The management of phenylketonuria in adult patients in Italy: a survey of six specialist metabolic centers.

Introduction: Phenylketonuria (PKU) is a rare autosomal recessive disorder caused by a deficiency of phenylalanine hydroxylase (PAH). Its prevalence is estimated to be 1:10,000 in Europe. PKU is the commonest congenital inborn error of metabolism.

Can Integrated Care Help in Meeting the Challenges Posed on Our Health Care Systems by COVID-19? Some Preliminary Lessons Learned from the European VIGOUR Project.

The COVID-19 pandemic puts health and care systems under pressure globally. This current paper highlights challenges arising in the care for older and vulnerable populations in this context and reflects upon possible perspectives for different systems making use of nested integrated care approaches adapted during the work of the EU-funded project VIGOUR ("Evidence based Guidance to Scale-up Integrated Care in Europe", funded by the European Union's Health Programme 2014-2020 under Grant Agreement Number 826640).

Summary of Expert Opinion on the Management of Children With Chronic Kidney Disease and Growth Failure With Human Growth Hormone.

The management of children and adolescents with chronic kidney disease (CKD) and growth failure candidate for recombinant human growth hormone therapy (rhGH) is based on an appraisal of the literature established on a 2006 consensus statement and 2019 Clinical practice recommendations. The performance of these guidelines has never been tested. The objective of this study was to establish the level of adherence to international guidelines based on the 2006 consensus and the 2019 criteria that lead to the initiation of growth hormone treatment by both pediatric endocrinologists and pediatric nephrologists.

Management strategies for newly diagnosed immune thrombocytopenia in Italian AIEOP Centres: do we overtreat? Data from a multicentre, prospective cohort study.

Background: The aim of the present study was to assess management strategies for immune thrombocytopenia (ITP) among Italian paediatric haematologists, and to compare these with those of recent international guidelines. Predictors of early remission or disease chronicity were also evaluated.

Materials And Methods: During a period of 1 year, 205 children (age: 1 month-18 years) with newly diagnosed ITP were prospectively enrolled by 16 centres belonging to the Italian Association of Paediatric Haematology and Oncology (AIEOP).

lncRNAs-mRNAs Co-Expression Network Underlying Childhood B-Cell Acute Lymphoblastic Leukaemia: A Pilot Study.

Long non-coding RNAs (lncRNAs) are emerging as key gene regulators in the pathogenesis and development of various cancers including B lymphoblastic leukaemia (B-ALL). In this pilot study, we used RNA-Seq transcriptomic data for identifying novel lncRNA-mRNA cooperative pairs involved in childhood B-ALL pathogenesis. We conceived a bioinformatic pipeline based on unsupervised PCA feature extraction approach and stringent statistical criteria to extract potential childhood B-ALL lncRNA signatures.

KCTD15 Protein Expression in Peripheral Blood and Acute Myeloid Leukemia.

Leukocytes are major cellular components of the inflammatory and immune response systems. After their generation in the bone marrow from hematopoietic stem cells, they maturate as granulocytes (neutrophils, eosinophils, and basophils), monocytes, and lymphocytes. The abnormal accumulation and proliferation of immature blood cells (blasts) lead to severe and widespread diseases such as leukemia.

Carrier frequency of CFTR variants in the non-Caucasian populations by genome aggregation database (gnomAD)-based analysis.

The complexity in the molecular diagnosis of Cystic Fibrosis (CF) also depends on the variable prevalence/incidence of the disease associated with the wide CFTR allelic heterogeneity among different populations. In fact, CF incidence in Asian and African countries is underestimated and the few patients reported so far have rare or unique CFTR pathogenic variants. To obtain insights into CF variants profile and frequency, we used the large population sequencing data in the Genome Aggregation Database (gnomAD).

Critical failures in the use of home ventilation medical equipment.

Home ventilation involves the use of medical devices at patient's home by personnel who are not healthcare practitioners. This implies new potential risks not fully addressed by current standards and guidelines. A methodological approach to investigate potential failures and define improvement actions to address the dangerous potential situations in HV is required.

