Interaction-focused music therapy with cancer-affected children and their significant others: a randomized controlled feasibility study with subsequent intervention (INMUT).

BACKGROUND: Paediatric oncology/haematology patients and their families are confronted with a life-threatening situation for which music therapy can be a cross-linguistic field of action. The creative act of making music together offers the possibility to strengthen competences and make conflicts tangible. Besides its complementing of evidence-based biomedical care, there is little research on the feasibility and efficacy of interactive music therapy including the diagnosed child and their significant others. METHODS: We conducted an assessor blind, prospective, multicentric feasibility randomized controlled trial (RCT) with subsequent intervention. Including overall 52 child-significant other dyads, INMUT investigates interaction-focused music therapy with cancer-affected children and their significant others (INMUT-KB; n = 21) compared to music therapy only with the child (MUT-K; n = 21) and a wait-list group (WLG; n = 10). The measurement points include the screening for a cancer diagnosis, psychometric baseline (pre-T1), initial assessment (T1/T2), music therapy sessions (T3-T9), final assessment (T10), final psychometric evaluation (post-T10), and 3-month follow-up (cat-T11). Feasibility and acceptability of the (1) research methodology, (2) intervention and (3) estimation of effect sizes will be assessed using qualitative and quantitative data. The proposed primary outcome includes the parent-child interaction (APCI), and the proposed secondary outcomes refer to subjective goal achievement (GAS), quality of life (KINDL), system-related functional level (EXIS), psychosocial stress (BAS), psychosomatic complaints (SCL-9k), and resources (WIRF). We plan to investigate the efficacy of INMUT-KB and MUT-K post-intervention (post-T10) within the RCT design and at 3-month follow-up (cat-T11). DISCUSSION: This study will provide insights into the feasibility of INMUT and the final sample needed for a confirmatory RCT. We will reflect on successfully implemented study procedures and, if necessary, provide recommendations for changes considering the design, procedures, measures, and statistical analyses. The discussion will conclude with an evaluation whether a confirmatory RCT is worth the investment of future resources, including the calculated number of child-significant other dyads needed based on the efficacy trends derived from this feasibility study. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05534282; date of registration: June 23, 2022.

Balancing economic and ecological functions in smallholder and industrial oil palm plantations.

The expansion of the oil palm industry in Indonesia has improved livelihoods in rural communities, but comes at the cost of biodiversity and ecosystem degradation. Here, we investigated ways to balance ecological and economic outcomes of oil palm cultivation. We compared a wide range of production systems, including smallholder plantations, industrialized company estates, estates with improved agronomic management, and estates with native tree enrichment. Across all management types, we assessed multiple indicators of biodiversity, ecosystem functions, management, and landscape structure to identify factors that facilitate economic-ecological win-wins, using palm yields as measure of economic performance. Although, we found that yields in industrialized estates were, on average, twice as high as those in smallholder plantations, ecological indicators displayed substantial variability across systems, regardless of yield variations, highlighting potential for economic-ecological win-wins. Reducing management intensity (e.g., mechanical weeding instead of herbicide application) did not lower yields but improved ecological outcomes at moderate costs, making it a potential measure for balancing economic and ecological demands. Additionally, maintaining forest cover in the landscape generally enhanced local biodiversity and ecosystem functioning within plantations. Enriching plantations with native trees is also a promising strategy to increase ecological value without reducing productivity. Overall, we recommend closing yield gaps in smallholder cultivation through careful intensification, whereas conventional plantations could reduce management intensity without sacrificing yield. Our study highlights various pathways to reconcile the economics and ecology of palm oil production and identifies management practices for a more sustainable future of oil palm cultivation.

Outcomes in ovarian Sertoli-Leydig cell tumor: A report from the International Pleuropulmonary Blastoma/DICER1 and Ovarian and Testicular Stromal Tumor Registries.

