Determinants of impairments in functioning, fatigue and participation ability in pediatric brain tumor survivors

Introduction Pediatric brain tumor survivors (PBTS) experience disease- and treatment-related sequelae. We aimed to investigate the occurrence of participation limitations, impairments in functioning, fatigue, and the association between patient, tumor- and treatment-related factors and these outcomes. Methods Children (4-18 years) after treatment for a brain tumor between 2005-2014 at the Erasmus Medical Center, Rotterdam, the Netherlands, were eligible. The parent-reported Child and Family Follow-up Survey developed to measure participation and impairments in functioning in youth with acquired brain injury, was used. Fatigue was assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale. Associations with patient, tumor- and treatment-related factors were explored using univariable analyses. Results Ninety-one PBTS (median age: 11.3 years [range: 9.5-14.1], time since treatment: 3.9 years [range: 4-6.2]) were included (response rate: 55%). Participation limitations were reported in 53% and were associated with impairments in functioning (15-67%) (p≤0.01) and fatigue (p≤0.03). Parent- and child-reported fatigue was increased compared to normative values (p=≤0.02). History of hydrocephalus was associated with increased fatigue (p≤0.04). Younger age at diagnosis and longer time since diagnosis were associated with impairments in functioning and cognitive fatigue (p=<0.05). Participation limitations, impairments in functioning and fatigue were similar in PBTS who were <3 or ≥3 years since completion of treatment. Conclusion More than half of PBTS reported limited participation ability, which is associated with impairments in functioning and fatigue. The complication hydrocephalus seems to lead to more fatigue. Participation limitations, impairments in functioning and fatigue appear not to diminish in the longer term.

OS10.3.A Predicting delirium after craniotomy in neuro-oncology

BACKGROUND Post-operative delirium (POD) is a frequent and severe complication after neurosurgical operations. Good prediction of POD after craniotomy in neuro-oncologic patients is important to install prophylactic measures, increase recognition and apply early treatment. Hence, we compared logistic regression with machine learning to build an accurate predictive model in a large dataset. MATERIAL AND METHODS POD was defined in case of a Delirium Observation Scale (DOS) ≥ 3 or start of antipsychotic treatment for delirium within 10 days after surgery. Adult patients undergoing a craniotomy for a neuro-oncologic disease in the Erasmus Medical Centre in Rotterdam were retrospectively included. The cohort was split into a training (75%), after three-fold cross validation, and test set (25%). Logistic regression and Lasso Elastic-Net Regularized Generalized Linear Models (GLMNet) were trained based on 19 pre- and intra-operative features and risk factors were identified based on the superior model. RESULTS We included 1025 neuro-oncologic craniotomies between June 2017 and September 2020. Overall incidence of POD was 18.6% (95%CI 17.4–19.8). Compared to logistic regression, Lasso GLMNet performed superior (AUC 0.73 vs. 0.76) based on the optimal tuning parameters (α=1, λ=0.014). Several non-modifiable risk factors such as age (OR1.01), prior delirium (OR1.04), memory problems (OR1.12), surgery duration (OR1.01) and modifiable risk factors, such as low potassium (OR0.97) levels and opioid administration (OR1.03), were identified. CONCLUSION POD is a frequent complication after craniotomy in neuro-oncologic patients. Lasso GLMNet was useful in predicting POD in this cohort. Validation in a prospective cohort of this model should be applied to further evaluate its value in diminishing POD.

Clinical signs, interventions, and treatment course of three different treatment protocols in patients with Crouzon syndrome with acanthosis nigricans

