Psychological Experiences of Parents of Pediatric Cancer Patients during and after COVID-19 Pandemic.

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.

Evaluation of Metabolic and Cardiovascular Risk Measured by Laboratory Biomarkers and Cardiopulmonary Exercise Test in Children and Adolescents Recovered from Brain Tumors: The CARMEP Study.

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-α, 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 than controls on the CPET. Furthermore, they showed higher endothelin-1 values than controls (p = 0.025). The CPET results showed an inverse correlation with leptin. The differences found highlight the greater cardiovascular risk of brain tumor survivors, and radiotherapy could be implicated in the genesis of this greater cardiovascular risk.

Neonatal outcomes and follow-up of children born to women with pregnancy-associated cancer: a prospective observational study.

BACKGROUND: During the last decade, there has been a growing number of cases of children born from pregnancy-associated cancer (PAC), however there are currently insufficient data on the follow up to be observed in this category of newborns. Objective of the study was to evaluate the neonatal outcomes of infants born to mother with PAC, the potential adverse effect of chemotherapy during pregnancy and the risk of metastasis to the fetus. METHODS: Maternal clinical data and neonatal outcomes of child born to mothers diagnosed with PAC were collected; infants were divided into those were and were not exposed to chemotherapy during fetal life and their outcomes were compered. RESULTS: A total of 37 newborn infants from 36 women with PAC were analyzed. Preterm delivery occurred in 83.8% of the cases. No significant differences in neonatal outcomes were found between infants who were and were not exposed to chemotherapy during pregnancy. The median follow-up period was 12 months. CONCLUSIONS: PAC treatment during the second or third trimester does not seem to be dangerous for the fetus, however infants born from PAC must be carefully evaluated for to rule out the consequences of chemotherapy and exclude the presence of metastasis. Long-term follow-up, especially in children exposed to chemotherapy, should be encouraged to obtain relevant data on long-term toxicity.

Anthropometric parameters as a tool for the prediction of metabolic and cardiovascular risk in childhood brain tumor survivors.

PURPOSE: To assess the prevalence of alterations in anthropometric parameters predictive of metabolic syndrome and cardiovascular risk among childhood brain tumor survivors. METHODS: Anthropometric parameters predictive of metabolic syndrome and cardiovascular risk were analyzed [height, weight, BMI, waist circumference, hip circumference, waist-height ratio (WHtR), waist-hip ratio (WHR, blood pressure] of 25 patients who survived childhood brain tumors. RESULTS: 21 patients (84%) showed alteration of at least one predictive anthropometric parameter. 11 patients (44%) showed a BMI > 75th percentile and 19 patients (76%) showed a pathological WHR value. A pathological WHtR (> 0.5), was identified in 17 patients (68%); the average WHtR observed was 0.53. 9 patients (36%) showed an alteration of all three anthropometric parameters considered. Comparing this subpopulation with the subpopulation with less than three altered parameters, a greater prevalence of the combined alteration was observed in the female sex compared to the male sex (67% vs. 26%). No significant differences were observed regarding the age of diagnosis and end of treatment nor the treatments carried out (chemotherapy, radiotherapy, steroid therapy) between the two groups. CONCLUSION: These results suggest that this population is at high risk of presenting pathological values of BMI, WHR and WHtR with consequent high risk of developing metabolic syndrome and cardiovascular diseases.

Aminoglycosides-Related Ototoxicity: Mechanisms, Risk Factors, and Prevention in Pediatric Patients.

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.

Timing and chemotherapy association for 131-I-MIBG treatment in high-risk neuroblastoma.

Prognosis of high-risk neuroblastoma is dismal, despite intensive induction chemotherapy, surgery, high-dose chemotherapy, radiotherapy, and maintenance. Patients who do not achieve a complete metastatic response, with clearance of bone marrow and skeletal NB infiltration, after induction have a significantly lowersurvival rate. Thus, it's necessary to further intensifytreatment during this phase. 131-I-metaiodobenzylguanidine (131-I-MIBG) is a radioactive compound highly effective against neuroblastoma, with32% response rate in relapsed/resistant cases, and only hematological toxicity. 131-I-MIBG wasutilized at different doses in single or multiple administrations, before autologous transplant or combinedwith high-dose chemotherapy. Subsequently, it was added to consolidationin patients with advanced NB after induction, but an independent contribution against neuroblastoma and for myelotoxicity is difficult to determine. Despiteresults of a 2008 paper demonstratedefficacy and mild hematological toxicity of 131-I-MIBG at diagnosis, no center had included it with intensive chemotherapy in first-line treatment protocols. In our institution, at diagnosis, 131-I-MIBG was included in a 5-chemotherapy drug combination and administered on day-10, at doses up to 18.3 mCi/kg. Almost 87% of objective responses were observed 50 days from start with acceptable hematological toxicity. In this paper, we review the literature data regarding 131-I-MIBG treatment for neuroblastoma, and report on doses and combinations used, tumor responses and toxicity. 131-I-MIBG is very effective against neuroblastoma, in particular if given to patients at diagnosis and in combination with chemotherapy, and it should be included in all induction regimens to improve early responses rates and consequently long-term survival.

