Adult Counterparts Research Articles

Affective and Behavioral Characteristics of Adolescent and Adult Borderline Personality Disorder.

Adults with borderline personality disorder (BPD) report greater affective lability, impulsivity, and aggression compared to same-age peers, but no studies have examined whether these findings are replicable among adolescents with BPD and their peers, or whether adolescents and adults with BPD report symptoms of comparable severity. One hundred and one adolescent (age 13-17) BPD inpatients and 60 age-matched, psychiatrically healthy adolescents completed self-report measures for affective lability, impulsivity, and aggression. Comparison samples included 29 and 41 adult outpatients with BPD and 127 community adults with BPD. Adolescents with BPD reported greater severity of all symptoms except nonplanning impulsiveness compared to peers. They reported similar symptom severity to adults but reported less severe verbal aggression and anger. Adolescents with BPD are distinguishable from typically developing adolescents on self-reported, dimensional affective and behavioral symptom measures, and may experience these symptoms at comparable severity to adult counterparts.

HGG-11. HIGH-GRADE GLIOMAS IN ADOLESCENTS AND YOUNG ADULTS HIGHLIGHT HISTOMOLECULAR DIFFERENCES WITH THEIR ADULT AND PAEDIATRIC COUNTERPARTS

BACKGROUNDConsidering that paediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs).METHODSWe performed a multicentric retrospective study of 112 AYAs from adult and paediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyse their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25-years, histopathological HGG diagnosis, available clinical data, pre-operative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next generation sequencing, whole exome sequencing and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 WHO classification.RESULTSBased on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of paediatric-subtypes (Histone H3-mutants, 40%) but also adult-subtypes (IDH-mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH-mutant and 1p/19q co-deleted and the relative high frequency of “rare adult IDH mutations” (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, the non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance.CONCLUSIONSHGGs in AYAs could benefit from a more personalized neuro-oncological management, driven by molecular subtyping rather than age group. Collaborative efforts are needed from paediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.

IMG-03. RESPONSE ASSESSMENT IN PEDIATRIC LOW-GRADE GLIOMA: RECOMMENDATIONS FROM THE RESPONSE ASSESSMENT IN PEDIATRIC NEURO-ONCOLOGY (RAPNO) WORKING GROUP

INTRODUCTIONPediatric low-grade gliomas (pLGG) show clinical and biological features that are distinct from their adult counterparts. Consequently, additional considerations are needed for response assessment in children compared to the established adult Response Assessment in Neuro-Oncology (RANO) criteria. Standardized response criteria in pediatric clinical trials are lacking, complicating comparisons of responses across studies. We therefore established an international committee of the Radiologic Assessment in Pediatric Neuro-Oncology (RAPNO) working group to develop consensus recommendations for response assessment in pLGG.METHODSThe committee consisted of 25 international experts in the areas of Pediatric Neuro-Oncology, Neuroradiology and Neurosurgery. The committee first developed a set of agreed upon topics they deemed necessary to understand the controversies of imaging utilization and assessment in pLGG. These topics were divided up among the committee members who presented all available literature to the entire RAPNO committee via web teleconference. Once presented, the group discussed these data and developed consensus statements and recommendations based on available literature, committee expertise and clinical experience. Each topic was discussed until a consensus was reached.RESULTSFinal consensus included recommendations about the following topics: specific imaging sequences, advanced imaging techniques, NF1-associated pLGG, molecular and histologic classification, assessment of cysts, vision and other functional outcomes as well as overall radiologic response assessment.CONCLUSIONSThe RAPNO pLGG consensus establishes systemic recommendations that represent an initial effort to uniformly collect and assess response in pLGG. These recommendations should now be evaluated internationally and prospectively in an effort to assess clinical utility, validate and modify as appropriate.

