Search

Background/Purpose Research to cure paralysis associated with myelomeningocele (MMC) is ongoing using the fetal sheep model of MMC. Despite decades of research using this model, no standardized motor function assessment exists. The purpose of this study is to develop a sensitive and reliable locomotor scale for assessing the functional status of sheep. Methods Twenty lambs were used to develop and validate the locomotor scale. Lambs (n = 15) underwent a surgically created MMC defect at gestational age (GA) 75 days, followed by repair with various methods at GA 100. One lamb underwent a sham operation (n = 1). Normal lambs (n = 4) served as controls. All lambs were born via spontaneous vaginal delivery, and motor function was assessed for 24 hours. A locomotor rating scale was developed based on behavioral observations of lambs. Inter-rater reliability testing was performed to determine if the scale could be reliably applied by different raters. Results Observations led to the definition of 7 categories of locomotor recovery. A scoring system was developed to rank these categories. The scale captured a wide variety of neurologic outcomes. Inter-rater reliability revealed minimal variability between examiners (average standard deviation ± 0.431). The average score for all raters was within 1 point of the consensus score 100% of the time. Conclusions The sheep locomotor rating scale is capable of capturing subtle differences in neurologic function with minimal inter-rater variability. We propose a standardized rating scale for neurologic outcomes and believe this is a critical component for assessing the validity of experimental treatments to cure paralysis in MMC.

RATIONALE: Studies have shown that cigarette smoke impacts respiratory host defense mechanisms; however, it is poorly understood how these smoke-induced changes impact the overall ability of the host to deal with pathogenic agents. OBJECTIVE: The objective of this study was to investigate the impact of mainstream cigarette smoke exposure on immune inflammatory responses and viral burden after respiratory infection with influenza A. METHODS: C57BL/6 mice were sham- or smoke-exposed for 3 to 5 mo and infected with either 2.5 x 10(3) pfu (low dose) or 2.5 x 10(5) pfu (high dose) influenza virus. MEASUREMENTS AND MAIN RESULTS: Although smoke exposure attenuated the airway's inflammatory response to low-dose infection, we observed increased inflammation in smoke-exposed compared with sham-exposed mice after infection with high-dose influenza, despite a similar rate of viral clearance. The heightened inflammatory response was associated with increased expression of tumor necrosis factor-alpha, interleukin-6, and type 1 IFN in the airway, and increased mortality. Importantly, smoke exposure did not interfere with the development of influenza-specific memory responses; sham- and smoke-exposed animals were equally protected upon viral rechallenge. CONCLUSION: Our study suggests that, in mice, cigarette smoke affects primary antiviral immune-inflammatory responses, whereas secondary immune protection remains intact. [ABSTRACT FROM AUTHOR]

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.

Background: Nephrogenic rests (NR) may represent precursor lesions for Wilms tumor (WT), but their clinical course is not fully understood and no guidelines for treatment exist. This study sought to evaluate the outcomes of pediatric patients with NRs related to traditional chemotherapy and surgery., Methods: A PRISMA-P-compliant literature search was conducted in MEDLINE, Embase, CINAHL, Web of Science, COCHRANE, and SCOPUS from inception to June 2021. Clinical questions regarding the treatment of NRs, including chemotherapy and surgery, were developed in the population, intervention, comparison, and outcome format., Results: Twenty-five studies including 1445 patients met inclusion criteria for evaluating chemotherapy compared to observation for NRs. Eighteen studies including 1392 patients met inclusion criteria for evaluating the role of surgery for NRs. Patients with isolated NRs who underwent observation progressed to WT 33% of the time; chemotherapy reduced the rate of WT to 3.9%. Observation of multiple NRs and diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) led to progression to WT 50% and 100% of the time, respectively. Chemotherapy reduced the rate of WT to 34% for multiple NRs and 46% for DHPLN. Surgery for isolated NRs reduced the risk of WT development from 23.7% in patients with incomplete excision to 3.3% with complete excision; however, 96% of patients with incompletely excised NRs had bilateral disease., Conclusions: Observation with close surveillance for isolated NRs is safe. Treatment with chemotherapy is