Pediatric Patients Research Articles

Pediatric living donor liver transplantation for small infants with biliary atresia using interposition portal vein grafts, multi-center cohort study.

Despite multiple techniques, portal vein (PV) inflow reconstruction during living donor liver transplantation (LDLT) for patients with biliary atresia (BA) and small-diameter PV remains a challenge. The use of PV interposition grafts has emerged as a promising therapeutic strategy to mitigate complications and reinterventions. We conducted a retrospective multi-center cohort study of patients under 3 years of age (n=85) undergoing LDLT for biliary atresia using PV interposition grafts. Our primary outcome was PV complications after LDLT, and secondary outcomes included long-term PV patency and death-censored graft survival. LDLT was performed on 85 patients. The PV diameter was 4.0±0.6mm. Cold-stored venous allografts were used in 26 cases, donor-derived grafts in 53, and autologous in six. The portal inflow was the PV in 38 cases, splenomesenteric confluence in 33, superior mesenteric vein in 3, and coronary vein in 1. The intraoperative PV thrombosis rate was 22.4% and the overall PV complication rate after LDLT was 23.5% (16 PV stenoses and 4 thromboses). Multivariate analysis revealed that the use of cold-stored venous allografts predicted PV complications (53.8% vs. 10.2%; RR, 15.9; 95%CI 2.9-86.2; p=0.001). Eleven patients underwent PV stent placement after LDLT with primary patency rates of 81.8% and secondary patency rates of 90.9%. The Long-term patency, death-censored graft survival, and patient survival rates were 96.5%, 96.5%, and 97.6%, respectively. Portal inflow reconstruction using interposition grafts during LDLT for biliary atresia achieves favorable long-term patency and patient and graft survival outcomes. This approach has the potential to mitigate morbidity and mortality in pediatric BA patients undergoing LDLT. Longer cold-stored venous allografts are associated with a higher risk of PV complications after LDLT.

Germline analysis of an international cohort of pediatric diffuse midline glioma patients.

Factors that drive the development of diffuse midline gliomas (DMG) are unknown. Our study aimed to determine the prevalence of pathogenic/likely pathogenic (P/LP) germline variants in pediatric patients with DMG. We assembled an international cohort of 252 pediatric patients with DMG, including diffuse intrinsic pontine glioma (n=153), with germline whole genome or whole exome sequencing. We identified P/LP germline variants in cancer predisposition genes in 7.5% (19/252) of patients. Tumor profiles differed, with absence of somatic drivers in the PI3K/mTOR pathway in patients with germline P/LP variants versus those without (P = 0.023). P/LP germline variants were recurrent in homologous recombination (n=9; BRCA1, BRCA2, PALB2) and Fanconi anemia genes (n=4). Somatic findings established that the germline variants definitively contributed to tumorigenesis in at least 1% of cases. One patient with recurrent DMG and pathogenic germline variants (BRCA2, FANCE) showed near-complete radiological response to PARP and immune checkpoint inhibition. Our study determined the prevalence of pathogenic germline variants in pediatric DMG, and suggests a role in tumorigenesis for a subset of patients.

LC-MS analysis of serum lipidomic and metabolomic signatures in pediatric patients with acute lymphoblastic leukemia

Abstract Background Acute lymphoblastic leukemia (ALL) is a prevalent hematologic malignancy that primarily affects children. The diagnosis and treatment of pediatric ALL remain challenging. This study aimed to identify differential lipids and metabolites that may hold potential for improving ALL treatment. Methods In this retrospective case-control study, serum samples obtained from children with ALL and healthy controls were analyzed. Serum lipidome and metabolome alterations of ALL were analyzed by comparing pediatric patients with ALL with healthy controls based on liquid chromatography high-resolution mass spectrometry analysis of serum lipidomic and metabolomic signatures. Results We identified 2,298 lipid features in the serum. Among them, 72 (3.13%) differed significantly in pediatric patients with ALL compared to healthy controls. Notably, sphingolipids (ceramide and sphingomyelin) and phospholipids exhibited the most pronounced changes. Targeted analysis of ceramides revealed significantly elevated levels of Cer 18:0 and Cer 20:0 in the serum of pediatric patients with ALL. Additionally, gut microbial-related lipids (such as sulfonolipids and fatty acid esters of hydroxy fatty acids) showed significant alterations. Metabolomic analysis identified 15 differential metabolites, indicating disrupted nucleotide and amino acid metabolism. Furthermore, the dysregulated lipids and metabolites correlated with various blood indicators, with ceramide and nucleosides positively associated with white blood cell count but negatively correlated with hemoglobin and platelet. Conclusion These findings shed light on abnormal molecular signatures contributing to pediatric ALL and may serve as potential biomarker panel for therapy of ALL.

