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Background: We recently reported an increased risk of Parkinson's disease (PD) in service members who resided at Marine Base Camp Lejeune, North Carolina, when water supplies were contaminated with trichloroethylene and other volatile organic compounds (VOCs). Prior studies suggest that environmental exposures may affect PD phenotype or progression, but this has not been reported for VOCs., Objective: The objective of this study was to test whether PD progression is faster in individuals exposed to VOCs in water at Camp Lejeune., Methods: A cohort of 172,128 marines residing at Camp Lejeune between 1975 and 1985 was previously assembled. We identified individuals with PD in Veterans Health Administration and Medicare databases between 2000 and 2021. Using estimates derived by the US Agency for Toxic Substances and Disease Registry, we classified individuals as exposed or unexposed to VOCs in residential water. We used Kaplan-Meier and Cox regression models to test differences between exposed and unexposed groups in the time from PD diagnosis until psychosis, fracture, fall, or death., Results: Among 270 persons with PD, 177 (65.6%) were exposed to VOCs in residential water. Median cumulative exposure was 4970 μg/L-months, >50-fold the permissible level. Time until psychosis, fracture, and fall were all shorter in the exposed group, with adjusted hazard ratios (HRs) exceeding 2: psychosis HR, 2.19 (95% confidence interval [CI]: 0.99-4.83); fracture HR, 2.44 (95% CI: 0.91-6.55); and fall HR, 2.64 (95% CI: 0.97-7.21). A significant dose response was observed for time to fall (P trend, 0.032). No differences were observed for time until death., Conclusions: PD progression may be faster in persons exposed to trichloroethylene and other VOCs in water decades earlier. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Neuroblastoma, the most common extracranial solid tumor in children under the age of 5, has been described as early as the 19th century, and its complexity has continued to intrigue researchers, as well as medical and surgical specialists. At one end of the phenotypic spectrum, neuroblastoma is self-limiting with minimal to no intervention required, while on the opposite end exists the challenge of refractory disease despite aggressive management and toxic systemic treatments. The goal of this review is to describe a comprehensive surgical perspective and contemporary approach to neuroblastoma., (© 2024 Wiley Periodicals LLC.)