recommended for patients with multiple NRs and DHPLN. Surgical management of NRs should focus on renal function preservation., Level of Evidence: Treatment study, Level III., Competing Interests: Conflicts of interest The authors have nothing to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Although survival for many pediatric cancers has improved with advances in conventional chemotherapeutic regimens and surgical techniques in the last several decades, it remains a leading cause of disease-related death in children. Outcomes in patients with recurrent, refractory, or metastatic disease are especially poor. Recently, the advent of alternative classes of therapies, including immunotherapies, have revolutionized systemic treatment for pediatric malignancies. Several classes of immunotherapies, including chimeric antigen receptor (CAR) T cell therapy, transgenic T-cell receptor (TCR)-T cell therapy, bispecific T-cell engagers, and monoclonal antibody checkpoint inhibitors have been FDA-approved or entered early-phase clinical trials in children and young adults. The pediatric surgeon is likely to encounter these therapies during the care of children with malignancies and should be familiar with the classes of therapy, indications, adverse events, and potential need for surgical intervention in these cases. This review from the APSA Cancer Committee offers a brief discussion of the three most encountered classes of immunotherapy in children and young adults and discusses surgical relevance. LEVEL OF EVIDENCE: IV., Competing Interests: Conflict of interest The authors have no competing interests in this work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Intraoperative nerve monitoring (IONM) is a technique used to decrease the possibility of nerve-associated morbidity and damage to nearby neural structures during complex surgical procedures. The use and potential benefits of IONM in pediatric surgical oncology are not well-described., Methods: An overview of the current literature was performed to elucidate the various techniques that may be useful to pediatric surgeons for resection of solid tumors in children., Results: The physiology and common types of IONM relevant to the pediatric surgeon are described. Important anesthetic considerations are reviewed. Specific applications for IONM that may be useful in pediatric surgical oncology are then summarized, including its use for monitoring the recurrent laryngeal nerve, the facial nerve, the brachial plexus, spinal nerves, and lower extremity nerves. Troubleshooting techniques regarding common pitfalls are then proposed., Conclusion: IONM is a technique that may be beneficial in pediatric surgical oncology to minimize nerve injury during extensive tumor resections. This review aimed to elucidate the various techniques available. IONM should be considered as an adjunct for the safe resection of solid tumors in children in the proper setting with the appropriate level of expertise. A multidisciplinary approach is advised. Additional studies are necessary to further clarify the optimal use and outcomes in this patient population., Levels of Evidence: Level III., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Resection of pediatric chest wall tumors can result in large defects requiring reconstruction for function and cosmesis. Multiple reconstructive methods have been described. We performed a systematic review of the literature to describe commonly used approaches and outcomes., Methods: A systematic literature search was performed for English-language publications describing chest wall tumor resection and reconstruction using implantable materials in patients ≤21 years, excluding soft tissue resection only, sternal resection, and reconstruction by primary repair or muscle flaps alone. Data were collected on diagnoses, reconstructive method, and outcomes. Rigid chest wall reconstruction was compared to mesh reconstruction., Results: There were 55 articles with 188 patients included. The median age was 12 years. Most tumors were malignant (n = 172, 91.5%), most commonly Ewing's sarcoma (n = 65, 34.6%), followed by unspecified sarcomas (n = 34, 18.1%), Askin's tumor (n = 16, 8.5%; a subset of Ewing's sarcoma) and osteosarcoma (n = 16, 8.5%). A median of 3 ribs were resected (range 1-12). Non-rigid meshes were most common (n = 138, 73.4%), followed by rigid prostheses (n = 50, 26.6%). There were 19 post-operative complications (16.8%) and 22.2% of patients developed scoliosis. There were no significant differences in complications (20.5% rigid vs. 10.6% non-rigid, p = 0.18) or scoliosis (22.7% vs. 14.0%, p = 0.23) by reconstruction method, but complications after rigid reconstruction were more likely to require surgery (90.0% vs. 