Bioaccumulation of legacy and emerging organophosphorus flame retardants and plasticizers in insects during metamorphosis

Seven insect taxa belonging to five different orders were collected from a former Chinese e-waste dumping site to investigate the occurrences of organophosphorus flame retardants (PFRs) and plasticizers. The total PFR and plasticizer concentrations were in the ranges of 2.3–91 ng/g ww (median: 20 ng/g ww) and 420–15600 ng/g ww (4040 ng/g ww), respectively. The contaminant patterns varied greatly among different insect taxa owing to their specific habitats and feeding habits. The larvae of litchi stinkbugs and grasshoppers exhibited significantly higher PFR concentrations than their adult counterparts. In contrast, the adults of butterflies, moths, and dragonflies exhibited significantly higher PFR concentrations than their larvae. Additionally, negative linear correlations were frequently observed between the ratios of PFR and plasticizer concentrations in adult to larva (A/L) and log KOW in the four studied insect taxa, which were different from those corresponding to persistent organic pollutants. Notably, the contaminant concentrations of dragonfly ecdysis were significantly higher than those of dragonfly larvae, indicating that ecdysis is an important pathway by which dragonflies remove PFRs and plasticizers.

Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells

The ever-increasing therapeutic and pharmaceutical demand for liver cells calls for systems that enable mass production of hepatic cells. Here we describe a large-scale suspension system that uses human endoderm stem cells (hEnSCs) as precursors to generate functional and transplantable hepatocytes (E-heps) or cholangiocytes (E-chos). hEnSC-derived hepatic populations are characterized by single-cell transcriptomic analyses and compared with hESC-derived counterparts, in-vitro-maintained or -expanded primary hepatocytes and adult cells, which reveals that hepatic differentiation of hEnSCs recapitulates invivo development and that the heterogeneities of the resultant populations can be manipulated by regulating the EGF and MAPK signaling pathways. Functional assessments demonstrate that E-heps and E-chos possess properties comparable with adult counterparts and that, when transplanted intraperitoneally, encapsulated E-heps were able to rescue rats with acute liver failure. Our study lays the foundation for cell-based therapeutic agents and invitro applications for liver diseases.

Predictors of outcome in pleomorphic xanthoastrocytoma.

Pleomorphic xanthoastrocytomas (PXA) are circumscribed gliomas that typically have a favorable prognosis. Limited studies have revealed factors affecting survival outcomes in PXA. Here, we analyzed the largest PXA dataset in the literature and identify factors associated with outcomes. Using the Surveillance, Epidemiology, and End Results (SEER) 18 Registries database, we identified histologically confirmed PXA patients between 1994 and 2016. Overall survival (OS) was analyzed using Kaplan-Meier survival and multivariable Cox proportional hazard models. In total, 470 patients were diagnosed with PXA (males = 53%; median age = 23 years [14-39 years]), the majority were Caucasian (n = 367; 78%). The estimated mean OS was 193 months [95% CI: 179-206]. Multivariate analysis revealed that greater age at diagnosis (≥39 years) (3.78 [2.16-6.59], P < .0001), larger tumor size (≥30 mm) (1.97 [1.05-3.71], P = .034), and postoperative radiotherapy (RT) (2.20 [1.31-3.69], P = .003) were independent predictors of poor OS. Pediatric PXA patients had improved survival outcomes compared to their adult counterparts, in which chemotherapy (CT) was associated with worse OS. Meanwhile, in adults, females and patients with temporal lobe tumors had an improved survival; conversely, tumor size ≥30 mm and postoperative RT were associated with poor OS. In PXA, older age and larger tumor size at diagnosis are risk factors for poor OS, while pediatric patients have remarkably improved survival. Postoperative RT and CT appear to be ineffective treatment strategies while achieving GTR confer an improved survival in male patients and remains the cornerstone of treatment. These findings can help optimize PXA treatment while minimizing side effects. However, further studies of PXAs with molecular characterization are needed.

Molecular Profiling of Pediatric and Adult Glioblastoma.

