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  • 1
    Online Resource
    Online Resource
    Serial measurements in COVID-19-induced acute respiratory disease to unravel heterogeneity of the disease course: design of the Maastricht Intensive Care COVID cohort (MaastrICCht)
    BMJ ; 2020
    In:  BMJ Open Vol. 10, No. 9 ( 2020-09), p. e040175-
    Details
    In: BMJ Open, BMJ, Vol. 10, No. 9 ( 2020-09), p. e040175-
    Abstract: The course of the disease in SARS-CoV-2 infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort (MaastrICCht). We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with a SARS-CoV-2 infection. Methods and analysis Mechanically ventilated patients admitted to the intensive care with a SARS-CoV-2 infection will be included. We will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, ECGs, echocardiography as well as other imaging modalities to assess heterogeneity of the course of a SARS-CoV-2 infection in critically ill patients. The MaastrICCht is also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national intensive care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. The spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS-CoV-2 infection in mechanically ventilated patients. Our study design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht. Ethics and dissemination Ethical approval has been obtained from the medical ethics committee (Medisch Ethische Toetsingscommissie 2020-1565/3 00 523) of the Maastricht University Medical Centre+ (Maastricht UMC+), which will be performed based on the Declaration of Helsinki. During the pandemic, the board of directors of Maastricht UMC+ adopted a policy to inform patients and ask their consent to use the collected data and to store serum samples for COVID-19 research purposes. All study documentation will be stored securely for fifteen years after recruitment of the last patient. The results will be published in peer-reviewed academic journals, with a preference for open access journals, while particularly considering deposition of the manuscripts on a preprint server early. Trial registration number The Netherlands Trial Register (NL8613).
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2020-040175
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2599832-8
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  • 2
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    Pulmonary pathophysiology development of COVID-19 assessed by serial Electrical Impedance Tomography in the MaastrICCht cohort
    Springer Science and Business Media LLC ; 2022
    In:  Scientific Reports Vol. 12, No. 1 ( 2022-08-25)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-08-25)
    Abstract: Patients with SARS-CoV-2 infection present with different lung compliance and progression of disease differs. Measures of lung mechanics in SARS-CoV-2 patients may unravel different pathophysiologic mechanisms during mechanical ventilation. The objective of this prospective observational study is to describe whether Electrical Impedance Tomography (EIT) guided positive end-expiratory pressure (PEEP) levels unravel changes in EIT-derived parameters over time and whether the changes differ between survivors and non-survivors. Serial EIT-measurements of alveolar overdistension, collapse, and compliance change in ventilated SARS-CoV-2 patients were analysed. In 80 out of 94 patients, we took 283 EIT measurements (93 from day 1–3 after intubation, 66 from day 4–6, and 124 from day 7 and beyond). Fifty-one patients (64%) survived the ICU. At admission mean PaO 2 /FiO 2 -ratio was 184.3 (SD 61.4) vs. 151.3 (SD 54.4) mmHg, ( p  = 0.017) and PEEP was 11.8 (SD 2.8) cmH 2 O vs. 11.3 (SD 3.4) cmH 2 O, ( p  = 0.475), for ICU survivors and non-survivors. At day 1–3, compliance was ~ 55 mL/cmH 2 O vs. ~ 45 mL/cmH 2 O in survivors vs. non-survivors. The intersection of overdistension and collapse curves appeared similar at a PEEP of ~ 12–13 cmH 2 O. At day 4–6 compliance changed to ~ 50 mL/cmH 2 O vs. ~ 38 mL/cmH 2 O. At day 7 and beyond, compliance was ~ 38 mL/cmH 2 O with the intersection at a PEEP of ~ 9 cmH 2 O vs. ~ 25 mL/cmH 2 O with overdistension intersecting at collapse curves at a PEEP of ~ 7 cmH 2 O. Surviving SARS-CoV-2 patients show more favourable EIT-derived parameters and a higher compliance compared to non-survivors over time. This knowledge is valuable for discovering the different groups.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-022-18843-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 3
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    Online Resource
    miRNAs Related to Different Processes of Fracture Healing: An Integrative Overview
    Frontiers Media SA ; 2021
    In:  Frontiers in Surgery Vol. 8 ( 2021-11-19)
    Details
    In: Frontiers in Surgery, Frontiers Media SA, Vol. 8 ( 2021-11-19)
    Abstract: Fracture healing is a complex, dynamic process that is directed by cellular communication and requires multiple cell types, such as osteoblasts, osteoclasts, and immune cells. Physiological fracture healing can be divided into several phases that consist of different processes, such as angiogenesis, osteogenesis, and bone resorption/remodelling. This is needed to guarantee proper bone regeneration after fracture. Communication and molecular regulation between different cell types and within cells is therefore key in successfully orchestrating these processes to ensure adequate bone healing. Among others, microRNAs (miRNAs) play an important role in cellular communication. microRNAs are small, non-coding RNA molecules of ~22 nucleotides long that can greatly influence gene expression by post-transcriptional regulation. Over the course of the past decade, more insights have been gained in the field of miRNAs and their role in cellular signalling in both inter- and intracellular pathways. The interplay between miRNAs and their mRNA targets, and the effect thereof on different processes and aspects within fracture healing, have shown to be interesting research topics with possible future diagnostic and therapeutic potential. Considering bone regeneration, research moreover focusses on specific microRNAs and their involvement in individual pathways. However, it is required to combine these data to gain more understanding on the effects of miRNAs in the dynamic process of fracture healing, and to enhance their translational application in research, as well as in the clinic. Therefore, this review aims to provide an integrative overview on miRNAs in fracture healing, related to several key aspects in the fracture healing cascade. A special focus will be put on hypoxia, angiogenesis, bone resorption, osteoclastogenesis, mineralization, osteogenesis, osteoblastogenesis, osteocytogenesis, and chondrogenesis.
