Objective
To identify PaCO2 trajectories and assess their associations with mortality in critically ill patients with coronavirus disease 2019 (COVID‐19) during the first and second waves of the ...pandemic in Denmark.
Design
A population‐based cohort study with retrospective data collection.
Patients
All COVID‐19 patients were treated in eight intensive care units (ICUs) in the Capital Region of Copenhagen, Denmark, between March 1, 2020 and March 31, 2021.
Measurements
Data from the electronic health records were extracted, and latent class analyses were computed based on up to the first 3 weeks of mechanical ventilation to depict trajectories of PaCO2 levels. Multivariable Cox regression analyses were used to calculate adjusted hazard ratios (aHRs) for Simplified Acute Physiology Score 3, sex and age with 95% confidence intervals (CIs) for death according to PaCO2 trajectories.
Main results
In latent class trajectory models, including 25,318 PaCO2 measurements from 244 patients, three PaCO2 latent class trajectories were identified: a low isocapnic (Class I; n = 130), a high isocapnic (Class II; n = 80), as well as a progressively hypercapnic (Class III; n = 34) trajectory. Mortality was higher in Class II aHR: 2.16 {1.26–3.68} and Class III aHR: 2.97 {1.63–5.40}) compared to Class I (reference).
Conclusion
Latent class analysis of arterial blood gases in mechanically ventilated COVID‐19 patients identified distinct PaCO2 trajectories, which were independently associated with mortality.
To identify PaCO
trajectories and assess their associations with mortality in critically ill patients with coronavirus disease 2019 (COVID-19) during the first and second waves of the pandemic in ...Denmark.
A population-based cohort study with retrospective data collection.
All COVID-19 patients were treated in eight intensive care units (ICUs) in the Capital Region of Copenhagen, Denmark, between March 1, 2020 and March 31, 2021.
Data from the electronic health records were extracted, and latent class analyses were computed based on up to the first 3 weeks of mechanical ventilation to depict trajectories of PaCO
levels. Multivariable Cox regression analyses were used to calculate adjusted hazard ratios (aHRs) for Simplified Acute Physiology Score 3, sex and age with 95% confidence intervals (CIs) for death according to PaCO
trajectories.
In latent class trajectory models, including 25,318 PaCO
measurements from 244 patients, three PaCO
latent class trajectories were identified: a low isocapnic (Class I; n = 130), a high isocapnic (Class II; n = 80), as well as a progressively hypercapnic (Class III; n = 34) trajectory. Mortality was higher in Class II aHR: 2.16 {1.26-3.68} and Class III aHR: 2.97 {1.63-5.40}) compared to Class I (reference).
Latent class analysis of arterial blood gases in mechanically ventilated COVID-19 patients identified distinct PaCO
trajectories, which were independently associated with mortality.
Xia-Gibbs syndrome (XGS) is a neurodevelopmental disorder characterized by intellectual disability, developmental delay, seizures, hypotonia, obstructive sleep apnoea and mild facial dysmorphism. ...Heterozygosity for loss-of-function variants in AHDC1, encoding the AT-hook DNA binding motif containing protein 1, were discovered in 2014 as the likely genetic cause of Xia-Gibbs syndrome. We present five patients with Xia-Gibbs syndrome caused by previously unreported variants in AHDC1. Two of the patients share a frameshift variant: c.2849del (p.(Pro950Argfs*192)) in AHDC1. Despite sharing this variant, the two patients show remarkable phenotypic differences underscoring the clinical heterogeneity of Xia-Gibbs syndrome. In addition, we present a case of Xia-Gibbs syndrome caused by mosaicism for an AHDC1 variant.
Genetic variants in α-actinin-2 (ACTN2) are associated with several forms of (cardio)myopathy. We previously reported a heterozygous missense (c.740C>T) ACTN2 gene variant, associated with ...hypertrophic cardiomyopathy, and characterized by an electro-mechanical phenotype in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Here, we created with CRISPR/Cas9 genetic tools two heterozygous functional knock-out hiPSC lines with a second wild-type (ACTN2wt) and missense ACTN2 (ACTN2mut) allele, respectively. We evaluated their impact on cardiomyocyte structure and function, using a combination of different technologies, including immunofluorescence and live cell imaging, RNA-seq, and mass spectrometry. This study showed that ACTN2mut presents a higher percentage of multinucleation, protein aggregation, hypertrophy, myofibrillar disarray, and activation of both the ubiquitin-proteasome system and the autophagy-lysosomal pathway as compared to ACTN2wt in 2D-cultured hiPSC-CMs. Furthermore, the expression of ACTN2mut was associated with a marked reduction of sarcomere-associated protein levels in 2D-cultured hiPSC-CMs and force impairment in engineered heart tissues. In conclusion, our study highlights the activation of proteolytic systems in ACTN2mut hiPSC-CMs likely to cope with ACTN2 aggregation and therefore directs towards proteopathy as an additional cellular pathology caused by this ACTN2 variant, which may contribute to human ACTN2-associated cardiomyopathies.
Seclusion and restraint (S/R) is a controversial topic in the field of psychiatry, due in part to the high rates of childhood physical and sexual abuse found among psychiatric inpatients. The ...trauma-informed care perspective suggests that the use of S/R with previously abused inpatients may result in retraumatization due to mental associations between childhood trauma and the experience during S/R. Thus, though one would expect to see efforts on the part of inpatient psychiatric facilities to limit S/R of previously abused inpatients, research suggests that trauma victims may be more likely to experience S/R. The current study sought to clarify this possibility by examining whether presence or absence and chronicity of childhood sexual and physical abuse differed among three groups of adult inpatients (N = 622) residing at a mid-Western state psychiatric hospital. These groups are empirically derived on the basis of dramatic differences in the patterning of their exposure to S/R over the course of hospitalization. Results of Chi-square and Kruskal—Wallis tests suggest that the classes did not significantly differ in presence or absence and chronicity of childhood sexual or physical abuse when male and female inpatients were analyzed separately. However, among the class of inpatients who experienced the most instances of S/R, 70% of the members have histories of childhood abuse. Implications for inpatients, clinicians, and policy makers are discussed.