Although glioblastoma (GBM) is rare in the pediatric population, it is the most common cause of death among children with central nervous system neoplasms. Recent molecular profiling of these neoplasms has demonstrated distinct differences in comparison to their adult counterparts. Moreover, many pediatric GBMs occur within the context of cancer predisposition syndromes, such as constitutional mismatch repair deficiency syndrome (CMMRD). Children with CMMRD who develop GBM exhibit a high tumor mutational burden and may benefit from treatment with immune checkpoint inhibitors. We performed next-generation sequencing and immunohistochemistry for mismatch repair proteins in our cohort of pediatric and adult GBMs to further characterize the molecular profiles of these groups. We examined a total of 11 pediatric and 11 adult GBMs. Pediatric patients had a higher number of alterations compared to their adult counterparts. They also had a higher frequency of alterations in the mismatch repair genes, which can be detected by immunohistochemistry (IHC). We also identified one pediatric patient with CMMRD syndrome. Our study highlighted the distinct molecular differences between pediatric and adult GBM. We also demonstrated that pediatric patients have a higher frequency of alterations in the mismatch repair genes, which may render them susceptible to treatment with immune checkpoint inhibitors. These alterations can be detected using routine IHC and should be performed on all pediatric GBM.

Effect of adenotonsillectomy in children with obstructive sleep apnea and major psychiatric disorders on obstructive apnea-hypopnea index and Epworth Sleepiness Scale scores.

This study evaluates the effectiveness of adenotonsillectomy in the treatment of obstructive sleep apnea in children with major psychiatric disorders as measured by polysomnography and the Epworth Sleepiness Scale (ESS) at a tertiary children's hospital. Adults with major psychiatric disorders often have higher rates of obstructive sleep apnea and decreased response to treatment. The goal was to determine if children with serious mental illness had outcomes similar to their adult counterparts. A retrospective chart review was undertaken to identify children with obstructive sleep apnea and major psychiatric disorders who underwent adenotonsillectomy as part of their treatment for obstructive sleep apnea and had undergone preoperative and postoperative polysomnography as well as ESS. A multivariable model was run for each of the postoperative outcomes (ESS, obstructive apnea-hypopnea index, or body mass index percentile), adjusting for their respective preoperative value, age, and group. There were 34 patients who qualified for this study and who were matched with 66 controls. There was no significant difference between the 2 groups in terms of change in ESS, obstructive apnea-hypopnea index, or body mass index percentile, both before and after adjusting for age. The only significant findings were that preoperative ESS and body mass index percentile were predictive of postoperative ESS and body mass index percentile for both groups. Children with psychiatric disorders in our institution respond to surgical management of obstructive sleep apnea similar to pediatric controls without mental illness despite comorbidities and central-acting medications that may alter sleep.

Child marriage and its impact on fertility and fertility-related outcomes in South Asian countries

Although South Asia (SA) is reported as a home of child marriage, the association of child marriage with fertility and fertility-related outcomes in this region is poorly explored. The most recent data of the Demographic and Health Survey of six SA countries – Afghanistan, Bangladesh, India, Maldives, Nepal and Pakistan – have been used in this article. The unit of analysis is 584,213 currently married women aged 20–49. The outcomes of interest are fertility and fertility-outcomes. Quantitatively important and reliable estimates were obtained from the statistical analyses. The results are presented by odds ratios with 95% CIs. Findings reveal that, overall, 42.1% of the respondents were married-off before age 18. The prevalence of child marriage was lowest in the Maldives and highest in Bangladesh at 20.5% and 74.4% respectively. The likelihood of early childbirth and repeated childbirth were significantly ( p &lt; 0.001) lower and that for high fertility, unintended pregnancy, lifetime pregnancy termination and use of a modern contraceptive method was significantly higher in the child married women compared to their adult married counterparts. Reforms should aim to have more girls remain in schooling for both personal and overall societal development and also to reduce adverse reproductive outcomes caused by child marriage.

