small bowel, a consensus panel was convened.

Results: Sensitivity of CCE to detect colon inflammation was 89%, and specificity was 100%. The positive predictive value (PPV) and negative predictive value (NPV) of CCE for colon inflammation were 100% and 91%, respectively. In the small bowel, CCE showed 90% sensitivity, 94% specificity, with PPV and NPV of 95% and 90%, respectively. Accuracy parameters for SICUS (sensitivity 90%, specificity 83%) and MRE (sensitivity 85%, specificity 89%) were lower than those for CCE. No serious adverse events related to the CCE procedure or preparation were reported.

Conclusions: CCE is of great usefulness in evaluating both small bowel and colon mucosa in pediatric CD. This single, noninvasive tool makes it possible to evaluate the small-bowel and the colon concurrently with high diagnostic accuracy. Future multicenter studies need to define the role of CCE in the routine management of pediatric patients with CD. (

Clinical Trial Registration Number: NCT02199626.).
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http://dx.doi.org/10.1016/j.gie.2015.08.070DOI Listing
May 2016

Severe early onset ethylmalonic encephalopathy with West syndrome.

Metab Brain Dis 2015 Dec 21;30(6):1537-45. Epub 2015 Jul 21.

Division of Child Neurology, Department of Paediatrics, Sapienza University of Rome, Rome, Italy.

Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder characterized by early onset encephalopathy, chronic diarrhoea, petechiae, orthostatic acrocyanosis and defective cytochrome c oxidase (COX) in muscle and brain. High levels of lactic, ethylmalonic and methylsuccinic acids are detected in body fluids. EE is caused by mutations in ETHE1 gene, a mitochondrial sulfur dioxygenase. Neurologic signs and symptoms include progressively delayed development, hypotonia, seizures, and abnormal movements. We report on the clinical, electroencephalographic and MRI findings of a baby with a severe early onset encephalopathy associated with novel ETHE1 gene mutation. This is the first case described in literature with an early pure epileptic onset, presenting with West syndrome.
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http://dx.doi.org/10.1007/s11011-015-9707-8DOI Listing
December 2015

High-Flow Nasal Cannula to Prevent Desaturation in Endotracheal Intubation: A Word of Caution.

Crit Care Med 2015 Aug;43(8):e327-8

Pediatric Intensive Care Unit (Dept. Pediatrics), Sapienza University of Rome, Rome, Italy Pediatric Intensive Care Unit (Dept. Pediatrics), Umberto I Policlinico of Rome, Rome, Italy.

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http://dx.doi.org/10.1097/CCM.0000000000001065DOI Listing
August 2015

Viral Load in Infants Hospitalized for Respiratory Syncytial Virus Bronchiolitis Correlates with Recurrent Wheezing at Thirty-Six-Month Follow-Up.

Pediatr Infect Dis J 2015 Oct;34(10):1131-2

From the *Department of Paediatrics and †Virology Laboratory, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.

The relationship between viral infection, host immune response in infants with respiratory syncytial virus (RSV) bronchiolitis and subsequent wheezing is discussed. We measured RSV-RNA load and interferon-λ1-3 expression in the nasopharyngeal washings from 68 infants hospitalized for RSV bronchiolitis, and wheezing was assessed 36 months after the first episode of bronchiolitis. Higher RSV-RNA load and higher interferon-λ2/3 levels were found in children with recurrent wheezing at 36-month follow-up.
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http://dx.doi.org/10.1097/INF.0000000000000825DOI Listing
October 2015

The use of piezosurgery in cranial surgery in children.

J Craniofac Surg 2015 May;26(3):840-2

*Maxillo-Facial Surgery Unit †Neurosurgery Unit ‡Departments of Odontostomatology §Genetics ||Pediatrics and Pediatric Neuropsychiatry ¶Gynecology and Obstetrics, Policlinico Umberto I, "Sapienza" University of Rome #Genetics Unit, S. Camillo-Forlanini Hospital **Department of Radiology and Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.

Piezosurgery is an alternative surgical technique, now widely tested, that uses ultrasounds for bone cutting. This device uses ultrasounds to section hard tissues without harming surrounding soft tissues. The authors analyzed their experience in craniomaxillofacial procedures with piezosurgery. A comparison between operation timing and complication rates between piezosurgery and traditional cutting instruments has been performed. A total of 27 patients were examined (15 females and 12 males; average age, of 5.5 months) affected by craniosynostosis. The aim of this study was to analyze the advantages and disadvantages of piezosurgery in pediatric craniofacial procedures. Piezoelectric device in this study has shown being a valid instrument for bone cutting in accurate procedures, because it allows performing a more precise and safer cutting, without the risk of harming surrounding tissues.
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http://dx.doi.org/10.1097/SCS.0000000000001574DOI Listing
May 2015

Electroencephalogram and magnetic resonance imaging comparison as a predicting factor for neurodevelopmental outcome in hypoxic ischemic encephalopathy infant treated with hypothermia.

Pediatr Rep 2014 Aug 1;6(3):5532. Epub 2014 Oct 1.

Division of Child Neurology, Department of Pediatrics, La Sapienza University , Rome, Italy.

Hypoxic-ischemic encephalopathy (HIE) is an important cause of acute neurological damage in newborns at (or near) term. Several trials in recent years have shown that moderate hypothermia by total body cooling or selective head is an effective intervention to reduce mortality and major disability in infants survived a perinatal hypoxic-ischemic attack. Follow-up in these patients is very important to establish neurodevelopmental outcome, and specific markers can lead us to detect predicting sign for good or poor outcome. We reported a few cases of newborn with HIE treated with hypothermia, in whom the comparison between electroencephalogram (EEG) and magnetic resonance imaging (MRI) represents the first marker for neurodevelopment outcome prediction. The continuous EEG monitoring showed a depressed EEG activity with diffuse burst depression in 7 patients. No epileptic abnormalities were registered. In 10 out of 20 patients no abnormalities of the background activity and no epileptic abnormalities were observed. We found that a depressed EEG activity during the first 72 h of life and a diffused alteration of basal ganglia at MRI were correlated with a poor neurodevelopmental outcome at 18 months of follow-up.
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http://dx.doi.org/10.4081/pr.2014.5532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292060PMC
August 2014

Proven Epstein-Barr encephalitis with negative EBV-DNA load in cerebrospinal fluid after allogeneic hematopoietic stem cell transplantation in a child with acute lymphoblastic leukemia.

Pediatr Transplant 2015 Feb 12;19(1):E19-24. Epub 2014 Nov 12.

Division of Hematology, Department of Cellular Biotechnologies and Hematology, "Sapienza" University, Rome, Italy.

We report a case of EBV encephalitis in a seven-yr-old child with Ph+ ALL. Two months after an allogeneic HSCT from his HLA mismatched mother, the patient showed an altered sensorium, generalized seizures, and a left hemiparesis. Brain MRI demonstrated multiple lesions highly suggestive for viral encephalitis. Blood and CSF PCR analyses were negative for the most common viruses involved in immunocompromised patients including EBV. A cerebral biopsy was performed, which showed intense gliosis and perivascular lymphocytic cuffing. PCR analysis performed on brain tissue was positive only for the EBV genome, while extensive investigations for other viral infections were negative. The patient's neurological symptoms rapidly worsened and he died two months later. This case report suggests that in patients presenting neurological and radiological signs of encephalitis after an HSCT, an EBV involvement should be considered, even in the absence of CSF and blood PCR virus detection.
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http://dx.doi.org/10.1111/petr.12386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167730PMC
February 2015