Twenty to thirty percent of psoriasis (Pso) patients will develop psoriatic arthritis (PsA). Detection of Pso patients that are (at risk for) developing PsA is essential to prevent structural damage. ...We conducted a systematic search of five bibliographic databases, up to May 2020. We searched for studies assessing markers (clinical, laboratory, genetic) associated with the development or presence of PsA in Pso patients. Study selection and quality assessment of the included studies was performed, followed by a qualitative best evidence synthesis to determine the level of evidence for a marker and its association with concomitant/developing PsA in Pso. Overall, 259 possible markers were identified in 119 studies that met the inclusion criteria. Laboratory markers related to inflammation and bone metabolism reached a strong level of evidence for the association (not prediction) of PsA in Pso. Only CXCL10 showed strong evidence for a positive predictive value for PsA in Pso. The importance of timely detecting PsA in a Pso population, and finding more (bio)markers contributing to early detection, remains high.
Abstract
Background
The incidence of pulmonary thromboembolism is high in SARS-CoV-2 patients admitted to the Intensive Care. Elevated biomarkers of coagulation (fibrinogen and D-dimer) and ...inflammation (c-reactive protein (CRP) and ferritin) are associated with poor outcome in SARS-CoV-2. Whether the time-course of fibrinogen, D-dimer, CRP and ferritin is associated with the occurrence of pulmonary thromboembolism in SARS-CoV-2 patients is unknown. We hypothesise that patients on mechanical ventilation with SARS-CoV-2 infection and clinical pulmonary thromboembolism have lower concentrations of fibrinogen and higher D-dimer, CRP, and ferritin concentrations over time compared to patients without a clinical pulmonary thromboembolism.
Methods
In a prospective study, fibrinogen, D-dimer, CRP and ferritin were measured daily. Clinical suspected pulmonary thromboembolism was either confirmed or excluded based on computed tomography pulmonary angiography (CTPA) or by transthoracic ultrasound (TTU) (i.e., right-sided cardiac thrombus). In addition, patients who received therapy with recombinant tissue plasminogen activator were included when clinical instability in suspected pulmonary thromboembolism did not allow CTPA. Serial data were analysed using a mixed-effects linear regression model, and models were adjusted for known risk factors (age, sex, APACHE-II score, body mass index), biomarkers of coagulation and inflammation, and anticoagulants.
Results
Thirty-one patients were considered to suffer from pulmonary thromboembolism ((positive CTPA (
n
= 27), TTU positive (
n
= 1), therapy with recombinant tissue plasminogen activator (
n
= 3)), and eight patients with negative CTPA were included. After adjustment for known risk factors and anticoagulants, patients with, compared to those without, clinical pulmonary thromboembolism had lower average fibrinogen concentration of − 0.9 g/L (95% CI: − 1.6 – − 0.1) and lower average ferritin concentration of − 1045 μg/L (95% CI: − 1983 – − 106) over time. D-dimer and CRP average concentration did not significantly differ, 561 μg/L (− 6212–7334) and 27 mg/L (− 32–86) respectively. Ferritin lost statistical significance, both in sensitivity analysis and after adjustment for fibrinogen and D-dimer.
Conclusion
Lower average concentrations of fibrinogen over time were associated with the presence of clinical pulmonary thromboembolism in patients at the Intensive Care, whereas D-dimer, CRP and ferritin were not. Lower concentrations over time may indicate the consumption of fibrinogen related to thrombus formation in the pulmonary vessels.
Abstract Background Patients with familial hypercholesterolemia (FH) are characterized by elevated atherogenic lipoprotein particles, predominantly low-density lipoprotein cholesterol (LDL-C), which ...is associated with accelerated atherogenesis and increased cardiovascular risk. Objectives This study used18 F-fluorodeoxyglucose positron emission tomography (18 FDG-PET) to investigate whether arterial inflammation is higher in patients with FH and, moreover, whether lipoprotein apheresis attenuates arterial wall inflammation in FH patients. Methods In total, 38 subjects were recruited: 24 FH patients and 14 normolipidemic controls. All subjects underwent FDG-PET imaging at baseline. Twelve FH patients who met the criteria for lipoprotein apheresis underwent apheresis procedures followed by a second FDG-PET imaging 3 days (range 1 to 4 days) after apheresis. Subsequently, the target-to-background ratio (TBR) of FDG uptake within the arterial wall was assessed. Results In FH patients, the mean arterial TBR was higher compared with healthy controls (2.12 ± 0.27 vs. 1.92 ± 0.19; p = 0.03). A significant correlation was observed between baseline arterial TBR and LDL-C (R = 0.37; p = 0.03) that remained significant after adjusting for statin use (β = 0.001; p = 0.02) and atherosclerosis risk factors (β = 0.001; p = 0.03). LDL-C levels were significantly reduced after lipoprotein apheresis (284 ± 118 mg/dl vs. 127 ± 50 mg/dl; p < 0.001). There was a significant reduction of arterial inflammation after lipoprotein apheresis (TBR: 2.05 ± 0.31 vs. 1.91 ± 0.33; p < 0.02). Conclusions The arterial wall of FH patients is characterized by increased inflammation, which is markedly reduced after lipoprotein apheresis. This lends support to a causal role of apoprotein B–containing lipoproteins in arterial wall inflammation and supports the concept that lipoprotein-lowering therapies may impart anti-inflammatory effects by reducing atherogenic lipoproteins.
