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This study aimed to evaluate how the COVID-19 pandemic affected the psychological well-being of parents of pediatric oncology patients two years after the pandemic started. The authors' objective was to make a detailed comparison between the data collected in the current study and the data gathered in the previous research with the aim of observing any changes, whether for better or worse, at the psychological level in the caregivers of the patients in question. This research could be of great use for monitoring the psychological health of the sample and for being able to intervene promptly in the event of the worsening of the reported symptoms. Background: Family members dealing with the devastating impact of a cancer diagnosis are now facing even greater vulnerability due to the COVID-19 pandemic. Alongside the already overwhelming trauma, they must also bear the distressing burden of the infection risks. The purpose of this study was to examine and explore the effects in parents of pediatric cancer patients two years after the start of the COVID-19 pandemic to compare these data with the previous data. Methods: We conducted a single-center prospective observational study, enrolling 75 parents of 42 pediatric oncology patients. Four questionnaires (IES-R; PSS; STAI-Y and PedsQL) were given to the parents 2 years after the first evaluation. Results: The bivariate matrix of correlation found a strong significant positive correlation between IES-R and PSS scores (r = 0.526, p < 0.001) as in T1. Stress symptoms (t = 0.00, p < 0.001) and levels of anxiety (trait) (t = 0.32, p < 0.001) remained unchanged; anxiety state levels appeared to have increased (t = 0.425, p < 0.001); there was a significant decrease in the PedsQL tot (t = 5.25, p < 0.001). Conclusions: The COVID-19 pandemic has influenced the levels of stress and anxiety of parents and the quality of life of patients, also correlating with the traumatic impact of the diagnosis.

Simple Summary Survivors of childhood brain tumors, because of the treatments they have undergone, have a greater risk of dying earlier from cardiovascular causes compared to the general population. The objective of this study was to evaluate differences between cardiovascular risk biomarkers and cardiopulmonary exercise test (CPET) results from childhood brain tumor survivors and healthy controls. We found worse CPET performance in survivors associated with higher endothelin-1 values compared to controls. Correlation analysis showed an inverse relationship between CPET results and leptin, emphasizing the role of radiotherapy as a possible cause in the genesis of a greater cardiovascular risk in survivors of childhood brain tumors.Abstract In recent decades, the improvement of treatments and the adoption of therapeutic protocols of international cooperation has led to an improvement in the survival of children affected by brain tumors. However, in parallel with the increase in survival, long-term side effects related to treatments have been observed over time, including the activation of chronic inflammatory processes and metabolic alterations, which can facilitate the onset of metabolic syndrome and increased cardiovascular risk. The aim of this study was to find possible statistically significant differences in the serum concentrations of early biomarkers of metabolic syndrome and in the results of cardiopulmonary exercise testing between survivors of childhood brain tumors and healthy controls. This is a prospective and observational study conducted on a group of 14 male patients who survived childhood brain tumors compared with the same number of healthy controls. The concentrations of early metabolic syndrome biomarkers [adiponectin, leptin, TNF-alpha, IL-1, IL-6, IL-10, endothelin-1, apolipoprotein B, and lipoprotein (a)] were measured and a cardiopulmonary exercise test (CPET) was performed. Results: Childhood brain tumor survivors performed worse on average

Repurposing approved non-antitumor drugs is a promising and affordable strategy in drug discovery to identify new therapeutic uses different from the original medical indication that may help increase the number of possible, effective anticancer drugs. The use of drugs in ways other than their original FDA-approved indications could offer novel avenues such as bypassing the chemoresistance and recurrence seen with conventional therapy and treatment; moreover, it can offer a safe and economic strategy for combination therapy. Recent works have demonstrated the anticancer properties of the FDA-approved drug Mebendazole. This synthetic benzimidazole proved effective against a broad spectrum of intestinal Helminthiasis. Mebendazole can penetrate the blood-brain barrier and has been shown to inhibit the malignant progression of glioma by targeting signaling pathways related to cell proliferation, apoptosis, or invasion/migration, or by increasing the sensitivity of glioma cells to conventional chemotherapy or radiotherapy. Moreover, several preclinical models and ongoing clinical trials explore the efficacy of Mebendazole in multiple cancers, including acute myeloid leukemia, brain cancer, oropharyngeal squamous cell carcinoma, breast cancer, gastrointestinal cancer, lung carcinoma, adrenocortical carcinoma, prostate cancer, and head and neck cancer. The present review summarizes central literature regarding the anticancer effects of MBZ in cancer cell lines, animal tumor models, and clinical trials to suggest possible strategies for safe and economical combinations of anticancer therapies in brain cancer. Mebendazole might be an excellent candidate for the treatment of brain tumors because of its efficacy both when used as monotherapy and in combination as an enhancement to standard chemotherapeutics and radiotherapy, due to its effectiveness on tumor angiogenesis inhibition, cell cycle arrest, apoptosis induction, and targeting of critical pathways involved in cancer s