53.9%, p = 0.09). The median follow-up duration was 24 months., Conclusions: In this review of the literature, there were no significant differences in overall post-operative complications or scoliosis development by reconstruction method, yet complications after rigid reconstruction were more likely to require surgical intervention., Level of Evidence: Level IV., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: An increased risk of Parkinson disease (PD) has been associated with exposure to the solvent trichloroethylene (TCE), but data are limited. Millions of people in the US and worldwide are exposed to TCE in air, food, and water., Objective: To test whether the risk of PD is higher in veterans who served at Marine Corps Base Camp Lejeune, whose water supply was contaminated with TCE and other volatile organic compounds (VOCs), compared with veterans who did not serve on that base., Design, Setting, and Participants: This population-based cohort study examined the risk for PD among all Marines and Navy personnel who resided at Camp Lejeune, North Carolina (contaminated water) (n = 172 128), or Camp Pendleton, California (uncontaminated water) (n = 168 361), for at least 3 months between 1975 and 1985, with follow-up from January 1, 1997, until February 17, 2021. Veterans Health Administration and Medicare databases were searched for International Classification of Diseases diagnostic codes for PD or other forms of parkinsonism and related medications and for diagnostic codes indicative of prodromal disease. Parkinson disease diagnoses were confirmed by medical record review., Exposures: Water supplies at Camp Lejeune were contaminated with several VOCs. Levels were highest for TCE, with monthly median values greater than 70-fold the permissible amount., Main Outcome and Measures: Risk of PD in former residents of Camp Lejeune relative to residents of Camp Pendleton. In those without PD or another form of parkinsonism, the risk of being diagnosed with features of prodromal PD were assessed individually and cumulatively using likelihood ratio tests., Results: Health data were available for 158 122 veterans (46.4%). Demographic characteristics were similar between Camp Lejeune (5.3% women, 94.7% men; mean [SD] attained age of 59.64 [4.43] years; 29.7% Black, 6.0% Hispanic, 67.6% White; and 2.7% other race and ethnicity) and Camp Pendleton (3.8% women, 96.2% men; mean [SD] age, 59.80 [4.62] years; 23.4% Black, 9.4% Hispanic, 71.1% White, and 5.5% other race and ethnicity). A total of 430 veterans had PD, with 279 from Camp Lejeune (prevalence, 0.33%) and 151 from Camp Pendleton (prevalence, 0.21%). In multivariable models, Camp Lejeune veterans had a 70% higher risk of PD (odds ratio, 1.70; 95% CI, 1.39-2.07; P < .001). No excess risk was found for other forms of neurodegenerative parkinsonism. Camp Lejeune veterans also had a significantly increased risk of prodromal PD diagnoses, including tremor, anxiety, and erectile dysfunction, and higher cumulative prodromal risk scores., Conclusions and Relevance: The study's findings suggest that the risk of PD is higher in persons exposed to TCE and other VOCs in water 4 decades ago. Millions worldwide have been and continue to be exposed to this ubiquitous environmental contaminant.

Background: Leadership in academic conferences is an important factor for academic advancement. Underrepresentation of women in academic surgical conferences has been demonstrated in other subspecialties, but it has not been well-studied in pediatric surgery., Methods: This retrospective descriptive study analyzes conference participation at 2 national pediatric surgery annual conference programs from 2003 to 2022. Moderator, speakers, and research presenter sex was collected. The primary outcome was the proportion of female participants in each of these roles. Mann-Kendall trend test was conducted to assess for significance., Results: Across 29 meetings, a total of 523 sessions were examined. Overall, female participation in all roles increased from 2003 to 2022. There were statistically positive trends of female participation in leadership roles as moderator (p = 0.003) and speaker (p = 0.01), with moderator role demonstrating the largest proportional female increase over time - with a 7-fold increase from 7.1% in 2003 to 50.0% in 2022. There was also a significant increasing trend in female participation as research presenters (p < 0.01) from 25.4% to 46.4%., Conclusion: Gender representation in pediatric surgery conferences has improved over the last two decades. Women now represent approximately half of all participatory roles, and efforts to continue providing equal opportunities for women at pediatric surgery academic conferences should continue., Level