OBJECTIVE: Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We sought to describe prognostic factors, treatment and outcomes for individuals with ovarian SLCT. METHODS: Individuals with SLCT were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and pathology was centrally reviewed when available. RESULTS: In total, 191 participants with ovarian SLCT enrolled, with most (92%, 175/191) presenting with FIGO stage I disease. Germline DICER1 results were available for 156 patients; of these 58% had a pathogenic or likely pathogenic germline variant. Somatic (tumor) DICER1 testing showed RNase IIIb hotspot variants in 97% (88/91) of intermediately and poorly differentiated tumors. Adjuvant chemotherapy was administered in 40% (77/191) of cases, and among these, nearly all patients received platinum-based regimens (95%, 73/77), and 30% (23/77) received regimens that included an alkylating agent. Three-year recurrence-free survival for patients with stage IA tumors was 93.6% (95% CI: 88.2-99.3%) compared to 67.1% (95% CI: 55.2-81.6%) for all stage IC and 60.6% (95% CI: 40.3-91.0%) for stage II-IV (p < .001) tumors. Among patients with FIGO stage I tumors, those with mesenchymal heterologous elements treated with surgery alone were at higher risk for recurrence (HR: 74.18, 95% CI: 17.99-305.85). CONCLUSION: Most individuals with SLCT fare well, though specific risk factors such as mesenchymal heterologous elements are associated with poor prognosis. We also highlight the role of DICER1 surveillance in early detection of SLCT, facilitating stage IA resection.

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.

Committed Lone Fighters And Group Experiences: An International Survey On Pediatric Hematology And Oncology Training In German-Speaking Countries.

INTRODUCTION: In German-speaking countries children with cancer are treated in about 70 hospitals. While national and European curricula for pediatric oncology and hematology (POH) have been developed, little is known, how far these curricula have been implemented into daily training and what topics are deemed urgent by instructors. METHODS AND MATERIALS: In 2022 the Didactics and Educational working party of the German Pediatric Hematology/Oncology Society conducted a survey plus interview by phone call on local educational conditions in POH and needs of educators. RESULTS: Thirty-two (45%) POH centers answered the questionary, half have appointed persons overseeing the training. A wide range educational scenarios were described in some centers. Trainees identified urgent needs in areas such as hybrid education and demanded training workshops on specific topics and intensified networking and a general curriculum implemented into daily care as mandatory. CONCLUSION: This is the first survey on educational issues in POH in German speaking centers, describing the current situation before and under pandemic conditions. Great individual efforts have already been achieved by dedicated teachers. A comprehensive training program in POH is still missing, which translates the national curriculum into daily practice, while improving networking and balancing the resources of the individual centers.

[Hospital-based Home Care for Children with Cancer from the Parents̓ Point of View - A Qualitative Exploration of Family Members]. / Die ambulant-aufsuchende Versorgung von an Krebs erkrankten Kindern aus Sicht der Erziehungsberechtigten.

BACKGROUND: About 2,200 children and adolescents in Germany per year are diagnosed with oncological diseases. Through now, there are almost no offers for home care services for these patients. There is a pilot program offering hospital-based home care for children and adolescents with cancer in Germany. The perspective of the parents will be researched by a qualitative exploring study. PATIENTS: In this interview study parents from children with cancer will be interviewed. METHOD: A qualitative exploring interview study, seeking the subjective perspective from parents on the hospital-based home care for children with cancer. The sample was drawn criterion-guided. The interviews were transcribed verbatim and analysed using qualitative content analysis. For socio- demographic characteristics the participants respond to an online questionnaire. RESULTS: Eleven women and three men aged between 30 and 60 years participated in the interviews. The average age of the ill children was 8.43 years. Five parents state that the children's illness did not lead to a reduction in working hours or to the termination of the employment relationship. Hospital-based home care results in subjectively perceived relief in everyday family life, especially in terms of time. Furthermore, a reduction in the psychological perception of stress is described. DISCUSSION/CONCLUSION: Due to the study design, the results presented here are to be regarded as indicative. In future studies the presented results should be supplemented by quantitative representative studies.

Culture-independent detection of low-abundant Clostridioides difficile in environmental DNA via PCR.