Psoriasis (Pso) is a chronic inflammatory skin disease, and up to 30% of Pso patients develop psoriatic arthritis (PsA), which can lead to irreversible joint damage. Early detection of PsA in Pso ...patients is crucial for timely treatment but difficult for dermatologists to implement. We, therefore, aimed to find disease-specific immune profiles, discriminating Pso from PsA patients, possibly facilitating the correct identification of Pso patients in need of referral to a rheumatology clinic. The phenotypes of peripheral blood immune cells of consecutive Pso and PsA patients were analyzed, and disease-specific immune profiles were identified via a machine learning approach. This approach resulted in a random forest classification model capable of distinguishing PsA from Pso (mean AUC = 0.95). Key PsA-classifying cell subsets selected included increased proportions of differentiated CD4+CD196+CD183-CD194+ and CD4+CD196-CD183-CD194+ T-cells and reduced proportions of CD196+ and CD197+ monocytes, memory CD4+ and CD8+ T-cell subsets and CD4+ regulatory T-cells. Within PsA, joint scores showed an association with memory CD8+CD45RA-CD197- effector T-cells and CD197+ monocytes. To conclude, through the integration of in-depth flow cytometry and machine learning, we identified an immune cell profile discriminating PsA from Pso. This immune profile may aid in timely diagnosing PsA in Pso.
Measurement of respiratory muscle function is important in the diagnosis of respiratory muscle disease, respiratory failure, to assess the impact of chronic diseases, and/or to evaluate respiratory ...muscle function after treatment.
To establish reference values for maximal inspiratory and expiratory pressure, and the tension-time index at rest in healthy children and adolescents aged 8-19 years, as well as to present sex- and age-related reference centiles normalized for demographic and anthropometric determinants.
In this cross-sectional observational study, demographic, anthropometric, and spirometric data were assessed, as well as data on respiratory muscle strength (PImax and PEmax) and work of breathing at rest (TT0.1), in a total of 251 children (117 boys and 134 girls; mean age 13.4 ± 2.9 years). Reference values are presented as reference centiles developed by use of the lambda, mu, sigma method.
Boys had significantly higher PImax and PEmax values. Next to sex and age, fat-free mass appeared to be an important predictor of respiratory muscle strength. Reference centiles demonstrated a slight, almost linear increase in PImax with age in boys, and a less steep increase with age in girls. TT0.1 values did not differ between boys and girls and decreased linearly with age.
This study provides reference values for respiratory muscle strength and work of breathing at rest. In addition to sex and age, fat-free mass was found to be an important predictor of respiratory muscle strength in boys and girls.
Extra-hepatic vitamin K-status, measured by dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), maintains vascular health, with high levels reflecting poor vitamin K status. The occurrence ...of extra-hepatic vitamin K deficiency throughout the disease of COVID-19 and possible associations with pulmonary embolism (PE), and mortality in intensive care unit (ICU) patients has not been studied. The aim of this study was to investigated the association between dp-ucMGP, at endotracheal intubation (ETI) and both ICU and six months mortality. Furthermore, we studied the associations between serially measured dp-ucMGP and both PE and mortality.
We included 112 ICU patients with confirmed COVID-19. Over the course of 4 weeks after ETI, dp-ucMGP was measured serially. All patients underwent computed tomography pulmonary angiography (CTPA) to rule out PE. Results were adjusted for patient characteristics, disease severity scores, inflammation, renal function, history of coumarin use, and coronary artery calcification (CAC) scores.
Per 100 pmol/L dp-ucMGP, at ETI, the odds ratio (OR) was 1.056 (95% CI: 0.977 to 1.141, p = 0.172) for ICU mortality and 1.059 (95% CI: 0.976 to 1.059, p = 0.170) for six months mortality. After adjustments for age, gender, and APACHE II score, the mean difference in plasma dp-ucMGP over time of ICU admission was 167 pmol/L (95% CI: 4 to 332, p = 0.047). After additional adjustments for c-reactive protein, creatinine, and history of coumarin use, the difference was 199 pmol/L (95% CI: 50 to 346, p = 0.010). After additional adjustment for CAC score the difference was 213 pmol/L (95% CI: 3 to 422, p = 0.051) higher in ICU non-survivors compared to the ICU survivors. The regression slope, indicating changes over time, did not differ. Moreover, dp-ucMGP was not associated with PE.