Background: Platinum compounds are a group of fundamental chemotherapeutics used in the treatment of solid tumors, but they are burdened by side effects, such as ototoxicity. The objective of this study was to evaluate the incidence of ototoxicity caused by platinum compounds and the risk factors affecting its appearance/progression. Methods: Data from 53 patients who received platinum compounds and who had been off therapy for at least 5 years were analyzed. We collected data relating to audiometry conducted annually from the end of treatment and for at least 5 subsequent years, as well as information concerning the oncological history and comorbidities. Results: At the end of the treatment, 17 patients (32.08%) presented ototoxicity, according to the Boston SIOP Ototoxicity Scale; the risk factors included a higher serum creatinine value at diagnosis, having undergone cranial radiotherapy, and needing magnesium supplementation. After 5 years from the end of the treatment, the number of patients with exhibiting ototoxicity was 31 (58.5%); the factors that influenced the onset/progression of the damage were having undergone radiotherapy (HR 1.23; p < 0.01) and having received therapy with aminoglycosides (HR 1.27; p < 0.01). Conclusions: Ototoxicity caused by platinum compounds can occur even after the conclusion of the treatments, and the factors affecting its progression are radiotherapy and the aminoglycosides therapy.

Background: Neurofibromatosis type 1 (NF1)-related gliomas appear to have a clinical behavior different from that of sporadic cases. The purpose of the study was to investigate the role of different factors in influencing the tumor response rate of children receiving chemotherapy for their symptomatic glioma. Methods: Between 1995 and 2015, 60 patients with low-grade glioma (42 sporadic cases and 18 cases with NF1) were treated. Patients with brainstem gliomas were excluded. Thirty-nine patients underwent exclusive or postsurgical chemotherapy (vincristine/carboplatin-based regimen). Results: Disease reduction was achieved in 12 of the 28 patients (42.8%) with sporadic low-grade glioma and in 9 of the 11 patients (81.8%) with NF1, with a significant difference between the 2 groups (P < 0.05). The response to chemotherapy in both the patient groups was not significantly influenced by sex, age, tumor site, and histopathology, although disease reduction occurred more frequently in children aged under 3 years. Conclusions: Our study showed that pediatric patients with low-grade glioma and NF1 are more likely to respond to chemotherapy than those with non-NF1.

Purpose: To assess the main imaging and clinical features in adult- and pediatric-onset atypical teratoid rhabdoid tumor (ATRT) in order to build a predefined pathway useful for the diagnosis. Methods: We enrolled 11 ATRT patients (10 children, one adult) and we conducted a literature search on PubMed Central using the key terms "adult" or "pediatric" and "atypical teratoid/rhabdoid tumor". We collected clinical and neuroradiological data reported in previous studies and combined them with those from our case series. A three step process was built to reach diagnosis by identifying the main distinctive clinical and imaging features. Results: Clinical evaluation: neurological symptoms were nonspecific. ATRT was more frequent in children under 3 years of age (7 out of 10 children) and infratentorial localization was reported more frequently in children under the age of 24 months. Midline/off-midline localization was influenced by the age. Imaging findings: Preferential location near the ventricles and liquor spaces and the presence of eccentric cysts were hallmark for ATRT; higher frequency of peripheral cysts was detected in children and in the supratentorial compartment (five out of eight patients with solid-cystic ATRT). Leptomeningeal dissemination at diagnosis was common (5 out of 10 children), while intratumoral hemorrhage, calcifications, and high cellularity were non-specific findings. Histopathological analysis: specific immunohistochemical markers were essential to confirm the diagnosis. Conclusion: In younger children, a bulky, heterogeneous mass with eccentric cystic components and development near ventricles or cisternal spaces may be suggestive of ATRT. ATRT diagnosis is more challenging in adults and relies exclusively on neuropathological examination.