Evaluation of the Patient-Specific Functional Scale for monitoring paediatric injury patients at a zonal referral hospital in Northern Tanzania

BackgroundInjuries are a major cause of morbidity and mortality among paediatric populations in low- and middle-income countries (LMICs). The Patient-Specific Functional Scale (PSFS) is a commonly used tool to assess...

Pubertal induction therapy in pediatric patients with Duchenne muscular dystrophy.

We conducted a scoping review and analyzed the medical literature on PubMed to assess any potential short-term and long-term benefits of pubertal induction in patients with DMD. We identified six articles from our research cumulatively reporting clinical data from 58 pediatric patients with DMD, of age between 12 and 17.7 years. All of them were on glucocorticoid therapy with variable duration and the longest follow-up of 11.7 years. In all patients, the induction protocol was successful (leading to appearance of secondary sexual characteristics); no secondary effects were reported by any analyzed studies. Three papers reported an objective improvement of patients' quality of life, while in four there was a benefit on the bone profile. Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder that affects approximately 1 in 5,000 live-born male children. Because of early and chronic exposure to glucocorticoids, used as standards of care, pubertal development may be variable. While some boys experience a normal pubertal growth spurt, others have testosterone levels below the normal range for age and require pubertal induction therapy to achieve an adequate testicular volume, development of secondary sexual characteristics, and peak bone mass. When and how to use pubertal induction therapy in pediatric patients with DMD is still object of controversy. The reported evidence of testosterone therapy in patients with DMD is still limited to small cohort sizes, which suggest efficacy and psychosocial benefits.

Device Survival After Pediatric Cochlear Implant Surgery: A 15-Year Single-Center Retrospective Analysis.

To evaluate device survival and identify risk factors for failure in pediatric cochlear implant (CI) surgery to guide strategies for minimizing failure rates and improving survival outcomes. A retrospective analysis was conducted on pediatric patients who underwent CI surgery at the Children's Hospital, Zhejiang University School of Medicine, from September 2008 to September 2023. Device survival was assessed using the Kaplan-Meier method while independent factors influencing device survival were analyzed using the log-rank test and Cox regression model. Among 602 children, the mean age at first CI surgery was 50.3 months (range = 8-155 months). The cohort included 353 males (58.6%) and 249 females (41.4%). Revision surgery was required in 28 cases (4.7%), primarily due to device failure (17/28, 60.7%), including 14 hard and 3 soft failures. Kaplan-Meier analysis showed CI survival rates of 99.1%, 98.1%, 96.7%, 96.4%, and 96.4% at 1, 2, 3, 5, and 10 years post-surgery, respectively. The log-rank test identified sex, age, and history of head trauma as significant factors affecting device survival (P < .05). Multivariate Cox regression confirmed that male sex, first implantation ≤3 years of years, and postoperative head trauma were independent risk factors for device failure. Pediatric cochlear implantation is generally safe and effective, though device failure remains a concern, necessitating revision surgery remains. Male children who undergo cochlear implantation at ≤3 years of age or have a history of postoperative head trauma require enhanced postoperative care. This includes avoiding vigorous head impacts and increasing follow-up visits to monitor device function and speech recovery. Manufacturers should prioritize developing more durable, impact-resistant cochlear implants to reduce failure rates and improve long-term device survival.

Eladocagene Exuparvovec for Aromatic L-Amino Acid Decarboxylase Deficiency.