Chronic sleep disruption induces depression-like behavior in adolescent male and female mice and sensitization of the hypothalamic-pituitary-adrenal axis in adolescent female mice

Depression is a prevalent mood disorder responsible for reduced quality of life for over 264 million people. Depression commonly develops during adolescence and becomes twice as prevalent in females than in males. However, the mechanisms underlying adolescent depression onset and sex differences in the prevalence rate remain unclear. Adolescent exposure to stress and subsequent sensitization of the hypothalamic-pituitary-adrenal (HPA) axis contributes to mood disorder development, and females are particularly vulnerable to HPA sensitization. Repeated exposure to stressors common to adolescent development, like sleep disruption, could partially be responsible for adolescent female susceptibility to depression. To address this possibility, 80 adolescent and adult CD-1 mice (Male, n = 40; Female, n = 40) were manually sleep disrupted for the first four hours of each rest cycle or allowed normal rest for eight consecutive days. Depression-like behavior was assessed with the forced swim test. 5-HT1A and glucocorticoid receptor expression and concurrent cellular activation via glucocorticoid receptor/c-Fos colocalization were examined in various brain regions to assess cellular correlates of depression and HPA-axis activation. Both adolescent male and female mice displayed significantly greater depression-like behavior and prelimbic c-Fos expression after chronic sleep disruption than non-sleep disrupted adolescent and sleep disrupted adult counterparts. However, sleep disrupted adolescent females demonstrated greater dorsal raphe 5-HT1A expression than sleep disrupted adolescent males. Adolescent females and males had decreased medial prefrontal 5-HT1A expression after chronic sleep disruption, but only adolescent females expressed decreased hippocampal 5-HT1A expression compared to controls. Chronic sleep disruption significantly increased corticosterone release, glucocorticoid expression in the CA1, and activation of glucocorticoid immunoreactive cells in the prelimbic cortex of adolescent females but not in adolescent males. These findings suggest that chronic sleep disruption during adolescence could give rise to depressive symptoms in male and female adolescents through differing signaling mechanisms.

Mental health presentations to a paediatric emergency department.

To explore trends in presentation and key performance indicators with respect to children seeking mental health services at The Prince Charles Hospital Children's Emergency Department (TPCH-CED), Brisbane. A retrospective audit was performed utilising data obtained from the local Emergency Department Information System for all mental health presentations between 1 January 2013 and 1 January 2018 to TPCH-CED. A total of 1078 children presented to TPCH-CED requiring mental health review between 2013 and 2018. Mental health presentations almost doubled over the 5 years (185 attendances in 2013; 342 in 2017); however, as a proportion of overall presentations, there was no significant increase. The percentage of mental health presentations meeting the National Emergency Access Target criteria dropped from 63% in 2013 to 39% in 2017 (P < 0.0001). Those requiring a mental health inpatient stay were more likely to have very extended length of stay within the CED. Suicidal ideation was the most common presenting complaint (72% of mental health presentations). Violence and aggression were noted in a consistent proportion of mental health presentations (4.4-12%). Despite failing to demonstrate an interval increase in the proportion of children presenting to TPCH-CED requiring mental health services, it is clear that children with mental health needs, like their adult counterparts, disproportionately experience delays to appropriate care when compared with children presenting with other emergency conditions. Ongoing research is warranted to assess standards of care and the impact of mental health presentations on CEDs.

Functional Movement Disorders in Children.

Functional movement disorders (FMDs) are not uncommon in children. The age at onset may have a bearing on the phenomenological pattern of abnormal movement, risk factors, and response to different treatment modalities in this age group. FMDs in children resemble their adult counterparts in terms of gender preponderance, but risk factors are quite different, and often influenced by cultural and demographic background. FMDs contribute to a significant proportion of acute pediatric movement disorder patients seen in emergency settings, ranging from 4.3 to 23% in different case series. The most common movement phenomenologies observed in pediatric FMDs patients are tremor, dystonia, gait disturbances, and functional tics. Various social, physical, and familial precipitating factors have been described. Common social risk factors include divorce of parents, sexual abuse, bullying at school, examination pressure, or other education-related issues, death of a close friend, relative, or family members. Physical trauma like minor head injury, immunization, tooth extraction, and tonsillectomy are also known to precipitate FMDs. The response to treatment appears to be better among pediatric patients. We aim to review FMDs in children to better understand the different aspects of their frequency, clinical features, precipitating factors, diagnosis, treatment, and outcome.

