NUT carcinoma in pediatric patients: Characteristics, therapeutic regimens, and outcomes of 11 cases registered with the German Registry for Rare Pediatric Tumors (STEP).

BACKGROUND AND AIMS: Nuclear protein of the testis (NUT) carcinoma (NC) is a rare and highly aggressive tumor defined by the presence of a somatic NUTM1 rearrangement, occurring mainly in adolescents and young adults. We analyzed the clinical and biological features of German pediatric patients (≤18 years) with NC. METHODS: This study describes the characteristics and outcome of 11 children with NC registered in the German Registry for Rare Pediatric Tumors (STEP). RESULTS: Eleven patients with a median age of 13.2 years (range 6.6-17.8) were analyzed. Malignant misdiagnoses were made in three patients. Thoracic/mediastinal tumors were found to be the primary in six patients, head/neck in four cases; one patient had multifocal tumor with an unknown primary. All patients presented with regional lymph node involvement, eight patients (72.7%) with distant metastases. Seven patients underwent surgery, eight radiotherapy with curative intent; polychemotherapy was administered in all patients. Novel treatment strategies including immunotherapy, targeted therapies, and virotherapy were applied in three patients. Median event-free survival and overall survival were 1.5 and 6.5 months, respectively. CONCLUSIONS: Every undifferentiated or poorly differentiated carcinoma should undergo testing for the specific rearrangement of NUTM1, in order to initiate an intense therapeutic regimen as early as possible. As in adults, only few pediatric patients with NC achieve prolonged survival. Thus, novel therapeutic strategies should be included and tested in clinical trials.

Frontopolar multifocal transcranial direct current stimulation reduces conditioned fear reactivity during extinction training: A pilot randomized controlled trial.

Exposure-based therapies for anxiety and related disorders are believed to depend on fear extinction learning and corresponding changes in extinction circuitry. Frontopolar multifocal transcranial direct current stimulation (tDCS) has been shown to improve therapeutic safety learning during in vivo exposure and may modulate functional connectivity of networks implicated in fear processing and inhibition. A pilot randomized controlled trial was completed to determine the effects of frontopolar tDCS on extinction learning and memory. Community volunteers (n = 35) completed a 3-day fear extinction paradigm with measurement of electrodermal activity. Participants were randomized (single-blind) to 20-min of sham (n = 17, 30 s. ramp in/out) or active (n = 18) frontopolar (anode over Fpz, 10-10 EEG) multifocal tDCS (20-min, 1.5 mA) prior to extinction training. Mixed ANOVAs revealed a significant group*trial effect on skin conductance response (SCR) to the conditioned stimulus (CS + ) during extinction training (p = 0.007, Cohen's d = 0.55). The effects of frontopolar tDCS were greatest during the first two extinction trials, suggesting that tDCS may have promoted fear inhibition prior to safety learning. Return of fear to the CS + during tests were comparable across conditions (ps > 0.50). These findings suggest that frontopolar tDCS may modulate the processing of threat cues and associated circuitry or promote the inhibition of fear. This has clear implications for the treatment of anxiety and related disorders with therapeutic exposure.

Perioperative Risk Assessment in Humanitarian Settings: A Scoping Review.

BACKGROUND: No validated perioperative risk assessment models currently exist for use in humanitarian settings. To inform the development of a perioperative mortality risk assessment model applicable to humanitarian settings, we conducted a scoping review of the literature to identify reports that described perioperative risk assessment in surgical care in humanitarian settings and LMICs. METHODS: We conducted a scoping review of the literature to identify records that described perioperative risk assessment in low-resource or humanitarian settings. Searches were conducted in databases including: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science, World Health Organization Catalog, and Google Scholar. RESULTS: Our search identified 1582 records. After title/abstract and full text screening, 50 reports remained eligible for analysis in quantitative and qualitative synthesis. These reports presented data from over 37 countries from public, NGO, and military facilities. Data reporting was highly inconsistent: fewer than half of reports presented the indication for surgery; less than 25% of reports presented data on injury severity or prehospital data. Most elements of perioperative risk models designed for high-resource settings (e.g., vital signs, laboratory data, and medical comorbidities) were unavailable. CONCLUSION: At present, no perioperative mortality risk assessment model exists for use in humanitarian settings. Limitations in consistency and quality of data reporting are a primary barrier, however, can be addressed through data-driven identification of several key variables encompassed by a minimum dataset. The development of such a score is a critical step toward improving the quality of care provided to populations affected by conflict and protracted humanitarian crises.

