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  • 1
    Online Resource
    Online Resource
    Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial
    Elsevier BV ; 2021
    In:  The Lancet Neurology Vol. 20, No. 4 ( 2021-04), p. 275-283
    Details
    In: The Lancet Neurology, Elsevier BV, Vol. 20, No. 4 ( 2021-04), p. 275-283
    Type of Medium: Online Resource
    ISSN: 1474-4422
    URL: Article
    DOI: 10.1016/S1474-4422(20)30494-4
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 2
    Online Resource
    Online Resource
    Predictors for extubation failure in COVID-19 patients using a machine learning approach
    Springer Science and Business Media LLC ; 2021
    In:  Critical Care Vol. 25, No. 1 ( 2021-12)
    Details
    In: Critical Care, Springer Science and Business Media LLC, Vol. 25, No. 1 ( 2021-12)
    Abstract: Determining the optimal timing for extubation can be challenging in the intensive care. In this study, we aim to identify predictors for extubation failure in critically ill patients with COVID-19. Methods We used highly granular data from 3464 adult critically ill COVID patients in the multicenter Dutch Data Warehouse, including demographics, clinical observations, medications, fluid balance, laboratory values, vital signs, and data from life support devices. All intubated patients with at least one extubation attempt were eligible for analysis. Transferred patients, patients admitted for less than 24 h, and patients still admitted at the time of data extraction were excluded. Potential predictors were selected by a team of intensive care physicians. The primary and secondary outcomes were extubation without reintubation or death within the next 7 days and within 48 h, respectively. We trained and validated multiple machine learning algorithms using fivefold nested cross-validation. Predictor importance was estimated using Shapley additive explanations, while cutoff values for the relative probability of failed extubation were estimated through partial dependence plots. Results A total of 883 patients were included in the model derivation. The reintubation rate was 13.4% within 48 h and 18.9% at day 7, with a mortality rate of 0.6% and 1.0% respectively. The grandient-boost model performed best (area under the curve of 0.70) and was used to calculate predictor importance. Ventilatory characteristics and settings were the most important predictors. More specifically, a controlled mode duration longer than 4 days, a last fraction of inspired oxygen higher than 35%, a mean tidal volume per kg ideal body weight above 8 ml/kg in the day before extubation, and a shorter duration in assisted mode ( 〈  2 days) compared to their median values. Additionally, a higher C-reactive protein and leukocyte count, a lower thrombocyte count, a lower Glasgow coma scale and a lower body mass index compared to their medians were associated with extubation failure. Conclusion The most important predictors for extubation failure in critically ill COVID-19 patients include ventilatory settings, inflammatory parameters, neurological status, and body mass index. These predictors should therefore be routinely captured in electronic health records.
    Type of Medium: Online Resource
    ISSN: 1364-8535
    URL: Article
    DOI: 10.1186/s13054-021-03864-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2051256-9
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  • 3
    Online Resource
    Online Resource
    Predicting responders to prone positioning in mechanically ventilated patients with COVID-19 using machine learning
    Springer Science and Business Media LLC ; 2022
    In:  Annals of Intensive Care Vol. 12, No. 1 ( 2022-10-20)
    Details
    In: Annals of Intensive Care, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-10-20)
    Abstract: For mechanically ventilated critically ill COVID-19 patients, prone positioning has quickly become an important treatment strategy, however, prone positioning is labor intensive and comes with potential adverse effects. Therefore, identifying which critically ill intubated COVID-19 patients will benefit may help allocate labor resources. Methods From the multi-center Dutch Data Warehouse of COVID-19 ICU patients from 25 hospitals, we selected all 3619 episodes of prone positioning in 1142 invasively mechanically ventilated patients. We excluded episodes longer than 24 h. Berlin ARDS criteria were not formally documented. We used supervised machine learning algorithms Logistic Regression, Random Forest, Naive Bayes, K-Nearest Neighbors, Support Vector Machine and Extreme Gradient Boosting on readily available and clinically relevant features to predict success of prone positioning after 4 h (window of 1 to 7 h) based on various possible outcomes. These outcomes were defined as improvements of at least 10% in PaO 2 /FiO 2 ratio, ventilatory ratio, respiratory system compliance, or mechanical power. Separate models were created for each of these outcomes. Re-supination within 4 h after pronation was labeled as failure. We also developed models using a 20 mmHg improvement cut-off for PaO 2 /FiO 2 ratio and using a combined outcome parameter. For all models, we evaluated feature importance expressed as contribution to predictive performance based on their relative ranking. Results The median duration of prone episodes was 17 h (11–20, median and IQR, N  = 2632). Despite extensive modeling using a plethora of machine learning techniques and a large number of potentially clinically relevant features, discrimination between responders and non-responders remained poor with an area under the receiver operator characteristic curve of 0.62 for PaO 2 /FiO 2 ratio using Logistic Regression, Random Forest and XGBoost. Feature importance was inconsistent between models for different outcomes. Notably, not even being a previous responder to prone positioning, or PEEP-levels before prone positioning, provided any meaningful contribution to predicting a successful next proning episode. Conclusions In mechanically ventilated COVID-19 patients, predicting the success of prone positioning using clinically relevant and readily available parameters from electronic health records is currently not feasible. Given the current evidence base, a liberal approach to proning in all patients with severe COVID-19 ARDS is therefore justified and in particular regardless of previous results of proning.
