Papers by Carolina Grassia
Early Human Development, 2008
PubMed, Feb 1, 2007
Aim: Optic pathway gliomas (OPG) are the predominant intracranial tumours associated with neurofi... more Aim: Optic pathway gliomas (OPG) are the predominant intracranial tumours associated with neurofibromatosis type 1 (NF1). The aim of this study was to evaluate the prevalence and the outcome of OPG in 200 NF1 patients (122 males and 78 females, aged 1-25 years) followed up to 16 years (mean of 6 years). Methods: All children were evaluated by a detailed physical, neurological and ophthalmological examination. Fifteen out of 200 (7.5%) of these patients (7 males, 8 females) were identified with evidence of optic pathway tumours. Results: Nine children had symptoms such as endocranial hypertension, seizures, headache; 4 patients only showed anomalies at ophthalmological examination; 2 patients had no symptoms or signs. All children had evidence of optic pathway tumour on magnetic resonance imaging. Three had a prechiasmal tumour, 2 had a chiasmal tumour, 1 had prechiasmal/chiasmal tumour, 2 had a prechiasmal/chiasmal and postchiasmal tumour, 2 had a chiasmal and postchiasmal tumour, 4 had a massive involvement of the optic system, 1 child exhibited a bilateral involvement of the optic nerves with additional impairment of the chiasm. Four patients had partial and/or subtotal spontaneous regression. Conclusions: Because optic pathway tumours arise in children younger than 6 years of age, all NF1 children should undergo yearly ophtalmologic examination and growth assessment to monitor signs of precocious puberty.
Pediatric Nephrology, Dec 1, 1997
mWe evaluated the effect of 2 years' therapy with an angiotensin converting enzyme inhibitor (cap... more mWe evaluated the effect of 2 years' therapy with an angiotensin converting enzyme inhibitor (captopril) in 16 patients who had severe reflux nephropathy and microalbuminuria. During the period of therapy, microalbuminuria decreased, glomerular filtration rate measured by diethylenetriamine pentaacetate scan, serum creatinine, and blood pressure remained stable. We suggest the captopril was useful in reducing microalbuminuria and may have slowed the progression of renal damage in our patients.
A genome search for primary vesicoureteral reflux shows further evidence for genetic heterogeneity
The Journal of Vascular Access, 2018
Purpose: The neonatologists of Sant’Anna and San Sebastiano Hospital of Caserta have carried out ... more Purpose: The neonatologists of Sant’Anna and San Sebastiano Hospital of Caserta have carried out a pilot study investigating the safety, feasibility, and accuracy of intracavitary electrocardiography for neonatal epicutaneous cava catheter tip positioning. Patients and methods: We enrolled 39 neonates (1–28 days of postnatal age or correct age lower than 41 weeks) requiring epicutaneous cava catheter in the district of superior vena cava (head–neck or upper limbs). Intracavitary electrocardiography was applicable in 38 neonates. Results: No significant complications related to intracavitary electrocardiography occurred in the studied neonates. The increase in P wave on intracavitary electrocardiography was detected in 30 cases. Of the remaining eight cases, six malpositioned catheters tipped out of cavoatrial junction–target zone (chest x-ray and echocardiographical control) and two were false negative (tip located in target zone). The match between intracavitary electrocardiography...
Trials, 2016
Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SURE) ... more Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SURE) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SURE method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SURE) with IN-SURE alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria.
Pediatric nephrology (Berlin, Germany), 2003
The aim of this study was to evaluate the relationship between blood pressure (BP), measured with... more The aim of this study was to evaluate the relationship between blood pressure (BP), measured with ambulatory blood pressure monitoring (ABPM), and the progression of renal damage in 100 (70 females, 30 males) normotensive children with reflux nephropathy (RN). The patients, mean age of 13.5+/-5 years and almost 5 years of follow-up, were divided according to degree of RN into group A (I/II) and group B (III/IV). For each subject, 24-h systolic and diastolic BP (SBP-DBP), load (percentage of BP readings that exceeded the age- and sex-specific 95th percentile), and biochemical parameters were recorded. There was no significant difference in casual BP between the groups. The mean 24-h SBP-DBP and load were significantly higher in group B than A. There was a significant difference in creatinine (Cr) levels between the groups, and Cr correlated with BP in both groups. In group B, microalbuminuria correlated with ambulatory BP, and plasma renin activity failed to decrease with chronologic...