Epilepsy-Work-Up and Management in Children.

Pediatric epilepsy is a highly variable condition due to age-related expression of syndromes that require specific diagnosis, evaluations, and treatments. Children with epilepsy differ from their adult counterparts in many important ways, mostly related to the age-related expression of specific epilepsy syndromes. This results in many important considerations related to the epilepsy diagnosis, classification, evaluations to determine an etiology, as well as treatment guidelines. A good understanding of these factors will help to establish an accurate epilepsy diagnosis, which in turn will guide appropriate testing and treatment decisions. In this way, patients will have improved seizure outcomes, and families will be educated appropriately and provided with the most accurate prognostic information available. The purpose of this article is to review the diagnosis, work-up, and management of pediatric epilepsy.

Measurable Residual Disease (MRD) in Elderly Acute Myeloid Leukemia (AML): Results from the Pethema-Flugaza Phase III Clinical Trial

The value of measurable residual disease (MRD) in elderly patients with acute myeloid leukemia (AML) is inconsistent between those treated with intensive vs hypomethylating drugs, and unknown after semi-intensive therapy. We investigated the role of MRD in refining complete remission (CR) and treatment duration in the phase 3 FLUGAZA clinical trial, which randomized 283 elderly AML patients to induction and consolidation with fludarabine plus cytarabine (FLUGA) vs 5-azacitidine. After consolidation, patients continued treatment if MRD was ≥0.01% or stopped if MRD was <0.01%, as assessed by multidimensional flow cytometry (MFC). On multivariate analysis including genetic risk and treatment arm, MRD status in patients achieving CR (N = 72) was the only independent prognostic factor for relapse-free survival (RFS) (HR, 3.45; P = .002). Achieving undetectable MRD significantly improved RFS of patients with adverse genetics (HR, 0.32; P = .013). Longer overall survival was observed in patients with undetectable MRD after induction though not after consolidation. Although leukemic cells from most patients displayed phenotypic aberrancies vs their normal counterpart (N = 259 of 265), CD34 progenitors from cases with undetectable MRD by MFC carried extensive genetic abnormalities identified by whole-exome sequencing. Interestingly, the number of genetic alterations significantly increased from diagnosis to MRD stages in patients treated with FLUGA vs 5-azacitidine (2.2-fold vs 1.1-fold; P = .001). This study supports MRD assessment to refine CR after semi-intensive therapy or hypomethylating agents, but unveils that improved sensitivity is warranted to individualize treatment and prolong survival of elderly AML patients achieving undetectable MRD.

Comparison of maternal and foetal outcomes between adolescent and adult pregnancies; a descriptive cross sectional study

