Prevalence and predictors of parental distress at the communication of positivity at newborn screening for metabolic diseases: an Italian longitudinal study.

Background: Receiving communication of positivity for metabolic diseases at Expanded Newborn Screening can be extremely stressful for parents, both in case of false positive and true positive cases. However, little is known about the predictors of distress and differential impact on mothers and fathers.

Methods: In this longitudinal study, 169 fathers and 171 mothers referred to one of the Italian metabolic centres for communication of positivity completed a survey including General Health Questionnaire-12, Emotion Thermometers (measuring stress, anxiety, depression, anger and need for help), Impact of Event Scale-Revised, Multidimensional Scale of Perceived Social Support and Emotion Regulation Questionnaire.

Parents' experience of the communication process of positivity at newborn screening for metabolic diseases: A qualitative study.

Background: The process of receiving a communication of positivity for metabolic diseases at expanded newborn screening (ENBS) is extremely articulated, involves a variety of actors (parents, maternal and child departments, clinical centres and laboratories) and is open to a variety of outcomes from false positive to true positive cases. Receiving communication of positivity can be highly stressful for parents and requires an adequate communication process to give clear and reliable information without causing excessive worry. This qualitative study describes the parents' experience of receiving a communication of positivity to metabolic diseases at ENBS, and their assessment of the quality of the communication process and steps, with the main aim to identify the process' strengths and weaknesses and to advance tailored recommendations to improve the communication process.

Hyperphenylalaninemias genotyping: Results of over 60 years of history in Lombardy, Italy.

Background: Hyperphenylalaninemias (HPA) are due to several gene mutations, of which the PAH gene is the most frequently involved. Prevalence and incidence of disease vary between populations, with genotype/phenotype correlations not always capable to correctly predict disease severity. The aim of this study was to give an overview of PAH mutations among one of the largest cohort of patients among Europe, born in Lombardy (Italy) starting from late 1970 s and including over a 60 years of activity; furthermore, to evaluate and discuss identified genotype/phenotype correlations and related reliability.

Breastfeeding in Phenylketonuria: Changing Modalities, Changing Perspectives.

Phenylketonuria (PKU) management aims to control phenylalanine (Phe) intakes. In newborns and infants this implies possible titration of Human milk (HM) with supplementation of Phe-free formula. HM benefits, better if prolonged, are well known in healthy populations, suggesting it may be used in PKU patients.

Mortality in patients with alpha-mannosidosis: a review of patients' data and the literature.

Background: Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder (LSD) caused by reduced activity of alpha-mannosidase. Clinical manifestations include skeletal dysmorphism, mental impairment, hearing loss and recurrent infections. The severe type of the disease leads to early childhood death, while patients with milder forms can live into adulthood.

L-alanine supplementation in Pompe disease (IOPD): a potential therapeutic implementation for patients on ERT? A case report.

Background: Pompe disease (PD) is a disorder of glycogen metabolism conditioning a progressive and life conditioning myopathy. Enzyme replacement therapy (ERT) is currently the best treatment option for PD, but is not resolutive. While other potential therapeutic approaches have been reported before, these have never been tried as co- treatments.

Telehealth and COVID-19: Empowering Standards of Management for Patients Affected by Phenylketonuria and Hyperphenylalaninemia.

Phenylketonuria (PKU) and Hyperphenylalaninemia (HPA) are inborn errors of metabolism (IEM) due to mutations in the gene resulting in increased blood phenylalanine (Phe) concentrations. Depending on the Phe levels, a lifelong dietary intervention may be needed. During the COVID-19 pandemic, finding new strategies to ensure follow-up and metabolic control for such patients became mandatory and telehealth was identified as the most eligible tool to provide care and assistance beyond barriers.

PKU and COVID19: How the pandemic changed metabolic control.

Background: COVID19 pandemic urged the need to take severe measures for reducing the epidemic spread. Lockdowns were imposed throughout countries and even Inborn errors of metabolism (IEMs) affected patients had to face it and adapt, with management strategies changes coming along. Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism causing, when not treated, blood Phe increases and consequent central nervous system (CNS) damage.

Challenges in Transition From Childhood to Adulthood Care in Rare Metabolic Diseases: Results From the First Multi-Center European Survey.