of Evidence: N/A., Type of Study: Retrospective Descriptive., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Early diagnosis of Parkinson's disease (PD) is important to identify treatments to slow neurodegeneration. People who develop PD often have symptoms before the disease manifests and may be coded as diagnoses in the electronic health record (EHR)., Methods: To predict PD diagnosis, we embedded EHR data of patients onto a biomedical knowledge graph called Scalable Precision medicine Open Knowledge Engine (SPOKE) and created patient embedding vectors. We trained and validated a classifier using these vectors from 3,004 PD patients, restricting records to 1, 3, and 5 years before diagnosis, and 457,197 non-PD group., Results: The classifier predicted PD diagnosis with moderate accuracy (AUC = 0.77 ± 0.06, 0.74 ± 0.05, 0.72 ± 0.05 at 1, 3, and 5 years) and performed better than other benchmark methods. Nodes in the SPOKE graph, among cases, revealed novel associations, while SPOKE patient vectors revealed the basis for individual risk classification., Discussion: The proposed method was able to explain the clinical predictions using the knowledge graph, thereby making the predictions clinically interpretable. Through enriching EHR data with biomedical associations, SPOKE may be a cost-efficient and personalized way to predict PD diagnosis years before its occurrence., Competing Interests: SEB is cofounder and holds shares in MATE Bioservices, a company that commercializes uses of SPOKE knowledge graph. CAN holds shares of MATE Bioservices. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Soman, Nelson, Cerono, Goldman, Baranzini and Brown.)

Introduction: Congenital diaphragmatic hernia (CDH) repair is an area of active research. Large defects requiring patches have a hernia recurrence rate of up to 50%. We designed a biodegradable polyurethane (PU)-based elastic patch that matches the mechanical properties of native diaphragm muscle. We compared the PU patch to a non-biodegradable Gore-Tex™ (polytetrafluoroethylene) patch., Methods: The biodegradable polyurethane was synthesized from polycaprolactone, hexadiisocyanate and putrescine, and then processed into fibrous PU patches by electrospinning. Rats underwent 4 mm diaphragmatic hernia (DH) creation via laparotomy followed by immediate repair with Gore-Tex™ (n = 6) or PU (n = 6) patches. Six rats underwent sham laparotomy without DH creation/repair. Diaphragm function was evaluated by fluoroscopy at 1 and 4 weeks. At 4 weeks, animals underwent gross inspection for recurrence and histologic evaluation for inflammatory reaction to the patch materials., Results: There were no hernia recurrences in either cohort. Gore-Tex™ had limited diaphragm rise compared to sham at 4 weeks (1.3 mm vs 2.9 mm, p = 0.003), but no difference was found between PU and sham (1.7 mm vs 2.9 mm, p = 0.09). There were no differences between PU and Gore-Tex™ at any time point. Both patches formed an inflammatory capsule, with similar thicknesses between cohorts on the abdominal (Gore-Tex™ 0.07 mm vs. PU 0.13 mm, p = 0.39) and thoracic (Gore-Tex™ 0.3 mm vs. PU 0.6 mm, p = 0.09) sides., Conclusion: The biodegradable PU patch allowed for similar diaphragmatic excursion compared to control animals. There were similar inflammatory responses to both patches. Further work is needed to evaluate long-term functional outcomes and further optimize the properties of the novel PU patch in vitro and in vivo., Level of Evidence: Level II, Prospective Comparative Study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Little is known about the impact of the dopamine system on development of cognitive impairment (CI) in Parkinson disease (PD)., Objectives: We used data from a multi-site, international, prospective cohort study to explore the impact of dopamine system-related biomarkers on CI in PD., Methods: PD participants were assessed annually from disease onset out to 7 years, and CI determined by applying cut-offs to four measures: (1) Montreal Cognitive Assessment; (2) detailed neuropsychological test battery; (3) Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) cognition score; and (4) site investigator diagnosis of CI (mild cognitive impairment or dementia). The dopamine system was assessed by serial Iodine-123 Ioflupane dopamine transporter (DAT) imaging, genotyping, and levodopa equivalent daily dose (LEDD) recorded at each assessment. Multivariate longitudinal analyses, with adjustment for multiple comparisons, determined the association between dopamine system-related biomarkers and CI, including persistent impairment., Results: Demographic and clinical variables associated with CI were higher age, male sex, lower education, non-White race, higher