Operative Trauma Courses: A Scoping Review to Inform the Development of a Trauma Surgery Course for Low-Resource Settings.

BACKGROUND: A multitude of operative trauma courses exist, most of which are designed for and conducted in high-resource settings. There are numerous barriers to adapting such courses to low- and low-middle-income countries (LMICs), including resource constraints and contextual variations in trauma care. Approaches to implementing operative trauma courses in LMICs have not been evaluated in a structured manner. METHODS: We conducted a scoping review of the literature including databases (e.g., PubMed, Web of Science, EMBASE), grey literature repositories, and structured queries of publicly available course materials to identify records that described operative trauma courses offered since 2000. RESULTS: The search identified 3,518 non-duplicative records, of which 48 relevant reports were included in analysis. These reports represented 23 named and 11 unnamed operative trauma courses offered in 12 countries. Variability existed in course format and resource requirements, ranging from USD 40 to 3,000 per participant. Courses incorporated didactic and laboratory components, which utilized simulations, cadavers, or live animals. Course content overlapped significantly but was not standardized. Data were lacking on course implementation and promulgation, credentialing of instructors, and standardized evaluation metrics. CONCLUSIONS: While many operative trauma courses have been described, most are not directly relatable to LMICs. Barriers include cost-prohibitive fees, lack of resources, limited data collection, and contextual variability that renders certain surgical care inappropriate in LMICs. Gaps exist in standardization of course content as well as transparency of credentialing and course implementation strategies. These issues can be addressed through developing an open-access operative trauma course for low-resource settings.

Characterization of Humanitarian Trauma Care by US Military Facilities During Combat Operations in Afghanistan and Iraq.

OBJECTIVE: To characterize humanitarian trauma care delivered by US military treatment facilities (MTFs) in Afghanistan and Iraq during combat operations. BACKGROUND: International Humanitarian Law, which includes the Geneva Conventions, defines protections and standards of treatment to victims of armed conflicts. In 1949, these standards expanded to include injured civilians. In 2001, the Global War on Terror began in Afghanistan and expanded to Iraq in 2003. US MTFs provided care to all military forces, civilians, and enemy prisoners. A thorough understanding of the scope, epidemiology, resource requirements, and outcomes of civilian trauma in combat zones has not been previously characterized. METHODS: Retrospective cohort analysis of the Department of Defense Trauma Registry from 2005 to 2019. Inclusion criteria were civilians and Non-North Atlantic Treaty Organization (NATO) Coalition Personnel (NNCP) with traumatic injuries treated at MTFs in Afghanistan and Iraq. Patient demographics, mechanism of injury, resource requirements, procedures, and outcomes were categorized. RESULTS: A total of 29,963 casualties were eligible from the Registry. There were 16,749 (55.9%) civilians and 13,214 (44.1%) NNCP. The majority of patients were age above 13 years [26,853 (89.6%)] and male [28,000 (93.4%)]. Most injuries were battle-related: 12,740 (76.1%) civilians and 11,099 (84.0%) NNCP. Penetrating trauma was the most common cause of both battle and nonbattle injuries: 12,293 (73.4%) civilian and 10,029 (75.9%) NNCP. Median Injury Severity Score (ISS) was 9 in each cohort with ISS≥25 in 2236 (13.4%) civilians and 1398 (10.6%) NNCP. Blood products were transfused to 35% of each cohort: 5850 civilians received a transfusion with 2118 (12.6%) of them receiving ≥10 units; 4590 NNCPs received a transfusion with 1669 (12.6%) receiving ≥10 units. MTF mortality rates were civilians 1263 (7.5%) and NNCP 776 (5.9%). Interventions, both operative and nonoperative, were similar between both groups. CONCLUSIONS: In accordance with International Humanitarian Law, as well as the US military's medical rules of eligibility, civilians injured in combat zones were provided the same level of care as NNCP. Injured civilians and NNCP had similar mechanisms of injury, injury patterns, transfusion needs, and ISS. This analysis demonstrates resource equipoise in trauma care delivered to civilians and NNCP. Hospitals in combat zones must be prepared to manage large numbers of civilian casualties with significant human and material resources allocated to optimize survival. The provision of humanitarian trauma care is resource-intensive, and these data can be used to inform planning factors for current or future humanitarian care in combat zones.

