Elevated Serum Amyloid A Is Associated With Cognitive Impairment in Ischemic Stroke Patients

Background and PurposeThe impact of serum amyloid A on cognitive impairment after ischemic stroke is unclear. We aimed to investigate the association between serum amyloid A (SAA) levels and post-stroke cognitive impairment (PSCI) at 3 months after ischemic stroke.MethodsOne hundred and ninety-eight patients were enrolled prospectively from June 2020 to April 2021. The SAA concentrations were measured using a commercially available enzyme-linked immunosorbent assay kit after admission. Cognitive function was assessed using the Montreal Cognitive Assessment score at 3 months after the symptom onset. We defined a Montreal Cognitive Assessment score <25 as cognitive impairment.ResultsDuring 3-month follow-up, 80 patients (40.4%) were diagnosed as having PSCI. As compared with patients with cognitively normal ischemic stroke, those with PSCI were older, more likely to have diabetes and white matter lesions, and had a higher baseline National Institutes of Health stroke score and SAA levels. After adjustment for age, the National Institutes of Health stroke score and other covariates, the OR for the highest quartile of SAA compared with the lowest quartile was 5.72 (95% CI, 2.17–15.04, P = 0.001) for PSCI. Also, ordinal logistic regression analysis showed that higher SAA concentrations were associated with increased risk of PSCI severity (OR, 4.31; 95% CI, 1.81–10.33, P = 0.001). Similar results were found when the SAA levels were analyzed as a continuous variable.ConclusionsThis present study demonstrated that increased SAA levels might be associated with PSCI at 3 months after ischemic stroke.

Cryo-EM demonstrates the in vitro proliferation of an ex vivo amyloid fibril morphology by seeding

Several studies showed that seeding of solutions of monomeric fibril proteins with ex vivo amyloid fibrils accelerated the kinetics of fibril formation in vitro but did not necessarily replicate the seed structure. In this research we use cryo-electron microscopy and other methods to analyze the ability of serum amyloid A (SAA)1.1-derived amyloid fibrils, purified from systemic AA amyloidosis tissue, to seed solutions of recombinant SAA1.1 protein. We show that 98% of the seeded fibrils remodel the full fibril structure of the main ex vivo fibril morphology, which we used for seeding, while they are notably different from unseeded in vitro fibrils. The seeded fibrils show a similar proteinase K resistance as ex vivo fibrils and are substantially more stable to proteolytic digestion than unseeded in vitro fibrils. Our data support the view that the fibril morphology contributes to determining proteolytic stability and that pathogenic amyloid fibrils arise from proteolytic selection.

Acute-phase protein concentrations in serum of clinically healthy and diseased European bison (Bison bonasus) – preliminary study

Background This is the first report describing levels of APPs in European bison. Serum concentration of acute phase proteins (APPs) may be helpful to assess general health status in wildlife and potentially useful in selecting animals for elimination. Since there is a lack of literature data regarding concentration of APPs in European bisons, establishment of the reference values is also needed. Methods A total of 87 European bison from Polish populations were divided into two groups: (1) healthy: immobilized for transportation, placing a telemetry collar and routine diagnostic purposes; and (2) selectively culled due to the poor health condition. The serum concentration of haptoglobin, serum amyloid A and α1-acid-glycoprotein were determined using commercial quantitative ELISA assays. Since none of the variables met the normality assumptions, non-parametric Mann-Whitney U test was used for all comparisons. Statistical significance was set at p < 0.05. Statistical analyses were performed using Statistica 13.3 (Tibco, USA). Results The concentration of haptoglobin and serum amyloid A was significantly higher in animals culled (euthanised) due to the poor condition in respect to the clinically healthy European bison. The levels of α1-acid-glycoprotein did not show statistical difference between healthy and sick animals. Conclusions Correlation between APPs concertation and health status was proven, therefore the determination of selected APPs may be considered in future as auxiliary predictive tool in assessing European bison health condition.