Clostridioides difficile represents a major burden to public health. As a well-known nosocomial pathogen whose occurrence is highly associated with antibiotic treatment, most examined C. difficile strains originated from clinical specimen and were isolated under selective conditions employing antibiotics. This suggests a significant bias among analyzed C. difficile strains, which impedes a holistic view on this pathogen. In order to support extensive isolation of C. difficile strains from environmental samples, we designed a detection PCR that targets the hpdBCA-operon and thereby identifies low abundances of C. difficile in environmental samples. This operon encodes the 4-hydroxyphenylacetate decarboxylase, which catalyzes the production of the antimicrobial compound para-cresol. Amplicon-based analyses of diverse environmental samples demonstrated that the designed PCR is highly specific for C. difficile and successfully detected C. difficile despite its absence in general 16S rRNA gene-based detection strategies. Further analyses revealed the potential of the hpdBCA detection PCR sequence for initial phylogenetic classification, which allows assessment of C. difficile diversity in environmental samples via amplicon sequencing. Our findings furthermore showed that C. difficile strains isolated under antibiotic treatment from environmental samples were originally dominated by other strains according to PCR amplicon results. This provided evidence for selective cultivation of under-represented but antibiotic-resistant isolates. Thereby, we revealed a substantial bias in C. difficile isolation and research.IMPORTANCEClostridioides difficile is a main cause of diarrheic infections after antibiotic treatment with serious morbidity and mortality worldwide. Research on this pathogen and its virulence has focused on bacterial isolation from clinical specimens under antibiotic treatment, which implies a substantial bias in isolated strains. Comprehensive studies, however, require an unbiased strain collection, which is accomplished by isolation of C. difficile from diverse environmental samples and avoidance of antibiotic-based enrichment strategies. Thus, isolation can significantly benefit from our C. difficile-specific detection PCR, which rapidly verifies C. difficile presence in environmental samples and further allows estimation of the C. difficile diversity by using next-generation sequencing.

Epidemiology of 7375 children and adolescents hospitalized with COVID-19 in Germany, reported via a prospective, nationwide surveillance study in 2020-2022.

By means of a nationwide, prospective, multicenter, observational cohort registry collecting data on 7375 patients with laboratory-confirmed SARS-CoV-2 admitted to children's hospitals in Germany, March 2020-November 2022, our study assessed the clinical features of children and adolescents hospitalized due to SARS-CoV-2, evaluated which of these patients might be at highest risk for severe COVID-19, and identified underlying risk factors. Outcomes tracked included: symptomatic infection, case fatality, sequelae at discharge and severe disease. Among reported cases, median age was one year, with 42% being infants. Half were admitted for reasons other than SARS-CoV-2. In 27%, preexisting comorbidities were present, most frequently obesity, neurological/neuromuscular disorders, premature birth, and respiratory, cardiovascular or gastrointestinal diseases. 3.0% of cases were admitted to ICU, but ICU admission rates varied as different SARS-CoV-2 variants gained prevalence. Main risk factors linked to ICU admission due to COVID-19 were: patient age (> 12 and 1-4 years old), obesity, neurological/neuromuscular diseases, Trisomy 21 or other genetic syndromes, and coinfections at time of hospitalization. With Omicron, the group at highest risk shifted to 1-4-year-olds. For both health care providers and the general public, understanding risk factors for severe disease is critical to informing decisions about risk-reduction measures, including vaccination and masking guidelines.

UNC93B1 variants underlie TLR7-dependent autoimmunity.

UNC93B1 is critical for trafficking and function of nucleic acid-sensing Toll-like receptors (TLRs) TLR3, TLR7, TLR8, and TLR9, which are essential for antiviral immunity. Overactive TLR7 signaling induced by recognition of self-nucleic acids has been implicated in systemic lupus erythematosus (SLE). Here, we report UNC93B1 variants (E92G and R336L) in four patients with early-onset SLE. Patient cells or mouse macrophages carrying the UNC93B1 variants produced high amounts of TNF-α and IL-6 and upon stimulation with TLR7/TLR8 agonist, but not with TLR3 or TLR9 agonists. E92G causes UNC93B1 protein instability and reduced interaction with TLR7, leading to selective TLR7 hyperactivation with constitutive type I IFN signaling. Thus, UNC93B1 regulates TLR subtype-specific mechanisms of ligand recognition. Our findings establish a pivotal role for UNC93B1 in TLR7-dependent autoimmunity and highlight the therapeutic potential of targeting TLR7 in SLE.

Melanoma of the central nervous system based on neurocutaneous melanocytosis in childhood: A rare but fatal condition.