    Type of Medium: Online Resource
    ISSN: 2110-5820
    URL: Article
    DOI: 10.1186/s13613-022-01070-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2617094-2
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  • 4
    Online Resource
    Online Resource
    Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein
    The American Association of Immunologists ; 2016
    In:  The Journal of Immunology Vol. 197, No. 4 ( 2016-08-15), p. 1074-1088
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 197, No. 4 ( 2016-08-15), p. 1074-1088
    Abstract: EBV is the major infectious environmental risk factor for multiple sclerosis (MS), but the underlying mechanisms remain obscure. Patient studies do not allow manipulation in vivo. We used the experimental autoimmune encephalomyelitis (EAE) models in the common marmoset and rhesus monkey to model the association of EBV and MS. We report that B cells infected with EBV-related lymphocryptovirus (LCV) are requisite APCs for MHC-E–restricted autoaggressive effector memory CTLs specific for the immunodominant epitope 40-48 of myelin oligodendrocyte glycoprotein (MOG). These T cells drive the EAE pathogenesis to irreversible neurologic deficit. The aim of this study was to determine why LCV infection is important for this pathogenic role of B cells. Transcriptome comparison of LCV-infected B cells and CD20+ spleen cells from rhesus monkeys shows increased expression of genes encoding elements of the Ag cross-presentation machinery (i.e., of proteasome maturation protein and immunoproteasome subunits) and enhanced expression of MHC-E and of costimulatory molecules (CD70 and CD80, but not CD86). It was also shown that altered expression of endolysosomal proteases (cathepsins) mitigates the fast endolysosomal degradation of the MOG40–48 core epitope. Finally, LCV infection also induced expression of LC3-II+ cytosolic structures resembling autophagosomes, which seem to form an intracellular compartment where the MOG40–48 epitope is protected against proteolytic degradation by the endolysosomal serine protease cathepsin G. In conclusion, LCV infection induces a variety of changes in B cells that underlies the conversion of destructive processing of the immunodominant MOG40–48 epitope into productive processing and cross-presentation to strongly autoaggressive CTLs.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1600124
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2016
    detail.hit.zdb_id: 1475085-5
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  • 5
    Online Resource
    Online Resource
    Guillain-Barré syndrome after SARS-CoV-2 infection in an international prospective cohort study
    Oxford University Press (OUP) ; 2021
    In:  Brain Vol. 144, No. 11 ( 2021-12-16), p. 3392-3404
    Details
    In: Brain, Oxford University Press (OUP), Vol. 144, No. 11 ( 2021-12-16), p. 3392-3404
    Abstract: In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barré syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies. The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization. Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016] . The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12–22). Patients with SARS-CoV-2 infection shared uniform neurological features, similar to those previously described in other post-viral GBS patients. The frequency (22%) of a preceding SARS-CoV-2 infection in our study population was higher than estimates of the contemporaneous background prevalence of SARS-CoV-2, which may be a result of recruitment bias during the pandemic, but could also indicate that GBS may rarely follow a recent SARS-CoV-2 infection. Consistent with previous studies, we found no increase in patient recruitment during the pandemic for our ongoing International GBS Outcome Study compared to previous years, making a strong relationship of GBS with SARS-CoV-2 unlikely. A case-control study is required to determine if there is a causative link or not.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awab279
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Risk factors for adverse outcomes during mechanical ventilation of 1152 COVID-19 patients: a multicenter machine learning study with highly granular data from the Dutch Data Warehouse
    Springer Science and Business Media LLC ; 2021
    In:  Intensive Care Medicine Experimental Vol. 9, No. 1 ( 2021-12)
    Details
    In: Intensive Care Medicine Experimental, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2021-12)