Background: The International Neuroblastoma Risk Group (INRG) classifier utilizes a staging system based on pretreatment imaging criteria in which image-defined risk factors (IDRFs) are used to evaluate the extent of locoregional disease. Children's Oncology Group (COG) study ANBL0531 prospectively examined institutional determination of IDRF status and compared that to a standardized central review., Methods: Between 9/2009-6/2011, patients with intermediate-risk neuroblastoma were enrolled on ANBL0531 and had IDRF assessment at treating institutions. Paired COG pediatric surgeons and radiologists performed blinded central review of diagnostic imaging for the presence or absence of IDRFs. Second blinded review was performed in cases of discordance. Comparison of local and central review was performed using the Kappa coefficient to determine concordance in IDRF assessment., Results: 211 patients enrolled in ANBL0531 underwent IDRF assessment; 3 patients were excluded due to poor image quality. Central reviewer pairs agreed on the presence or absence of any IDRF in 170/208 (81.7%; κ = 0.48) cases. Thirteen (6.3%) cases could not be adjudicated after second blinded review. Radiologists were more likely to identify IRDFs as present than surgeons (p < 0.001). Local and central reviewers agreed on the presence or absence of any IDRF in only108/208 (51.9%; κ = 0.06) cases., Conclusions: Among experienced pediatric surgeons and radiologists participating in central review, concordance was moderate, with agreement in 81.7% of cases. On comparison of local and central assessment of IDRFs, concordance was poor. These data indicate that greater standardization, education, technology, and training are needed to improve the assessment of IDRFs in children with neuroblastoma., Level of Evidence: Treatment Study, Level III., Competing Interests: Conflict of interset Author AN serves on a data safety monitoring board for Novartis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Historically, surgical biopsy (SB) for diagnosis of pediatric solid tumors was considered necessary to provide adequate tissue for histologic and molecular analysis. Less invasive biopsy techniques such as image-guided core needle biopsy (CNB), have shown comparable accuracy with decreased morbidity in some adult studies. However, data regarding the safety and efficacy of CNB in pediatric tumors is limited. This study's aim was to assess the overall rate of successful diagnosis and safety of CNB compared to SB in children with malignancies., Methods: A PRISMA compliant systematic review was performed in MEDLINE via PubMed, Embase and CINAHL Plus database searches from 2010 to 2023. Studies were included with relevance to the following clinical question: For children with concern for malignancy requiring biopsy for diagnosis, how does CNB compare to open or laparoscopic/thoracoscopic SB in terms of safety and diagnostic efficacy? Data for patients ≤21 years requiring biopsy for diagnosis of liver tumors, neuroblastoma (NB), soft tissue sarcoma (STS), and lymphoma were included., Results: Twenty-seven studies including 2477 patients met inclusion criteria, with 2065 undergoing CNB and 412 SB. Of the 2477 patients, 820 patients had NB, 307 liver tumors, 96 STS, 151 lymphoma, and 1103 patients were from studies that included multiple diagnoses. The average complication rate for CNB was 2.9% compared to 21.4% for SB (p < 0.001). Bleeding was the most common complication in both groups, but significantly higher after SB (22.1% vs 2.3%) (p < 0.001). CNB was diagnostic in 90.8% of patients compared to 98.8% who underwent SB (p < 0.001)., Conclusions: Rates of successful diagnosis were greater than 90% for both CNB and SB, though significantly higher for SB. Conversely, complication rates were close to ten times higher after SB compared to CNB. Given its relatively lower risk profile, CNB can be a safe and useful diagnostic tool for children with solid malignancies. Research focused on enhancing CNB's diagnostic accuracy while maintaining low morbidity should be further explored., Level of Evidence: Treatment study, Level III., Competing Interests: Declaration of competing interest The authors have nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Tunneled central venous catheters (CVCs) are the cornerstone of modern oncologic practice. Establishing best practices for catheter management in children with cancer is essential to optimize care, but few guidelines exist to guide placement and management., Objectives: To address four questions: 1) Does catheter composition influence the incidence of complications; 2) Is there a platelet count below which catheter placement poses an increased risk of complications; 3) Is there an absolute neutrophil count (ANC) below which catheter placement poses an increased risk of complications; and 4) Are there best practices for the management of a central line associated bloodstream infection (CLABSI)?, Methods: Data Sources: English language articles in Ovid Medline, PubMed, Embase, Web of Science, and Cochrane Databases., Study Selection: Independently performed by 2 reviewers, disagreements resolved by a third reviewer., Data Extraction: Performed by 4 reviewers on forms designed by consensus, quality assessed by GRADE methodology., Results: Data were extracted from 110 manuscripts. There was no significant difference in fracture rate, venous thrombosis, catheter occlusion or infection by catheter composition. Thrombocytopenia with minimum thresholds of 30,000-50,000 platelets/mcl was not associated with major hematoma. Limited evidence suggests a platelet count <30,000/mcL was associated with small increased risk of hematoma. While few studies found a significant increase in CLABSI in CVCs placed in neutropenic patients with ANC<500Kcells/dl, meta-analysis suggests a small increase in this population. Catheter removal remains recommended in complicated or persistent infections. Limited evidence supports antibiotic, ethanol, or hydrochloric lock therapy in definitive catheter salvage. No high-quality data were available to answer any of the proposed questions., Conclusions: Although over 15,000 tunneled catheters are placed annually in North America into children with cancer, there is a paucity of evidence to guide practice, suggesting multiple opportunities to improve care., Level of Evidence: III. This study was registered as PROSPERO 2019 CRD42019124077., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Central venous access through tunneled central venous catheters (CVCs) are one of the cornerstones of modern oncologic practice in pediatric patients since CVCs provide a reliable access route for the administration of chemotherapy. Establishing best practices for CVC management in children with cancer is essential to optimize care. This article reviews current best practices, including types of devices, their placement, complications, and long-term outcomes. Additionally, nutrition status and nutritional support are also very important determinants of outcomes and care in pediatric surgical oncology patients. We review current nutritional assessment, support, access for enteral and parenteral nutrition delivery, and their complications, mainly from a surgical perspective. Overall, access surgery, whether for CVCs, or for enteral access can be challenging, and best practice guidelines supported by current though limited evidence are necessary to minimize complications and optimize outcomes., (© 2024 Wiley Periodicals LLC.)

Purpose: Our objectives were to compare overall survival (OS) and pulmonary relapse between patients with metastatic Ewing sarcoma (EWS) at diagnosis who achieve rapid complete response (RCR) and those with residual pulmonary nodules after induction chemotherapy (non-RCR)., Patients and Methods: This retrospective cohort study included children under 20 years with metastatic EWS treated from 2007 to 2020 at 19 institutions in the Pediatric Surgical Oncology Research Collaborative. Chi-square tests were conducted for differences among groups. Kaplan-Meier curves were generated for OS and pulmonary relapse., Results: Among 148 patients with metastatic EWS at diagnosis, 61 (41.2%) achieved RCR. Five-year OS was 71.2% for patients who achieved RCR, and 50.2% for those without RCR (p = .04), and in multivariable regression among patients with isolated pulmonary metastases, RCR (hazards ratio [HR] 0.42; 95% confidence interval [CI]: 0.17-0.99) and whole lung irradiation (WLI) (HR 0.35; 95% CI: 0.16-0.77) were associated with improved survival. Pulmonary relapse occurred in 57 (37%) patients, including 18 (29%) in the RCR and 36 (41%) in the non-RCR groups (p = .14). Five-year pulmonary relapse rates did not significantly differ based on RCR (33.0%) versus non-RCR (47.0%, p = .13), or WLI (38.8%) versus no WLI (46.0%, p = .32)., Discussion: Patients with EWS who had isolated pulmonary metastases at diagnosis had improved OS if they achieved RCR and received WLI, despite having no significant differences in rates of pulmonary relapse., (© 2024 Wiley Periodicals LLC.)