Simultaneous EEG and pupillary evidence for post-error arousal during a speeded performance task.

Arousal evoked by detecting a performance error may provide a mechanism by which error detection leads to either adaptive or maladaptive changes in attention and performance. By pairing EEG data acquisition with simultaneous measurements of pupil diameter, which is thought to reflect norepinephrinergic arousal, this study tested whether transient changes in EEG oscillations in the alpha frequency range (8-12 Hz) following performance mistakes may reflect error-evoked arousal. In the inter-trial interval following performance mistakes (approximately 8% of trials), pupil diameter increased and EEG alpha power decreased, compared to the inter-trial interval following correct responses. Moreover when trials were binned based on pupil diameter on a within-subjects basis, trials with greater pupil diameter were associated with lower EEG alpha power during the inter-trial interval. This pattern of association suggests that error-related alpha suppression, like pupil dilation, reflects arousal in response to error commission. Errors were also followed by worse next-trial performance, implying that error-evoked arousal may not always be beneficial for adaptive control.

Health interventions among mobile pastoralists: a systematic review to guide health service design.

OBJECTIVE: Mobile pastoralists are one of the last populations to be reached by health services and are frequently missed by health campaigns. Since health interventions among pastoralists have been staged across a range of disciplines but have not yet been systematically characterised, we set out to fill this gap. METHODS: We conducted a systematic search in PubMed/MEDLINE, Scopus, Embase, CINAL, Web of Science, WHO Catalog, AGRICOLA, CABI, ScIELO, Google Scholar and grey literature repositories to identify records that described health interventions, facilitators and barriers to intervention success, and factors influencing healthcare utilisation among mobile pastoralists. No date restrictions were applied. Due to the heterogeneity of reports captured in this review, data were primarily synthesised through narrative analysis. Descriptive statistical analysis was performed for data elements presented by a majority of records. RESULTS: Our search yielded 4884 non-duplicate records, of which 140 eligible reports were included in analysis. 89.3% of reports presented data from sub-Saharan Africa, predominantly in East Africa (e.g. Ethiopia, 30.0%; Kenya, 17.1%). Only 24.3% of reports described an interventional study, while the remaining 75.7% described secondary data of interest on healthcare utilisation. Only two randomised controlled trials were present in our analysis, and only five reports presented data on cost. The most common facilitators of intervention success were cultural sensitivity (n = 16), community engagement (n = 12) and service mobility (n = 11). CONCLUSION: Without adaptations to account for mobile pastoralists' unique subsistence patterns and cultural context, formal health services leave pastoralists behind. Research gaps, including neglect of certain geographic regions, lack of both interventional studies and diversity of study design, and limited data on economic feasibility of interventions must be addressed to inform the design of health services capable of reaching mobile pastoralists. Pastoralist-specific delivery strategies, such as combinations of mobile and 'temporary fixed' services informed by transhumance patterns, culturally acceptable waiting homes, community-directed interventions and combined joint human-animal One Health design as well as the bundling of other health services, have shown initial promise upon which future work should build.

