Dalmonte P.,Irccs G Gaslini Childrens Hospital |
Granata C.,Irccs G Gaslini Childrens Hospital |
Fulcheri E.,University of Genoa |
Vercellino N.,Irccs G Gaslini Childrens Hospital |
And 2 more authors.
Journal of Pediatric Orthopaedics | Year: 2012
Background: Intra-articular venous malformations (IAVM) of the knee represent a rare group of low-flow vascular malformations, mainly reported in the literature as synovial hemangiomas, usually with an onset in early childhood. The main symptoms and signs are knee pain, swelling, and hemarthrosis. These lesions are slowly progressive and can lead to chronic synovitis and joint damage. Confusing nomenclature and classification of these lesions have often led to misdiagnosis and inappropriate treatment. We report our experience in the treatment of 14 consecutive patients affected by knee IAVM. Methods: We carried out a retrospective study based on the review of the medical records and diagnostic imaging of the patients admitted to our department from October 1999 to June 2009, and discharged with the final diagnosis of IAVM of the knee. Results: We observed 14 consecutive patients (8 boys, 6 girls); the median age at symptom onset was 5 years (range, 2.5 to 13 y). Magnetic resonance imaging was diagnostic in all cases. Surgical resection associated with a wide synoviectomy was the therapeutic procedure of choice in all cases. Within 6 months after surgery and physiotherapy, all the patients were symptom free with a full or at least acceptable knee range of motion. CD34 staining carried out in the last 7 cases of our series showed labeling of the endothelium of the thick-walled vessels, whereas the endothelium of the thin-walled vascular spaces was not stained. This finding of unstained vascular spaces suggests that a component of lymphatic vessels mixed with dysplastic blood vessels may be frequently present in these abnormalities. Conclusions: Magnetic resonance imaging plays a pivotal role in identifying the lesion. Surgical excision is always indicated and should be performed as early as possible to avoid lesion progression and to reduce the risk of chondral degeneration. According to the microscopic features of our resected specimens, we suggest that these lesions of the knee should be more properly named as IAVM instead of hemangiomas. Level of Evidence: Level IV. © 2012 by Lippincott Williams & Wilkins.
Influence of image-defined risk factors on the outcome of patients with localised neuroblastoma. A report from the LNESG1 study of the European International Society of Paediatric Oncology Neuroblastoma Group
Monclair T.,University of Oslo |
Mosseri V.,University Pierre and Marie Curie |
Cecchetto G.,University of Padua |
De Bernardi B.,Giannina Gaslini Childrens Hospital |
And 2 more authors.
Pediatric Blood and Cancer | Year: 2015
The European multicenter study LNESG1 was designed to evaluate the safety and efficacy of surgical treatment alone in patients with localised neuroblastoma. In a retrospective, observational study we examined the impact of image-defined risk factors (IDRF) on operative complications and survival (EFS and OS). Procedure: 534 patients with localised, non-MYCN amplified neuroblastoma were recruited between 1995 and 1999. Group 1 consisted of 291 patients without IDRF (Stage L1 in the International Neuroblastoma Risk Group (INRG) staging system), all treated with primary surgery. Group 2: 118 patients with IDRF (INRG Stage L2), also treated with primary surgery. Group 3: 125 patients in whom primary surgery was not attempted, 106 receiving neo-adjuvant chemotherapy. Results: In L1 patients (Group 1) 5-year EFS was 92% and OS 98%. In L2 patients (Group 2 and 3) EFS was 79% and OS 89%. The differences in both EFS and OS were significant. EFS and OS in Group 2 (86% and 95%) were significantly better than 73% and 83% in Group 3. In INSS stage 1, 2 and 3, EFS were respectively 94%, 81% and 76%. Except between stage 2 and 3 the differences were significant. OS were respectively 99%, 93% and 83%, all significantly different. The 17% operative complication rate in L2 patients was significantly higher than 5% in L1 patients. Conclusions: In localised neuroblastoma, IDRF at diagnosis are associated with worse survival rates and higher rates of operative complications. The impact of IDRF should become an integrated part of therapy planning. © 2015 Wiley Periodicals, Inc.
