Consensus on COVID-19 Vaccination in Pediatric Oncohematological Patients, on Behalf of Infectious Working Group of Italian Association of Pediatric Hematology Oncology.

Vaccines represent the best tool to prevent the severity course and fatal consequences of the pandemic by the new Coronavirus 2019 infection (SARS-CoV-2). Considering the limited data on vaccination of pediatric oncohematological patients, we developed a Consensus document to support the Italian pediatric hematological oncological (AIEOP) centers in a scientifically correct communication with families and patients and to promote vaccination. The topics of the Consensus were: SARS-CoV-2 infection and disease (COVID-19) in the pediatric subjects; COVID-19 vaccines (type, schedule); who and when to vaccinate; contraindications and risk of serious adverse events; rare adverse events; third dose and vaccination after COVID-19; and other general prevention measures. Using the Delphi methodology for Consensus, 21 statements and their corresponding rationale were elaborated and discussed with the representatives of 31 centers, followed by voting. A high grade of Consensus was obtained on topics such as the potential risk of severe COVID-19 outcome in pediatric oncohematological patients, the need for vaccination as a preventative measure, the type, schedule and booster dose of vaccine, the eligibility of the patients for vaccination, and the timing, definition, and management of contraindications and serious adverse events, and other general prevention measures. All 21 of the statements were approved. This consensus document highlights that children and adolescents affected by hematological and oncological diseases are a fragile category. Vaccination plays an important role to prevent COVID-19, to permit the regular administration of chemotherapy or other treatments, to perform control visits and hospital admissions, and to prevent treatment delays.

Cardiovascular events and treatment of children with high risk medulloblastoma.

BACKGROUND: Children with high-risk medulloblastoma are treated with chemotherapeutic protocols which may affect heart function. We aimed to assesscardiovascular events (CVE) in children with medulloblastoma/primitive neuroectodermal tumors (PNET). METHODS: We retrospectively collected data from a case series of 22 children with high-risk medulloblastoma/PNET admitted to the Santobono-Pausilipon Hospital, Naples, Italy from 2008 to 2016. All patients received the Milan HART protocol for high-risk brain malignancies as first line treatment (induction phase), followed by a consolidation phase with Thiotepa and hematopoietic stem cells transplantation, except for 1 patient who received the Milan HART as second line therapy. Four patients also received second line treatment, while 4 patients also received maintenance therapy. Patients underwent cardiac examination, including ECG, echocardiography and serum biomarkers, before antineoplastic treatment initiation and then when clinically needed. Six patients developed CVE (CVE group); 16 patients had no CVE (NO-CVE group). FINDINGS: In the CVE group, 3 patients presented acute CVE during chemotherapy (2 patients with left ventricular (LV) dysfunction, 1 patient with arterial hypertension), while 3 patients presented chronic CVE after chemotherapy completion (2 patients with LV dysfunction, 1 patient with ectopic atrial tachycardia). After a 51 months median follow-up, 9 patients died: 4 from the CVE group (in 2 cases heart failure-related deaths) and 5 from the NO-CVE group (progression of disease). INTERPRETATION: A relevant percentage of children treated for medulloblastoma/PNET develops CVE. Heart failure potentially due to chemotherapy may represent a cause of death. Hence, in these patients, strict cardiac surveillance is essential. FUNDING: No funding was associated with this study.

Analysis of the mutational status of SIX1/2 and microRNA processing genes in paired primary and relapsed Wilms tumors and association with relapse.

Whereas 90% of patients with Wilms tumor (WT) reach cure, approximately half of patients developing a recurrent tumor die of the disease. Therefore, to disclose events leading to recurrence represents a clinical need. To study paired primary/recurrent tumor samples, being aware of the intra-tumoral heterogeneity, might help finding these answers. We previously suggested that mutations in SIX1 and DROSHA underlie WT recurrence. With the aim to better investigate this scenario, we collected 19 paired primary/recurrent tumors and 10 primary tumors from relapsing patients and searched for mutations in the SIX1/2 genes and microRNA processing genes (miRNAPGs). We found SIX1 mutation in one case, miRNAPGs mutations in seven cases, and the co-occurrence of SIX1 and miRNAPG mutations in one case. We could observe that, whereas in primary tumors the mutations could be heterogeneously present, in all cases they were positively selected and homogeneously present in the recurrent disease, as also indicated by a "moderate" and "almost perfect" agreement (according to the Landis and Koch classification criteria) between paired samples. Analysis of SIX1/2 genes and miRNAPGs in 50 non-relapsing WTs disclosed SIX2 mutation in one case and miRNAPGs mutations in seven. A borderline statistically significant association was observed between miRNAPGs mutations and the occurrence of relapse (p value: 0.05). These data suggest that SIX1 and miRNAPGs mutations may provide an advantage during tumor progression to recurrence and can represent oncogenic drivers in WT development.