    Type of Medium: Online Resource
    ISSN: 2296-875X
    URL: Article
    DOI: 10.3389/fsurg.2021.786564
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2773823-1
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  • 4
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    Online Resource
    DataSheet1.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Chemistry Vol. 9 ( 2022-3-3)
    Details
    In: Frontiers in Chemistry, Frontiers Media SA, Vol. 9 ( 2022-3-3)
    Abstract: Background: Fracture healing is a complex process, involving cell-cell interactions, various cytokines, and growth factors. Although fracture treatment improved over the last decades, a substantial part of all fractures shows delayed or absent healing. The fracture hematoma (fxh) is known to have a relevant role in this process, while the exact mechanisms by which it influences fracture healing are poorly understood. To improve strategies in fracture treatment, regulatory pathways in fracture healing need to be investigated. Lipids are important molecules in cellular signaling, inflammation, and metabolism, as well as key structural components of the cell. Analysis of the lipid spectrum in fxh may therefore reflect important events during the early healing phase. This study aims to develop a protocol for the determination of lipid signals over time, and the identification of lipids that contribute to these signals, with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in fxh in healthy fracture healing. Methods: Twelve fxh samples (6 porcine; 6 human) were surgically removed, snap frozen, sectioned, washed, and analyzed using MALDI-MSI in positive and negative ion mode at different time points after fracture (porcine: 72 h; human samples: range 1–19 days). A tissue preparation protocol for lipid analysis in fxh has been developed with both porcine and human fxh. Data were analyzed through principal component- and linear discriminant analyses. Results: A protocol for the preparation of fxh sections was developed and optimized. Although hematoma is a heterogeneous tissue, the intra-variability within fxh was smaller than the inter-variability between fxh. Distinctive m/ z values were detected that contributed to the separation of three different fxh age groups: early (1–3 days), middle (6–10 days), and late (12–19 days). Identification of the distinctive m/ z values provided a panel of specific lipids that showed a time dependent expression within fxh. Conclusion: This study shows that MALDI-MSI is a suitable analytical tool for lipid analysis in fxh and that lipid patterns within fxh are time-dependent. These lipid patterns within fxh may serve as a future diagnostic tool. These findings warrant further research into fxh analysis using MALDI-MSI and its possible clinical implications in fracture treatment.
    Type of Medium: Online Resource
    ISSN: 2296-2646
    URL: Article
    URL: Article
    DOI: 10.3389/fchem.2021.780626
    DOI: 10.3389/fchem.2021.780626.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711776-5
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  • 5
    Online Resource
    Online Resource
    Appropriateness of empirical antibiotic therapy and added value of adjunctive gentamicin in patients with septic shock: a prospective cohort study in the ICU
    Informa UK Limited ; 2021
    In:  Infectious Diseases Vol. 53, No. 11 ( 2021-11-02), p. 830-838
    Details
    In: Infectious Diseases, Informa UK Limited, Vol. 53, No. 11 ( 2021-11-02), p. 830-838
    Type of Medium: Online Resource
    ISSN: 2374-4235 , 2374-4243
    URL: Article
    DOI: 10.1080/23744235.2021.1942543
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2805836-7
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  • 6
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    Online Resource
    Surgical suction filter-derived bone graft displays osteogenic miRNA and mRNA patterns
    Springer Science and Business Media LLC ; 2023
    In:  European Journal of Trauma and Emergency Surgery
    Details
    In: European Journal of Trauma and Emergency Surgery, Springer Science and Business Media LLC
    Abstract: Recently, a surgical suction filter device was introduced which aims at generating a suction filter-derived bone grafting substitute (SF-BGS). The osteogenic capacity of this grafting material, however, is unclear. MicroRNAs (miRNAs) and osteogenic mRNAs may influence these processes. The aim of this study was therefore to investigate the quality of the SF-BGS by determining the expression of miRNAs and osteogenic mRNAs. Methods Samples were collected during non-union surgery. Upon exposure of the intramedullary canal, the surgical vacuum system was fitted with the suction filter device containing collagen complex and synthetic β-TCP: (Ca 3 (PO 4 ) 2 , granule size 5–8 mm, total volume 10 mL (Cerasorb Foam ® , Curasan AG, Kleinostheim, Germany). As a control, venous blood was used as in current clinical practice. Samples were snap-frozen and mechanically disrupted. MiRNAs and mRNAs were isolated, transcribed, and pooled for qPCR analysis. Lastly, mRNA targets were determined through in silico target analyses. Results The study population consisted of seven patients with a posttraumatic long bone non-union (4♀; mean age 54 ± 16 years). From the array data, distinct differences in miRNA expression were found between the SF-BGS and control samples. Osteogenic marker genes were overall upregulated in the SF-BGS. Qiagen IPA software identified 1168 mRNA targets for 43 of the overall deregulated miRNAs. Conclusion This study revealed distinctly deregulated and exclusively expressed osteogenic miRNAs in SF-BGS, as well as overall enhanced osteogenic marker gene expression, as compared to the venous blood control group. These expression profiles were not seen in control samples, indicating that the derived material displays an osteogenic profile. It may therefore be a promising tool to generate a BGS or graft extender when needed.
    Type of Medium: Online Resource
    ISSN: 1863-9933 , 1863-9941
    URL: Article
    DOI: 10.1007/s00068-023-02350-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2276432-X
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