Inherited Metabolic Diseases (IMDs) are rare diseases caused by genetic defects in biochemical pathways. Earlier diagnosis and advances in treatment have improved the life expectancy of IMD patients over the last decades, with the majority of patients now surviving beyond the age of 20. This has created a new challenge: as they grow up, the care of IMD patients' needs to be transferred from metabolic pediatricians to metabolic physicians specialized in treating adults, through a process called "transition.

Secreting Germ Cell Tumors of the Central Nervous System: A Long-Term Follow-up Experience.

Introduction: Due to the rarity of nongerminomatous germ cell tumors (NGGCT) with non-standard treatment as yet, we report retrospectively our 30 year experience with chemotherapy followed by craniospinal irradiation (CSI), plus a boost of whole ventricular irradiation (WVI)/tumor bed (TB), tailored to pre-radiation chemotherapy response.

Methods: Between 1988 and 2016, 28 patients received four cycles of PEB (cisplatin/etoposide/bleomycin), then CSI, and two further PEB cycles. Between 1988 and1994, CSI was 25.

Primary metastatic osteosarcoma: results of a prospective study in children given chemotherapy and interleukin-2.

To improve the poor prognosis for children with metastatic osteosarcoma (OS), interleukin-2 (IL-2) was added to the standard treatment due to its capacity to activate lymphocytes and differentiate lymphocyte subsets into lymphokine-activated killer (LAK) cells that are capable of recognizing and killing various tumor cells. This study concerns a cohort of unselected patients aged < 18 years with metastatic OS, who were treated with IL-2, high-dose methotrexate, doxorubicin, cisplatin, ifosfamide, LAK reinfusion, and surgery, between 1995 and 2010. Thirty-five patients aged 4-17 years were involved.

Predictability and inconsistencies in the cognitive outcome of early treated PKU patients.

Long-term cognitive outcome and treatment of adult early treated (ET)PKU patients is a main issue in PKU research. We questioned whether the intellectual development of ETPKU patients is stable and to what extent its variation may be predicted by the quality of metabolic control. The aims of the present longitudinal retrospective study were to assess in young adult ETPKU patients: i) the relationship between IQ and metabolic control during the first two decades of life; and ii) the intra- and interindividual variability in the developmental trajectory which cannot be predicted by the disease's biomarkers.

Clinical and subclinical cardiac late effects in pediatric Hodgkin's lymphoma survivors.

Purpose: Cardiac late effects are responsible for a significant burden of mortality and morbidity among pediatric Hodgkin's lymphoma (HL) survivors (HLS). The aim of our study was to assess clinical and subclinical cardiac sequelae in a cohort of childhood HLS treated in the 1980s with doxorubicin, bleomycin, vinblastine, and dacarbazine (the ABVD regimen) and limited-field radiotherapy (RT).

Methods: We retrospectively examined a series of HLS treated from 1979 to 1989.

Do patients with tuberous sclerosis complex have an increased risk for malignancies?

Tuberous Sclerosis Complex (TSC) is generally characterized by the presence of benign tumors, but some patients with malignancies have been reported in the literature. We examined a large Italian TSC population (240 individuals followed from 2001 to 2015, aged 3 months-74 years), assessing the frequency of malignancies to determine whether there is an increased risk for cancer in this disorder, and looking for possible features associated with the development of neoplasia. Fifteen patients had malignancies (6.

Nonmetastatic osteosarcoma of the extremity. Neoadjuvant chemotherapy with methotrexate, cisplatin, doxorubicin and ifosfamide. An Italian Sarcoma Group study (ISG/OS-Oss).

Background: Based on the results of the ISG/OS-1 study, the MAP regimen (methotrexate [MTX], doxorubicin [ADM] and cisplatin [CDP] with the addition of ifosfamide [IFO] in poor-responder patients) was investigated in patients with nonmetastatic osteosarcoma of the extremity (ISG/OS-Oss study).

Patients And Methods: Compared with the ISG/OS-1 study (cumulative doses: ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), IFO 30 g/m(2)), the ISG/OS-Oss study reduced the number of MTX cycles from 10 to 5 (cumulative MTX dose: 60 g/m(2)) in order to diminish treatment duration and toxicity.

Results: From January 2007 to June 2011, 171 patients (median age 16 years, 60% males) were registered.

Randomized controlled trial of a protein substitute with prolonged release on the protein status of children with phenylketonuria.