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. The PATZ1 gene has been recently shown to be expressed in adult gliomas, including glioblastomas, where it correlates with the proneural subtype and with a better prognosis. Here, we analyzed the expression of PATZ1 in pediatric gliomas, first at mRNA level in a public database, and then at protein level, by immunohistochemistry, in a cohort of 52 glial brain tumors from young patients aged from 6 months to 16 years. As for adult tumors, we show that PATZ1 is enriched in glial tumors compared to the normal brain, where it correlates positively and negatively with a proneural and mesenchymal signature, respectively. Moreover, we show that PATZ1 is expressed at variable levels in our cohort of tumors. Higher expression was detected in high-grade than low-grade gliomas, suggesting a correlation with the malignancy. Among high-grade gliomas, higher levels of PATZ1 have consistently been found to correlate with worse event-free survival. Therefore, our study may imply new diagnostic opportunities for pediatric gliomas.

Symptomatic malignant spinal cord compression in children: a single-center experience.

BACKGROUND: Malignant spinal cord compression (MSCC) is associated withpoor prognosis and may lead to permanent paralysis, sensory loss, and sphincter dysfunction. Very limited data are available on incidence and etiology of MSCC in pediatric population. We aimed to examine etiology, clinical presentation and treatment of pediatric patient with MSCC admitted to the Santobono-Pausilipon Children's Hospital, Naples, Italy. METHODS: Forty-four children under 18 yearsadmitedsince 2007 and assessed for MSCC clinical presentations, evaluation, and treatment.were retrospectively collected from our institutional pediatric oncology and neurosurgery database. RESULTS: The median age at time of MSCC diagnosis was 52 months, with a peak in young (≤3 years) patients. The leading cause of MSCC was extramedullary tumors (63.6%), in particular neuroblastoma (27.2%) followed by Ewing sarcomas (15.9%). Cord compression was the presenting feature of a new malignancy in 33 (75%) patients, and a consequence of metastatic disease progression or relapse in the remaining 11 (25%) patients. Motor deficit was the initial symptoms of spinal compression in all patients, while pain was present in about 60% of patients, followed by sphincteric deficit (43.2%). The primary tumor site was located in the neck in 3 (6.8%) patients, thorax in 16 (36.4%), cervico-thoracic region in 3 (6.8%), thoraco-lumbar region in 8 (18.2%), abdomen in 5 (11.4%), lumbar-sacral region in 7 (15.9%) and thoracic-lumbar-sacral region in 1 (2.3%). The median length of the interval between symptom onset and tumor diagnosis varied widely from 0 to 360 days in the entire population, however this interval was significantly shorter in patients with known neoplasia in comparisonto patients with new diagnosis (at relapse 7 days [interquartile range 3-10] vs at diagnosis 23 days [7-60]). Pre and post-operative spine magnetic resonance imagingwas performed in all cases, and most(95%) patients underwent neurosurgical treatment as first treatment. Severe motor deficit was associated with younger age and severe motor deficit at diagnosis was associated withworst motor outcomes at discharge from neurosurgery. Patients with progression or relapsed disease showed a worst prognosis, while the majority of patients (70.5%) were alive at 5 years after diagnosis. CONCLUSIONS: The natural history of MSCC in children is associated to permanent paralysis, sensory loss, and sphincter dysfunction, thus prompt diagnosis and correct management are needed to minimize morbidity. Treatment strategies differed widely among cancer types and study groups in the absence of optimal evidence-based treatment guidelines. When the diagnosis is uncertain, surgery provides an opportunity to biopsy the lesion in addition to treating the mass.

Lung Ultrasound Findings Undetectable by Chest Radiography in Children with Community-Acquired Pneumonia.

The purpose of our study was to evaluate any differences between lung ultrasonography and chest radiography (CR) images in children with a diagnosis of community-acquired pneumonia (CAP) and, if there are any, to analyze the reasons and possible clinical implications. We reviewed the medical records of patients admitted to the pediatric ward from January 2014 to December 2016 and selected only cases discharged with a diagnosis of CAP who had undergone performed lung ultrasound (LUS) and CR within 24 h of each other. All radiologic and sonographic images of the selected cases were examined blindly by a senior radiologist and a skilled sonographer, respectively, with respect to number, position and size of lung injuries. Of the 47 cases of pneumonia, 28 lung lesions spotted by LUS were undetected by CR. Compared with CR, LUS detects more cases of pneumonia, a greater number of cases of double pneumonia and minimal pleural effusions. LUS should be considered the first-line imaging tool for CAP.

Lung ultrasound in the diagnosis of pneumonia in children: proposal for a new diagnostic algorithm.