This JAMA Insights discusses the US Food and Drug Administration approval of Kebilidi, eladocagene exuparvovec, for the treatment of aromatic L-amino acid decarboxylase deficiency in adult and pediatric patients.

Diagnostic characterization and morbi-mortality in pediatric patients with diagnosis of vascular ring

To analyze the clinical characteristics and natural history of pediatric patients with a diagnosis of vascular ring. We retrospectively studied the records of 110 patients of pediatric age, from January 2014 to December 2022, with the following variables: age, clinical manifestations, associated cardiac lesions, diagnostic method and surgical approach. Of the total, 60 (55%) were female and 50 (45%) were male. Diagnosis was made, on average, at 47 months of life. The vascular rings found were aberrant subclavian artery (82.8%), circumflex aorta (8.1%), double aortic arch (6.3%) and left pulmonary artery sling (1.8%). Ninety percent of the cases were associated with other congenital heart disease, mainly tetralogy of Fallot, pulmonary valve atresia and ventricular septal defect. Forty-five percent of the cases produced compression of structures and 77% of the patients were asymptomatic. Twenty-one percent of the patients received surgical treatment of which 35% presented postoperative complications: sepsis (26%), mediastinitis (4.3%) and cardiogenic shock (4.3%). Postoperative mortality was 17%. Within the natural history of symptomatic patients who remained in expectant management, 100% resolved their symptoms. In this series, the most frequent type of vascular ring was aberrant subclavian artery. Diagnosis is late due to the lack of specificity of its symptoms, being mainly respiratory. The symptoms of mild involvement resolve in most cases, associated with the growth of the affected structures and their laxity.

A Clinical, Morphologic, and Molecular Comparison of Bonafide Spitz Melanomas and ASTs in the Pediatric Population.

Pediatric Spitz melanoma (SM) with bonafide metastatic disease is rare. In this study, we assembled the largest cohort to date of pediatric SM with a verified Spitz-associated genomic driver and clinical follow-up demonstrating bonafide metastasis. We compared the clinical, morphologic, and molecular features of these SMs to a control cohort of 57 pediatric atypical Spitz tumors (ASTs). Pediatric SM patients were older than AST patients (12 vs. 8years of age), also statistically more likely to be heavily pigmented (5/8 SMs vs. 11/57 ASTs), have severe nuclear atypia (7/8 SMs vs. 20/57 ASTs), have greater mitotic activity (avg of 5.4/mm2 in SMs and 2.7/mm2 in ASTs) and more likely to have a sheet-like growth pattern (4/8 SMs vs. 8/57 ASTs). However, none of these features were specific and could also be seen in ASTs. The presence of homozygous deletions of 9p21 in conjunction with TERT promoter hot spot mutations or PTEN deletions (n=3), as well as MYC overexpression or amplification (n=2) were only seen in the SMs and none of the ASTs. These findings were mutually exclusive in the SM group and mutually exclusive with the presence of complex chromosomal copy number aberrations, which were seen in the remaining 3 pediatric SMs. This study demonstrates that there are multiple pathways to malignancy for pediatric SMs and none of our commonly used biomarkers have a particularly high sensitivity. Hence, the optimal distinction of pediatric SM from ASTs will continue to require the integration of clinical, histologic, and molecular data.

Case Report and Literature Review of 10 Pediatric Cases of Knee Pigmented Villonodular Synovitis.

This study was aimed to analyze 10 pediatric cases of pigmented villonodular synovitis (PVNS) of the knee to elucidate their clinical features, diagnosis, treatments, and prognosis for providing reference regarding its clinical management in children. A retrospective analysis was made pertaining to the clinical manifestations, magnetic resonance imaging (MRI) findings, pathology, immunohistochemical results, treatment methods, and follow-up outcomes of 10 pediatric PVNS patients of the knee treated from January 2022 to January 2024 at our hospital. They were compared and analyzed with existing literature. (1) All 10 patients had joint swelling with restricted movement, mainly in older female children with male-to-female ratio of 3:7 and average age of 14.1 ± 3.6 years; (2) diagnostic positive rate of MRI was 80%; (3) significant features of PVNS were the appearance of villous and nodular hyperplasia on synovial surface and deposition of brownish-yellow granular hemosiderin. Immunohistochemical staining results were clusterin (synovial cells+), D2-40 (synovial cells+), CD163 (histiocytes+), KP-1 (histiocytes+), CD31 (vascular+), P63 (-), and Ki67 (+, 1%-10%); and (4) all patients underwent arthroscopic surgery with 20% recurrence rate. Pediatric knee PVNS is more prevalent in older female children. The PVNS diagnosis is carried out by MRI, pathology, and immunohistochemistry. Arthroscopic surgery is effective for treating this condition in children.

