A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile.

The complement system plays a central role in the pathogenesis of Systemic Lupus Erythematosus (SLE), but most studies have focused on the classical pathway. Ficolin-3 is the main initiator of the lectin pathway of complement in humans, but its role in systemic autoimmune disease has not been conclusively determined. Here, we combined biochemical and genetic approaches to assess the contribution of ficolin-3 to SLE risk and disease manifestations. Ficolin-3 activity was measured by a functional assay in serum or plasma samples from Swedish SLE patients (n = 786) and controls matched for age and sex (n = 566). Genetic variants in an extended 300 kb genomic region spanning the FCN3 locus were analyzed for their association with ficolin-3 activity and SLE manifestations in a Swedish multicenter cohort (n = 985). Patients with ficolin-3 activity in the highest tertile showed a strong enrichment in an SLE cluster defined by anti-Sm/DNA/nucleosome antibodies (OR 3.0, p < 0.001) and had increased rates of hematological disease (OR 1.4, p = 0.078) and lymphopenia (OR = 1.6, p = 0.039). Genetic variants associated with low ficolin-3 activity mapped to an extended haplotype in high linkage disequilibrium upstream of the FCN3 gene. Patients carrying the lead genetic variant associated with low ficolin-3 activity had a lower frequency of hematological disease (OR 0.67, p = 0.018) and lymphopenia (OR 0.63, p = 0.031) and fewer autoantibodies (p = 0.0019). Loss-of-function variants in the FCN3 gene were not associated with SLE, but four (0.5 %) SLE patients developed acquired ficolin-3 deficiency where ficolin-3 activity in serum was depleted following diagnosis of SLE. Taken together, our results provide genetic and biochemical evidence that implicate the lectin pathway in hematological SLE manifestations. We also identify lectin pathway activation through ficolin-3 as a factor that contributes to the autoantibody response in SLE.

Pre-operative transthoracic echocardiography in ambulatory surgery-A cross-sectional study.

BACKGROUND: Cardiac disease and aberrations in central volume status are risk factors for perioperative complications, and should be identified prior to surgery. This study investigated the benefit of transthoracic echocardiography (TTE) for pre-operative identification of cardiac disease and hypovolemia in ambulatory surgery. METHODS: Ninety-six patients, with a mean age of 63.5 ± 12.2 years and body mass index of 27.0 ± 4.3 kg/m2 , scheduled for ambulatory surgery (breast, thyroid, and minor gastrointestinal), were consecutively enrolled in this prospective observational study. Pre-operative comprehensive TTE was performed in order to assess heart failure (HF), asymptomatic left ventricular dysfunction, valvular disease, and aberrations in central volume status. RESULTS: Pre-operative TTE identified a total of 28 cases of HF, 13 cases of HF with reduced or moderately reduced, ejection fraction (EF), and 15 cases of HF with preserved EF. Furthermore, 46 cases of asymptomatic left ventricular (LV) dysfunction were identified. 44/96 patients were hypovolemic, 16 of whom in severe hypovolemia. Seven cases of previously unknown obstructive valvular or myocardial disease and six cases of right ventricular systolic dysfunction were identified. A total of 24% (23/96) were classified as potential critical hemodynamic findings. The number needed (NNT) to treat for pre-operative TTE in order to find one critical finding was 4.2. CONCLUSION: In this ambulatory surgical cohort, a high prevalence of pre-operative LV dysfunction and aberrations in volume status was observed. The results demonstrate that pre-operative TTE contributed valuable hemodynamic information. The standard pre-operative assessment for this cohort might need to be revised.

Effect of preoperative fluid therapy on hemodynamic stability during anesthesia induction, a randomized study.

BACKGROUND: Preserving perfusion pressure during anesthesia induction is crucial. Standardized anesthesia methods, alert fluid therapy and vasoactive drugs may help maintain adequate hemodynamic conditions throughout the induction procedure. In this randomized study, we hypothesized that a pre-operative volume bolus based on lean body weight would decrease the incidence of significant blood pressure drops (BPD) after induction with target-controlled infusion (TCI) or rapid sequence induction (RSI). METHODS: Eighty individuals scheduled for non-cardiac surgery were randomized to either a pre-operative colloid fluid bolus of 6 ml kg-1 lean body weight or no bolus, and then anesthetized by means of TCI or RSI. The main outcome measure was blood pressure drops below the mean arterial pressure 65 mm Hg during the first 20 minutes after anesthesia induction. ClinicalTrials.com Identifier: NCT03394833. RESULTS: Pre-operative fluid therapy decreased the incidence of BPDs fivefold, from 23 of 40 (57.5%) individuals without fluids to 5 of 40 (12.5%) with fluid management, P < .001. The mean BPD was greater in the groups without pre-operative fluids compared to the groups with fluid management; 53 ± 18 mm Hg vs 43 ± 14 mm Hg, P = .007. The overall mean volume of pre-operative fluid bolus infused was 387 ± 52 ml. There was no difference in hemodynamic stability between TCI and RSI. No correlation was shown between incidence of BPDs and increasing age, medication, hypertension, diabetes, renal failure, or low physical capacity. CONCLUSIONS: Pre-operative fluid bolus decreased the incidence of significant blood pressure drops during TCI and RSI induction of general anesthesia.