Introduction: Adolescent pregnancy is a global issue and the trend is increasing specially in South East Asia. Pregnancies at a younger age have major maternal and fetal health consequences. The aim of this study was to compare selected maternal and fetal outcomes of adolescent pregnancies with its adult counterpart in atertiary care center. Methods: A hospital based descriptive study was conducted at Teaching Hospital Mahamodara (THM), Galle. One hundred adolescent mothers (10-19 years) were compared with 100 adult mothers (20 -35 years) who had singleton uncomplicated pregnancy. Pre-tested interviewer administered questionnaire was used as the tool to collect data on basic demography, perinatal, maternal outcomes and mode of delivery. Chi-squared test and t-test were used to compare data and presented as proportions, mean (SD), with 95% CI. Results: Mean (SD) age at delivery of adolescent and adult mothers were 18 (0.2) and 27 (0.8) years respectively. Of the adolescent mothers 16% were unmarried. More adolescent mothers had anaemia compared to adults (38% vs. 32%), but the difference was not statistically significant (p=0.37). Adolescent mothers had higher pre term delivery rate compared to adult mothers (23% vs.15%) but the difference was not statistically significant (p=0.18). There were no significant differences in birth weight (2.77 vs. 2.82; p=0.5) rate of admissions to premature baby unit (6% vs. 7%; p=0.8) and mean APGAR scores (9.9 vs 9.8; p=0.3) between the two groups. A significantly greater proportion of vaginal deliveries were carried out in adolescents compared to adults (75% vs. 55%; p= 0.003). Conclusions: Adolescent mothers underwent a significantly larger proportion of vaginal deliveries compared to adults. Though not significant, anaemia and preterm deliveries were higher than in their adult counter-parts. There was no significant difference between the two groups for the selected perinatal outcomes.

Developing Human Skin Contains Lymphocytes Demonstrating a Memory Signature

SummaryLymphocytes in barrier tissues play critical roles in host defense and homeostasis. These cells take up residence in tissues during defined developmental windows, when they may demonstrate distinct phenotypes and functions. Here, we utilized mass and flow cytometry to elucidate early features of human skin immunity. Although most conventional αβ T (Tconv) cells in fetal skin have a naive, proliferative phenotype, a subset of CD4+ Tconv and CD8+ cells demonstrate memory-like features and a propensity for interferon (IFN)γ production. Skin regulatory T cells dynamically accumulate over the second trimester in temporal and regional association with hair follicle development. These fetal skin regulatory T cells (Tregs) demonstrate an effector memory phenotype while differing from their adult counterparts in expression of key effector molecules. Thus, we identify features of prenatal skin lymphocytes that may have key implications for understanding antigen and allergen encounters in utero and in infancy.

Iron deficiency anaemia and low BMI among adolescent girls in India: the transition from 2005 to 2015.

The current study explored changes in trend of anaemia and BMI among currently pregnant nullipara adolescent women against socio-economic determinants in India from 2005 through 2015. The association between anaemia in currently pregnant nullipara adolescent women v. currently pregnant nullipara older women of reproductive age was also explored. We used the 2005 and the 2015 nationally representative Indian Demographic and Health Surveys (DHS). The outcomes of interest, anaemia and BMI, were measured based on the DHS methodology following WHO standards and indicators. Place of residence, educational attainment and wealth quintiles were used as determinants in the analysis. India. In total, 696 adolescent girls from the India 2005 DHS and 3041 adolescent girls from the India 2015 DHS. The 10-year transition from 2005 to 2015 showed differences between the least and most wealthy sections of society, with heaviest gains in anaemia reduction over time among the latter (from 50·0 to < 40·0 %). The odds of anaemia were significantly higher among the adolescent population when compared with adult women both in 2005 and in 2015 (OR = 1·2). Despite an overall improvement in the prevalence of both BMI < 18·5 and anaemia among adolescents nullipara in India, the adjusted risk of anaemia in the latter category was still significantly higher as compared with their adult counterparts. Since the inequalities evidenced during the first round of DHS remained unchanged in 2015, more investments in universal health care are needed in India.

Higher Frequency and Increased Expression of Molecules Associated with Suppression on T Regulatory Cells from Newborn Compared with Adult Nonhuman Primates