Posaconazole delayed-release tablets in paediatric haematology-oncology patients.

Background: To date, there are few studies that describe pharmacokinetics, safety and efficacy of posaconazole delayed-release tablet (DRT) formulation in the paediatric population.

Objectives: We evaluated retrospectively posaconazole plasma concentrations and safety of posaconazole DRT in paediatric haematology-oncology patients.

Patients And Methods: Posaconazole DRT was assessed in 28 haematological paediatric patients with a median age 15 of years (range 5-18) and a median body weight of 50 kg (range 22-83 kg).

A Prospective Study of Hematologic Complications and Long-Term Survival of Italian Patients Affected by Shwachman-Diamond Syndrome.

Objective: To describe the hematologic outcome and long-term survival of patients enrolled in the Shwachman-Diamond syndrome Italian Registry.

Study Design: A retrospective and prospective study of patients recorded in the Shwachman-Diamond syndrome Italian Registry.

Results: The study population included 121 patients, 69 males and 52 females, diagnosed between 1999 and 2018.

Occurrence of long-term effects after hematopoietic stem cell transplantation in children affected by acute leukemia receiving either busulfan or total body irradiation: results of an AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) retrospective study.

Patients given allogeneic hematopoietic stem cell transplantation (alloHSCT) present an increased incidence of long-term toxicities that can be attributed to the preparative regimen. We retrospectively analyzed in a population of 670 children receiving allo-HSCT for acute leukemia the occurrence of different late effects in function of the choice made between total body irradiation (TBI) and busulfan, as part of the preparative regimen. In univariable analysis, we found that patients treated with TBI developed cataract in 24% of the cases compared with 4% in patients treated with BU (p = 0.

KCTD15 is overexpressed in human childhood B-cell acute lymphoid leukemia.

Leukemic cells originate from the malignant transformation of undifferentiated myeloid/lymphoid hematopoietic progenitors normally residing in bone marrow. As the precise molecular mechanisms underlying this heterogeneous disease are yet to be disclosed, the identification and the validation of novel actors in leukemia is of extreme importance. Here, we show that KCTD15, a member of the emerging class of KCTD ((K)potassium Channel Tetramerization Domain containing) proteins, is strongly upregulated in patients affected by B-cell type acute lymphoblastic leukemia (B-ALL) and in continuous cell lines (RS4;11, REH, TOM-1, SEM) derived from this form of childhood leukemia.

An 1H NMR study of the cytarabine degradation in clinical conditions to avoid drug waste, decrease therapy costs and improve patient compliance in acute leukemia.

Cytarabine, the 4-amino-1-(β-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C) is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers' instructions, once the components-sterile water and cytarabine powder-are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4°C. To evaluate how to avoid wasting the drug in short-term, low-dose treatment regimens, the reconstituted samples, stored at 25°C and 4°C, were analyzed every day of the test week by reversed-phase HPLC and high-field NMR spectroscopy.

PATZ1 Is Overexpressed in Pediatric Glial Tumors and Correlates with Worse Event-Free Survival in High-grade Gliomas.

Glial tumors are the leading cause of cancer-related death and morbidity in children. Their diagnosis, mainly based on clinical and histopathological factors, is particularly challenging because of their high molecular heterogeneity. Thus, tumors with identical histotypes could result in variable biological behaviors and prognoses.

Loop characteristics and audio-vestibular symptoms or hemifacial spasm: is there a correlation? A multiplanar MRI study.

Aim: We investigated if loop characteristics correlate with audio-vestibular symptoms or hemifacial spasm in patients with a vascular loop in the root entry zone (VII and VIII) and in the internal auditory canal.

Materials And Methods: A retrospective, multicenter study analyzed 2622 consecutive magnetic resonance imaging (MRI) scans of the cerebellopontine angle of patients with asymmetric audio-vestibular symptom or hemifacial spasm; patients' symptoms were confirmed by clinical tests. MRIs displaying vascular loops visible in the axial view were analyzed using multiplanar reconstruction.