Pediatric nephrology (Berlin, Germany), 1999
Pediatric Nephrology, 2008
Vesicoureteral reflux (VUR) is the most common disease of the urinary tract in children. In order... more Vesicoureteral reflux (VUR) is the most common disease of the urinary tract in children. In order to identify gene(s) involved in this complex disorder, we performed a genome-wide search in a selected sample of 31 patients with primary VUR from eight families originating from southern Italy. Sixteen additional families with 41 patients were included in a second stage. Nonparametric, affected-only linkage analysis identified four genomic areas on chromosomes 1, 3, and 4 (p<0.05); the best result corresponded to the D3S3681-D3S1569 interval on chromosome 3 (nonparametric linkage score, NPL= 2.75, p = 0.008). This region was then saturated with 26 additional markers, tested in the complete group of 72 patients from 24 families (NPL=2.01, p=0.01). We identified a genomic area on 3q22.2-23, where 26 patients from six multiplex families shared overlapping haplotypes. However, we did not find evidence for a common ancestral haplotype. The region on chromosome 1 was delimited to 1p36.2-34.3 (D1S228-D1S255, max. NPL=1.70, p=0.03), after additional fine typing. Furthermore, on chromosome 22q11.22-12.3, patients from a single family showed excess allele sharing (NPL=3.35, p=0.015). Only the chromosome 3q region has been previously reported in the single genome-wide screening available for primary VUR. Our results suggest the presence of several novel loci for primary VUR, giving further evidence for the genetic heterogeneity of this disorder.
Pediatric Nephrology, 2004
Journal of the American Society of Nephrology, 2008
The SLIT2 receptor ROBO2 plays a key role in the formation of the ureteric bud, and its inactivat... more The SLIT2 receptor ROBO2 plays a key role in the formation of the ureteric bud, and its inactivation in mice leads to supernumerary ureteric bud development, lack of ureter remodeling, and improper insertion of the ureters into the bladder. Recently, two heterozygous ROBO2 missense mutations were identified in two families with primary vesicoureteral reflux occurring in combination with congenital anomalies of the kidney and urinary tract (VUR/CAKUT). This study investigated a possible causal role of ROBO2 gene variants in 95 unrelated patients with primary VUR (n ϭ 78) or VUR/CAKUT. Eighty-two percent of all patients had a family history of genitourinary anomalies. Twenty-four ROBO2 gene variants were identified by direct sequencing of all 26 exons and the exon-intron boundaries. Of these, four led to amino acid substitutions: Gly328Ser, Asn515Ile, Asp766Gly, and Arg797Gln. When the families were examined, the missense variants co-segregated with VUR (three families) or VUR/CAKUT (one family). These variants were not found in 190 control subjects, and the affected amino acids have been conserved through evolution. In conclusion, a relatively high frequency of ROBO2 variants (5.1%) was found in familial cases; however, functional studies and validation in other cohorts are warranted.
International Journal of Cardiology, 2005
Background: Hypertension is frequently associated with neurofibromatosis type 1 (NF1), a common i... more Background: Hypertension is frequently associated with neurofibromatosis type 1 (NF1), a common inherited disease that limits life expectancy. No data are available on cardiac damage in NF1 patients with hypertension. We evaluated cardiac function in NF1 patients with hypertension diagnosed by 24-h ambulatory blood pressure monitoring (ABPM), compared with normal children. Methods: We studied 73 NF1 patients (41 boys; mean age 12 years) and 30 normal children comparable for age and sex, using standard 2D echocardiography, standard Doppler and Doppler tissue imaging (DTI). Twelve patients (16%) showed 24-h systolic blood pressure (SBP) or 24-h diastolic blood pressure (DBP) > 95th percentile for age and sex. We divided the NF1 group into two subgroups: group A, patients with 24-h SBP and DBP V 95th percentile for age and sex, and group B, patients with 24-h SBP or DBP >95th percentile for age and sex. Results: Group B presented a thicker end-diastolic interventricular septum (p < 0.0001), posterior wall (p = 0.02), LVMI (p < 0.001) and relative wall thickness (p < 0.03) than group A and controls. Left atrial dimension in group B was also significantly larger. Examination by standard Doppler showed a deceleration and isovolumic relaxation time significantly prolonged in group B. DTI parameters were significantly higher in NF1 patients than controls. In group B, myocardial early diastolic (E m) and systolic (S m) velocities were significantly lower than group A. Myocardial early/late diastolic ratio (E m /A m) in NF1 patients was lower than controls and 19% of group A and 20% of group B showed an E m /A m ratio < 1. No healthy subjects presented an E m /A m ratio < 1. Conclusions: We demonstrated early cardiac morphologic and functional changes in young NF1 patients with hypertension. Because DTI directly studies cardiac muscle, it can detect changes induced by hypertension as well as those independent of blood pressure.