Impact of Sepsis on High-Density Lipoprotein Metabolism

Background: High-density lipoproteins (HDL) are thought to play a protective role in sepsis through several mechanisms, such as promotion of steroid synthesis, clearing bacterial toxins, protection of the endothelial barrier, and antioxidant/inflammatory activities. However, HDL levels decline rapidly during sepsis, but the contributing mechanisms are poorly understood.Methods/Aim: In the present study, we investigated enzymes involved in lipoprotein metabolism in sepsis and non-sepsis patients admitted to the intensive care unit (ICU).Results: In 53 ICU sepsis and 25 ICU non-sepsis patients, we observed significant differences in several enzymes involved in lipoprotein metabolism. Lecithin-cholesterol acyl transferase (LCAT) activity, LCAT concentration, and cholesteryl transfer protein (CETP) activity were significantly lower, whereas phospholipid transfer activity protein (PLTP) and endothelial lipase (EL) were significantly higher in sepsis patients compared to non-sepsis patients. In addition, serum amyloid A (SAA) levels were increased 10-fold in sepsis patients compared with non-sepsis patients. Furthermore, we found that LCAT activity was significantly associated with ICU and 28-day mortality whereas SAA levels, representing a strong inflammatory marker, did not associate with mortality outcomes.Conclusion: We provide novel data on the rapid and robust changes in HDL metabolism during sepsis. Our results clearly highlight the critical role of specific metabolic pathways and enzymes in sepsis pathophysiology that may lead to novel therapeutics.

Familial Mediterranean fever in the pediatric population

Familial Mediterranean fever (FMF) is the most frequent autoinflammatory disorder characterized by short, repeated, and self-limiting crises of fever and serositis. The disease was described as autosomal recessive hereditary transmission secondary to variants of the MEFV (MEditerranean FeVer) gene, even though a variable proportion of patients only present a heterozygous variant. FMF is very common in certain ethnic groups (Turkish, Armenian, Arab, and Jewish), even though it has been described throughout the Mediterranean and elsewhere in the world. The clinical manifestations are variable, with secondary amyloidosis being the most serious complication of the disorder. Treatment and prophylaxis are mainly based on the administration of colchicine, which prevents the crises and avoids complications in most cases. This study reviews the course of seven pediatric patients diagnosed with FMF during the period 2010–2018 at a district hospital. Most of the patients were of Caucasian origin, with onset at an early age in the form of fever as the main symptom, and some patients moreover presented less frequent manifestations (pericardial effusion, sensorineural hearing loss). Two cases presented plasmatic amyloid A protein elevation that subsided with the treatment. All the patients initially received colchicine, and one of them required prescription of anakinra, which was replaced by canakinumab due to a serious adverse reaction. There were no cases of consanguinity, and all the patients were of Mediterranean origin. The subjects showed a favorable course over the years, which was attributed to the early diagnosis and treatment provided.

Measurement of Plasma Resistin Concentrations in Horses with Metabolic and Inflammatory Disorders

Obesity and its associated complications, such as metabolic syndrome, are an increasing problem in both humans and horses in the developed world. The expression patterns of resistin differ considerably between species. In rodents, resistin is expressed by adipocytes and is related to obesity and ID. In humans, resistin is predominantly produced by inflammatory cells, and resistin concentrations do not reflect the degree of obesity, although they may predict cardiovascular outcomes. The aim of this study was to investigate the usefulness of resistin and its relationship with ID and selected indicators of inflammation in horses. Seventy-two horses, included in one of the four following groups, were studied: healthy controls (C, n = 14), horses with inflammatory conditions (I, n = 21), horses with mild ID (ID1, n = 18), and horses with severe ID (ID2, n = 19). Plasma resistin concentrations were significantly different between groups and the higher values were recorded in the I and ID2 groups (C: 2.38 ± 1.69 ng/mL; I: 6.85 ± 8.38 ng/mL; ID1: 2.41 ± 2.70 ng/mL; ID2: 4.49 ± 3.08 ng/mL). Plasma resistin was not correlated with basal insulin concentrations. A significant (r = 0.336, p = 0.002) correlation was found between resistin and serum amyloid A. Our results show that, as is the case in humans, plasma resistin concentrations in horses are predominantly related to inflammatory conditions and not to ID. Horses with severe ID showed an elevation in resistin that may be secondary to the inflammatory status associated with metabolic syndrome.