Identification of distinct clinical profiles of sepsis risk in paediatric emergency department patients using Bayesian profile regression

BackgroundSepsis affects 25 million children and neonates annually, causing significant mortality and morbidity. Early identification and treatment are crucial for improving outcomes. Identifying children at risk is challenging due to...

Cardiogenic Shock Risk Score at Diagnosis of Multisystem Inflammatory Syndrome in Children: A Multicenter Study.

Severe cardiovascular involvement is associated with mortality in multisystem inflammatory syndrome in children (MIS-C). This study aimed to test a previously published cardiogenic shock risk score at diagnosis of MIS-C and build a new screening tool in a larger pediatric cohort. The first score published in a single-center cohort (age > 8years, time to diagnosis ≥ 6days, and NT-proBNP at diagnosis ≥ 11.103ng/L) was tested in a multicenter cohort of pediatric patients diagnosed with MIS-C from 2020 to 2023. In the multicenter cohort, the factors associated with the occurrence of cardiogenic shock were determined and a new score was built using a multivariate regression model. In 127 children with MIS-C, (median age [interquartile range] 8.6 [5.2; 11.5] years, 67 (53%) patients with cardiogenic shock), age > 8years, time to treatment ≥ 6days, dyspnea, altered mental status, general deterioration, gastrointestinal symptoms, ≤ 1 Kawasaki sign, absence of rhinopharyngitis signs, NT-proBNP ≥ 11.103ng/L, high C-Reactive Protein (CRP), and high leucocytes at diagnosis of MIS-C were associated with a high risk of cardiogenic shock. The new score was 0.128*Age(year) + 1.195*(1 if dyspnea, 0 otherwise) + 0.007*CRP(mg/L)-2.6732. The sensitivity was 0.88 and negative likelihood ratio 0.23 (cutoff -0.4761). The score correlated with the minimal left ventricular ejection fraction (ρ = 0.51, p < 0.001). In a multicenter cohort, each item of the previous score was associated with the occurrence of cardiogenic shock. The new score, combining age, dyspnea, and CRP at diagnosis of MIS-C, had a high sensitivity.

Clinical evaluation and risk factors of head-up tilt test in children.

The head-up tilt test (HUTT) is a fundamental tool for the clinical diagnosis of unexplained syncope. While HUTT has been extensively employed in adult populations for over three decades, its application in pediatric cases remains relatively limited. A comprehensive literature review was conducted to perform a multi-dimensional evaluation of HUTT in pediatric patients. This review focused on the differences in methodologies and diagnostic criteria for children versus adults, described diagnostic accuracy and safety of HUTT, and summarized risk factors of syncope events during the HUTT. Notable differences in HUTT between children and adults are evident across various parameters such as tilt angle, tilt duration, and the administration of pharmacological agents. In pediatric patients, HUTT not only helps in determining the subtype of orthostatic intolerance but also facilitates the identification of the etiology of unexplained symptoms such as syncope, sighing, palpitations, chest pain, and abdominal pain. Severe adverse events are uncommon; nevertheless, registered events include different types of arrhythmias or even cardiac arrest, temporary aphasia, convulsions, seizure-like activities, and psychological and psychiatric symptoms. Furthermore, the occurrence of syncope events during the HUTT is influenced by multiple factors including age, sex, height, weight, systolic blood pressure, diastolic blood pressure, hemodynamic type, average hemoglobin concentration levels of creatine kinase activity levels genetic predispositions, multivitamin status among others.