    Abstract: The identification of risk factors for adverse outcomes and prolonged intensive care unit (ICU) stay in COVID-19 patients is essential for prognostication, determining treatment intensity, and resource allocation. Previous studies have determined risk factors on admission only, and included a limited number of predictors. Therefore, using data from the highly granular and multicenter Dutch Data Warehouse, we developed machine learning models to identify risk factors for ICU mortality, ventilator-free days and ICU-free days during the course of invasive mechanical ventilation (IMV) in COVID-19 patients. Methods The DDW is a growing electronic health record database of critically ill COVID-19 patients in the Netherlands. All adult ICU patients on IMV were eligible for inclusion. Transfers, patients admitted for less than 24 h, and patients still admitted at time of data extraction were excluded. Predictors were selected based on the literature, and included medication dosage and fluid balance. Multiple algorithms were trained and validated on up to three sets of observations per patient on day 1, 7, and 14 using fivefold nested cross-validation, keeping observations from an individual patient in the same split. Results A total of 1152 patients were included in the model. XGBoost models performed best for all outcomes and were used to calculate predictor importance. Using Shapley additive explanations (SHAP), age was the most important demographic risk factor for the outcomes upon start of IMV and throughout its course. The relative probability of death across age values is visualized in Partial Dependence Plots (PDPs), with an increase starting at 54 years. Besides age, acidaemia, low P / F -ratios and high driving pressures demonstrated a higher probability of death. The PDP for driving pressure showed a relative probability increase starting at 12 cmH 2 O. Conclusion Age is the most important demographic risk factor of ICU mortality, ICU-free days and ventilator-free days throughout the course of invasive mechanical ventilation in critically ill COVID-19 patients. pH, P / F ratio, and driving pressure should be monitored closely over the course of mechanical ventilation as risk factors predictive of these outcomes.
    Type of Medium: Online Resource
    ISSN: 2197-425X
    URL: Article
    DOI: 10.1186/s40635-021-00397-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2740385-3
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  • 7
    Online Resource
    Online Resource
    Health-Related Quality of Life in Patients with Spinocerebellar Ataxia: a Validation Study of the EQ-5D-3L
    Springer Science and Business Media LLC ; 2023
    In:  The Cerebellum
    Details
    In: The Cerebellum, Springer Science and Business Media LLC
    Abstract: Although health-related quality of life (HRQoL) has developed into a crucial outcome parameter in clinical research, evidence of the EQ-5D-3L validation performance is lacking in patients with spinocerebellar ataxia (SCA) types 1, 2, 3, and 6. The objective of this study is to assess the acceptability, validity, reliability, and responsiveness of the EQ-5D-3L. For n = 842 predominantly European SCA patients of two longitudinal cohort studies, the EQ-5D-3L, PHQ-9 (Patient Health Questionnaire), and ataxia-specific clinical assessments (SARA: Scale for Assessment and Rating of Ataxia; ADL: activities of daily living as part of Friedreich’s Ataxia Rating Scale; INAS: Inventory of Non-Ataxia Signs) were assessed at baseline and multiple annual follow-ups. The EQ-5D-3L was evaluated regarding acceptability, distribution properties, convergent and known-groups validity, test-retest reliability, and effect size measures to analyze health changes. The non-item response was low (EQ-5D-3L index: 0.8%; EQ-VAS: 3.4%). Ceiling effects occurred in 9.9% (EQ-5D-3L) and 3.0% (EQ-VAS) with a mean EQ-5D-3L index of 0.65 ± 0.21. In total, convergent validity showed moderate to strong Spearman’s rho ( r s 〉 0.3) coefficients comparing EQ-5D-3L and EQ-VAS with PHQ-9, SARA, ADL, and INAS. EQ-5D-3L could discriminate between groups of age, SARA, ADL, and INAS. Intra-class correlation coefficients (EQ-5D-3L ICC : 0.95/EQ-VAS ICC : 0.88) and Kappa statistics (range 0.44 to 0.93 for EQ-5D-3L items) indicated tolerable reliability. EQ-5D-3L shows small (effect size 〈 0.3) to moderate (effect size 0.3–0.59) health changes regarding ataxia severity. The analysis confirms an acceptable, reliable, valid, and responsive recommended EQ-5D-3L in SCA patients, measuring the HRQoL adequately, besides well-established clinical instruments.