OBJECTIVE Crouzon syndrome with acanthosis nigricans (CAN) is a rare and clinically complex subtype of Crouzon syndrome. At three craniofacial centers, this multicenter study was undertaken to assess clinical signs in relation to the required interventions and treatment course in patients with CAN. METHODS A retrospective cohort study of CAN was performed to obtain information about the clinical treatment course of these patients. Three centers participated: Erasmus Medical Centre, Rotterdam, the Netherlands; John Radcliffe Hospital, Oxford, United Kingdom; and Hôpital Necker-Enfants Malades, Paris, France. RESULTS Nineteen patients (5 males, 14 females) were included in the study. All children were operated on, with a mean of 2.2 surgeries per patient (range 1–6). Overall, the following procedures were performed: 23 vault expansions, 10 monobloc corrections, 6 midface surgeries, 11 foramen magnum decompressions, 29 CSF-diverting surgeries, 23 shunt-related interventions, and 6 endoscopic third ventriculostomies, 3 of which subsequently required a shunt. CONCLUSIONS This study demonstrates that patients with the mutation c.1172C>A (p.Ala391Glu) in the FGFR3 gene have a severe disease trajectory, requiring multiple surgical procedures. The timing and order of interventions have changed among patients and centers. It was not possible to differentiate the effect of a more severe clinical presentation from the effect of treatment order on outcome.

Procalcitonin Predicts Intensive Care Unit Admission and Mortality in Patients With A COVID-19 Infection in The Emergency Department

IntroductionPatients with a severe COVID-19 infection often require admission at an intensive care unit (ICU) when they develop acute respiratory distress syndrome (ARDS). Hyperinflammation plays an important role in the development of ARDS in COVID-19. Procalcitonin (PCT) is a biomarker which may be a predictor of hyperinflammation. When patients with COVID-19 are in the emergency department (ED), PCT could be a predictor of severe COVID-19 infection. The goal of this study is to investigate the predictive value of PCT on severe COVID-19 infections in the ED. MethodsThis was a retrospective cohort study including patients with confirmed COVID-19 infection who visited the ED of Erasmus Medical Center in Rotterdam, the Netherlands, between March and December 2020. The primary endpoint was a severe COVID-19 infection, which was defined as patients who required ICU admission, in-hospital mortality and 30-day mortality after hospital discharge. PCT levels were measured during the ED visit. We used logistic regression to calculate the odds ratio (OR) of PCT on a severe COVID-19 infection, adjusting for bacterial coinfections, age, gender and comorbidities. ResultsA total of 332 patients were included in the final analysis of this study, of which 105 patients reached the composite endpoint of a severe COVID-19 infection. PCT showed an unadjusted OR of 4.19 (CI: 2.52-7.69) on a severe COVID-19 infection. Corrected for bacterial coinfection, the OR of PCT was 4.05 (2.45 – 7.41). Adjusted for gender, bacterial coinfection, age and comorbidities, PCT was still an independent predictor of severe COVID-19 infection with an adjusted OR of 3.82 (CI: 2.26-7.48).ConclusionPCT is a predictor of severe COVID-19 infections in patients with a COVID-19 infection in the ED. The routine measurement of PCT in patients with a COVID-19 infection in the ED may assist physicians in the clinical decision making process regarding ICU disposition when PCT levels are elevated.

Procalcitonin Predicts Intensive Care Unit Admission and Mortality in Patients With a COVID-19 Infection in the Emergency Department

IntroductionPatients with a severe COVID-19 infection often require admission at an intensive care unit (ICU) when they develop acute respiratory distress syndrome (ARDS). Hyperinflammation plays an important role in the development of ARDS in COVID-19. Procalcitonin (PCT) is a biomarker which may be a predictor of hyperinflammation. When patients with COVID-19 are in the emergency department (ED), PCT could be a predictor of severe COVID-19 infection. The goal of this study is to investigate the predictive value of PCT on severe COVID-19 infections in the ED. MethodsThis was a retrospective cohort study including patients with confirmed COVID-19 infection who visited the ED of Erasmus Medical Center in Rotterdam, the Netherlands, between March and December 2020. The primary endpoint was a severe COVID-19 infection, which was defined as patients who required ICU admission, in-hospital mortality and 30-day mortality after hospital discharge. PCT levels were measured during the ED visit. We used logistic regression to calculate the odds ratio (OR) of PCT on a severe COVID-19 infection, adjusting for bacterial coinfections, age, gender and comorbidities. ResultsA total of 332 patients were included in the final analysis of this study, of which 105 patients reached the composite endpoint of a severe COVID-19 infection. PCT showed an unadjusted OR of 4.19 (CI: 2.52-7.69) on a severe COVID-19 infection. Corrected for bacterial coinfection, the OR of PCT was 4.05 (2.45 – 7.41). Adjusted for gender, bacterial coinfection, age and comorbidities, PCT was still an independent predictor of severe COVID-19 infection with an adjusted OR of 3.82 (CI: 2.26-7.48).ConclusionPCT is a predictor of severe COVID-19 infections in patients with a COVID-19 infection in the ED. The routine measurement of PCT in patients with a COVID-19 infection in the ED may assist physicians in the clinical decision making process regarding ICU disposition when PCT levels are elevated.