Retrospective Study on Staphylococcus aureus Resistance Profile and Antibiotic Use in a Pediatric Population.

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.

Pediatric low-grade glioma and neurofibromatosis type 1: A single-institution experience.

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.

Early and Long-Term Ototoxicity Noted in Children Due to Platinum Compounds: Prevalence and Risk Factors.

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.

Atypical Teratoid Rhabdoid Tumor: Proposal of a Diagnostic Pathway Based on Clinical Features and Neuroimaging Findings.

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.

Emerging Perspectives on the Antiparasitic Mebendazole as a Repurposed Drug for the Treatment of Brain Cancers.

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 such as Hedgehog signaling. Therefore, attention to MBZ repurposing has recently increased because of its potential therapeutic versatility and significant clinical implications, such as reducing medical care costs and optimizing existing therapies. Using new treatments is essential, particularly when current therapeutics for patients with brain cancer fail.

1.5T MR-Guided Daily-Adaptive SBRT for Prostate Cancer: Preliminary Report of Toxicity and Quality of Life of the First 100 Patients.

Purpose: The present study reports the preliminary outcomes in terms of adverse events and quality of life in the first 100 patients treated with 1.5T MR-guided daily-adaptive stereotactic body radiotherapy for prostate cancer. Methods: From October 2019 to December 2020, 100 patients, enrolled in a prospective study, received MR-guided SBRT for prostate cancer. Rectal spacer insertion was optional and administered in 37 patients. In total, 32 patients received androgen deprivation therapy in accordance with international guidelines. A prospective collection of data regarding toxicity and quality of life was performed. Results: The median age was 71 years (range, 52-84). The median total dose delivered was 35 Gy (35-36.25 Gy) in five sessions, either on alternate days (n = 25) or consecutive days (n = 75). For acute toxicity, we recorded: seven cases of acute G2 urinary pain and four cases of G2 gastrointestinal events. The median follow-up was 12 months (3-20), recording three late G2 urinary events and one G3 case, consisting of a patient who required a TURP 8 months after the treatment. For gastrointestinal toxicity, we observed 3 G ≥ 2 GI events, including one patient who received argon laser therapy for radiation-induced proctitis. Up to the last follow-up, all patients are alive and with no evidence of biochemical relapse, except for an M1 low-volume patient in distant progression two months after radiotherapy. QoL evaluation reported a substantial resolution of any discomfort within the second follow-up after radiotherapy, with the only exception being sexual items. Notably, after one year, global health items were improved compared to the baseline assessment. Conclusions: This study reports very promising outcomes in terms of adverse events and QoL, supporting the role of 1.5T MR-guided SBRT for prostate cancer. To date, this series is one of the first and largest available in the literature. Long-term results are warranted.

Induction Regimen in High-Risk Neuroblastoma: A Pilot Study of Highly Effective Continuous Exposure of Tumor Cells to Radio-Chemotherapy Sequence for 1 Month. The Critical Role of Iodine-131-Metaiodobenzylguanidine.

The prognosis of high-risk neuroblastoma (NB) continues to be poor. The early development of resistance often leads to disease recurrence. In the present study, an innovative induction regimen, including an intensive initial radio-chemotherapy sequence based on the use of iodine-131-metaiodobenzylguanidine (131-I-MIBG), was investigated. The duration of the regimen lasted only one month. Fifteen newly diagnosed patients aged >18 months with high-risk NB were treated with cisplatin, etoposide, cyclophosphamide, and vincristine, followed on day 10 by 131-I-MIBG (dose: 12−18.3 mCi/kg). Cisplatin and vincristine were administered on day 20 and 21 followed by the re-administration of vincristine, cyclophosphamide, and doxorubicin on day 29 and 30. Non-hematologic toxicity was not observed. Moderate hematologic toxicity was present probably attributable to chemotherapy. The evaluation of response was performed approximately 50 days after the initiation of treatment, yielding four complete responses, eight very good partial responses, one partial response, and two non-responses. Importantly, a complete metastatic response was achieved in 87% of patients. The present pilot study, which includes 131-I-MIBG, allows for a highly effective continuous exposure of tumor cells to both chemotherapy and radiotherapy. Furthermore, early high-dose chemotherapy followed by stem cell rescue may achieve high levels of tumor cell clearance and improve the prognosis of high-risk NB.