OBJECTIF: Les éleveurs nomades sont l'une des dernières populations à être touchées par les services de santé et sont souvent ratés par les campagnes de santé. Etant donné que les interventions de santé parmi ces éleveurs ont été programmées dans une gamme de disciplines mais n'ont pas encore été systématiquement caractérisées, nous avons entrepris de combler cette lacune. MÉTHODES: Nous avons effectué une recherche systématique dans les répertoires PubMed/MEDLINE, Scopus, EMBASE, CINAL, Web of Science, WHO Catalog, AGRICOLA, CABI, ScIELO, Google Scholar et de la littérature grise pour identifier les reports décrivant les interventions de santé, les facilitateurs et les obstacles au succès de l'intervention ainsi que les facteurs influençant l'utilisation des soins de santé chez les éleveurs nomades. Aucune restriction de date n'a été appliquée. En raison de l'hétérogénéité des rapports capturés dans cette revue, les données ont été principalement synthétisées au moyen d'une analyse narrative. Une analyse statistique descriptive a été effectuée pour les éléments de données présentés par une majorité des reports. RÉSULTATS: Notre recherche a révélé 4.884 rapports non dupliqués, dont 140 éligibles ont été inclus dans l'analyse. 89,3% des rapports présentaient des données d'Afrique subsaharienne, principalement en Afrique de l'Est (ex: Ethiopie, 30,0%; Kenya, 17,1%). Seuls 24,3% des rapports décrivaient une étude interventionnelle, tandis que les 75,7% restants décrivaient des données d'intérêt secondaires sur l'utilisation des soins de santé. Seuls deux essais contrôlés randomisés étaient présents dans notre analyse, et seuls cinq rapports présentaient des données sur le coût. Les facilitateurs les plus courants du succès des interventions étaient la sensibilité culturelle (n=16), l'engagement communautaire (n=12) et la mobilité des services (n=11). CONCLUSION: Sans adaptations pour tenir compte des modèles de subsistance et du contexte culturel uniques des éleveurs nomades, les services de santé formels les laissent de côté. Les lacunes de la recherche, y compris la négligence de certaines régions géographiques, le manque d'études interventionnelles et la diversité de la conception des études, et les données limitées sur la faisabilité économique des interventions doivent être comblées pour éclairer la conception de services de santé capables d'atteindre les éleveurs nomades. Des stratégies de prestation spécifiques aux éleveurs nomades, telles que des combinaisons de services mobiles et «fixes temporaires¼ éclairés par des schémas de transhumance, des maisons d'attente culturellement acceptables, des interventions dirigées par la communauté et une conception conjointe d'une seule santé homme-animal ainsi que le regroupement d'autres services de santé, ont montré une promesse initiale sur laquelle les travaux futurs devraient s'appuyer.

Epidemiology of Injuries Sustained by Civilians and Local Combatants in Contemporary Armed Conflict: An Appeal for a Shared Trauma Registry Among Humanitarian Actors.

BACKGROUND: Conflict-related injuries sustained by civilians and local combatants are poorly described, unlike injuries sustained by US, North Atlantic Treaty Organization, and coalition military personnel. An understanding of injury epidemiology in twenty-first century armed conflict is required to plan humanitarian trauma systems capable of responding to population needs. METHODS: We conducted a systematic search of databases (e.g., PubMed, Embase, Web of Science, World Health Organization Catalog, Google Scholar) and grey literature repositories to identify records that described conflict-related injuries sustained by civilians and local combatants since 2001. RESULTS: The search returned 3501 records. 49 reports representing conflicts in 18 countries were included in the analysis and described injuries of 58,578 patients. 79.3% of patients were male, and 34.7% were under age 18 years. Blast injury was the predominant mechanism (50.2%), and extremities were the most common anatomic region of injury (33.5%). The heterogeneity and lack of reporting of data elements prevented pooled analysis and limited the generalizability of the results. For example, data elements including measures of injury severity, resource utilization (ventilator support, transfusion, surgery), and outcomes other than mortality (disability, quality of life measures) were presented by fewer than 25% of reports. CONCLUSIONS: Data describing the needs of civilians and local combatants injured during conflict are currently inadequate to inform the development of humanitarian trauma systems. To guide system-wide capacity building and quality improvement, we advocate for a humanitarian trauma registry with a minimum set of data elements.