The "TIP algorithm" for the accurate diagnosis of pediatric otitis media.

Objectives: The authors studied the correlation between the grading TIP which evaluates three otoendoscopic characteristics of the tympanic membrane (TM) (transparency, integrity and position) with the gold standard represented by the impedenzometry.

Methods And Materials: Cross-sectional studies with independent and blind comparison with the gold standard diagnostic. The setting was primary care and ambulatory.

GATA-1 isoforms differently contribute to the production and compartmentation of reactive oxygen species in the myeloid leukemia cell line K562.

Maintenance of a balanced expression of the two isoforms of the transcription factor GATA-1, the full-length protein (GATA-1 ) and a shorter isoform (GATA-1 ), contributes to control hematopoiesis, whereas their dysregulation can alter the differentiation/proliferation potential of hematopoietic precursors thereby eventually leading to a variety of hematopoietic disorders. Although it is well established that these isoforms play opposite roles in these remarkable processes, most of the molecular pathways involved remain unknown. Here, we demonstrate that GATA-1 and GATA-1 are able to differently influence intracellular redox states and reactive oxygen species (ROS) compartmentation in the erythroleukemic K562 cell line, thus shedding novel mechanistic insights into the processes of cell proliferation and apoptosis resistance in myeloid precursors.

Single center experience on efficacy and safety of Aprepitant for preventing chemotherapy-induced nausea and vomiting (CINV) in pediatric Hodgkin Lymphoma.

Chemotherapy-induced nausea and vomiting (CINV) is a distressing treatment side-effect that could negatively affect children's quality of life (QoL). Different scoring systems for CINV were applied and different antiemetic drugs were used; however, few studies have been performed in children undergoing chemotherapy with Aprepitant. Herein, we report a pediatric experience on efficacy and safety of Aprepitant as part of triple antiemetic prophylaxis, in a cohort of thirty-two children and adolescents with Hodgkin Lymphoma (HL), treated with moderate/highly emetogenic chemotherapy (MEC/HEC) regimens in a single Hemato-Oncology Institution.

Whole-Exome Sequencing in the Isolated Populations of Cilento from South Italy.

The present study describes the genetic architecture of the isolated populations of Cilento, through the analysis of exome sequence data of 245 representative individuals of these populations. By annotating the exome variants and cataloguing them according to their frequency and functional effects, we identified 347,684 variants, 67.4% of which are rare and low frequency variants, and 1% of them (corresponding to 319 variants per person) are classified as high functional impact variants; also, 39,946 (11.

An Ex Vivo Test of Complement Activation on Endothelium for Individualized Eculizumab Therapy in Hemolytic Uremic Syndrome.

Rationale & Objective: Although primary atypical hemolytic uremic syndrome (aHUS) is associated with abnormalities in complement genes and antibodies to complement factor H, the role of complement in secondary aHUS remains debatable. We evaluated the usefulness of an ex vivo test to: (1) detect complement activation within the endothelium in primary and secondary aHUS, (2) differentiate active disease from remission, (3) monitor the effectiveness of eculizumab therapy, and (4) identify relapses during eculizumab dosage tapering and after discontinuation of treatment.

Study Design: Case series.

Non-collagen genes role in digenic Alport syndrome.

Background: Alport syndrome is a clinically heterogeneous nephropathy characterized by severe symptomatology at kidney level due to ultrastructural lesions of the glomerular basement membrane (GBM) as consequence of mutations in COL4 genes. The disease has been linked to COL4A3/COL4A4/COL4A5 mutations, which impair GBM functionality and can be inherited in a dominant, recessive or X-linked transmission. Although a targeted Next Generation Sequencing approach has allowed identifying families with pathogenic mutations in more than one COL4 α3-α4-α5 heterotrimer encoding genes, leading to conclude for a digenic pattern of inheritance, the role of non-collagen genes in digenic Alport syndrome has not yet been established.