Catheter-related complications in onco-hematologic children: A retrospective clinical study on 227 central venous access devices.

BACKGROUND: The use of central venous access devices (CVADs) is of paramount importance to safely deliver antiblastic and support therapies in children with cancer. Though, in pediatric patients, as much as in adults, CVADs are potentially associated with severe complications which may result in unscheduled interruption of therapy, hospitalization, increased morbidity/mortality, and increased cost of care. METHODS: We have reviewed retrospectively our experience with CVADs in children with solid tumors and hematologic diseases, with the purpose of verifying if the adoption of well-defined insertion and maintenance bundles might be effective in reducing catheter-related complications, and in particular catheter-related thrombosis. RESULTS: A total of 227 CVADs were analyzed: 175 peripherally inserted central catheters (PICCs), 50 centrally inserted central catheters (CICCs), and 2 femorally inserted central catheters. All CVADs were non-valved, non-cuffed power injectable polyurethane catheters; 81% were tunneled. Median dwelling time of CVADs was 172 days, for a total number of 39,044 catheter days. A very low incidence of both symptomatic catheter-related thrombosis (0.9%) and catheter-related blood stream infection (0.56 episodes per 1000 catheter days) was found. Unscheduled removal or guidewire replacement because of mechanic complications occurred in 15.7% of CVADs. There was no difference in terms of complications between PICCs and CICCs or between tunneled and non-tunneled catheters. CONCLUSIONS: Our experience with CVADs in oncologic and hematologic children suggests that catheter-related complications may be minimized by the adoption of appropriate insertion and maintenance bundles.

BRAF and MEK Targeted Therapies in Pediatric Central Nervous System Tumors.

BRAF is a component of the MAPK and PI3K/AKT/mTOR pathways that play a crucial role in cellular proliferation, differentiation, migration, and angiogenesis. Pediatric central nervous system tumors very often show mutations of the MAPK pathway, as demonstrated by next-generation sequencing (NGS), which now has an increasing role in cancer diagnostics. The MAPK mutated pathway in pediatric CNS tumors is the target of numerous drugs, approved or under investigation in ongoing clinical trials. In this review, we describe the main aspects of MAPK and PI3K/AKT/mTOR signaling pathways, with a focus on the alterations commonly involved in tumorigenesis. Furthermore, we reported the main available data about current BRAF and MEK targeted therapies used in pediatric low-grade gliomas (pLLGs), pediatric high-grade gliomas (pHGGs), and other CNS tumors that often present BRAF or MEK mutations. Further molecular stratification and clinical trial design are required for the treatment of pediatric CNS tumors with BRAF and MEK inhibitors.

Transplacental Passage and Fetal Effects of Antineoplastic Treatment during Pregnancy.

The incidence of PAC is relatively infrequent among pregnant women. However, it has gradually increased in recent years, becoming a challenging area for clinicians that should take into account in the same way maternal benefits and fetal potential risks correlated to the antineoplastic treatment. None of the antineoplastic drugs is completely risk-free during the pregnancy, the timing of exposure and transplacental transfer properties influence the toxicity of the fetus. Despite the lack of guidelines about the management of PAC, several studies have described the use and the potential fetal and neonatal adverse events of antineoplastic drugs during pregnancy. We provide a review of the available literature about the transplacental passage and fetal effects of chemotherapy and targeted agents, to guide the clinicians in the most appropriate choices for the management of PAC.

Biomarkers Predictive of Metabolic Syndrome and Cardiovascular Disease in Childhood Cancer Survivors.

The improvement in childhood cancer treatments resulted in a marked improvement in the survival of pediatric cancer patients. However, as survival increased, it was also possible to observe the long-term side effects of cancer therapies. Among these, metabolic syndrome is one of the most frequent long-term side effects, and causes high mortality and morbidity. Consequently, it is necessary to identify strategies that allow for early diagnosis. In this review, the pathogenetic mechanisms of metabolic syndrome and the potential new biomarkers that can facilitate its diagnosis in survivors of pediatric tumors are analyzed.