The wandering mind oscillates: EEG alpha power is enhanced during moments of mind-wandering.

What is your brain doing while your mind is wandering? This study used a within-subjects experience-sampling design to test whether episodes of mind-wandering during a demanding cognitive task are associated with increases in EEG alpha power. Alpha refers to cyclic oscillations in EEG activity at 8-12 Hz, and has been previously correlated with internally rather than externally directed cognition. Participants completed a speeded performance task with more than 800 trials while EEG was recorded. Intermittent experience-sampling probes asked participants to indicate whether their mind was wandering or on-task. Participants reported mind-wandering in response to approximately half of the probes. EEG alpha power was significantly higher preceding probes to which participants reported mind-wandering, compared with probes to which participants reported being on task. These findings imply that dynamic changes in alpha power may prove a valuable tool in studying momentary fluctuations in mind-wandering.

Assessment of Comorbid Obsessive-Compulsive Disorder and Posttraumatic Stress Disorder.

Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) are commonly comorbid and share prominent features (e.g., intrusions, safety behaviors, and avoidance). Excellent self-report and clinician-administered assessments exist for OCD and PTSD individually, but few assess both disorders, and even fewer provide instruction on differential diagnosis or detection of comorbid OCD and PTSD. To address this gap in the literature, the current paper aims to (1) highlight diagnostic and functional similarities and differences between OCD and PTSD to inform differential diagnosis, (2) outline assessment recommendations for individuals with suspected comorbid OCD and PTSD, OCD with a significant trauma history or posttraumatic symptoms, or PTSD with significant obsessive-compulsive symptoms, and (3) explore future directions to evaluate and improve methods for assessing co-occurring OCD and PTSD.

Characterization of PRAME immunohistochemistry reveals lower expression in pediatric melanoma compared to adult melanoma.

Pediatric melanomas are rare tumors that have clinical and histological differences from adult melanomas. In adult melanoma, the immunohistochemical marker PRAME is increasingly employed as a diagnostic adjunct. PRAME is also under investigation as a target structure for next-generation immunotherapies including T-cell engagers. Little is known about the characteristics of PRAME expression in pediatric melanoma. In this retrospective study, samples from 25 pediatric melanomas were compared with control groups of melanomas in young adults (18-30 years; n = 32), adult melanoma (>30 years, n = 30), and benign melanocytic nevi in children (0-18 years; n = 30) with regard to the immunohistochemical expression of PRAME (diffuse PRAME expression >75%/absolute expression). Pediatric melanomas show lower diffuse PRAME expression (4%) and lower absolute PRAME expression (25%) compared to young adult melanomas (15.6%/46.8%) and adult melanomas (50%/70%). A significant age-dependent expression could be observed. An analysis of event-free survival shows no prognostic role for PRAME in pediatric melanoma and young adult melanoma, but a significant association with diffuse PRAME expression in adulthood. The age dependency of PRAME expression poses a potential pitfall in the diagnostic application of melanocytic tumors in young patients and may limit therapeutic options within this age group. The immunohistochemical expression of the tumor-associated antigen PRAME is an increasingly important diagnostic marker for melanocytic tumors and is gaining attention as a possible immunotherapeutic target in melanoma. As the available data primarily stem from adult melanoma, and given the clinical and histological distinctions in pediatric melanomas, our understanding of PRAME expression in this specific patient group remains limited. The age-dependent low PRAME expression shown here constrains the use of this marker in pediatric melanoma and may also limit the use of immunotherapeutic strategies against PRAME in young patients.