First person – Frederike Riemslagh

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Frederike Riemslagh is first author on ‘Inducible expression of human C9ORF72 36× G4C2 hexanucleotide repeats is sufficient to cause RAN translation and rapid muscular atrophy in mice’, published in DMM. Frederike conducted the research described in this article while a PhD Candidate in Prof. Dr Rob Willemse's lab at Erasmus Medical Center, Department of Clinical Genetics, Rotterdam, The Netherlands. She is now a Postdoctoral Fellow in the lab of Dr Christian Mosimann at the University of Colorado, USA, investigating genetic diseases that affect the heart and brain.

Homologous and heterologous antibodies to coronavirus 229E, NL63, OC43, HKU1, SARS, MERS and SARS-CoV-2 antigens in an age stratified cross-sectional serosurvey in a large tertiary hospital in The Netherlands

Understanding the coronavirus (CoV) antibody landscape in relation to disease and susceptibility is critical for modelling of steps in the next phase during the current covid-19 pandemic. In March 2020, during the first month of the epidemic in The Netherlands, we performed cross sectional studies at two time points amongst patients of the Erasmus Medical Centre in Rotterdam, to assess the presence of antibodies against seasonal human coronaviruses (OC43, 229E, NL63, HKU1), emerging zoonotic coronaviruses (SARS, MERS) and SARS-CoV-2 in nine different age groups. We observed minimal SARS-CoV-2 reactivity early March (0.7% of sera), increasing to 3.0%, four weeks later, suggesting probably undetected cases during this early phase of the epidemic. Antibody responses were mostly coronavirus species specific at young age, but possible cross-reactivity between human seasonal CoVs was observed with increasing age.

Lymphopaenia as a predictor of sarcoidosis in patients with a first episode of uveitis

Background/aimsThe diagnostic properties of conventional diagnostic tests (ACE and chest radiography) for sarcoidosis-associated uveitis are not ideal. The diagnostic value of lymphopaenia for sarcoidosis-associated uveitis is investigated.MethodsA retrospective study of 191 consecutive patients with a first uveitis episode visiting the ophthalmology department (Erasmus Medical Center, Rotterdam, The Netherlands). Receiver operating characteristics (ROC) analysis was performed and compared with known ROC values from literature of conventional diagnostic tests for sarcoidosis-associated uveitis. An ideal cut-off was determined for lymphopaenia by calculation of the highest Youden index.ResultsOut of all patients with first uveitis attack, 32/191 or 17% were subsequently diagnosed with biopsy-proven or radiological diagnosis of sarcoidosis. Lymphopaenia (<1.5×109/L) was significantly more often observed in patients with sarcoidosis-associated uveitis compared with patients with non-sarcoidosis-associated uveitis (p<0.05). The sensitivity and specificity of lymphopaenia was 75 % and 77 %, respectively. The optimal cut-off for lymphopaenia for diagnosing sarcoidosis-associated uveitis was 1.47 ×109/L. Lymphopaenia resulted in a 12.0 (95% CI 4.7 to 30.5 fold risk for having sarcoidosis, corrected for sex, race and age at onset of uveitis in patients with a first uveitis attack.ConclusionLymphopaenia is a non-invasive and useful marker for diagnosing sarcoidosis-associated uveitis.