Prunotto M.,Hoffmann-La Roche |
Ghiggeri G.M.,Giannina Gaslini Childrens Hospital |
Candiano G.,Giannina Gaslini Childrens Hospital |
Lescuyer P.,University of Geneva |
And 2 more authors.
Journal of Proteome Research | Year: 2011
Chronic kidney disease (CKD) is becoming a worldwide public health problem. The identification of a specific set of early biomarkers for CKD is extremely relevant to progress in disease knowledge, improving diagnosis, treatment, or development, and monitoring efficacy of new drugs. As kidney fibrosis can be considered the common pathological way to end stage renal failure, independent of the initial renal insult, these biomarkers are therefore biomarkers of early tubulo-interstitial fibrosis. The availability of a specific set of biomarkers for CKD is the mandatory condition to create new dedicated drugs and validate them in clinics without waiting years for a functional response in patients. We suggest here specific cohorts of patients where this early signature of fibrosis may be simpler to be identified. © 2011 American Chemical Society.
Economou M.,Aristotle University of Thessaloniki |
Banov L.,Giannina Gaslini Childrens Hospital |
Ljung R.,Skåne University Hospital
European Journal of Haematology | Year: 2014
Haemophilia is an X-linked recessive genetic disease of haemostasis. Women carriers may present with a bleeding tendency similar to milder forms of the disease. Haemophilic newborns present risk factors and patterns of bleeding that are challenging. Identification of carriers and genetic counselling before conception is considered optimal to help decide on available conception options and during pregnancy to help minimise bleeding risks for both carrier mother and affected baby. Preimplantation genetic diagnosis is attractive to many couples at risk of having a child with haemophilia and relevant technology is becoming more available although it has both practical and ethical limitations. Pregnancy in carriers should be managed by a multidisciplinary team in a comprehensive treatment centre. The optimal mode of delivery for carriers expecting a baby known to have or being at risk of haemophilia is an issue of great debate. The general consensus among authors is avoidance of instrumental delivery, foetal scalp electrodes and blood sampling in pregnancies at risk of carrying an affected foetus, as well as early recourse to Caesarean section as guided by obstetric indications. Intracranial haemorrhage, although infrequent, is one the most devastating types of bleeding in haemophilic newborns and can occur regardless of the mode of delivery or the severity of haemophilia. Early screening is proposed for all infants with severe or moderate haemophilia who have had traumatic delivery and/or have evidence of extracranial haemorrhage. Women with postpartum haemorrhage should have a bleeding work-up. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Mulder E.J.H.,University Utrecht |
Tegaldo L.,San Carlo Hospital |
Bruschettini P.,Giannina Gaslini Childrens Hospital |
Visser G.H.A.,University Utrecht
Journal of Psychopharmacology | Year: 2010
Little is known about the effect on the human foetus of long-term and acute exposure to caffeine. We studied the organisation of foetal sleep-wake states in 13 healthy near-term foetuses over a wide range of maternal plasma caffeine concentrations (0-13 μg/mL) reflecting normal lifestyle conditions (day 0) and again following intake of two cups of regular coffee (∼300 mg of caffeine) intermitted by 50 h of abstinence (day 2; acute effects). On either day, 2 h simultaneous recordings were made of foetal heart rate, general-, eye-, and breathing-movements. The recordings were analysed for the presence of each of four foetal behavioural states: quiet- and active-sleep, quiet- and active-wakefulness. There was a linear relationship between maternal caffeine content and the incidence of foetal general movements during active sleep on day 0 (R = 0.74; P < 0.02). After coffee loading on day 2, foetuses of non- or low-caffeine consumers showed increases in active wakefulness (P < 0.001), general movements (P < 0.05) and heart rate variation (P < 0.01) but lower basal heart rate (P < 0.01) compared with their day 0 values. The changes in foetal heart rate (variation) and behaviour occurred between 90 and 180 min post-consumption. In contrast, foetuses of habitual caffeine consumers remained unaffected suggestive of foetal tolerance to caffeine. The results indicate differential performance between foetuses regularly exposed to caffeine and those caffeine-naive, both under normal maternal lifestyle conditions and in response to maternal coffee ingestion. © The Author(s), 2010.
