Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of NRAS (n = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. In summary, we provide future diagnostic and therapeutic guidance for PDLMM and first insights into the use of liquid biopsy and in vitro models for this orphan cancer type.

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Objectives: In critical care it is crucial to appropriately assess the risk of mortality for each patient. This is especially relevant in pediatrics, with its need for accurate and repeatable scoring. Aim of this study was to evaluate an age-adapted version of the expanded Simplified Acute Physiology Score II; (p-SAPS II), a repeatable, newly-designed scoring system compared to established scores (Pediatric Sequential Organ Failure Assessment Score/pSOFA, Pediatric Logistic Organ Dysfunction Score-2/PELOD-2 and Pediatric Index of Mortality 3/PIM3).Design: This retrospective cohort pilot study included data collected from patients admitted to the Pediatric Intensive Care Unit (PICU) at the Medical University of Vienna between July 2017 through December 2018.Patients: 231 admissions were included, comprising neonates (gestational age of ≥ 37 weeks) and patients up to 18 years of age with a PICU stay longer than 48 h.Main Outcomes: Mortality risk prediction and discrimination between survivors and non-survivors were the main outcomes of this study. The primary statistical methods for evaluating the performance of each score were the area under the receiver operating characteristic curve (AUROC) and goodness-of-fit test.Results: Highest AUROC curve was calculated for p-SAPS II (AUC = 0.86; 95% CI: 0.77–0.96; p < 0.001). This was significantly higher than the AUROCs of PELOD-2/pSOFA but not of PIM3. However, in a logistic regression model including p-SAPS II and PIM3 as covariates, p-SAPS II had a significant effect on the accuracy of prediction (p = 0.003). Nevertheless, according to the goodness-of-fit test for p-SAPS II and PIM3, p-SAPS II overestimated the number of deaths, whereas PIM3 showed acceptable estimations. Repeatability testing showed increasing AUROC values for p-SAPS II throughout the clinical stay (0.96 at day 28) but still no significant difference to PIM 3. The prediction accuracy, although improved over the days and even exceeded PIM 3.Conclusions: The newly-created p-SAPS II performed better than the established PIM3 in terms of discriminating between survivors and non-survivors. Furthermore, p-SAPS II can be assessed repeatably throughout a patient's PICU stay what improves mortality prediction. However, there is still a need to optimize calibration of the score to accurately predict mortality sooner throughout the clinical stay.

Aim: Successful mother-child-bonding is a fundamental step for a healthy development of the child. Different factors like postpartum depression can hinder the bonding process. This study aimed to investigate how intensive care treatment due to congenital heart diseases of the infant alters bonding and how mothers cope with the situation.Methods: Validated questionnaires were used to analyse postpartum depression, mother-child bonding, stress factors and coping strategies for mothers at a paediatric intensive care unit (PICU; n = 38) and a group of mothers without known psychiatric disorders attending a babywell visit with their child (n = 91). Descriptive statistics and interaction models were calculated. Results:The PICU group showed on average higher total scores on the postpartum bonding questionnaire indicating mother-child bonding impairment and a higher proportion of mothers with depression was observed (76% vs 11%). The model showed a significant interaction between effective coping strategies and mother infant bonding (p = 0.04). Ineffective coping had no effect on bonding or depression in the PICU group. Conclusion: Mothers of children treated at an ICU due a congenital heart disease are at increased risk for the development of depression and difficulties in different aspects of postpartum bonding. Our results show that coping mechanisms might significantly influence postpartum bonding. Implementation of tailored support is needed to optimise maternal outcomes.

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