Background. Despite guideline recommendations, chest radiography (CR) for the diagnosis of community-acquired pneumonia (CAP) in children is commonly used also in mild and/or uncomplicated cases. The aim of this study is to assess the reliability of lung ultrasonography (LUS) as an alternative test in these cases and suggest a new diagnostic algorithm. Methods. We reviewed the medical records of all patients admitted to the pediatric ward from February 1, 2013 to December 31, 2014 with respiratory signs and symptoms. We selected only cases with mild/uncomplicated clinical course and in which CR and LUS were performed within 24 h of each other. The LUS was not part of the required exams recorded in medical records but performed independently. The discharge diagnosis, made only on the basis of history and physical examination, laboratory and instrumental tests, including CR (without LUS), was used as a reference test to compare CR and LUS findings. Results. Of 52 selected medical records CAP diagnosis was confirmed in 29 (55.7%). CR was positive in 25 cases, whereas LUS detected pneumonia in 28 cases. Four patients with negative CR were positive in ultrasound findings. Instead, one patient with negative LUS was positive in radiographic findings. The LUS sensitivity was 96.5% (95% CI [82.2%-99.9%]), specificity of 95.6% (95% CI [78.0%-99.9%]), positive likelihood ratio of 22.2 (95% CI [3.2-151.2]), and negative likelihood ratio of 0.04 (95% CI [0.01-0.25]) for diagnosing pneumonia. Conclusion. LUS can be considered as a valid alternative diagnostic tool of CAP in children and its use must be promoted as a first approach in accordance with our new diagnostic algorithm.

Constitutional 11q14-q22 chromosome deletion syndrome in a child with neuroblastoma MYCN single copy.

Constitutional 11q deletion is a chromosome imbalance possibly found in MCA/MR patients analyzed for chromosomal anomalies. Its role in determining the phenotype depends on extension and position of deleted region. Loss of heterozygosity of 11q (region 11q23) is also associated with neuroblastoma, the most frequent extra cranial cancer in children. It represents one of the most frequent cytogenetic abnormalities observed in the tumor of patients with high-risk disease even if germline deletion of 11q in neuroblastoma is rare. Hereby, we describe a 18 months old girl presenting with trigonocephaly and dysmorphic facial features, including hypotelorism, broad depressed nasal bridge, micrognathia, synophrys, epicanthal folds, and with a stage 4 neuroblastoma without MYCN amplification, carrying a germline 11q deletion (11q14.1-q22.3), outside from Jacobsen syndrome and from neuroblastoma 11q critical regions. The role of 11q deletion in determining the clinical phenotype and its association with neuroblastoma development in the patient are discussed.

Symptomatic epidural compression in infants with neuroblastoma: a single-center experience with 5 cases.

Infants affected by neuroblastoma with symptomatic epidural compression require early diagnosis and appropriate treatment to avoid severe late complications. However, no established guidelines are available regarding the optimal treatment of these patients. We describe 5 such infants. The interval between the onset of symptoms and tumor diagnosis was 3 to 8 days in 4/5 cases. None developed paraplegia before or after treatment. Treatment for epidural compression included first-line laminoplasty followed by chemotherapy in 3 patients, and chemotherapy first in the remaining 2. To date, all are alive and none have developed severe complications after a follow-up of 9 to 39 months (median, 20).

[Assessment of simulation and dissimulation in the MMPI-2 test profiles]. / La valutazione della simulazione e della dissimulazione nei profili del test MMPI-2.

UNLABELLED: The aim of this study is to identify the criteria which would allow a differentiation between the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) profiles, obtained from patients who present with problems of minimization of attitude (dissembling) who have shown a minimization of their problems; from patients who answered in a spontaneous and genuine fashion. METHODS: Six hundred and fifty five MMPI profiles of outpatients of the Clinical Psychology Unit, University Hospital, Sapienza University of Rome. Patients were subdivided into two groups, based on the reason for attending: those who submitted voluntarily to a psychodiagnostic assessment and those who were assessed by request of an outside authority, e.g., in the case of those whose driving license was suspended. It has hypothesized that the latter group would not present with problems which would preclude obtaining the benefits required. The variables analyzed were the clinical scale and the validity scale MMPI-2, index F-K and the Ds scale of Gough. On the basis of the values of the F-K index and Ds scale, the patients were reclassified into three simulation categories: spontaneous registration; defended and doubtful's. RESULTS: All indexes, validity scales and clinical scales of the standard profile were found to have significant differences between the "dissimulation" and "normal" groups. Sensibility and specificity of profile classification was according to both indexes 76%. CONCLUSIONS: Current evidence indicates that simulation of pathology is identifiable in MMPI-2 profiles. Our data demonstrate that it is possible to identify case of defensive minimization. These results confirm the hypothesis that simulation is a dimensional characteristic of MMPI which can reach extreme values in both ways: worsening of slight problems or suppression of existing problems.