depression and anxiety scores and higher MDS-UPDRS motor score. For the dopamine system, lower baseline mean striatum dopamine transporter values ( P range 0.003-0.005) and higher LEDD over time ( P range <0.001-0.01) were significantly associated with increased risk for CI., Conclusions: Our results provide preliminary evidence that alterations in the dopamine system predict development of clinically-relevant, cognitive impairment in Parkinson's disease. If replicated and determined to be causative, they demonstrate that the dopamine system is instrumental to cognitive health status throughout the disease course., Trial Registration: Parkinson's Progression Markers Initiative is registered with ClinicalTrials.gov (NCT01141023)., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Neuroblastoma, Wilms tumor, and hepatoblastoma are the most common pediatric abdominal malignancies. Management of these diseases is a multidisciplinary process that continues to evolve based on the results of international collaborative trials and advances in understanding of tumor biology. Each of these tumors has unique characteristics and behavior which are reflected in their respective staging systems. It is important for clinicians involved in the care of children with abdominal malignancies to be familiar with current staging guidelines and imaging recommendations. This article reviews the current role of imaging in the management of these common pediatric abdominal malignancies, with emphasis on initial staging., Competing Interests: Declaration of Competing Interest The 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 © 2023. Published by Elsevier Inc.)

Introduction: In attempts to quell the spread of COVID-19, shelter-in-place orders were employed in most states. Increased time at home, in combination with parents potentially balancing childcare and work-from-home duties, may have had unintended consequences on pediatric falls from windows. We aimed to investigate rates of falls from windows among children during the first 6 mo of the COVID-19 pandemic., Methods: Patients <18 y old admitted to three pediatric trauma centers (two - level 1, one - level 2) between 3/19/20 and 9/19/20 (COVID-era) were compared to a pre-COVID cohort (3/19/19 to 9/19/19). The primary outcome was the rate of falls from windows. Secondary outcomes included injury severity score (ISS), injuries sustained, and mortality., Results: Of 1011 total COVID-era pediatric trauma patients, 36 (3.6%) sustained falls from windows compared to 23 of 1108 (2.1%) pre-COVID era patients (OR 1.7, P = 0.05). The median ISS was seven pre-COVID versus four COVID-era (P = 0.43). The most common injuries sustained were skull fractures (30.5%), extremity injuries (30.5%), and intracranial hemorrhage (23.7%). One-fifth of patients underwent surgery (21.7% pre-COVID versus 19.4% COVID-era, P = 1.0). There was one mortality in the COVID-era cohort and none in the pre-COVID cohort (P = 1.0)., Conclusions: Despite overall fewer trauma admissions during the first 6 mo of the COVID-19 pandemic, the rate of falls from windows nearly doubled compared to the prior year, with substantial associated morbidity. These findings suggest a potential unintended consequence of shelter-in-place orders and support increased education on home safety and increased support for parents potentially juggling multiple responsibilities in the home., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The COVID-19 pandemic has widespread effects, including enhanced psychosocial stressors and stay-at-home orders which may be associated with higher rates of child abuse. We aimed to evaluate rates of child abuse, neglect, and inadequate supervision during the COVID-19 pandemic., Methods: Patients ≤5 y old admitted to a level one pediatric trauma center between 3/19/20-9/19/20 (COVID-era) were compared to a pre-COVID cohort (3/19/19-9/19/19). The primary outcome was the rate of child abuse, neglect, or inadequate supervision, determined by Child Protection Team and Social Work consultations. Secondary outcomes included injury severity score (ISS), mortality, and discharge disposition., Results: Of 163 total COVID-era pediatric trauma patients, 22 (13.5%) sustained child abuse/neglect, compared to 17 of 206 (8.3%) pre-COVID era patients (P = 0.13). The ISS was similar between cohorts (median 9 pre-COVID versus 5 COVID-era, P = 0.23). There was one mortality in the pre-COVID era and none during COVID (P = 0.45). The rate of discharge with someone other than the primary caregiver at time of injury was significantly higher pre-COVID (94.1% versus 59.1%, P = 0.02). In addition, foster family placement rate was twice as high pre-COVID (50.0% versus 22.7%, P = 0.10)., Conclusions: The rate of abuse/neglect among young pediatric trauma patients during COVID did not differ compared to pre-pandemic, but discharge to a new caregiver was significantly lower. While likely multifactorial, this data suggests that resources during COVID may have been limited and the clinical significance of this is concerning. Larger studies are warranted to further evaluate COVID-19's effect on this vulnerable population., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Optimal management of pediatric perforated appendicitis remains a topic of active investigation. Our institutional clinical practice guidelines (CPGs) were modified to discontinue antibiotics on discharge for patients with normal white blood cell count (WBC) without left shift. We hypothesized that patients would receive fewer antibiotics without increased complications., Methods: Patients <18 y old with perforated appendicitis who underwent laparoscopic appendectomy between November 1, 2016 and May 31, 2021 at a tertiary care children's hospital were included. Primary outcome was adverse events: postdischarge surgical site infection (SSI), 30-day emergency department (ED) visits, or readmissions. Outcomes were compared before and after CPG modification. Multivariable regression was performed to identify factors associated with SSI., Results: There were 113 patients pre- and 97 patients post-CPG modification. 23.1% of patients in the pre-cohort had an elevated discharge WBC or left shift compared to 18.9% of patients in the post-cohort (P = 0.48). Significantly fewer patients were prescribed antibiotics on discharge in the post-cohort (70.8% pre versus 14.4% post, P < 0.0001) and for fewer days (2 pre versus 0 post, P < 0.0001). Total antibiotic days decreased significantly (6.1 pre versus 4.6 post, P < 0.0001). There was an increase in postdischarge SSIs on univariate analysis (1.8% pre versus 9.3% post, P = 0.03), ED visits (9.7% pre versus 19.6% post, P = 0.04), and readmissions (5.3% pre versus 11.3% post, P = 0.13). On multivariable analysis, being in the post-cohort was not significantly associated with post-discharge SSIs after adjusting for sex, symptom duration, initial WBC, and discharge antibiotic duration (OR 0.25, 95% CI 0.04-1.4, P = 0.11)., Conclusions: Modification of a pediatric perforated appendicitis clinical practice guideline to discontinue antibiotics on discharge with a normal WBC without left shift was effective in decreasing antibiotic duration. This was associated with an increase in SSIs on univariate analysis, which did not persist on multivariable analysis and requires further investigation., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Loneliness has been linked to cardiovascular health outcomes in older adulthood. One proposed mechanism by which loneliness influences cardiovascular health is through atypical cardiovascular reactivity (CVR) to stress. This study is an examination of loneliness and CVR in older adults, comparing associations across two stressors and two commonly used measures of loneliness, with a particular focus on underlying hemodynamic variables including cardiac output, total peripheral resistance, and ejection time (EJT). Eighty older adults, ranging in age from 55 to 88 years (M = 68.93, SD = 8.28), completed two versions of the UCLA loneliness scale (a 20-item and a briefer, three-item) and took part in a laboratory stress-testing procedure which included a mental arithmetic challenge and a public speaking task. Cardiovascular activity was monitored continuously throughout. For the 20-item version of the UCLA loneliness scale, loneliness was not significantly related to CVR, and was only significantly associated with lower levels of overall EJT. For the three-item version of the UCLA, no associations withstood adjustment for multiple testing. Loneliness was not reliably associated with CVR. Further, although greater loneliness was related to lower levels of overall EJT, this was only observed for the 20-item scale. The findings do not strongly provide support for reactivity to acute stress as a pathway linking loneliness to disease outcomes, and highlight key methodological issues related to the assessment of loneliness-reactivity associations for future., (© 2022 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Background and Objectives: There is growing interest in health-related quality of life (HRQOL) as a comprehensive view of the patient's well-being, guiding concept for the treating clinician, and therapeutic trial outcome measure for patients with Parkinson disease (PwPD). The key determinants of HRQOL have not been investigated in large populations of PwPD. Our objective was to evaluate correlates of HRQOL in a large, online cohort of