High prevalence of low-level viremia among infants initiated on antiretroviral drugs following mother-to-child transmission of HIV

BackgroundWith the current elimination of mother to child transmission (EMTCT) of HIV, the number of HIV-positive newborns has greatly reduced. Some countries have successfully eliminated HIV infections among newborn babies.MethodsThis study was nested within the DRIBS (Drug Resistance testing among Infants at Baseline Study), which enrolled 100 infants at the time of treatment initiation between 2017 and 2023. Infants were followed for two years. Viral load (VL) was measured every six months and after completion of the three sessions of intensified adherence counseling (IAC). IAC and HIV drug resistance testing were performed for VL greater than 1000 copies/ml.ResultsThe median age at diagnosis was 79 (IQR, 57.75;140.75) days, with 4% of patients diagnosed within 6 weeks after delivery. The median age at the initiation of therapy was 110.5 (IQR, 87.0–162.0) days. The median baseline %CD4 was 26 (IQR, 18.75;32), with 9% of the babies being severely immunosuppressed (%CD4 < 15%). The median baseline log viral load was 4.44 (IQR, 3.19–5.58). At six months, 30% and 60% of the patients had a VL < 50 and < 1000 copies/ml, respectively. At 12 months, 36% and 69% of patients had a VL < 50 and < 1000 copies/ml, respectively. At 24 months, 63% and 83% had VL < 50 and < 1000 copies/ml, respectively. Post-IAC VL revealed that 35% of the children had low-level viremia (LLV) compared to mothers 11.5%. Kaplan-Meyer survival estimates showed that while it took 72 weeks for 50% of the mothers and infants to attain a VL less than 1000 copies/ml, it took 96 weeks for the infants to attain a VL < 50 copies/ml.ConclusionA Viral load < 1000 copies/ml is achieved much more slowly in pediatric patients, implying that it might take longer for babies to achieve the third 95 (95% virally suppressed) of the UNAIDS targets. Furthermore, the greater prevalence of LLV in pediatric patients than in mothers has important implications for the response to therapy.

Virulence factors, molecular characteristics, and resistance mechanisms of carbapenem-resistant Pseudomonas aeruginosa isolated from pediatric patients in Shanghai, China

BackgroundThe investigation into virulence factors, clinical and molecular characteristics, and resistance mechanisms of carbapenem-resistant Pseudomonas aeruginosa (CRPA) in pediatric populations is currently inadequate.PurposeThis study aimed to investigate the virulence factors, clinical and molecular characteristics, and resistance mechanisms of 135 CRPA isolates in Shanghai, China.MethodsAnalysis of virulence-associated genes and multilocus sequence typing (MLST) provided epidemiological and molecular insights into the isolates. Resistance mechanisms were identified via PCR, sequencing, and qRT-PCR.ResultsThe predominant resistance mechanism to carbapenems was the decreased production of outer membrane porin OprD (75.6%), accompanied by mutational inactivation of the oprD (87.4%). However, elevated production of AmpC (7.4%) and mexB overexpression (5.2%) were uncommon. Thirty-five sequence types (STs) were identified, with clonal complex 244 (CC244;59.3%) representing the majority of infections. Sixteen virulence factor genes were detected, with a significant portion of isolates (40.7%) concurrently possessing Toxin A (toxA), Elastase B (lasB), Exoenzyme S (exoS), staphylolysin (lasA), and Pilin (pilA). Almost all CC244 isolates carried toxA (100%), exoS (100%), pilA (100%), lasB (98.6%), and lasA (82.5%) while all ST2100, ST274, ST1129, ST446, and ST2069 isolates contained exoY. CC244 + isolates exhibited significantly increased antibiotic resistance, and the isolates from diseased or discharged patients showed comparatively higher resistance than others, except against gentamicin. Most patients (71.9%) received combination therapy, with 65.2% achieving clinical cure or improvement.ConclusionThis study predominantly identified OprD-mediated carbapenem resistance in pediatric patients. The CRPA isolates were characterized by a variety of STs and a widespread distribution of virulence-associated genes. CC244 demonstrated significantly higher resistance, with potential outbreaks occurring in 2018 and 2019. These findings could aid in managing nosocomial CRPA infections and enhancing clinical practices.