T regulatory cells (Tregs) play a critical role in controlling the immune response, often limiting pathogen-specific cells to curb immune-mediated damage. Studies in human infants have reported an increased representation of Tregs in these individuals. However, how these cells differ from those in adults at various sites and how they respond to activation signals is relatively unknown. In this study, we used a newborn nonhuman primate model to assess Treg populations present at multiple sites with regard to frequency and phenotype in comparison with those present in adult animals. We found that Foxp3+ cells were more highly represented in the T cell compartment of newborn nonhuman primates for all sites examined (i.e., the spleen, lung, and circulation). In the spleen and circulation, newborn-derived Tregs expressed significantly higher levels of Foxp3 and CD25 compared with adults, consistent with an effector phenotype. Strikingly, the phenotype of Tregs in the lungs of adult and infant animals was relatively similar, with both adult and newborn Tregs exhibiting a more uniform PD-1+CD39+ phenotype. Finally, in vitro, newborn Tregs exhibited an increased requirement for TCR engagement for survival. Further, these cells upregulated CD39 more robustly than their adult counterpart. Together, these data provide new insights into the quantity of Tregs in newborns, their activation state, and their potential to respond to activation signals.

Mesothelioma in children and adolescents: the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) contribution.

Very little is known about the characteristics of mesothelial tumours in the paediatric population. In adults with malignant mesothelioma, the pemetrexed-based regimen with cytoreductive surgery (CRS) is a standard of care in limited tumours, but long-term survival is uncommon. The European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT) retrospectively reviewed children, adolescentsand young adults (≤21 year) diagnosed with mesothelial tumours treated between 1987 and 2018. Thirty-three patients were identified, 15 male and 18 female patients. One patient's exposure to asbestos was documented. Primary tumour was mainly in the peritoneum (23 patients). Histology was multicystic mesothelioma of the peritoneum (MCM) (six patients) or malignant mesothelioma (MM) (27 patients). Among MM, the first-line treatment comprised preoperative chemotherapy (14 cases), surgery only (three cases), chemotherapy only (five cases), adjuvant chemotherapy (three cases)or palliative treatment (two cases). The response rate to cisplatin-pemetrexed was 50% (6/12 cases). CRS with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) was performed in 19 patients (upfront in three, after neoadjuvant therapy in 12, or after tumour progression in six patients, including three twice). After a median follow-up of 6.7 years (range, 0-20), five-year overall and event-free survivals were 82.3% (95% CI, confidential interval ((CI), 67.8-99.9) and 45.1% (95% CI, 28.4-71.7), respectively. All patients with MCM are alive after surgery (five patients) and CRS-HIPEC (one patient). Paediatric mesothelioma is exceptional and seems to be different from its adult counterpart with few asbestos exposures, more peritoneal primary, and a better outcome. The cisplatin-pemetrexed regimen showed promising efficacy. Relapses could be salvaged with active therapy including CRS-HIPEC.

Therapeutic challenges in managing pediatric psoriasis.

BackgroundEach year, 20,000 patients aged <10 years are diagnosed with psoriasis. Pediatric-onset psoriasis has many similarities to adult-onset disease, and previous studies suggest that the incidence might be increasing in both populations.ObjectiveThe challenges that arise when treating patients with psoriasis, especially those age <12 years, are summarized, as well as the limited available treatment options for treating pediatric patients with psoriasis and the evidence supporting each of them.MethodsRecently published guidelines by the American Academy of Dermatology and the National Psoriasis Foundations, as well as guidelines published by the German Society of Dermatology, provide considerable insight in managing patients who have this condition. The latest studies on pediatric psoriasis treatment were reviewed, including recent and current clinical trials with U.S. Food and Drug Administration approved and nonapproved medications, case reports, case series, and reviews. The authors also reviewed American and European guidelines, as well as recommendations from expert panels.ResultsCurrently, only six medications are approved by the U.S. Food and Drug Administration for the treatment of pediatric psoriasis: three biologics and three topical. Many off-label topical treatments have been used in pediatric psoriasis, with variable effectiveness and safety profiles. Data from adult clinical trials, as well as case reports and series from pediatric patients, suggest that other biologic medications are effective for pediatric psoriasis.ConclusionMany questions remain unanswered, leaving clinicians facing multiple challenges when encountering pediatric patients with psoriasis. This summation will help provide an overview of current on- and off-label medications for pediatric psoriasis. Pediatric clinical trials should be implemented to obtain data that can result in expanding the therapeutic spectrum for this population, parallel to their adult counterparts.