Competing Interests: The authors report no conflicts of interest.

Objective: Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy in the United States, and biomarkers of patient outcomes are limited. Data using immunohistochemical (IHC) analysis are mixed regarding whether and which tumor infiltrating lymphocytes (TILs) impact survival, and IHC does not adequately quantify rare cell populations, including CD137+ (4-1BB) tumor-reactive TILs. Our study investigates if a higher percentage of CD3+ CD137+ TILs is associated with improved overall survival (OS) in OC., Methods: Flow cytometry was performed on viably banked OC digests. Chart review and statistical analysis were performed. Forty-seven patients were included, 40 of whom were diagnosed with high-grade serous ovarian carcinoma (HGSOC), papillary serous carcinoma, or undifferentiated histology., Results: A high percentage of CD3+ CD137+ TILs correlated with improved OS (n = 40, r = 0.48, P = 0.0016). Subjects were divided into CD3+ CD137+ TIL high and low groups by the median. Subjects with high CD3+CD137+ TIL frequencies (>9.6%) had longer OS (Wilcoxon rank-sum test; P = 0.0032) and improved OS (logrank test; P = 0.007). Differences in CD3+ or CD3+ CD8+ TILs did not impact survival. CD3+ CD137+ TILs were predictive of OS regardless of germline mutation or debulking status. Analysis of subgroups including late stage HGSOC and late stage HGSOC with primary optimal cytoreduction indicated CD3+ CD137+ TILs correlated with improved OS after adjusting for age and PARP inhibitor use (P = 0.034 and P = 0.016, respectively)., Conclusions: Prevalence of CD3+ CD137+ TILs in digested OC specimens is associated with improved OS, while general TIL markers are not. CD137 has the potential to be a novel biomarker for survival in OC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DJP holds patents and received royalties on CD137-specific cell enrichment methodologies and treatments. DJP received payments for advisory service from InsTIL Bio related to TIL therapy products. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Pediatric patients treated at trauma centers demonstrate improved outcomes, but investigation of optimal resource utilization surrounding the transfer is ongoing. We evaluated characteristics of operative pediatric trauma transfer patients for resource optimization., Methods: A retrospective review of pediatric trauma patients transferred to a level 1 pediatric trauma center from 2009 to 2019 was performed. Patients were categorized by initial operative subspecialty., Results: Of 4164 transferred patients, 33.9 ​% required operative intervention. 65 ​% of operations were performed on orthopedic patients, who were significantly less injured compared to other patients. General surgery patients were more likely to undergo surgery on day of transfer compared to orthopedic patients (39.4%vs 56.3 ​%, OR 2.0, CI 1.4-2.8)., Conclusions: One-third of pediatric trauma transfer patients required operative intervention. The majority of surgeries were on orthopedic patients, who were less likely to undergo surgery on day of transfer. Critical evaluation of this patient population is required to safely utilize a less resource-intensive transfer process., Competing Interests: Declaration of competing interest The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health (grant number UL1 TR001860) for author EGB. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was presented at Pediatric Trauma Society 8th annual meeting. This project represents original work by the authors. During the preparation of this work, the authors did not use generative AI and AI-assisted technologies in the writing process., (Copyright © 2023. Published by Elsevier Inc.)

Background: The penetrance of common genetic risk variants for Parkinson's disease (PD) is low. Pesticide exposure increases PD risk, but how exposure affects penetrance is not well understood., Objective: To determine the relationship between occupational pesticide exposure and PD in people with LRRK2 and GBA risk variants., Methods: Participants of the Parkinson's Progression Markers Initiative (PPMI) with a LRRK2-G2019 S or GBA risk variant provided information about occupational pesticide exposure. We compared exposure in carriers with and without PD. Among carriers with PD, we used Cox proportional hazard models to compare time-to impairment in balance, cognition, and activities of daily living (ADLs) between participants with and without prior occupational pesticide exposure., Results: 378 participants with a risk variant provided exposure information; 176 with LRRK2-G2019 S (54 with and 122 without PD) and 202 with GBA variants (47 with and 155 without PD). Twenty-six participants reported pesticide exposure. People with a GBA variant and occupational pesticide exposure had much higher odds of PD (aOR: 5.4, 95% CI 1.7-18.5, p < 0.01). People with a LRRK2 variant and a history of occupational pesticide exposure had non-significantly elevated odds of PD (aOR 1.3, 95% CI 0.4-4.6, p = 0.7). Among those with PD, pesticide exposure was associated with a higher risk of balance problems and cognitive impairment in LRRK2-PD and functional impairment in GBA-PD, although associations were not statistically significant., Conclusions: Occupational pesticide exposure may increase penetrance of GBA-PD and may be associated with faster symptom progression. Further studies in larger cohorts are necessary.