Stereotactic body radiotherapy for pulmonary oligometastases: a monoinstitutional analysis of clinical outcomes and potential prognostic factors.

PURPOSE: We report the retrospective data of a cohort of patients who received stereotactic body radiotherapy for pulmonary oligometastases, aiming to assess the clinical factors potentially affecting clinical outcomes. METHODS: The present series reports the outcomes of a cohort of 71 patients with pulmonary oligometastases with no extrapulmonary disease. All patients were treated with stereotactic body radiotherapy (SBRT) performed with volumetric modulated arc therapy-image guided radiotherapy (VMAT-IGRT) to up to five secondary lesions. Survival estimates were performed using the Kaplan-Meier method. RESULTS: A total of 98 lesions in 71 patients were treated from February 2014 to August 2020. The most frequent histologies were colorectal in 37.7%, lung cancer in 44.8%, head and neck cancer in 8.1%, and other in 9.4%. Median age was 71 years (range 32-93 years). Concurrent systemic therapy was administered in 32.3%. SBRT was delivered to a median total dose of 60 Gy (range 55-70 Gy) in 3-10 fractions for a median BED10 = 105 Gy (range 96-180 Gy). Median follow-up was 29.5 months (range 6-81), with no acute or late G > 2 adverse event. Our LC rates at 2 and 4 years were 92.4 and 89.8%, respectively. DPFS rates at 2 and 4 years were 45.3 and 27.2%, respectively. A second SBRT course was proposed in 21 patients (29.5%) who developed an oligoprogression, resulting in median time to second progression of 9 months (range 2-44) and 2­year PFS2 rate of 42.4%. At univariate analysis, patients with sequential oligometastases reported better OS rates (p = 0.002), which was also confirmed at multivariate analysis, where distant progression was also related to worse OS (p = 0.022). Higher local control rates relate to better PFS (p = 0.04). The 2­ and 4­year OS rates were 61 and 39.7% CONCLUSION: SBRT is feasible for pulmonary oligometastases with favorable outcomes and toxicity. At multivariate analysis, patients with sequential oligometastatic progression maintain a survival advantage. Also, local control was found to be related to improved PFS rates.

Clostridioides difficile Infection in Children: A 5-Year Multicenter Retrospective Study.

While there are numerous studies regarding Clostridioides difficile infection (CDI) in adults, literature on the pediatric population is scarce. Therefore, we performed a 5-year retrospective study between January 2014 and December 2018 in two referral centers in Rome, Italy. There were 359 patients tested for CDI who were enrolled: 87 resulted in positive and 272 in negative. CDI children had a higher number of previous-day hospital admissions (p = 0.024), hospitalizations (p = 0.001), and total hospital admissions (p = 0.008). Chronic comorbidities were more frequent in the CDI group (66.7% vs. 33.3%). Previous use of proton pump inhibitors and antibiotics was associated with CDI (p < 0.001). Among the antibiotics, only fluoroquinolones were significantly associated with CDI. Also, CDI children were more frequently exposed to antibiotics during the episode of hospitalization when children were tested. Our study provides an updated clinical and epidemiological analysis of children with CDI compared with a control group of children who tested negative. Further prospective studies could better define risk factors and preventive methods.

Oral Microbiota during Childhood and Its Role in Chemotherapy-Induced Oral Mucositis in Children with Cancer.

The human oral cavity harbors the second most abundant microbiota after the gastrointestinal tract, with over 700 species currently identified in the oral microflora. The oral microbiota develops from intrauterine life and after birth is continuously shaped by several influencing factors. The perturbation of the diversity and proportions of species within the oral microbiota leads to dysbiosis and associated increased risk of local and systemic diseases. In children who receive chemotherapy for cancer, oral mucositis is a common and painful side effect that decreases quality of life (QoL) and treatment adherence. The oral microbiota undergoes a substantial dysbiosis as an effect of cancer and its treatment, characterized by lower richness and less diversity. Furthermore, this dysbiosis seems to promote pro-inflammatory cytokine release and pro-apoptotic mediators, enhancing the oral tissue damage. Further studies on the role of the oral microbiota in the pathogenesis of oral mucositis should be performed among children with cancer who receive chemotherapy, to find preventive and protective factors against the pathogenesis of oral mucositis.