Association of Social Determinants of Health With Genetic Test Request and Completion Rates in Children With Neurologic Disorders.

Genetic testing is critical for optimal diagnosis and management of pediatric neurology patients, but access is challenging. We investigated whether social determinants of health (SDOH) were associated with genetic testing among pediatric neurology patients in a retrospective observational study. Electronic health record data were extracted from pediatric outpatients (0-18 years) evaluated at a single tertiary care institution between July 2018 and January 2020. Genetic testing requests, insurance denials, and test completion rates were compared among non-Hispanic single-racial or multiracial Black (Black) vs non-Hispanic single-racial White (White) patients. SDOH and clinical variables including ethnoracial identity, insurance type, Area Deprivation Index, rural urban commuting area, sex, age, diagnoses, and number of neurology visits were evaluated to identify associations with chromosomal microarray (CMA), multigene panel (MGP), and exome/genome sequencing (ES/GS) test completion. Of 11,371 patients (mean age 9.25 years; 46.1% female), 554 (4.9%) completed ≥1 genetic test in the study interval, with White patients nearly twice as likely to have completed ≥1 genetic test compared with Black patients (aOR 1.88, 95% CI 1.41-2.51). Outpatient pediatric neurology was the most common specialty through which testing was completed. Neurology provider request rates for genetic testing did not differ by patient ethnoracial identity, but insurance denial rates after neurology request were lower for White vs Black patients (relative rate ratio [RR] 0.44, 95% CI 0.27-0.73), and those with public insurance were less likely to complete genetic testing after it was requested through neurology (aOR 0.59, 95% CI 0.35-0.97). However, when considering individual genetic test types completed through any specialty, insurance type was significantly associated only with MGP completion (public vs private OR 0.56, 95% CI 0.40-0.77), not CMA or ES/GS. Marked ethnoracial disparities in genetic testing completion were identified despite equivalent rates of genetic testing requests by neurologists. While Black patients had higher rates of insurance denials, insurance type itself accounted for the disparity in MGP but not CMA or ES/GS completion. Other unmeasured barriers stemming from systemic racism likely affected genetic testing among Black patients.

We are obligated to exercise due diligence-but what does this look like in practice?

Expert reports analyze medical malpractice in urology based on selected case studies and assess their medical and legal implications. Common sources of error include noncompliance with clinical guidelines, inadequate patient information, insufficient diagnostics, and alack of interdisciplinary coordination. The cases include, among others, incorrect biopsy techniques, delayed stroke diagnoses, failure to communicate pathological findings, and problematic coercive measures in pediatric patients. The legal assessments highlight the importance of thorough documentation and effective patient communication in mitigating liability risks. In several cases, diagnostic errors result in areversal of the burden of proof in favor of the patient. The expert report emphasizes the necessity of astructured, evidence-based, and interdisciplinary approach to minimize treatment errors and their consequences.

Refeeding syndrome and rumination in a pediatric patient: A case report reflecting an underdiagnosed pediatric emergency

AbstractRefeeding syndrome (RS) is a potentially life‐threatening acute metabolic deterioration, affecting malnourished individuals. Although it is a well described condition, the evidence in pediatric population is limited. Herein, we describe a case of a 7‐year‐old patient with rumination syndrome and developmental delay, complicated with RS during the course of an acute gastroenteritis.

Vascularized fibular epiphyseal transfer for biological reconstruction of bone defects following resection in children with proximal humeral sarcoma