PwPD., Methods: As part of an ongoing online cohort study, we performed a cross-sectional analysis at enrollment of 23,058 PwPD. We conducted univariate and stepwise multivariate linear regression analyses of HRQOL as measured by the EQ-5D-5L tool. In addition, we performed an interaction analysis to evaluate heterogeneity of the effect of motor symptoms on HRQOL and Spearman correlation analysis to evaluate the association of nonmotor symptoms with HRQOL., Results: In the multivariate linear regression model, participants with moderate or severe depression, more severe motor symptoms, and a higher burden of medical comorbidities had the most substantially decreased HRQOL as measured by the EQ index (β -0.11, -0.18, -0.02, -0.01, respectively; p < 0.001 for all). An interaction analysis showed that more severe motor symptoms had a higher effect on individuals with female sex, lower educational level, lower income, more severe depression, or more severe cognitive impairment (p ≤ 0.01 for interaction terms). Neuropsychiatric symptoms and falls had the most negative associations with HRQOL (ρ -0.31 to 0.37; p < 0.0001)., Discussion: Potentially treatable motor and nonmotor symptoms, particularly neuropsychiatric symptoms, account for a large amount of the variation in HRQOL in PwPD. Motor symptoms may have differential effects on HRQOL in different demographic and clinical subpopulations, highlighting important areas for future health disparities research. Our findings provide targets for clinician intervention and future research on symptom management to optimize HRQOL in PD., Classification of Evidence: This study provides Class II evidence that motor and neuropsychiatric symptoms are associated with HRQOL in PwPD., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: People with Parkinson disease (PD) have a variety of complex medical problems that require detailed review at each clinical encounter for appropriate management. Care of other complex conditions has benefited from digital health solutions that efficiently integrate disparate clinical information. Although various digital approaches have been developed for research and care in PD, no digital solution to personalize and improve communication in a clinical encounter is readily available., Objective: We intend to improve the efficacy and efficiency of clinical encounters with people with PD through the development of a platform (PD-BRIDGE) with personalized clinical information from the electronic health record (EHR) and patient-reported outcome (PRO) data., Methods: Using human-centered design (HCD) processes, we engaged clinician and patient stakeholders in developing PD-BRIDGE through three phases: an inspiration phase involving focus groups and discussions with people having PD, an ideation phase generating preliminary mock-ups for feedback, and an implementation phase testing the platform. To qualitatively evaluate the platform, movement disorders neurologists and people with PD were sent questionnaires asking about the technical validity, usability, and clinical relevance of PD-BRIDGE after their encounter., Results: The HCD process led to a platform with 4 modules. Among these, 3 modules that pulled data from the EHR include a longitudinal module showing motor ratings over time, a display module showing the most recently collected clinical rating scales, and another display module showing relevant laboratory values and diagnoses; the fourth module displays motor symptom fluctuation based on an at-home diary. In the implementation phase, PD-BRIDGE was used in 17 clinical encounters for patients cared for by 1 of 11 movement disorders neurologists. Most patients felt that PD-BRIDGE facilitated communication with their clinician (n=14, 83%) and helped them understand their disease trajectory (n=11, 65%) and their clinician's recommendations (n=11, 65%). Neurologists felt that PD-BRIDGE improved their ability to understand the patients' disease course (n=13, 75% of encounters), supported clinical care recommendations (n=15, 87%), and helped them communicate with their patients (n=14, 81%). In terms of improvements, neurologists noted that data in PD-BRIDGE were not exhaustive in 62% (n=11) of the encounters., Conclusions: Integrating clinically relevant information from EHR and PRO data into a visually efficient platform (PD-BRIDGE) can facilitate clinical encounters with people with PD. Developing new modules with more disparate information could improve these complex encounters even further., (©Ethan G Brown, Erica Schleimer, Ian O Bledsoe, William Rowles, Nicolette A Miller, Stephan J Sanders, Katherine P Rankin, Jill L Ostrem, Caroline M Tanner, Riley Bove. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 06.05.2022.)

