Michaela Nathrath

Background: Specialized outpatient palliative care (SOPC) provides home-based care for terminally ill patients and is associated with improved quality of life and prolonged survival. Due to its decentralized structure and growing demand, SOPC is a key target for digital transformation. Telehealth, mobile health, and AI offer considerable potential benefits but also present challenges, particularly with regard to user acceptance. Although both children and adults receive SOPC under the German statutory health insurance system, services differ in terms of patient characteristics, duration of care, and geographic coverage. Moreover, there is limited knowledge regarding the extent to which digital health applications are transferable across different areas of palliative care. Objective: This study assesses the extent to which needs and concerns regarding digitalization in SOPC for children are transferable to adult SOPC, using the PalliDoc Mobile app as a case example. Methods: Two adult SOPC teams using the PalliDoc Mobile app (a pediatric-origin mobile app) were surveyed between March 2022 and March 2025 using an embedded mixed methods design to assess digitalization needs and concerns. Therefore, a focus group study took place in the respective offices of the included teams. Twenty-five members from both teams, who were recruited via the personal network of the authors, participated, representing urban and rural care areas in Germany. Using an open-ended interview guide, the needs and concerns were first discussed with all participating members of each team. In a second step, the participants were allocated to profession-specific subgroups to further explore and prioritize the identified needs using a quantitative voting format. The focus group discussions were analyzed using qualitative content analysis, while the analysis of the prioritization votes was performed using descriptive statistics. Results: The triangulation of qualitative and quantitative findings revealed a total of 13 needs within the examined care teams for adults, with functions focusing on voice control being the highest priority (n=8 positive votes and no negative votes for voice input; n=6 positive votes and no negative votes for voice output). Additionally, functions relating to digitization and organizational tasks were viewed as predominantly helpful. Unlike in pediatrics, telehealth functions like video contacts, telemetry, and electronic patient-reported outcome measures are neither used here now nor intended to be used in the future. The identified concerns predominantly addressed the potential risk of AI-assisted documentation (n=2 positive votes and n=7 negative votes) altering or distorting health care professionals’ perception of information related to patients. Conclusions: Cross-setting telehealth applications may work, but they are no “plug-and-play solution.” Needs and concerns in each setting should be addressed to guarantee customized services.

High-risk pediatric sarcomas have a dismal prognosis. Current precision oncology approaches have not substantially improved patient outcomes. Immunotherapy offers a unique opportunity to develop more effective treatment strategies, but its successful implementation is hindered by a limited understanding of the tumor microenvironment (TME). We generated a TME classification platform by performing single-nucleus RNA sequencing of 89 pediatric sarcoma samples representing the major entities and integrating these data with high-dimensional spatial imaging. We identified distinct stromal, myeloid, and lymphoid cell states, revealing both entity-specific and conserved functional programs. Compositional analyses demonstrated marked differences in immune and stromal infiltration, with inflammatory myeloid cells dominating most tumors. We defined twelve TME archetypes and identified convergent multicellular niches, including stroma-, vasculature-, and T cell-rich regions, validated by multiplex imaging. Cell-cell interaction analyses uncovered shared and entity-specific communication networks, providing a comprehensive atlas of pediatric sarcoma TMEs and a framework for rational immunotherapeutic development.

Deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease with diverse phenotypes. We describe the genetics, phenotypes, and treatment of n = 48 DADA2 patients from Germany, Austria, and Switzerland. We report a high incidence of hematological (83%) and immunological features (85%), a comparatively low anti-tumor necrosis factor full-response rate (58%), and a high decision probability (21%) for hematopoietic cell transplantation (HCT). We establish a correlation between genetic variant ADA2 activity and patient ADA2 activity. Remarkably, lower patient ADA2 activity is predictive of neutropenia and shows a trend toward HCT decision, whereas higher patient ADA2 activity is predictive of vasculitis symptoms. Genetic variants with low residual ADA2 activity are significantly more common among patients receiving HCT. Our study corroborates previous observations connecting ADA2 activity and clinical phenotype, which up to now have been mainly based on in vitro data.

BACKGROUND Telehealth and artificial intelligence are increasingly used in specialized palliative outpatient care, offering potential benefits but facing challenges, particularly regarding user acceptance. To date, there is a lack of knowledge about the extent to which digital health applications may be transferable between different areas of palliative care. OBJECTIVE This study evaluates the transferability of concrete needs, expectations, and concerns regarding telehealth and artificial intelligence from specialized outpatient palliative care for children to specialized outpatient palliative care for adults, using the example of the PalliDoc Mobile App. METHODS Two specialized outpatient palliative care teams for adults using PalliDoc (a pediatric-origin mobile app) were surveyed employing a sequential mixed-methods approach to conduct the needs assessment: a focus group study with quantitative needs prioritization, followed by a questionnaire survey on user acceptance. 25 members from both teams, representing urban and rural care areas in Germany, participated in the focus groups. 17 responded to the questionnaire. RESULTS A total of 13 needs were identified within the examined care teams for adults, with functions focusing on voice input and output as well as organizational tasks being the highest priority. Unlike in pediatrics, video contacts, telemetry and electronic patient-reported outcome measures are neither used here now nor intended to be used in the future. The identified concerns predominantly addressed the potential risk of artificial intelligence–assisted documentation altering or distorting healthcare professionals’ perception of patient-related information. CONCLUSIONS Cross-setting telehealth applications may work but are no “plug-and-play solution”. Needs and concerns in each setting should be addressed to guarantee customized services. CLINICALTRIAL This study is registered in the German Register of Clinical Trials under the ID DRKS00036054 (https://www.drks.de/search/de/trial/DRKS00036054/details).