BackgroundThe functional reconstruction of bone defects following resection of proximal humerus tumors in children poses a significant challenge. This study utilized vascularized fibular epiphyseal transfer for proximal humerus reconstruction to evaluate the outcome, complications, and survival rates.MethodsIn this study, we conducted a retrospective analysis of 13 pediatric patients who underwent vascularized fibular epiphyseal transfer for biological reconstruction following oncologic resection of the proximal humerus between 2019 and 2021. All patients received adequate preoperative preparation and evaluation, and complications were meticulously recorded. Regular functional follow-ups and imaging evaluations were performed.ResultsA total of 13 patients with an average age of 9.8 years were included in this study. The average length of the humerus defect after surgical resection was 13.7 cm (9.4–17.8 cm). Delayed wound healing was observed in 2 patients, and one patient experienced brief common peroneal nerve palsy. There were 3 cases of graft fracture, all of which occurred within 1 year after operation. These cases were successfully managed through the application of draping plaster or brace fixation. The mean follow-up period was 39.8 months (ranging from 19 to 57 months). The mean Musculoskeletal Tumor Society (MSTS) score was 21.5 (18–24). All patients reported no persistent pain.ConclusionIn conclusion, we assert that vascularized fibular epiphyseal transfer provides a reliable and promising option for reconstruction in pediatric patients undergoing proximal humerus tumor resection surgery. Graft fractures were the most prevalent complication, emphasizing the importance of cautionary measures to prevent falls or trauma. However, further validation through increased case numbers and extended follow-up periods is necessary.

Abstract B031: Enhancing clinical decision-making: ex vivo drug sensitivity profiling to rapidly complement molecular profiling in pediatric precision medicine

Abstract Pediatric patients with high-risk extra-cranial solid tumors face a 5-year survival rate below 50%. As molecular profiling alone is insufficient to guide clinical decisions, functional profiling is essential to improve precision medicine. Current pre-clinical models are costly and too slow to benefit patients. We propose ex vivo short-term drug screening of tumor material as feasible model for predicting drug sensitivities in solid tumors, providing rapid, actionable insights to guide treatment. The ITCC-P4 consortium established 350 pediatric cancer PDX models. The Princess Máxima Center selected 37 models for ex vivo short-term screens, where the fresh tissue is cultured for a short period of time before drug sensitivity testing. In the Curie institute, an additional 33 models were selected. Drug sensitivity was assessed for 77-224 compounds, depending on the cell number. Whole genome sequencing, RNA sequencing, and methylation profiling were performed on the original patient tumor and PDX models. Drug sensitivity profiling of 70 pediatric pan-cancer models was successfully performed within 14 days after receiving the sample. The profiles demonstrate reliable, clinically relevant drug responses. In addition to identifying effective compounds for individual tumor types, biomarkers of response were identified within subgroups. For example, TP53 inactivation corresponded to significantly decreased sensitivity to idasanutlin and selinexor, and ALK-inhibitor sensitivity was confirmed in cases with increased ALK expression. Interestingly, sensitivity to cytotoxic compounds that target the cytoskeleton and topoisomerase inhibitors both show a strong dependency on the growth rate of the models. Importantly, screening results from both institutes consistently identified top effective drugs for models from the same patient (n = 6). Serial in vitro models of two Ewing patients, including primary and progression under treatment samples, show tumor progression and shifting therapeutic windows. Our results indicate that functional profiling can expand treatment possibilities found by molecular profiling. By determining drug hits using AUC and IC50 based criteria, we identified drug hits for 95% of samples (n=35) from the Princess Maxima Cohort. This includes 7 patients for whom molecular profiling failed to identify targetable alterations. Additionally, functional profiling refines drug choice by testing multiple therapeutic options for a genetic alteration. Ex vivo short-term screening is a feasible and rapid method to determine drug sensitivities of fresh tumor tissue. It confirms known genetic-drug response associations and provides novel insights into compound effectiveness in pediatric tumors. Shifting therapeutic responses in serial models highlight the importance of functional profiling at different timepoints. Currently, this method is expanded to include fresh patient samples. Ex vivo short-term screens offer a valuable tool for clinical decision-making, enabling precise, individualized treatments for high-risk pediatric solid tumors. Citation Format: Marlinde C. Schoonbeek, Pierre Gestraud, Lindy Vernooij, Eleonora J. Looze, Sarah E. M. Swaak, Vicky Amo-Addae, Elaine Del Nery, Angela Bellini, Jan Koster, Selma Eising, Sander Van Hooff, Marlinde L. van den Boogaard, Gudrun Schleiermacher, Jan J Molenaar. Enhancing clinical decision-making: ex vivo drug sensitivity profiling to rapidly complement molecular profiling in pediatric precision medicine [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr B031.