Zin A.,University of Padua |
Zin A.,Instituto Of Ricerca Pediatrica Citta Della Speranza |
Bertorelle R.,University of Padua |
Dall'Igna P.,University of Padua |
And 6 more authors.
American Journal of Surgical Pathology | Year: 2014
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma and is mostly represented by the embryonal (ERMS) and alveolar (ARMS) histotypes. Whereas ERMS shows variable genetic alterations including TP53, RB1, and RAS mutations, ARMS carries a gene fusion between PAX3 or PAX7 and FOXO1. Epithelioid RMS is a morphologic variant of RMS recently described in adults. Five cases of epithelioid RMS were identified after histologic review of 85 cases of ARMS enrolled in Italian therapeutic protocols. Immunostaining analyses (muscle-specific actin, desmin, myogenin, AP-2β, EMA, cytokeratins, INI-1) and reverse transcription polymerase chain reaction assays to detect MyoD1, myogenin, and PAX3/7-FOXO1 transcripts were performed. In 4 cases DNA sequencing of TP53 was performed; and RB1 allelic imbalance and homozygous deletion were analyzed by quantitative real-time polymerase chain reaction. Histologically, epithelioid RMS displayed sheets of large cells without rhabdomyoblastic differentiation or anaplasia in 3 and prominent rhabdoid cells in 2; necrosis was evident in 4, often with a geographic pattern. Immunostainings for INI, desmin, myogenin (scattered cells in 4, diffuse in 1) were positive in all; EMA and MNF116 were positive in 2; AP-2β was negative. PAX3/7-FOXO1 transcripts were absent. In all cases RB1 was wild type, and a TP53 mutation at R273H codon was found in 1. All patients are in complete remission, with a median follow-up of 6 years. Epithelioid RMS may occur in children and is probably related to ERMS, as suggested by lack of fusion transcripts, weak staining for myogenin, negative AP-2β, evidence of TP53 mutation (although only in 1 case), and a favorable clinical course. Copyright © 2013 by Lippincott Williams & Wilkins.
Prunotto M.,Giannina Gaslini Childrens Hospital
Laboratory investigation; a journal of technical methods and pathology | Year: 2010
Epithelial-to-mesenchymal transition (EMT) is involved in embryonic development as well as in several pathological conditions. Literature indicates that polyamine availability may affect transcription of c-myc, matrix metalloproteinase (MMP)1, MMP2, TGFbeta(1), and collagen type I mRNA. The aim of this study was to elucidate polyamines role in EMT in vitro. Madin-Darby canine kidney (MDCK) cells were subjected to experimental manipulation of intracellular levels of polyamines. Acquisition of mesenchymal phenotype was evaluated by means of immunofluorescence, western blots, and zymograms. MDCK cells were then subjected to 2D gel proteomic study and incorporation of a biotinilated polyamine (BPA). Polyamine endocellular availability modulated EMT process. Polyamine-depleted cells treated with TGFbeta(1) showed enhanced EMT with a marked decrease of E-cadherin expression at plasma membrane level and an increased expression of mesenchymal markers such as fibronectin and alpha-smooth muscle actin. Polyamine-depleted cells showed a twofold increased expression of the rough endoplasmic reticulum (ER)-stress proteins GRP78, GRP94, and HSP90 alpha/beta in 2D gels. The latter data were confirmed by western blot analysis. Administration of BPA showed that polyamines are covalently linked, within the cell, to ER-stress proteins. Intracellular polyamine availability affects EMT in MDCK cells possibly through the modulation of ER-stress protein homeostasis.
Ravani P.,University of Calgary |
Rossi R.,Giannina Gaslini Childrens Hospital |
Bonanni A.,Giannina Gaslini Childrens Hospital |
Quinn R.R.,University of Calgary |
And 14 more authors.