Background: Testicular germ cell tumors are uncommon tumors that are encountered by pediatric surgeons and urologists and require a knowledge of appropriate contemporary evaluation and surgical and medical management., Method: A review of the recommended diagnostic evaluation and current surgical and medical management of children and adolescents with testicular germ cell tumors based upon recently completed clinical trials was performed and summarized in this article., Results: In this summary of childhood and adolescent testicular germ cell tumors, we review the initial clinical evaluation, surgical and medical management, risk stratification, results from recent prospective cooperative group studies, and clinical outcomes. A summary of recently completed clinical trials by pediatric oncology cooperative groups is provided, and best surgical practices are discussed., Conclusions: Testicular germ cell tumors in children are rare tumors. International collaborations, data-sharing, and enrollment of patients at all stages and risk classifications into active clinical trials will enhance our knowledge of these rare tumors and most importantly improve outcomes of patients with testicular germ cell tumors., Level of Evidence: This is a review article of previously published and referenced level 1 and 2 studies, but also includes expert opinion level 5, represented by the American Pediatric Surgical Association Cancer Committee., (Copyright © 2021. Published by Elsevier Inc.)

Background: Drowning is a leading cause of death in children ≤5 years old. Detailed data on the epidemiology of drowning in this high-risk population can inform preventative efforts. We aimed to study trends in incidence and case fatality rates (CFR) in the USA among young children hospitalised after drowning., Methods: Children ≤5 years old hospitalised in the USA after drowning were identified from the Kids Inpatient Database 2000-2016. Incidence and CFRs by calendar year, age, sex, race/ethnicity and hospital region were calculated. Trends over time were evaluated. Factors associated with fatal drowning were assessed., Results: Among 30 560 804 hospitalised children ≤5 years old, 9261 drowning cases were included. Patients were more commonly male (62.3%) and white (47.4%). Two years old had the highest incidence of hospitalisation after drowning, regardless of race/ethnicity, sex and region. Overall drowning hospitalisations decreased by 49% from 2000 to 2016 (8.38-4.25 cases per 100 000 children). The mortality rate was 11.4% (n=1060), and most occurred in children ≤3 years old (83.0%). Overall case fatality decreased between 2000 and 2016 (risk ratio (RR) 0.44, 95% CI 0.25 to 0.56). The lowest reduction in incidence and case fatality was observed among Black children (Incidence RR 0.92, 95% CI 0.75 to 1.13; case fatality RR 0.80, 95% CI 0.41 to 1.58)., Conclusions: Hospitalisations and CFRs for drowning among children ≤5 years old have decreased from 2000 to 2016. Two years old are at the highest risk of both fatal and non-fatal drowning. Disparities exist for Black children in both the relative reduction in drowning hospitalisation incidence and case fatality. Interventions should focus on providing equitable preventative care measures to this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Identifying pediatric patients who may benefit from gastrostomy tube (GT) placement can be challenging. We hypothesized that many GTs would no longer be in use after 6 months., Methods: Inpatient GT placements in patients < 18 years old at a tertiary children's hospital from 9/2014 to 2/2020 were included. The primary outcome was GT use <6 months (short-term). Secondary outcomes included age at placement, indication for GT, and operations for GT-related issues., Results: Fifteen percent (22/142) of GTs were used for <6 months post-operatively. The median duration of short-term GT use was 1.6 months (IQR 0.9-3.4 months). Short-term GTs were more likely to be placed in patients with traumatic brain injury (TBI) (18.2% vs. 4.2%, p = 0.03) and adolescents (≥12 years old, 22.7% vs. 4.0%, p = 0.005). Gastrocutaneous fistula closure was required in 33.3% of short-term patients who had their GTs removed (n = 6/18), with median total hospital charges of $29,989 per patient., Conclusion: Fifteen percent of pediatric GTs placed as inpatients were used for <6 months, more commonly among adolescents and in TBI patients. One-third of patients with short-term GTs required gastrocutaneous fistula closure. Adolescents and TBI patients may benefit from consideration of short-term nasogastric tube (NGT) feeds rather than surgical GT placement., Level of Evidence: III., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2021. Published by Elsevier Inc.)