PURPOSE: Recent studies reveal that 5%-18% of children with cancer harbor pathogenic variants in known cancer-predisposing genes. However, DNA damage repair (DDR) genes, which are frequently somatically altered in pediatric tumors, have not been systematically examined as a source of novel cancer-predisposing signals. METHODS: To address this gap, we interrogated 189 DDR genes for presence of germline predisposing variants (PV) among 5,993 childhood cancer cases and 14,477 adult noncancer controls (discovery cohort). PV were determined using a tiered approach incorporating ClinVar annotations, InterVar classification, and in silico tools (REVEL, CADD, and MetaSVM). Using logistic and firth regression, we identified genes with PV statistically enriched in the germline of children with tumors and replicated findings among 1,497 additional childhood cancer cases across three independent cohorts. RESULTS: Analysis across all cases with cancer revealed enrichment of TP53 PV. Cancer-specific analyses confirmed known associations including germline TP53 PV in adrenocortical carcinoma, high-grade glioma (HGG), and medulloblastoma (MB), PMS2 in HGG and non-Hodgkin lymphoma (NHL), MLH1 in HGG, BRCA2 in NHL, and BARD1 in neuroblastoma. In addition, four novel associations were uncovered, including BRCA1 in ependymoma, SPIDR in HGG, SMC5 in MB, and SMARCAL1 in osteosarcoma (OS). Importantly, the SMARCAL1 :OS association was significant in the discovery (6/230, 2.6%, false discovery rate [FDR] _logistic = 0.0189) as well as all three replication cohorts (Childhood Cancer Survivor Study: 8/275, 2.9%; P _Fisher < .0001; Cancer Predisposition Syndrome-German Childhood Cancer Registry: 4/135, 3%, P _Fisher = .002; Individualized Therapy for Relapsed Malignancies in Childhood: 4/217, 1.8%, P _Fisher = .012). The remaining wild-type SMARCAL1 allele was deleted in three of four OS tumors with available data. CONCLUSION: Our study confirms the relevance DDR genetic variation in pediatric cancer risk and establishes SMARCAL1 as a novel OS predisposing gene, providing insights into tumor biology and creating opportunities to optimize care for patients with this challenging tumor.

Purpose: Teleangiectatic osteosarcoma is a histologic subtype of osteosarcoma that can mimic aneurysmal bone cysts and has so far been incompletely characterized. Patients and Methods: We used the database of the Cooperative Osteosarcoma Study Group COSS (patient‐registration 1980–2019) to better understand this rare histologic variant. Results: 223 eligible patients were identified, 164 having reference pathology (median age 15.9 (3.7–69.7) years; male 134, female 89; tumor sites limb 208 (201 metaphyses, 66 pathologic fractures), trunk 13, head & neck 2; 26 with primary metastases). Known tumor‐predisposition syndromes were rare. Therapy included surgery in 215, radiotherapy in 10, and chemotherapy in all patients. Tumor response to preoperative treatment was good in 71% of 165 cases with available data. After a median follow‐up of 7.1 (0.2–32.1) years for all patients and 10.5 (0.2–32.1) years for 152 survivors, 5‐/10‐year actuarial event‐free and overall survival expectancies were 61%/57% and 73%/66%, respectively. Five unrelated malignancies occurred during this period. The presence of primary metastases, pathologic fracture, poor response to neoadjuvant chemotherapy, and not obtaining a complete macroscopic remission were associated with inferior outcomes for both event‐free and overall survival ( p < 0.01). Discussion: This large analysis proves teleangiectatic osteosarcoma to be a disease predominantly of the metaphyses of the young. While detected only rarely, the true incidence of genetic tumor predispositions would require prospective assessments. Behaving like other osteosarcoma subtypes in many other ways, this variant may show greater chemosensitivity and hence somewhat better outcomes than other subtypes.