Expression of the tumor antigens NY-ESO-1, tyrosinase, MAGE-A3, and TPTE in pediatric and adult melanoma: a retrospective case control study.

Tumor-associated antigens (TAAs) are potential targets for T cell-based immunotherapy approaches in cutaneous melanoma. BNT111, an investigational lipoplex-formulated mRNA-based therapeutic cancer vaccine encoding melanoma TAAs NY-ESO-1, tyrosinase, MAGE-A3, and TPTE, is undergoing clinical testing in adults. Expression of these TAAs in pediatric melanoma is unclear but is a prerequisite for feasibility of this treatment approach in children with melanoma. Our main objective was to characterize expression of those TAAs in pediatric melanomas compared to control cohorts. In this retrospective case control study, protein and transcript expression of NY-ESO-1, tyrosinase, MAGE-A3, and TPTE were analyzed in a cohort of 25 pediatric melanomas, 31 melanomas of young adults, 29 adult melanomas, and 30 benign melanocytic nevi in children using immunohistochemical staining and digital pathology (QuPath) and reverse transcription quantitative PCR. Based on IHC analysis, pediatric melanomas expressed tyrosinase (100.0%), TPTE (44.0%), MAGE-A3 (12.0%), and NY-ESO-1 (8.0%). Young adult melanomas expressed tyrosinase (96.8%), NY-ESO-1 (19.4%), MAGE-A3 (19.4%), and TPTE (3.2%). Adult melanomas expressed tyrosinase (86.2%), MAGE-A3 (75.9%), NY-ESO-1 (48.3%), and TPTE (48.3%). Childhood melanocytic nevi only expressed tyrosinase (93.3%). Expression prevalence of individual TAAs did not differ between subtypes of pediatric melanoma, and no association with prognosis was found. All four TAAs were expressed in pediatric melanoma, albeit NY-ESO-1 and MAGE-A3 to a lesser extent than in adult melanoma. These data support the possibility of investigating vaccines targeting these TAAs for the treatment of pediatric melanoma.

Latent classes of symptom trajectories during partial hospitalization for major depressive disorder and generalized anxiety disorder.

BACKGROUND: A variety of treatments have been empirically validated in the treatment of major depressive disorder and generalized anxiety disorder. Researchers commonly evaluate symptom change during treatment using single model curves, however, modeling multiple curves simultaneously allows for the identification of subgroups of patients that progress through treatment on distinct paths. METHODS: Latent growth mixture modeling was used to identify and characterize distinct classes of symptom trajectories among two samples of patients with either MDD or GAD receiving treatment in a daily partial hospital program. RESULTS: Four depression symptom trajectories were identified in the MDD sample, and three anxiety symptom trajectories were identified in the GAD sample. Both samples shared symptom trajectory classes of responders, rapid responders, and minimal responders, while the MDD sample demonstrated an additional class of early rapid responders. In both samples, low symptom severity at baseline was associated with membership in the responder class, though few other patterns emerged in baseline characteristics predicting trajectory class membership. At treatment discharge, those in the minimal responder class reported poorer outcomes on every clinical measure. Patients within each class reported similar scores at discharge as compared to each other class, indicating that class membership affects clinical measures beyond symptom severity. LIMITATIONS: Patient demographic characteristics were relatively homogeneous. Group-based trajectory modeling inherently involves some degree of uncertainty regarding the number and shape of trajectories. CONCLUSIONS: Identifying symptom trajectories can provide information regarding how patients are likely to progress through treatment, and thus inform clinicians when a patient deviates from expected progress.

Disparities in detection of suspected child abuse.

