COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of ...thrombotic complications are however not available.
We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.
We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.
The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.
We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals. In ...answering questions raised regarding our study, we updated our database and repeated all analyses.
We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.
We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%). The median follow-up duration increased from 7 to 14 days. All patients received pharmacological thromboprophylaxis. The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval CI 41–57%). The majority of thrombotic events were PE (65/75; 87%). In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio HR 0.29, 95%CI 0.091–0.92). Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4–12). Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35–1.8).
In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.
The goal of this manuscript is to present and summarize several rare pediatric syndromes (Zellweger syndrome, Kartagener syndrome, Prader-Willi syndrome, Schinzel-Giedion syndrome, Fanconi anemia, ...Joubert-Boltshauser syndrome, Poretti-Boltshauser syndrome, and Langer-Giedion syndrome) who have been named after luminary “Swiss” physicians (pediatricians, pediatric neurologists, or pediatric radiologists) who recognized, studied, and published these syndromes. In this manuscript, a brief historical summary of the physicians is combined with the key clinical symptoms at presentation and the typical imaging findings. This manuscript is not aiming to give a complete comprehensive summary of the syndromes, nor does it ignore the valuable contributions of many “Swiss” scientists who are not included here, but focuses on several rare syndromes that benefit from imaging data.
PD-L1 immunohistochemistry correlates only moderately with patient survival and response to PD-(L)1 treatment. Heterogeneity of tumor PD-L1 expression might limit the predictive value of small ...biopsies. Here we show that tumor PD-L1 and PD-1 expression can be quantified non-invasively using PET-CT in patients with non-small-cell lung cancer. Whole body PD-(L)1 PET-CT reveals significant tumor tracer uptake heterogeneity both between patients, as well as within patients between different tumor lesions.
De novo mutations arising in the germline are a source of genetic variation and their discovery broadens our understanding of genetic disorders and evolutionary patterns. Although the number of de ...novo single nucleotide variants (dnSNVs) has been studied in a number of species, relatively little is known about the occurrence of de novo structural variants (dnSVs). In this study, we investigated 37 deeply sequenced pig trios from two commercial lines to identify dnSVs present in the offspring. The identified dnSVs were characterised by identifying their parent of origin, their functional annotations and characterizing sequence homology at the breakpoints.
We identified four swine germline dnSVs, all located in intronic regions of protein-coding genes. Our conservative, first estimate of the swine germline dnSV rate is 0.108 (95% CI 0.038-0.255) per generation (one dnSV per nine offspring), detected using short-read sequencing. Two detected dnSVs are clusters of mutations. Mutation cluster 1 contains a de novo duplication, a dnSNV and a de novo deletion. Mutation cluster 2 contains a de novo deletion and three de novo duplications, of which one is inverted. Mutation cluster 2 is 25 kb in size, whereas mutation cluster 1 (197 bp) and the other two individual dnSVs (64 and 573 bp) are smaller. Only mutation cluster 2 could be phased and is located on the paternal haplotype. Mutation cluster 2 originates from both micro-homology as well as non-homology mutation mechanisms, where mutation cluster 1 and the other two dnSVs are caused by mutation mechanisms lacking sequence homology. The 64 bp deletion and mutation cluster 1 were validated through PCR. Lastly, the 64 bp deletion and the 573 bp duplication were validated in sequenced offspring of probands with three generations of sequence data.
Our estimate of 0.108 dnSVs per generation in the swine germline is conservative, due to our small sample size and restricted possibilities of dnSV detection from short-read sequencing. The current study highlights the complexity of dnSVs and shows the potential of breeding programs for pigs and livestock species in general, to provide a suitable population structure for identification and characterisation of dnSVs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Traditionally, patients with pulmonary embolism (PE) are initially treated in the hospital with low molecular weight heparin (LMWH). The results of a few small non‐randomized studies ...suggest that, in selected patients with proven PE, outpatient treatment is potentially feasible and safe. Objective: To evaluate the efficacy and safety of outpatient treatment according to predefined criteria in patients with acute PE. Patients and Methods: A prospective cohort study of patients with objectively proven acute PE was conducted in 12 hospitals in The Netherlands between 2008 and 2010. Patients with acute PE were triaged with the predefined criteria for eligibility for outpatient treatment, with LMWH (nadroparin) followed by vitamin K antagonists. All patients eligible for outpatient treatment were sent home either immediately or within 24 h after PE was objectively diagnosed. Outpatient treatment was evaluated with respect to recurrent venous thromboembolism (VTE), including PE or deep vein thrombosis (DVT), major hemorrhage and total mortality during 3 months of follow‐up. Results: Of 297 included patients, who all completed the follow‐up, six (2.0%; 95% confidence interval CI 0.8–4.3) had recurrent VTE (five PE 1.7% and one DVT 0.3%). Three patients (1.0%, 95% CI 0.2–2.9) died during the 3 months of follow‐up, none of fatal PE. Two patients had a major bleeding event, one of which was fatal intracranial bleeding (0.7%, 95% CI 0.08–2.4). Conclusion: Patients with PE selected for outpatient treatment with predefined criteria can be treated with anticoagulants on an outpatient basis. (Dutch Trial Register No 1319; http://www.trialregister.nl/trialreg/index.asp).
