Maternal serum laeverin (aminopeptidase Q) measured in the first trimester of pregnancy does not predict preeclampsia

Objective: The aim of this study was to compare the laeverin level in maternal serum from first trimester (11–14 weeks) of pregnancy between normal pregnancies and pregnancies that later developed preeclampsia (PE).

Material and methods: This was a case-cohort study. The laeverin concentration was measured in cases with preterm PE (n?=?55), term PE (n?=?95), and a reference group of randomly selected women with normal pregnancy outcome (n?=?200) in stored serum samples collected from the double-test as part of the combined first trimester trisomy 21 screening program. The samples were thawed and analyzed for laeverin. The median gestational age at blood sampling was 77 days (range 57–96 days). Multiple regression analysis was performed to establish a normal median. Concentrations were converted to multiples of the median (MoM) and groups were compared using the Mann–Whitney U-test.

Results: In the reference group, laeverin was significantly correlated with gestational age (r?=?0.18, p?=?.01) and its concentration ranged from 41–393 µg/L. No significant differences in the median laeverin MoM were found between the reference group (1.01 MoM) and cases with preterm PE (0.98 MoM) or term PE (0.96 MoM).

Conclusions: First trimester maternal serum laeverin level cannot be used to predict preeclampsia.     

Plaque Composition as a Predictor of Plaque Ulceration in Carotid Artery Atherosclerosis: The Plaque At RISK Study

BACKGROUND AND PURPOSE:Plaque ulceration is a marker of previous plaque rupture. We studied the association between atherosclerotic plaque composition at baseline and plaque ulceration at baseline and follow-up.MATERIALS AND METHODS:We included symptomatic patients with a carotid stenosis of <70% who underwent MDCTA and MR imaging at baseline (n = 180). MDCTA was repeated at 2 years (n = 73). We assessed the presence of ulceration using MDCTA. Baseline MR imaging was used to assess the vessel wall volume and the presence and volume of plaque components (intraplaque hemorrhage, lipid-rich necrotic core, and calcifications) and the fibrous cap status. Associations at baseline were evaluated with binary logistic regression and reported with an OR and its 95% CI. Simple statistical testing was performed in the follow-up analysis.RESULTS:At baseline, the prevalence of plaque ulceration was 27% (49/180). Increased wall volume (OR  = 12.1; 95% CI, 3.5–42.0), higher relative lipid-rich necrotic core (OR = 1.7; 95% CI, 1.3–2.2), higher relative intraplaque hemorrhage volume (OR = 1.7; 95% CI, 1.3–2.2), and a thin-or-ruptured fibrous cap (OR = 3.4; 95% CI, 1.7–6.7) were associated with the presence of ulcerations at baseline. In 8% (6/73) of the patients, a new ulcer developed. Plaques with a new ulceration at follow-up had at baseline a larger wall volume (1.04 cm³ [IQR, 0.97–1.16 cm³] versus 0.86 cm³ [IQR, 0.73–1.00 cm³]; P = .029), a larger relative lipid-rich necrotic core volume (23% [IQR, 13–31%] versus 2% [IQR, 0–14%]; P = .002), and a larger relative intraplaque hemorrhage volume (14% [IQR, 8–24%] versus 0% [IQR, 0–5%]; P < .001).CONCLUSIONS:Large atherosclerotic plaques and plaques with intraplaque hemorrhage and lipid-rich necrotic cores were associated with plaque ulcerations at baseline and follow-up.

Atherosclerosis in the carotid arteries is one of the leading causes of ischemic stroke with arterio-arterial embolism as the main mechanism.^1,2 The degree of lumen stenosis and the symptomatic status of the patient are currently used for risk assessment and treatment decision-making.^3,4 Patients with severe (≥70%) and moderate (50%–69%) carotid artery stenosis benefit from carotid endarterectomy; however, the number needed to treat to prevent recurrent stroke is relatively high.⁵ Moreover, almost half of neurologic events occur in patients with a low degree of stenosis.^6,7 This finding has triggered investigations into other markers that may help to identify patients with a high risk of recurrent stroke. Much attention has been paid to markers of atherosclerosis, like plaque composition and plaque ulceration, with the aim of identifying vulnerable plaques.⁸ These vulnerable plaques have a high risk of rupture, which results in thrombus formation and embolization of plaque material and/or thrombus migrating into the intracranial circulation, thereby causing vascular occlusion and a subsequent ischemic stroke.²Plaque composition is predictive of future cerebrovascular events.^9-12 Atherosclerotic plaque ulceration, visible as plaque-surface disruption, which is a marker of previous plaque rupture, is also correlated with recurrent symptoms and associated with a higher risk of ischemic stroke.^13,14 However, the relation between vulnerable plaque components and plaque rupture is rarely investigated. Both plaque composition and ulceration can be assessed in vivo with different imaging modalities, but MR imaging is the best technique to assess plaque composition due to its superior soft-tissue contrast,¹⁵ whereas MDCTA exceeds MR imaging in the detection of plaque ulcerations due to its excellent spatial resolution with the possibility of multiplanar reconstruction.^16,17Most previous studies investigated the relation between plaque ulcerations and plaque features using a cross-sectional study design. Generally, it was found that intraplaque hemorrhage (IPH), large lipid-rich necrotic core (LRNC), and thinning or ruptured fibrous cap were associated with the presence of ulcerations,^18-21 while the presence of calcifications was inversely related to ulcerations.¹⁹ A prospective study in asymptomatic patients with severe carotid artery stenosis revealed that LRNC volume was a predictor of new surface disruption.^22,23 The aim of the current study was to investigate, in symptomatic patients with mild-to-moderate (30%–69%) carotid artery stenosis, which plaque components at baseline are predictive of plaque rupture at follow-up.     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Limb lengthening and deformity correction with externally controlled motorized intramedullary nails: evaluation of 50 consecutive lengthenings