BACKGROUND: Child abuse is a significant cause of injury and death among children, but accurate identification is often challenging. This study aims to assess whether racial disparities exist in the identification of child abuse. METHODS: The 2010-2014 and 2016-2017 National Trauma Data Bank was queried for trauma patients ages 1-17. Using ICD-9CM and ICD-10CM codes, children with injuries consistent with child abuse were identified and analyzed by race. RESULTS: Between 2010-2014 and 2016-2017, 798,353 patients were included in NTDB. Suspected child abuse victims (SCA) accounted for 7903 (1%) patients. Of these, 51% were White, 33% Black, 1% Asian, 0.3% Native Hawaiian/Other Pacific Islander, 2% American Indian, and 12% other race. Black patients were disproportionately overrepresented, composing 12% of the US population, but 33% of SCA patients (p < 0.001). Although White SCA patients were more severely injured (ISS 16-24: 20% vs 16%, p < 0.01) and had higher in-hospital mortality (9% vs. 6%, p = 0.01), Black SCA patients were hospitalized longer (7.2 ± 31.4 vs. 6.2 ± 9.9 days, p < 0.01) despite controlling for ISS (1-15: 4. 5.7 ± 35.7 vs. 4.2 ± 6.2 days, p < 0.01). In multivariate regression, Black children continued to have longer lengths of stay despite controlling for ISS and insurance type. CONCLUSIONS: Utilizing a nationally representative dataset, Black children were disproportionately identified as potential victims of abuse. They were also subjected to longer hospitalizations, despite milder injuries. Further studies are needed to better understand the etiology of the observed trends and whether they reflect potential underlying unconscious or conscious biases of mandated reporters. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: III.

UV-radiation and MC1R germline mutations are risk factors for the development of conventional and spitzoid melanomas in children and adolescents.

BACKGROUND: Genomic characterisation has led to an improved understanding of adult melanoma. However, the aetiology of melanoma in children is still unclear and identifying the correct diagnosis and therapeutic strategies remains challenging. METHODS: Exome sequencing of matched tumour-normal pairs from 26 paediatric patients was performed to study the mutational spectrum of melanomas. The cohort was grouped into different categories: spitzoid melanoma (SM), conventional melanoma (CM), and other melanomas (OT). FINDINGS: In all patients with CM (n = 10) germline variants associated with melanoma were found in low to moderate melanoma risk genes: in 8 patients MC1R variants, in 2 patients variants in MITF, PTEN and BRCA2. Somatic BRAF mutations were detected in 60% of CMs, homozygous deletions of CDKN2A in 20%, TERTp mutations in 30%. In the SM group (n = 12), 5 patients carried at least one MC1R variant; somatic BRAF mutations were detected in 8.3%, fusions in 25% of the cases. No SM showed a homozygous CDKN2A deletion nor a TERTp mutation. In 81.8% of the CM/SM cases the UV damage signatures SBS7 and/or DBS1 were detected. The patient with melanoma arising in giant congenital nevus (CNM) demonstrated the characteristic NRAS Q61K mutation. INTERPRETATION: UV-radiation and MC1R germline variants are risk factors in the development of conventional and spitzoid paediatric melanomas. Paediatric CMs share genomic similarities with adult CMs while the SMs differ genetically from the CM group. Consistent genetic characterization of all paediatric melanomas will potentially lead to better subtype differentiation, treatment, and prevention in the future. FUNDING: Found in Acknowledgement.

Strengthening the emergency health response to children wounded by explosive weapons in conflict.

The 2022 war in Ukraine has highlighted the unacceptable consequences wrought on civilians and health infrastructure by conflict. Children are among the most vulnerable of those affected and constitute an increasing percentage of non-combatants injured in conflicts globally. A disproportionate number of these injuries are caused by blast mechanisms from munitions including 'conventional' landmines and indiscriminate explosive weapons such as barrel bombs and improvised explosive devices. In 21st century conflict, children are no longer only accidental casualties of war, but are increasingly targeted by parties through acts such as bombing of school buses and playgrounds, conscription as child soldiers, and use as human shields. In the present viewpoint article, we review the state of pediatric blast injury studies, synthesizing current understandings of injury epidemiology and identifying gaps in research to advance the field towards a concrete agenda to improve care for this vulnerable population.