Role of Clinical Characteristics and Biomarkers at Admission to Predict One-Year Mortality in Elderly Patients with Pneumonia

Background: A hospitalization for community-acquired pneumonia results in a decrease in long-term survival in elderly patients. We assessed biomarkers at admission to predict one-year mortality in a cohort of elderly patients with pneumonia. Methods: A prospective observational study included patients >65 years hospitalized with pneumonia. Assessment of PSI, CURB-65, and biomarkers (C-reactive protein (CRP), procalcitonin (PCT), NT-pro-B-type natriuretic peptide (NT-proBNP), interleukin (IL)-6 and -8, tumor necrosis factor alpha (TNF-α), serum amyloid A (SAA), neopterin (NP), myeloperoxidase (MPO), anti-apolipoprotein A-1 IgG (anti-apoA-1), and anti-phosphorylcholine IgM (anti-PC IgM)) was used to calculate prognostic values for one-year mortality using ROC curve analyses. Post hoc optimal cutoffs with corresponding sensitivity (SE) and specificity (SP) were determined using the Youden index. Results: A total of 133 patients were included (median age 83 years [IQR: 78–89]). Age, dementia, BMI, NT-proBNP (AUROC 0.65 (95% CI: 0.55–0.77)), and IL-8 (AUROC 0.66 (95% CI: 0.56–0.75)) were significantly associated with mortality, with NT-proBNP (HR 1.01 (95% CI 1.00–1.02) and BMI (HR 0.92 (95% CI 0.85–1.000) being independent of age, gender, comorbidities, and PSI with Cox regression. At the cutoff value of 2200 ng/L, NT-proBNP had 67% sensitivity and 70% specificity. PSI and CURB-65 were not associated with mortality. Conclusions: NT-proBNP levels upon admission and BMI displayed the highest prognostic accuracy for one-year mortality and may help clinicians to identify patients with poor long-term prognosis.

Encapsulated Allogeneic Synovial Membrane Mesenchymal Stem Cells Provide Better Outcomes of Chondral Lesions in Horses

Osteoarthritis is the main cause of equine lameness, and its treatment remains ineffective. Synovial membrane mesenchymal stem cells (SMMSCs) provide satisfactory outcomes in joint injuries, mainly due to their immunomodulatory and reparative properties. This study aimed to evaluate the effect of SMMSCs, either encapsulated in alginate hydrogel or free, in chondral lesions of horses.Methods: Chondral lesions were surgically induced in the medial trochlea of the talus of fifteen horses. Animals were treated with PBS free SMMSCs or encapsulated SMMSCs. Physical evaluations, assignment of lameness scores and synovial fluid analysis were performed (cytological analysis and dosage of IL-1, IL-10, IL-6, INF-Ɣ, TNF 𝛼, P substance, serum amyloid A, TGF-β, IGF and PGE2) for two weeks. Cartilage biopsies were performed 150 days after induction for histological analysis and immunohistochemistry staining.Results: All groups initially presented inflammation. Although free SMMSCs showed moderate tissue repair, encapsulated SMMSCs had a lower grade of inflammation with superior tissue macro- and microscopic aspects at the end, while the control group showed fibrosis and poor cartilage aspect. This study suggests better effectiveness of stem cells in chondral defects when encapsulated MSCs are used.Conclusion: While the absence of treatment perpetuates cartilage degradation, encapsulated SMMSCs respond better to initial inflammation, interacting and modulating the environment through the release of anti-inflammatory cytokines. Better outcomes observed in encapsulated MSCs were related to the immuno- and physical barriers provided by the alginate hydrogel, allowing a longer period of permanence and interaction between MSCs and the environment.