Background and purpose — Limb lengthening with an intramedullary motorized nail is a relatively new method. We investigated if lengthening nails are reliable constructs for limb lengthening and deformity correction in the femur and the tibia.

Patients and methods — 50 lengthenings (34 Precice and 16 Fitbone devices) in 47 patients (mean age 23 years [11–61]) with ≥12 months follow-up are included in this study. 30 lengthenings were done due to congenital and 20 because of posttraumatic deformity (21 antegrade femora, 23 retrograde femora, 6 tibiae). Initial deformities included a mean shortening of 42?mm (25–90). In 15 patients, simultaneous axial correction was done using the retrograde nailing technique.

Results — The planned amount of lengthening was achieved in all but 2 patients. 5 patients who underwent simultaneous axial correction showed minor residual deformity; unintentionally induced minor deformities were found in the frontal and sagittal plane. The consolidation index was 1.2 months/cm (0.6–2.5) in the femur and 2.5 months/cm (1.6–4.0) in the tibia. 2 femoral fractures occurred in retrograde femoral lengthenings after consolidation due to substantial trauma. There were 8 complications, all of which were correctable by surgery, with no permanent sequelae.

Interpretation — Controlled acute axial correction of angular deformities and limb lengthening can be achieved by a motorized intramedullary nail. A thorough preoperative planning and intraoperative control of alignment are required to avoid residual and unintentionally induced deformity. In the femur relatively fast consolidation could be observed, whereas healing was slower in the tibia.     

[Sar1, Ile4, Ile8]‐angiotensin II Potentiates Insulin Receptor Signalling and Glycogen Synthesis in Hepatocytes

The angiotensin II type I receptor (AT1R) is involved in the regulation of cardiovascular function. Excessive activation of AT1R by angiotensin II (Ang II) leads to cardiovascular disease and may be involved in the development of insulin resistance and diabetes. Functionally selective Ang II analogues, such as the [Sar1, Ile4, Ile8]‐angiotensin II (SII Ang II) analogue, that only activate a subset of signalling networks have been demonstrated to have beneficial effects on cardiovascular function in certain settings, including lowering blood pressure and increasing cardiac performance. Here, we studied the effect of SII Ang II on insulin receptor (IR) signalling and glucose metabolism in primary rat hepatocytes. We show that long‐term pre‐treatment of hepatocytes with SII Ang II increased insulin‐stimulated glycogen synthesis, while Ang II and the AT1R antagonist losartan had no effect. Insulin‐stimulated suppression of hepatic glucose output was not affected by Ang II or SII Ang II. It is well known that insulin regulates glycogen synthesis and glucose output through Akt‐mediated phosphorylation of glycogen synthase kinase α/β (GSK3α/β) and forkhead box protein O1 (FOXO1), respectively. In line with this, we show that SII Ang II potentiated insulin‐stimulated phosphorylation of Akt and GSK3α/β, but not FOXO1. Furthermore, we demonstrate that the effect of SII Ang II on insulin‐stimulated signalling and glycogen synthesis was dependent on Src and Gαq, as inhibitors of these proteins abolished the potentiating effect of SII Ang II. Thus, our results demonstrate that SII Ang II may have a positive effect on IR signalling and glucose metabolism in hepatocytes.     

Secular trends of dental status in five 70-year-old cohorts between 1971 and 2001

Abstract – Objective: The aims of this study, which are part of the gerontological and geriatric population studies in Göteborg, Sweden (H70), were to describe cohort differences and trends in dental status and utilization of dental care in 70‐year‐olds. The study is based on five cohorts examined in 1971/72, 1976/77, 1981/82, 1992/93 and 2000/01 (called cohort I, II, III, V and VI, respectively). The total number of participants was 2290 and varied between 386 and 583 in the different cohorts. The proportion of dentate 70‐year‐olds changed gradually from 49% in the first to 93% in the last cohort. The mean number of teeth in the dentate 70‐year‐olds was 14 in cohort I and 21 in cohort VI. The proportion of subjects with 20 or more teeth changed from 13% in cohort I, to 20% in cohort III, and to 65% in cohort VI. In cohort I, 76% of the 70‐year‐olds had some kind of removable denture; 37% in cohort III, but only 17% in cohort VI. About 20% of all 70‐year‐olds in cohort I reported regular yearly visits to a dentist. The corresponding figures in cohort III and cohort VI were 50% and 80%, respectively. Even though positive cohort trends were observed in all studied subgroups, factors such as low education, smoking, being un‐married, having high waist circumference and being physically inactive were negatively associated with dental status at the end of the study period as well as at the beginning.