BACKGROUND: Melanomas of the central nervous system (CNS) based on neurocutaneous melanocytosis (NCM) are exceptionally rare in childhood and have been described only sporadically. Rapidly progressive disease may represent a major challenge for treating physicians, especially given the limited knowledge about this condition. This analysis aimed to increase knowledge about the occurrence and treatment of these malignancies. PROCEDURE: Data on diagnosis, treatment, and outcome of patients aged 0-18 years with CNS melanoma based on NCM recorded in the German Registry for Rare Pediatric Tumors (STEP registry) were analyzed. Additionally, published case reports on this condition were analyzed. RESULTS: In STEP, five patients with leptomeningeal melanoma based on NCM were identified, with a median age at melanoma diagnosis of 3.7 years. Various multimodal treatments were performed: (partial) resection (n = 4), irradiation (n = 2), trametinib (n = 3), different cytostatics (n = 2), and anti-GD2 immunotherapy (n = 1). All patients died between 0.3 and 0.8 years after diagnosis. Including published case reports, 27 patients were identified with a median age of 2.8 years at melanoma diagnosis (range: 0.2-16.6). Fourteen of 16 cases with reported data had a NRAS alteration (88%), particularly NRAS p.Q61K (85%). In the expanded cohort, no patient survived longer than 1 year after diagnosis despite multimodal therapy (including trametinib; n = 9), with a median survival of 0.4 years (range 0.1-0.9). CONCLUSIONS: CNS melanomas based on NCM in childhood are aggressive malignancies without curative treatment to date. Therapeutic approaches must be individualized. Genetic tumor sequencing is essential to improve understanding of tumorigenesis and potentially identify new therapeutic targets.

High burden of acute respiratory tract infections leading to hospitalization at German pediatric hospitals: fall/winter 2022-2023.

PURPOSE: Given reduced immunity levels for seasonally occurring respiratory infections and the experience of an unusually early, severe wave of RSV infections during 2021, a preexisting clinician-led reporting system (CLRS) was updated to prospectively monitor the anticipated high burden of respiratory infections (ARI) in German pediatric hospitals during fall/winter 2022-2023. METHODS: From September 13, 2022 through March 31, 2023, children hospitalized with ARI as a primary diagnosis were monitored via a national CLRS established by the German Society for Pediatric Infectious Diseases (DGPI). Once a week, the CLRS collected overall number of new hospital admissions, ARI-related admissions according to pathogen (SARS-CoV-2, RSV, influenza, and other), plus number of patients admitted to ICU with ARI as a primary diagnosis. RESULTS: With a high participation among children's hospitals across Germany (22.8%), 76 centers submitted 1,053 survey reports. ARI-related hospital admissions showed a steep rise starting in late September 2022 and reached their highpoint in early December 2022 (50.1% of all admissions). In parallel, the average number of newly admitted patients (aNA) with RSV (3.6) peaked, as did those with influenza (2.1) one week later. The average highpoint of ARI patients on ICU (aICU) (2.9) was reached shortly thereafter. Again, RSV (1.6) und influenza (1.2) were predominant pathogens. CONCLUSION: In fall/winter 2022-2023, German hospitals reported a sharp increase in patients with ARIs. While RSV and influenza represented the greatest proportion of ARI, SARS-CoV-2 played a less significant role. Systematic, dynamic collection of ARI data is critical for assessing real burdens on the health care system.

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.

Pan-genome analysis of six Paracoccus type strain genomes reveal lifestyle traits.