Aminoglycosides are broad-spectrum antibiotics largely used in children, but they have potential toxic side effects, including ototoxicity. Ototoxicity from aminoglycosides is permanent and is a consequence of its action on the inner ear cells via multiple mechanisms. Both uncontrollable risk factors and controllable risk factors are involved in the pathogenesis of aminoglycoside-related ototoxicity and, because of the irreversibility of ototoxicity, an important undertaking for preventing ototoxicity includes antibiotic stewardship to limit the use of aminoglycosides. Aminoglycosides are fundamental in the treatment of numerous infectious conditions at neonatal and pediatric age. In childhood, normal auditory function ensures adequate neurocognitive and social development. Hearing damage from aminoglycosides can therefore strongly affect the normal growth of the child. This review describes the molecular mechanisms of aminoglycoside-related ototoxicity and analyzes the risk factors and the potential otoprotective strategies in pediatric patients.

The growing phenomenon of antibiotic resistance and the presence of limited data concerning the pediatric area prompted us to focus on Staphylococcus aureus infection in this study, its antibiotic resistance profile, and the therapeutic management of affected children. We conducted a retrospective study by collecting clinical data on infants and children with antibiogram-associated S. aureus infection. We enrolled 1210 patients with a mean age of 0.9 years. We analyzed the resistance patterns and found 61.5% resistance to oxacillin, 58.4% resistance to cephalosporins, 41.6% resistance to aminoglycosides, and 38.3% resistance to fluoroquinolones. Importantly, we found no resistance to glycopeptides, a key antibiotic for MRSA infections whose resistance is increasing worldwide. We also found that the main risk factors associated with antibiotic resistance are being aged between 0 and 28 days, the presence of devices, and comorbidities. Antibiotic resistance is a growing concern; knowing the resistance profiles makes it possible to better target the therapy; however, it is important to use antibiotics according to the principles of antibiotic stewardship to limit their spread.

Nutritional status plays a vital role in the growth of children. In pediatric patients, disease-related malnutrition is a dynamic and multifactorial process supported by several factors such as inflammation, increased energy expenditure, decreased intake or reduced utilization of nutrients. In pediatric patients with malignancies, sarcopenia may coexist with malnutrition, amplifying its negative impact on prognosis. Careful monitoring of nutritional status both at diagnosis and during chemotherapy treatment allows early detection of the risk and/or presence of malnutrition. A rapid and personalized nutritional intervention can improve adherence to treatment, reduce complications and improve the patients' quality of life.

Background: We evaluated nutritional and sarcopenia status and their clinical impact in pediatric patients affected by bone and soft tissue sarcomas. Methods: Body mass index (BMI), prognostic nutritional index (PNI), and total psoas muscle area (tPMA) at diagnosis and after 12 months were analyzed. tPMA was measured from single cross-sectional computed tomography (CT) images at L4-L5. Age-specific and sex-specific tPMA Z-scores were retrieved from an online calculator. Results: A total of 21 patients were identified between February 2013 and December 2018. Twelve patients (57.1%) experienced sarcopenia at diagnosis, although not statistically associated with overall survival (OS) (p = 0.09). BMI Z-score, PNI, and tPMA Z-score significantly decreased between diagnosis and after 12 months of treatment (p < 0.05). Univariate analysis showed significant associations between poor OS and the presence of metastasis (p = 0.008), the absence of surgery (p = 0.005), PNI decrease (p = 0.027), and the reduction in tPMA > 25% (p = 0.042) over the 12 months. Conclusions: Sarcopenia affects more than half of the patients at diagnosis. Decreased PNI during 12 months of treatment has significant predictive value for OS. The role of tPMA derived from CT scan among pediatric patients with sarcoma should be investigated in further prospective and larger studies.