    Type of Medium: Online Resource
    ISSN: 1473-4230
    URL: Article
    DOI: 10.1007/s12311-023-01597-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2071266-2
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  • 8
    Online Resource
    Online Resource
    SCAview: an Intuitive Visual Approach to the Integrative Analysis of Clinical Data in Spinocerebellar Ataxias
    Springer Science and Business Media LLC ; 2023
    In:  The Cerebellum
    Details
    In: The Cerebellum, Springer Science and Business Media LLC
    Abstract: With SCAview, we present a prompt and comprehensive tool that enables scientists to browse large datasets of the most common spinocerebellar ataxias intuitively and without technical effort. Basic concept is a visualization of data, with a graphical handling and filtering to select and define subgroups and their comparison. Several plot types to visualize all data points resulting from the selected attributes are provided. The underlying synthetic cohort is based on clinical data from five different European and US longitudinal multicenter cohorts in spinocerebellar ataxia type 1, 2, 3, and 6 (SCA1, 2, 3, and 6) comprising  〉  1400 patients with overall  〉  5500 visits. First, we developed a common data model to integrate the clinical, demographic, and characterizing data of each source cohort. Second, the available datasets from each cohort were mapped onto the data model. Third, we created a synthetic cohort based on the cleaned dataset. With SCAview, we demonstrate the feasibility of mapping cohort data from different sources onto a common data model. The resulting browser-based visualization tool with a thoroughly graphical handling of the data offers researchers the unique possibility to visualize relationships and distributions of clinical data, to define subgroups and to further investigate them without any technical effort. Access to SCAview can be requested via the Ataxia Global Initiative and is free of charge.
    Type of Medium: Online Resource
    ISSN: 1473-4230
    URL: Article
    DOI: 10.1007/s12311-023-01546-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2071266-2
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  • 9
    Online Resource
    Online Resource
    The frequency of non-motor symptoms in SCA3 and their association with disease severity and lifestyle factors
    Springer Science and Business Media LLC ; 2023
    In:  Journal of Neurology Vol. 270, No. 2 ( 2023-02), p. 944-952
    Details
    In: Journal of Neurology, Springer Science and Business Media LLC, Vol. 270, No. 2 ( 2023-02), p. 944-952
    Abstract: Non-motor symptoms (NMS) are a substantial burden for patients with SCA3. There are limited data on their frequency, and their relation with disease severity and activities of daily living is not clear. In addition, lifestyle may either influence or be affected by the occurrence of NMS. Objective To characterize NMS in SCA3 and investigate possible associations with disease severity and lifestyle factors. Methods In a prospective cohort study, we performed a cross-sectional analysis of NMS in 227 SCA3 patients, 42 pre-ataxic mutation carriers, and 112 controls and tested for associations with SARA score, activities of daily living, and the lifestyle factors alcohol consumption, smoking and physical activity. Results Sleep disturbance, restless legs syndrome, mild cognitive impairment, depression, bladder dysfunction and pallhypesthesia were frequent among SCA3 patients, while mainly absent in pre-ataxic mutation carriers. Except for restless legs syndrome, NMS correlated significantly with disease severity and activities of daily living. Alcohol abstinence was associated with bladder dysfunction. Patients with higher physical activity showed less cognitive impairment and fewer depressive symptoms, but these differences were not significant. Conclusion This study revealed a clear association between disease severity and NMS, likely driven by the progression of the widespread neurodegenerative process. Associations between lifestyle and NMS can probably be attributed to the influence of NMS on lifestyle.
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
    URL: Article
    DOI: 10.1007/s00415-022-11441-z
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1421299-7
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  • 10
    Online Resource
    Online Resource
    CerebNet: A fast and reliable deep-learning pipeline for detailed cerebellum sub-segmentation
    Elsevier BV ; 2022
    In:  NeuroImage Vol. 264 ( 2022-12), p. 119703-
    Details
    In: NeuroImage, Elsevier BV, Vol. 264 ( 2022-12), p. 119703-
    Type of Medium: Online Resource
    ISSN: 1053-8119
    URL: Article
    DOI: 10.1016/j.neuroimage.2022.119703
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 1471418-8
    SSG: 5,2
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