The genus Paracoccus capable of inhabiting a variety of different ecological niches both, marine and terrestrial, is globally distributed. In addition, Paracoccus is taxonomically, metabolically and regarding lifestyle highly diverse. Until now, little is known on how Paracoccus can adapt to such a range of different ecological niches and lifestyles. In the present study, the genus Paracoccus was phylogenomically analyzed (n = 160) and revisited, allowing species level classification of 16 so far unclassified Paracoccus sp. strains and detection of five misclassifications. Moreover, we performed pan-genome analysis of Paracoccus-type strains, isolated from a variety of ecological niches, including different soils, tidal flat sediment, host association such as the bluespotted cornetfish, Bugula plumosa, and the reef-building coral Stylophora pistillata to elucidate either i) the importance of lifestyle and adaptation potential, and ii) the role of the genomic equipment and niche adaptation potential. Six complete genomes were de novo hybrid assembled using a combination of short and long-read technologies. These Paracoccus genomes increase the number of completely closed high-quality genomes of type strains from 15 to 21. Pan-genome analysis revealed an open pan-genome composed of 13,819 genes with a minimal chromosomal core (8.84%) highlighting the genomic adaptation potential and the huge impact of extra-chromosomal elements. All genomes are shaped by the acquisition of various mobile genetic elements including genomic islands, prophages, transposases, and insertion sequences emphasizing their genomic plasticity. In terms of lifestyle, each mobile genetic elements should be evaluated separately with respect to the ecological context. Free-living genomes, in contrast to host-associated, tend to comprise (1) larger genomes, or the highest number of extra-chromosomal elements, (2) higher number of genomic islands and insertion sequence elements, and (3) a lower number of intact prophage regions. Regarding lifestyle adaptations, free-living genomes share genes linked to genetic exchange via T4SS, especially relevant for Paracoccus, known for their numerous extrachromosomal elements, enabling adaptation to dynamic environments. Conversely, host-associated genomes feature diverse genes involved in molecule transport, cell wall modification, attachment, stress protection, DNA repair, carbon, and nitrogen metabolism. Due to the vast number of adaptive genes, Paracoccus can quickly adapt to changing environmental conditions.

Metagenome-assembled genomes from particle-associated microbial communities in the mesopelagic zone of the Pacific Ocean.

We report 10 particle-associated metagenome-assembled genomes (MAGs) from the mesopelagic zone of Pacific Ocean seawaters. MAGs comprise members of Flavobacteria Halomonas, Blastomonas, Brevundimonas, Alteromonas, Shingomonas, Sphingopyxis, Tabrizicola, Proteobacteria, and Gammaproteobacteria. Functional annotation suggests that these bacteria are involved in central particulate organic carbon conversion, nitrogen cycling, and phosphorus cycling.

Biallelic MAD2L1BP (p31comet) mutation is associated with mosaic aneuploidy and juvenile granulosa cell tumors.

MAD2L1BP-encoded p31comet mediates Trip13-dependent disassembly of Mad2- and Rev7-containing complexes and, through this antagonism, promotes timely spindle assembly checkpoint (SAC) silencing, faithful chromosome segregation, insulin signaling, and homology-directed repair (HDR) of DNA double-strand breaks. We identified a homozygous MAD2L1BP nonsense variant, R253*, in 2 siblings with microcephaly, epileptic encephalopathy, and juvenile granulosa cell tumors of ovary and testis. Patient-derived cells exhibited high-grade mosaic variegated aneuploidy, slowed-down proliferation, and instability of truncated p31comet mRNA and protein. Corresponding recombinant p31comet was defective in Trip13, Mad2, and Rev7 binding and unable to support SAC silencing or HDR. Furthermore, C-terminal truncation abrogated an identified interaction of p31comet with tp53. Another homozygous truncation, R227*, detected in an early-deceased patient with low-level aneuploidy, severe epileptic encephalopathy, and frequent blood glucose elevations, likely corresponds to complete loss of function, as in Mad2l1bp-/- mice. Thus, human mutations of p31comet are linked to aneuploidy and tumor predisposition.

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.

Solid pseudopapillary neoplasms of the pancreas in childhood and adolescence-an analysis of the German Registry for Rare Pediatric Tumors (STEP).

