Vitronectin Levels in the Plasma of Neuroblastoma Patients and Culture Media of 3D Models: A Prognostic Circulating Biomarker?

Vitronectin is a glycoprotein present in plasma and the extracellular matrix that is implicated in cell migration. The high amount of vitronectin found in neuroblastoma biopsies has been associated with poor prognosis. Moreover, increased vitronectin levels have been described in the plasma of patients with different cancers. Our aim was to assess vitronectin as a potential circulating biomarker of neuroblastoma prognosis. Vitronectin concentration was quantified using ELISA in culture media of four neuroblastoma cell lines grown in a monolayer and in 3D models, and in the plasma of 114 neuroblastoma patients. Three of the neuroblastoma cell lines secreted vitronectin to culture media when cultured in a monolayer and 3D models. Vitronectin release was higher by neuroblastoma cells cultured in 3D models than in the monolayer and was still elevated when cells were grown in 3D scaffolds with cross-linked vitronectin. Vitronectin secretion occurred independently of cell numbers in cultures. Its concentration in the plasma of neuroblastoma patients ranged between 52.4 and 870 µg/mL (median, 218 µg/mL). A ROC curve was used to establish a cutoff of 361 µg/mL, above which patients over 18 months old had worse prognosis (p = 0.0018). Vitronectin could be considered a new plasma prognostic biomarker in neuroblastoma and warrants confirmation in collaborative studies. Drugs inhibiting vitronectin interactions with cells and/or the extracellular matrix could represent a significant improvement in survival for neuroblastoma patients.

Cancer is not a risk factor for severe COVID-19 in children, except in patients with recent allogeneic hematopoietic stem cell transplantation or comorbidities.

The EPICO (Spanish general registry of COVID-19 in children)-SEHOP (Spanish Society of Pediatric Hematology and Oncology) platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 14.7%), except in children with recent alloHSCT (less than 300 days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies.

Outcomes and impact of multidisciplinary team care on immunologic and hemato-oncologic pediatric patients

Introduction: Immunologic and hemato-oncologic disorders in the pediatric population represent an interrelated and complex group of conditions whose approach, diagnosis, and management could be difficult. Multidisciplinary teams have been proved beneficial in treating such complexities. Methods: We conducted a retrospective observational study at a tertiary hospital in Madrid, Spain, which is a pediatric immunology and onco-hematology referral center. We included all patients of multidisciplinary outpatient consultation, comprising a working group of pediatric oncohematologists and immunologists, between April 2016 and December 2019. Epidemiologic, clinical, and laboratory data were collected. We analyzed these data and established a relationship between age and findings of final diagnosis as well as variance on diagnoses prior to their multidisciplinary assessment and number of visits to the consultation. Results: In all, 93 children and adolescents were included in this study. Laboratory abnormalities were the most frequent reason for being referred to our unit (87.2%); 78% of children had a previously diagnosed comorbidity. Before starting follow-up in the multidisciplinary consultation, 14% of patients were diagnosed, and after the study by the multidisciplinary team, the final diagnosis was reached in 58.1% of patients. No correlation was discovered between final diagnosis and gender (P = 0.29), age (biserial correlation coefficient, r = 0.036, P = 0.70), and number of visits (P = 0.07). Conclusion: A multidisciplinary approach to immunologic, hematologic, and oncologic pediatric diseases is feasible. It can be a powerful and useful tool for diagnosis and treatment, especially in complex pediatric patients (AU)

Bromocriptine for the treatment of postoperative cerebellar mutism syndrome in pediatric patients: Three case reports.

INTRODUCTION: Cerebellar mutism syndrome (CMS) is a common complication after posterior fossa tumor resection. It is characterized by a significant lack or loss of speech. Its biological origin remains unclear and there are no standardized treatments. However, bromocriptine seems to be a possible treatment for this condition. CASE REPORT: In this paper, we present three cases of pediatric patients (4, 5, and 17-year old) who developed CMS after posterior fossa tumor surgery. They were treated with bromocriptine to improve neurological symptoms.Management and outcome: Bromocriptine was started at a low dose and was progressively increased to reach the minimum effective dose. After four months of treatment, a normal and fluid speech was observed in the three patients. No discontinuation due to adverse events were reported. DISCUSSION: Bromocriptine has shown to be an effective and safe treatment for CMS in pediatric patients after posterior fossa tumor resection.

Congenital dyserythropoietic anemia types Ib, II, and III: novel variants in the CDIN1 gene and functional study of a novel variant in the KIF23 gene.

Congenital dyserythropoietic anemias (CDA) are disorders characterized by ineffective erythropoiesis and morphological anomalies in erythrocytes and erythroblasts. The purpose of this study is to identify the gene variants in patients diagnosed with CDA. We analyzed five unrelated patients and two siblings with a targeted panel of genes to CDA: CDAN1, CDIN1, SEC23B, KIF23, KLF1, and GATA1 genes. We found three novel variants in the CDIN1 gene (p.Leu136Val, p.Tyr247Cys, and p.Ile273Thr), four known variants in the SEC23B gene (p.Arg14Trp, p.Arg554Ter, p.Asp239Gly, and p.Ser436Leu), and one novel variant in the KIF23 gene (p.Leu945Trpfs*31). The in silico analysis of novel variants predict that they are pathogenic and, the in vitro study confirms the functional impact of the KIF23 variant on the protein location.

Omeprazole-induced hypertrichosis in two children.

Omeprazole significantly increases duodenal prostaglandin E2 synthesis. Prostaglandins are involved in hair growth regulation: prostaglandin E2 and prostaglandin F2 alpha stimulate hair growth, and prostaglandin D2 has an inhibitory effect. The use of omeprazole can cause acquired generalized hypertrichosis by increasing prostaglandin E2 levels.

Kaposiform Hemangioendothelioma Presenting as Hydrops Fetalis.

We describe the case of a 33-week preterm infant who developed nonimmune hydrops fetalis secondary to a kaposiform hemangioendothelioma (KHE). The tumor was successfully treated with vincristine, prednisone, ticlopidine, and aspirin. KHE can be an unusual cause of hydrops fetalis; in such cases, diagnosis can be challenging since generalized edema can obscure KHE.

DICER1 mutation and tumors associated with a familial tumor predisposition syndrome: practical considerations.

The familial tumor predisposition syndrome known as DICER1-pleuropulmonary blastoma (PPB) or DICER1 tumor predisposition syndrome was first described in 2009, and it involves an increased risk in the occurrence of various tumors, like cystic nephroma and PPB. Here is presented a girl with a cystic nephroma and two cystic lung lesions who was diagnosed years later with the DICER1 gene mutation. This mutation was also found in one of her parents. Thus, the screening for the DICER1 gene mutation may be important in children with certain/multiple tumors and their families.