Objective: To examine whether a phenylalanine-free protein substitute with prolonged release may be beneficial to the protein status of children with phenylketonuria (PKU) compared to conventional substitutes.

Methods: Sixty children with PKU, 7 to 16 years of age, were randomly allocated to receive either a prolonged-release (test) or the current conventional protein substitute for 30 days. Subjects were additionally sex and age matched with 60 subjects with mild hyperphenylalaninemia and 60 unaffected subjects.

Temozolomide is an active agent in children with recurrent medulloblastoma/primitive neuroectodermal tumor: an Italian multi-institutional phase II trial.

Background: The aim of this study was to assess the objective response rate (ORR) of children and young adults with recurrent medulloblastoma/primitive neuroectodermal tumor (MB/PNET) treated with temozolomide (TMZ). The secondary purpose was to analyze the toxicity profile of TMZ when administered orally for 5 days in 3 divided daily doses every 28 days.

Methods: Forty-two patients with recurrent MB/PNET, aged 21 years and younger, were recruited.

Occurrence of breast cancer after chest wall irradiation for pediatric cancer, as detected by a multimodal screening program.

Purpose: To assess the occurrence of breast cancer (BC) after exposure to ionizing radiation for pediatric cancer, by means of a multimodal screening program.

Patients And Methods: We identified 86 patients who had received chest wall radiation therapy for pediatric cancer. Clinical breast examination (CBE), ultrasound (US), and mammography (MX) were performed yearly.

Neoadjuvant chemotherapy with methotrexate, cisplatin, and doxorubicin with or without ifosfamide in nonmetastatic osteosarcoma of the extremity: an Italian sarcoma group trial ISG/OS-1.

Purpose: We compared two chemotherapy regimens that included methotrexate (MTX), cisplatin (CDP), and doxorubicin (ADM) with or without ifosfamide (IFO) in patients with nonmetastatic osteosarcoma of the extremity.

Patients And Methods: Patients age ≤ 40 years randomly received regimens with the same cumulative doses of drugs (ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), and IFO 30 g/m(2)) but with different durations (arm A, 44 weeks; arm B, 34 weeks). IFO was given postoperatively when pathologic response to MTX-CDP-ADM was poor (arm A) or given in the primary phase of chemotherapy with MTX-CDP-ADM (arm B).

Long-term results of combined preradiation chemotherapy and age-tailored radiotherapy doses for childhood medulloblastoma.

To reduce the sequelae of craniospinal irradiation (CSI) in children under 10 (≥3) years old and to improve the prognosis for high-risk medulloblastoma in adolescents, we adjusted postoperative chemotherapy and CSI doses to patients' stage and age. From 1986 to 1995, 73 patients entered the study. Children under 10 and adolescents with metastases, residual disease (RD) or stage >T3 received postoperative IV vincristine and high-dose (HD) ± intrathecal (IT) methotrexate, while standard-risk adolescents were given IV vincristine and IT methotrexate.

TSH suppression as a possible means of protection against hypothyroidism after irradiation for childhood Hodgkins lymphoma.

Hypothyroidism remains a common late effect after irradiation of the neck/mediastinum for Hodgkins lymphoma (HL). We evaluated the protective effect of TSH suppression during neck/mediastinum irradiation. From 1998 to 2001, 14 consecutive euthyroid children were given, before and until the end of their radiotherapy on neck/mediastinum, L-thyroxine at TSH-suppressive doses.

Neuroblastoma in patients over 12 years old: a 20-year experience at the Istituto Nazionale Tumori of Milan.

Aims And Background: Neuroblastoma is the most common solid extracranial tumor in children. The median age of onset is 2 years, with more than 95% of patients younger than 10 years at diagnosis. As neuroblastoma is rare in adolescents and exceedingly rare in adults, few series are reported in the literature.

Prolonged 14-day continuous infusion of high-dose ifosfamide with an external portable pump: feasibility and efficacy in refractory pediatric sarcoma.

Background: Ifosfamide is currently used to treat pediatric sarcomas and increasing its dosage may be associated with a better response rate. Prolonged continuous infusion seems an attractive administration modality.

Methods: Ifosfamide 14 g/m(2) (with mesna 14 g/m(2)) was administered through an ambulatory portable pump over 14 days as a continuous infusion, starting every 3 weeks, in 14 patients with relapsing sarcomas.