Archives of Ophthalmology, 2003
Angiology, 2000
Neurofibromatosis regroups at least two different autosomal dominant genetic disorders: neurofibr... more Neurofibromatosis regroups at least two different autosomal dominant genetic disorders: neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). Vascular disease is an underestimated complication of NF1. Few studies are available on this, all based on case reports. Neurofibromin, NF1 protein product, has also been detected in aortic smooth muscle. The purpose of this study was to evaluate the physical properties of the vessels, by measuring the carotid-femoral pulse wave velocity (PWV). This parameter was assessed by the Complior®, a new noninvasive, validated device, used to screen a large population. The authors studied 64 neurofibromatosis patients (34 boys and 30 girls) with a mean age of 12 years (range 5-25 years). To investigate the presence of vascular lesions, aortic stiffness was evaluated by carotid-femoral PWV by using an automatic processor (Complior®). They compared data from the PWV with a control group (30 healthy children, 17 boys and 13 girls, mean age 11...
The American Journal of Cardiology, 2001
American Heart Journal, 2002
Comprehensive data are unavailable for cardiac abnormalities in patients with neurofibromatosis t... more Comprehensive data are unavailable for cardiac abnormalities in patients with neurofibromatosis type 1 (NF1). The goal of this study was to evaluate the prevalence of cardiovascular abnormalities with echocardiography with color Doppler scan (ECHO) in a large, consecutive series of patients with NF1. We studied 48 patients with NF1 (mean age, 10 years). Thirty healthy subjects comparable for age and sex served as the control group. All ECHO studies were performed by the same cardiologist and reviewed by a second cardiologist blinded to the physical findings of the subjects. Cardiac abnormalities were found in 13 of the 48 young patients (27%). A secundum atrial septal defect with a left to right shunt was found in 2 children. ECHO evidence of mild left pulmonary artery stenosis was found in 1 participant. A moderate coarctation of the thoracic aorta was found in 1 patient. ECHO criteria for mitral valve prolapse and evidence of trivial mitral regurgitation with myxomatous mitral valve was present in 1 case. Mild mitral regurgitation was found in 2 patients. A regurgitant mild flow signal was detected from the aortic valve in 2 subjects. Atrial septal aneurysm was found in 2 patients without patent foramen ovale. Two patients had septal to posterior left ventricular free wall ratio greater than 1.5, suggesting hypertrophic cardiomyopathy. This is the first attempt to evaluate the prevalence of cardiovascular abnormalities in patients with NF1 with ECHO. The study&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s most striking finding is the high prevalence of cardiovascular abnormalities. Congenital lesions have potential long-term hemodynamic consequences that justify an early diagnosis. Thus, a cardiologic assessment at regular intervals, including ECHO study, is mandatory for patients with NF1.
The Lancet Respiratory Medicine, 2021
Background The importance of lung recruitment before surfactant administration has been shown in ... more Background The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E]). Methods We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SURE or IN-SURE using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766. Findings Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SURE group (43 [40%] of 107) compared with the IN-SURE group (60 [54%] of 111; adjusted RR 0•75, 95% CI 0•57-0•98; p=0•037), with a number needed to treat of 7•2 (95% CI 3•7-135•0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SURE group vs 37 [33%] of 111 in the IN-SURE group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111). Interpretation A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SURE technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy.
Minerva pediatrica, 2007
Optic pathway gliomas (OPG) are the predominant intracranial tumours associated with neurofibroma... more Optic pathway gliomas (OPG) are the predominant intracranial tumours associated with neurofibromatosis type 1 (NF1). The aim of this study was to evaluate the prevalence and the outcome of OPG in 200 NF1 patients (122 males and 78 females, aged 1-25 years) followed up to 16 years (mean of 6 years). All children were evaluated by a detailed physical, neurological and ophthalmological examination. Fifteen out of 200 (7.5%) of these patients (7 males, 8 females) were identified with evidence of optic pathway tumours. Nine children had symptoms such as endocranial hypertension, seizures, headache; 4 patients only showed anomalies at ophthalmological examination; 2 patients had no symptoms or signs. All children had evidence of optic pathway tumour on magnetic resonance imaging. Three had a prechiasmal tumour, 2 had a chiasmal tumour, 1 had prechiasmal/chiasmal tumour, 2 had a prechiasmal/chiasmal and postchiasmal tumour, 2 had a chiasmal and postchiasmal tumour, 4 had a massive involvem...
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Papers by Carolina Grassia