Solid pseudopapillary neoplasms (SPNs) are the most common entity among pediatric pancreatic tumors. Still, these are rare tumors with an annual incidence of 0.1-0.2/1,000,000, and little is known about their optimal treatment. This analysis aimed to increase knowledge about the occurrence and treatment strategies of SPN in childhood. Data regarding diagnostics, treatment, and outcome of children aged 0-18 years with SPN recorded in the German Registry for Rare Pediatric Tumors (STEP) were analyzed. Thirty-eight patients were identified with a median age of 14.5 years at diagnosis (range: 8-18) and a female preponderance (81.6%). The most frequent location of the tumor was the pancreatic tail. In histopathological and immunohistochemical examination, pseudopapillary, solid, and cystic lesions as well as expression of beta-catenin, progesterone receptors, and cyclin D1 were the most common findings. All patients underwent surgical resection. Most patients underwent open resection, predominantly tail resection for tumors in the tail region and pylorus-preserving pancreaticoduodenectomy for tumors in the head region. The main postoperative sequela was exogenous pancreatic insufficiency (23.7%), especially with SPN in the pancreatic head. No recurrence occurred during follow-up, although two patients underwent resection with microscopic residue. CONCLUSION: SPN of the pancreas in childhood are low-grade malignancies with usually favorable treatment outcomes. However, therapy can lead to relevant long-term sequelae. To prevent recurrence, complete surgical resection is recommended, sparing as much healthy pancreatic tissue as possible. Interdisciplinary collaboration between specialists is essential to optimize treatment. Molecular genetic analysis of these tumors could improve understanding of their genesis. WHAT IS KNOWN: • Solid pseudopapillary neoplasms (SPNs) of the pancreas are very rare tumors in childhood. • Little is known about tumorigenesis, and there are no specific guidelines for treatment and follow-up in pediatric patients. WHAT IS NEW: • Characteristics, treatment, and outcome were comprehensively assessed in a large cohort of pediatric patients with SPN. • We propose recommendations for diagnosis, treatment, and follow-up of children with SPN, based on our analysis and considering published experience.

Response of protists to nitrogen addition, arbuscular mycorrhizal fungi manipulation, and mesofauna reduction in a tropical montane rainforest in southern Ecuador.

The tropical Andes are a species-rich and nitrogen-limited system, susceptible to increased nitrogen (N) inputs from the atmosphere. However, our understanding of the impacts of increased N input on belowground systems, in particular on protists and their role in nutrient cycling, remains limited. We explored how increased N affects protists in tropical montane rainforests in Ecuador using high-throughput sequencing (HTS) of environmental DNA from two litter layers. In addition, we manipulated the amount of arbuscular mycorrhizal fungi (AMF) and mesofauna, both playing a significant role in N cycling and interacting in complex ways with protist communities. We found that N strongly affected protist community composition in both layers, while mesofauna reduction had a stronger effect on the lower layer. Changes in concentration of the AMF marker lipid had little effect on protists. In both layers, the addition of N increased phagotrophs and animal parasites and decreased plant parasites, while mixotrophs decreased in the upper layer but increased in the lower layer. In the upper layer with higher AMF concentration, mixotrophs decreased, while in the lower layer, photoautotrophs increased and plant parasites decreased. With reduced mesofauna, phagotrophs increased and animal parasites decreased in both layers, while plant parasites increased only in the upper layer. The findings indicate that to understand the intricate response of protist communities to environmental changes, it is critical to thoroughly analyze these communities across litter and soil layers, and to include HTS.

Bronchial carcinoid tumors in children and adolescents - A report and management considerations from the German MET studies.

OBJECTIVES: Bronchial carcinoid tumors (BC) are exceptionally rare in childhood, with an incidence of <0.2/1,000,000 per year. Typical low-grade BCs are distinguished from atypical, intermediate-grade BCs. Little is known about BCs in pediatric patients and management guidelines are missing. In this study, we explored characteristics and outcome of pediatric patients with BC prospectively registered with the Malignant Endocrine Tumor studies. MATERIAL AND METHODS: We performed a retrospective multicenter study in children, adolescents, and young adults (aged 0-20 years) with BC reported to the German MET registry between January 1997 and December 2022. Data were last updated on 28 of February 2023. RESULTS: Thirty-two patients were diagnosed at a median age of 15.0 years (range, 9.8-19.2). Atypical BCs (23.3%) were less frequent than typical, but more common than in adulthood. Lymph node metastases were present in 14.3% of cases (atypical BC: 28.6%, typical BC: 10.5%), distant metastases in one (3.1%) patient with atypical BC. 92.6% of patients were in complete remission after surgical resection (median follow-up: 2.7 years). The patient with metastatic spread and one patient with atypical BC and multiple recurrences were on treatment at last follow-up. 5-year event-free survival of typical BC was 100% and 83.3% in atypical BC. CONCLUSIONS: Completely resected localized BCs in pediatric patients have a favorable outcome also with lung tissue sparing surgery. Atypical BC with risk of metastatic spread and recurrence occurred more frequently compared to adults. Interdisciplinary management and collaborative efforts are needed to improve our understanding and the management of pediatric BC.