ICU mortality in COVID-19 patients was associated with higher dp-ucMGP levels over 4 weeks, independent of age, gender, and APACHE II score, and not explained by inflammation, renal function, history of coumarin use, and CAC score. No association with PE was observed. At ETI, higher levels of dp-ucMGP were associated with higher OR for both ICU and six month mortality in crude and adjusted modes, although not statistically significantly.
Coronavirus Disease 2019 (COVID-19) patients often present with thromboembolic events. In COVID-19 patients, routine hemostatic assays cannot correctly identify patients at risk for thromboembolic ...events. Viscoelastic testing with rotational thromboelastometry (ROTEM) might improve the characterization of COVID-19-associated coagulopathy.
To unravel underlying coagulopathy and fibrinolysis over time as measured by serial assessment heparin-independent (FIBTEM and EXTEM) and fibrinolysis illustrating (tissue plasminogen activator; tPA) ROTEM assays.
Between April 23 and June 12, consecutive adult patients enrolled within the Maastricht Intensive Care COVID (MaastrICCht) cohort were included, and a comprehensive set of clinical, physiological, pharmaceutical, and laboratory variables were collected daily. Twice per week, EXTEM, FIBTEM, and tPA ROTEM were performed. Clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), lysis onset time (LOT), and lysis time (LT) were determined to assess clot development and breakdown and were compared to routine hemostatic assays.
In 36 patients, 96 EXTEM/FIBTEM and 87 tPA ROTEM tests were performed during a 6-week follow-up. CT prolongation was present in 54% of EXTEM measurements, which were not matched by prothrombin time (PT) in 37%. Respectively, 81 and 99% of all EXTEM and FIBTEM MCF values were above the reference range, and median MCF remained elevated during follow-up. The ROTEM fibrinolysis parameters remained prolonged with median LOT consequently >49 min and unmeasurable LT in 56% of measurements, suggesting a severe hypofibrinolytic phenotype.
ROTEM tests in COVID-19 ICU patients show hypercoagulability and severe hypofibrinolysis persisting over at least 6 weeks.
Coronavirus disease 2019 (COVID-19) has emerged as a pandemic at the end of 2019 and continues to exert an unfavorable worldwide health impact on a large proportion of the population. A remarkable ...feature of COVID-19 is the precipitation of a hypercoagulable state, mainly in severe cases, leading to micro- and macrothrombosis, respiratory failure, and death. Despite the implementation of various therapeutic regimes, including anticoagulants, a large number of patients suffer from such serious complications. This review aims to describe the current knowledge on the pathophysiology of the coagulation mechanism in COVID-19. We describe the interplay between three important mediators of the disease and how this may lead to a hyperinflammatory and prothrombotic state that affects outcome, namely, the endothelium, the immune system, and the coagulation system. In line with the hypercoagulability state during COVID-19, we further review on the rare but severe vaccine-induced thrombotic thrombocytopenia. We also summarize and comment on available anticoagulant treatment options and include suggestions for some future treatment considerations for COVID-19 anticoagulation therapy.
Abstract
Objectives
We aimed to investigate the disease activity and overall disease burden of (subgroups of) patients with PsA using the Psoriatic Arthritis Disease Activity Score (PASDAS) in an ...already tightly monitored cohort.
Methods
This is a cross-sectional study evaluating data from the first visit of 855 PsA patients after implementation of the PASDAS in our tightly monitored cohort e.g. DAS 28 (DAS28) was provided as an anchor. Differences in clinical outcomes between subgroups of patients using established cut-offs for disease activity status i.e. very low (VLDA), low (LDA), moderate (MDA), and high disease activity (HDA) were examined.
Results
Based on the PASDAS, 53.1% of patients were in VLDA/LDA. 29.5% of patients had ≥1 swollen joint, 20.6% had ≥1 enthesitis index point and 3.0% had active dactylitis. Based on DAS28, 77.5% of the patients were in VLDA/LDA. Patients reaching both DAS28 VLDA/LDA status and PASDAS VLDA/LDA status N = 445 (52.0%) were compared with patients reaching only DAS28 VLDA/LDA status N = 218 (25.5%). For these latter patients, significantly worse scores on separate parameters were found in measures used for PASDAS/DAS28 calculation (e.g. swollen and tender joint count and patient’s visual analogue scale global disease activity) as well as other disease measures (e.g. function and inflammatory back pain). This result remained, even when the stricter VLDA cut-off was used for the DAS28.
Conclusion
PASDAS implementation uncovered relevant residual disease activity in a quarter of patients previously assessed as being in DAS28 VLDA/LDA, underscoring the potential value of PASDAS measurements in PsA clinical care.
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.
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