Background: Invasive fungal diseases (IFD) pose significant challenges in paediatric oncology. Their management is complicated by limited paediatric‐specific evidence, lack of standardised protocols and variability in resources across centres. This study assessed current practices and addressed the challenges in the prevention, diagnosis and treatment of IFDs in paediatric oncology centres across Germany, Austria and Switzerland.Methods: A questionnaire was distributed to senior paediatric oncologists in 70 paediatric oncology centres across Germany, Austria and Switzerland, gathering data on centre infrastructure, infectious disease (ID) expertise, annual cumulative IFD incidence in 2023, diagnostic tools, antifungal prophylaxis, treatment and follow‐up practices for IFD. Responses were analysed descriptively.Results: Sixty‐two centres responded, with a median of 56 (IQR 40–75) new oncological diagnoses per centre; 54.8% of centres managed allogeneic HCT patients. IFDs were reported in 88.7% of centres, with a median cumulative IFD incidence of 4.6% (IQR 3.0%–5.9%). No significant association was found between cumulative IFD incidence and the number of transplants, antifungal prophylaxis protocols and availability of ID consultation services. ID consultation was available in 58.1% of centres, with 24/7 support provided in 41.7% of these centres. Larger centres more frequently had paediatric ID specialists, ID consultation services and access to therapeutic drug monitoring.Conclusions: The observed heterogeneity in mycology expertise and IFD management strategies across centres reflects the inherent complexity of IFDs and the diagnostic and therapeutic uncertainties amid limited evidence. Strengthening oncology‐ID networks and implementing digital consultation platforms may promote high‐quality, equitable care, particularly for those with fewer in‐house resources.

Background: The exponential growth of telehealth is revolutionizing health care delivery, but its evaluation has not matched the pace of its uptake. Various forms of assessment, from single-item to more extensive questionnaires, have been used to assess telehealth and digital therapeutics and their usability. The most frequently used questionnaire is the “Telehealth Usability Questionnaire” (TUQ). The use of the TUQ is limited by its restricted availability in languages other than English and its feasibility. Objective: The aims of this study were to create a translated German TUQ version and to derive a short questionnaire for patients—“Telehealth Usability and Perceived Usefulness Short Questionnaire for patients” (TUUSQ). Methods: As a first step, the original 21-item TUQ was forward and back-translated twice. In the second step, 13 TUQ items were selected for their suitability for the general evaluation of telehealth on the basis of expert opinion. These 13 items were surveyed between July 2022 and September 2023 in 4 studies with patients and family members of palliative care, as well as patients with chronic autoimmune diseases, evaluating 13 health care apps, including digital therapeutics and a telehealth system (n1=128, n2=220, n3=30, and n4=12). Psychometric exploratory factor analysis was conducted. Results: The analysis revealed that a parsimonious factor structure with 2 factors (“perceived usefulness in health care” and “usability”) is sufficient to describe the patient’s perception. Consequently, the questionnaire could be shortened to 6 items without compromising its informativeness. Conclusions: We provide a linguistically precise German version of the TUQ for assessing the usability and perceived usefulness of telehealth. Beyond that, we supply a highly feasible shortened version that is versatile for general use in telehealth, mobile health, and digital therapeutics, which distinguishes between the 2 factors “perceived usefulness in health care” and “usability” in patients. Trial Registration: German Clinical Trials Register DRKS00030546; https://drks.de/search/de/trial/DRKS00030546

Background: Osteosarcoma may arise as a secondary malignancy following rhabdomyosarcoma (RMS). We utilized the Cooperative Osteosarcoma Study Group (COSS) database to better understand this association. Patients and methods: The COSS database (1980‐05/2023) was searched for patients whose osteosarcoma was preceded by RMS. Eligible patients were analyzed for patient‐, tumor‐, and treatment‐related variables as well as outcomes. Results: The search revealed 28 eligible osteosarcomas (27 high‐grade central, one periosteal; male:female = 16:12; median age RMS 2.1 [range: 0.9–10.0] years, osteosarcoma 13.5 [7.2–29.0] years). Genetic tumor‐predisposition syndromes were documented in 12 patients. One patient had had a distinct malignancy prior to RMS, two intermittently, seven following osteosarcoma. Local RMS treatment had included radiotherapy in 20/26 cases (two unknown). Secondary osteosarcoma sites were extremity 13, trunk seven, head and neck eight; 15 osteosarcomas were radiation‐associated. There was only one case of primary osteosarcoma metastases. Osteosarcoma treatment included chemotherapy (27), surgery (26), or radiotherapy (2). A macroscopically complete remission of all osteosarcoma sites was achieved in 24 cases. Median follow‐up was 5.8 (range: 0.5–18.4) years after osteosarcoma and 8.1 (1.0–15.4) years for 14 survivors. Actuarial 5‐year overall and event‐free survival were 66% (standard error 9%) and 45% (10%), respectively. Five of 14 deaths were caused by further malignancies. Conclusion: This series offers a benchmark for patients who develop a secondary osteosarcoma after RMS. Affected patients are generally still in the pediatric age. The results obtained strongly argue for genetic predisposition testing in RMS and against therapeutic leniency in comparable situations.