Journal of the American Society of Nephrology | Year: 2015
Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity fromsteroids or steroid-sparing agents. This open-label,noninferiority,randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and weremaintained in remission with high prednisone doses (≥0.7mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m2; intervention). Prednisone was tapered in both groups after 1month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m2 per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome).We followed participants for ≥1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for ≤60 months (median, 22months). Three-month proteinuria was 42%lower in the rituximab group (geometricmean ratio, 0.58; 95%confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6months; median timeto relapse in the rituximab group was 18months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS. Copyright © 2015 by the American Society of Nephrology.
Torre M.,Giannina Gaslini Childrens Hospital |
Rapuzzi G.,Giannina Gaslini Childrens Hospital |
Carlucci M.,Giannina Gaslini Childrens Hospital |
Carlucci M.,University of Genoa |
And 3 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2012
Sternal cleft is a chest wall malformation that can expose mediastinal viscera and vessels to injuries. It can be classified into two forms, complete and partial. Its etiology and incidence are unknown and it is often associated with other defects. The aim of this article is to review the literature and report our experience with this rare anomaly, focusing on clinical presentation and management. We reviewed the English written literature about sternal cleft and collected the clinical data of all the published series. We present seven new cases that we have observed and treated since 1999. Literature reports 51 series including 86 patients, more frequently female (62%) and affected with partial superior form (67%). Sternal cleft is often asymptomatic (74%) and associated with other defects (72%). Surgical treatments include primary closure (73%), bone graft interposition (10%), prosthetic closure (7%), and muscle flap interposition (3%). In our series, primary closure was possible in four cases, while in three cases we placed a prosthesis. Five patients had associated defects and two were affected with PHACES (posterior fossa abnormalities, hemangiomas, arterial lesions, cardiac abnormalities/aortic coarctation, abnormalities of the eye, and sternum defects) syndrome. We report for the first time the association of sternal cleft with connectival nevi in three of our patients. At follow-up, we observed no major complication or recurrences. Although primary closure is the preferred option and should be performed in the neonatal period, the use of prostheses warrants good results as well. Prior to treatment, associated defects and syndromes should be excluded. © The Author 2011. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
De Caro E.,Giannina Gaslini Childrens Hospital |
Smeraldi A.,Giannina Gaslini Childrens Hospital |
Trocchio G.,Giannina Gaslini Childrens Hospital |
Calevo M.,Giannina Gaslini Childrens Hospital |
And 2 more authors.
Pediatric Blood and Cancer | Year: 2011
Background: Although anthracycline cardiotoxicity is clearly related to the cumulative dose administered, subclinical cardiac dysfunction has been reported across a wide range of treatment regimens, and its clinical significance is still unclear. Purpose of this study is to investigate by exercise echocardiography for subclinical cardiac dysfunction in survivors of pediatric cancer treated with low-moderate anthracycline doses, and to evaluate whether it may alter the response of the cardiovascular system to dynamic exercise. Procedure: Post-exercise left ventricular end-systolic wall stress (ESS), left ventricular posterior wall dimension and percent thickening at end systole, and cardiopulmonary exercise test-derived indexes of cardiac function were examined in 55 apparently healthy patients (mean age 13.5 ± 2.9 years, median anthracycline cumulative dose 240 mg/m 2) and in 63 controls. Results: Subclinical cardiac dysfunction was identified in 17 patients (30%) presenting reduced left ventricular posterior wall dimension or percent thickening, or increased values of left ventricular ESS as compared to controls (group A), while the remaining patients formed group B. Reduced oxygen consumption at peak exercise in both groups of patients was the only cardiopulmonary exercise test variable resulting significantly different between patients and controls: no differences were found among the groups of patients. Conclusions: Our results confirm that even patients treated with a median anthracycline dose of 240 mg/m 2 (range 100-490) are at considerable risk of exhibiting subclinical cardiac dysfunction that, however, does not seem to alter the physiologic response of the cardiovascular system to dynamic exercise. © 2010 Wiley-Liss, Inc.