Summary
Background
There has been debate over how patients with pulmonary embolism (PE) can be safely selected for outpatient treatment.
Objectives
To compare the Hestia criteria with the European ...Society of Cardiology (ESC) criteria for selecting low‐risk patients with PE for outpatient treatment.
Methods
From 2008 to 2010, 496 patients with acute, symptomatic PE were screened and 275 treated at home and 221 treated in the hospital according to the Hestia Study protocol. The Hestia criteria were used to select patients for outpatient treatment. Right and left ventricular (RV and LV) diameters were measured on computed tomography images. RV dysfunction was defined as an RV/LV ratio > 1.0. Patients were classified according to the ESC criteria into low, intermediate and high‐risk groups, based on blood pressure and RV dysfunction. During 3 months follow‐up adverse events were scored.
Results
Adverse events occurred in 22 patients (4.5%) treated in the hospital vs. none of the patients treated at home (P < 0.001). Sensitivity and negative predictive value for adverse outcome were 100% for the Hestia criteria and 96% and 99% for the ESC criteria, respectively. Of the patients treated at home according to the Hestia criteria, 35% were normotensive but had RV dysfunction and were classified as intermediate risk according to the ESC criteria. No adverse events happened in these patients treated at home.
Conclusions
Clinical criteria, such as the Hestia criteria, could be helpful in selecting patients, including those with RV dysfunction who have a low risk of adverse clinical outcome and could be candidates for outpatient treatment.
Objective Glial fibrillary acidic protein (GFAP) is specific to astrocytes in the central nervous system. We hypothesized that serum GFAP would be increased in neonates with hypoxic-ischemic ...encephalopathy (HIE) treated with whole-body cooling. Study Design We measured GFAP at birth and daily for up to 7 days for neonates in the intensive care unit. We compared neonates with HIE treated with whole-body cooling to gestational age–matched controls without neurological injury and neonates with HIE by brain abnormalities on magnetic resonance imaging (MRI). Results Neonates with HIE had increased GFAP levels compared with controls. Neonates with HIE and abnormal brain imaging had elevated GFAP levels compared with neonates with HIE and normal imaging. Conclusion Serum GFAP levels during the first week of life were increased in neonates with HIE and were predictive of brain injury on MRI. Biomarkers such as GFAP could help triage neonates with HIE to treatment, measure treatment efficacy, and provide prognostic information.
Background
Migraine is a disabling neurological disorder whose diagnosis is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the underlying ...neurobiological factors and sex-specific complications in migraine such as cardio- and cerebrovascular disease. Biomarker research can help to improve disease characterization and identify pathophysiological mechanism underlying these comorbidities.
Objective
In this narrative review we searched for sex-specific metabolomics research to identify markers that may explain the migraine-cardiovascular disease (CVD) relationship.
Discussion
Large-scale plasma metabolome analyses revealed alterations in migraine. Sex-specific findings showed a less CVD-protective HDL metabolism as well as the ApoA1 lipoprotein, especially for women with migraine. To explore other possible pathophysiological pathways, we expanded our review to include inflammatory markers, endothelial and vascular markers and sex hormones. Biological sex differences may affect the pathophysiology of migraine and its complications.
Conclusions
There is no general large dyslipidemia profile in migraine patients, in line with findings that the increased risk of CVD in migraine patients seems not to be due to (large artery) atherosclerosis. Sex-specific associations are indicative towards a less CVD-protective lipoprotein profile in women with migraine. Future studies into the pathophysiology of CVD and migraine need to take sex specific factors into account. By establishing the overlapping pathophysiological mechanism of migraine and CVD, and unraveling the associated effects these diseases exert on each other, better preventative measures can be identified.
Key points
• There is no general large dyslipidemia profile in migraine patients, in line with findings that the increased risk of CVD in migraine patients seems not to be due to (large artery) atherosclerosis.
• Sex-specific associations are indicative towards a less CVD-protective lipoprotein profile in women with migraine.
• Future studies into the pathophysiology of CVD and migraine need to take sex specific factors into account.
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