Multi-omics analysis of the gut microbiome and metabolites associated with the psychoneurological symptom cluster in children with cancer receiving chemotherapy.

BACKGROUND: Children with cancer receiving chemotherapy commonly report a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, depression, and cognitive dysfunction. The role of the gut microbiome and its functional metabolites in PNS is rarely studied among children with cancer. This study investigated the associations between the gut microbiome-metabolome pathways and PNS in children with cancer across chemotherapy as compared to healthy children. METHODS: A case-control study was conducted. Cancer cases were recruited from Children's Healthcare of Atlanta and healthy controls were recruited via flyers. Participants reported PNS using the Pediatric Patient-Reported Outcomes Measurement Information System. Data for cases were collected pre-cycle two chemotherapy (T0) and post-chemotherapy (T1), whereas data for healthy controls were collected once. Gut microbiome and its metabolites were measured using fecal specimens. Gut microbiome profiling was performed using 16S rRNA V4 sequencing, and metabolome was performed using an untargeted liquid chromatography-mass spectrometry approach. A multi-omics network integration program analyzed microbiome-metabolome pathways of PNS. RESULTS: Cases (n = 21) and controls (n = 14) had mean ages of 13.2 and 13.1 years. For cases at T0, PNS were significantly associated with microbial genera (e.g., Ruminococcus, Megasphaera, and Prevotella), which were linked with carnitine shuttle (p = 0.0003), fatty acid metabolism (p = 0.001) and activation (p = 0.001), and tryptophan metabolism (p = 0.008). Megasphaera, clustered with aspartate and asparagine metabolism (p = 0.034), carnitine shuttle (p = 0.002), and tryptophan (p = 0.019), was associated with PNS for cases at T1. Gut bacteria with potential probiotic functions, along with fatty acid metabolism, tryptophan, and carnitine shuttle, were more clustered in cancer cases than the control network and this linkage with PNS needs further studies. CONCLUSIONS: Using multi-omics approaches, this study indicated specific microbiome-metabolome pathways linked with PNS in children with cancer across chemotherapy. Due to limitations such as antibiotic use in cancer cases, these findings need to be further confirmed in a larger cohort.

How to Maintain a Healthy Gut Microbiome in Children with Cancer? Gut Microbiome Association with Diet in Children with Solid Tumors Postchemotherapy.

Malnutrition is a common complication in children with cancer. Cancer treatment and malnutrition can disrupt gut microbiome diversity and composition. The gut microbiome is of broad interest to better understand the mechanisms of malnutrition in cancer therapy. This study aimed to compare the gut microbiome between children with solid tumors postchemotherapy and healthy controls, and investigated the association of the putative microbiome differences with diet. Study participants were 27 children (7-18 years) with solid tumors within the first year after the completion of chemotherapy and 22 healthy controls. The study groups did not have a statistically significant difference in age, race, sex, and body mass index. At study intake, the participants completed the Block Kids Food Screener for dietary intakes in the past week. Fecal specimens were collected and analyzed for the gut microbiome. The cancer and control groups differed in gut microbial ß-diversity and abundance analyses. The macronutrient intakes such as carbohydrates, fiber, beta-carotene, and vitamin B6 were positively associated with α-diversity. Children with adequate vitamin B6 had a higher Chao1 diversity index than children with inadequate or excessive intake (p = 0.0004). Children with excessive selenium intake had a trend for higher Pielou's_e index than children with inadequate intake (p = 0.091). Maintaining a healthy gut microbiome is critical among children with cancer. This study provides new insights on the linkages between dietary intakes and the gut microbiome in children with solid tumors postchemotherapy. These findings, if replicated in future independent studies, may help anticipate malnutrition and plan for personalized nutrition approaches during chemotherapy in pediatric cancers.

Functional Performance Measures Used for Return-to-Sport Criteria in Youth Following Lower-Extremity Injury.

CONTEXT: As sport participation increases globally, so will injury-related risks. The process used to determine return-to-sport following injury is vital to future sport participation and injury prevention. Early specialization along with poor management of sport participation causes an increase in injury risk and potential long-term health consequences for youth athletes. OBJECTIVES: Previous injury is a common intrinsic risk factor for new injuries. Identifying functional performance deficits, defined by return-to-sport criteria, minimizes these risk factors and provides athletes with guidelines to return safely to sport. The purposes of this clinical commentary and literature review are to provide a summary of current concepts and clinical practices and to identify functional performance measures as clinical assessment tools for return-to-play criteria in the youth population. EVIDENCE: A literature review was completed using numerous databases, where 154 relevant articles were reviewed and 22 articles were included in this commentary. Of the 22 articles using functional performance measures for return-to-sport criteria, 6 were specific to youth, 12 had mixed populations of adults and youth, and 4 were normative samples for specific youth populations. Acquisition: The gaps in the literature pertaining to functional performance measures in the youth population are addressed, and future research needs for return-to-sport criteria are identified. EVIDENCE SYNTHESIS: This descriptive literature review identifies 22 articles that meet the search criteria for the youth population discussing the use of clinical functional performance measures in order to identify return-to-sport criteria for lower-extremity injuries. CONCLUSIONS: Due to the inconsistencies in terminology, definitions, and standardization of clinical assessment tools, it seems necessary to create a comprehensive functional performance test battery for the lower extremity that can be used as return-to-sport criteria.

Intracavitary cisplatin therapy for pediatric malignancies.

BACKGROUND: Local control is essential for the successful treatment of pediatric solid tumors. Complete excision is often not possible and local control therapies are limited. Intracavitary cisplatin (IC-CDDP) may be utilized to supplement local control. The aim of the study was to determine the toxicity and efficacy of locally instilled intracavitary cisplatin in patients with recurrent tumors in closed body cavities. PROCEDURE: From 2001 to 2009, 12 patients (1-20 years) with recurrent or unresectable malignant tumors were treated with IC-CDDP. Nine had pulmonary lesions. Three patients had abdominal tumors. CDDP (200 mg/m(2)) was instilled by chest tube or Tenckhoff catheter. Patients were shifted every 15-30 min to allow distribution. After 4 hr, residual was drained by gravity. In 10/13 courses, sodium thiosulfate (STS) was administered to prevent nephrotoxicity. Three other patients received amifostine. RESULTS: Malignant pleural effusions resolved in 5/7 patients. This response was temporary in three patients. No patients had ascites prior to treatment. Three patients are alive and disease-free, 18 months, 4 years, and 6 years from treatment. They also had surgery and chemotherapy. Transient renal toxicity was noted in most patients. One patient, treated with amifostine, had persistent renal dysfunction. CONCLUSIONS: IC-CDDP was effective in treating malignant pleural effusions and may be a palliative option for refractory disease. Long-term survival was achieved in two patients, treated at first diagnosis. The benefit of IC-CDDP in these patients is difficult to assess. Renal dysfunction is usually mild, and typically resolves, but warrants preventive measures with IC-CDDP therapy.

Irinotecan as maintenance therapy in high-risk hepatoblastoma.

Children with high-risk hepatoblastoma (metastatic disease or a low alpha-fetoprotein at presentation) and those with recurrent disease have an extremely poor prognosis and are in need of novel therapeutic agents and strategies. We describe three patients who were treated with irinotecan (two in combination with vincristine). In two patients, this contributed to a clinical remission. All three patients received a 1- to 2-year course of irinotecan as maintenance therapy and all remain disease free. Treatment was well tolerated with minimal toxicity. Further evaluation of the use of irinotecan as maintenance therapy in high-risk and recurrent HB patients is warranted.