Prognostic value of serum amyloid A protein as a biomarker in the diagnosis of 2019 novel coronavirus disease (COVID-19).

BACKGROUND: The current study aimed to evaluate the prognostic value of serum amyloid A protein)SAA(protein as a biomarker in diagnosing 2019 novel coronavirus disease)COVID-19(infection. METHODS: The study was conducted on 123 patients with definitive COVID-19 infection referred to Shahid Beheshti and Sina hospitals in Hamedan province, Iran. Five-milliliter blood samples were taken from all included patients and serum was isolated using a centrifuge at 10,000 rpm for 10 min. Laboratory tests were conducted, including c-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), potassium level, sodium blood test, platelets (PLT), complete blood count (CBC), lymphocyte count, and neutrophil count. The SAA enzyme-linked immunosorbent assay (ELISA) Kit was applied to measure the SAA level in serum samples. RESULTS: 123 patients included 73 males and 50 females, age ±50. Sixty-six (53.7 %) patients had negative CRP while 80 (65 %) patients had normal ESR. Potassium levels were not normal among 111 (94.9 %) patients. Seventy-seven (63.1 %) patients had normal CBC, while 108 (87.8 %) patients had neutrophils above the normal range. 94 (97.9 %) patients over the age of 50 were positive for SAA. In terms of gender, men were the most frequent patients with SAA. There was a statistically significant relationship between the serum level of SAA and outcomes of patients with COVID-19 (p = 0.0001). 94 % of patients with SAA ≤50 were recovered from COVID-19 infection. The sensitivity rate of SAA compared to polymerase chain reaction (PCR) and computed tomography scan (CT scan) tests was 93 % and 99 %, respectively. Moreover, the accuracy of SAA compared to PCR and CT scan tests was 52 % and 96 %, respectively. CONCLUSION: Results indicate the SAA is a sensitive, but not specific biomarker in the early detection of COVID-19. The quantitative levels of SAA can be useful in predicting treatment outcomes among patients with COVID-19.

Serum Amyloid A as a Potential Biomarker for Disease Activity in Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is an inflammatory skin disease with a complex physiopathology. Serum amyloid A (SAA), an acute-phase reactant, has been proposed as a potential biomarker in urticaria but has yet to be studied in a population with CSU or correlated with disease activity as indicated by the Urticaria Activity Score summed over 7 days (UAS7). OBJECTIVE: We sought to determine SAA-1 levels in patients with CSU and correlate them with its activity and control, as well as with clinical features of CSU and other potential blood biomarkers. METHODS: We conducted a retrospective multicenter study of 67 patients with CSU, from whom we obtained demographic and clinical data, UAS7 as an indicator of CSU activity, and blood and serum markers. RESULTS: SAA-1 levels positively correlated with UAS7 (rs = 0.47, P < .001). SAA-1 levels were higher in patients with noncontrolled (UAS7 > 6) CSU than in those with controlled (UAS ≤ 6) CSU (P < .001) and were also higher in patients with concomitant angioedema (P = .003) or delayed pressure urticaria (P = .003). CONCLUSION: We propose SAA-1 as a potential biomarker for activity in CSU. Further studies are required to evaluate its potential role as a biomarker for other CSU outcomes, such as response to treatment.

Clinical Characteristics of Mycoplasma Pneumoniae Infection and Factors Associated with Co-infections in Children / 医学研究杂志

Objective To analyze the clinical characteristics of mycoplasma pneumoniae pneumonia(MPP)in children with atopic constitution and exploring the predictors of disease conditions.Methods A total of 250 children diagnosed with MPP in the Department of Pediatric Respiratory Medicine,Xinhua Hospital,Shanghai Jiaotong University School of Medicine from September 2019 to September 2022 were selected and divided into atopic group(n=149)and non-atopic group(n=101)according to whether they were atopic,to explore the clinical characteristics of MPP in children with atopic constitution and the risk factors of severe mycoplasma pneumoniae pneu-monia(SMPP).The efficacy of the combined test of lactate dehydrogenase(LDH),immunoglobulin E(IgE)and serum amyloid A(SAA)in predicting the development of SMPP in MPP children with atopic constitution was evaluated by the receiver operating character-istic(ROC)curve.Results Children in the atopic group had more pronounced symptoms of cough,wheezing,nasal congestion,croup,combined pleural effusion with severe pneumonia and the proportion requiring hormone therapy than those in the non-atopic group,and the differences were statistically significant(P＜0.05).Logistic regression analysis showed that serum IgE,SAA and LDH levels were in-dependent risk factors for the development of SMPP in MPP children with atopic constitution(P＜0.05);ROC curve analysis showed that the combined test of IgE,LDH and SAA could be used to predict the development of SMPP in MPP children with atopic constitution,with an area under the curve(AUC)of 0.881,sensitivity of 81.0％,and specificity of 85.0％.Conclusion MPP children with atopic con-stitution are more likely to develop SMPP and require hormone therapy.The combined detection of serum IgE,SAA and LDH can effec-tively predict the occurrence of SMPP in MPP children with atopic constitution.

Effects of budegforo combined with doxofylline on inflammatory indexes, monocyte chemotactic protein 1 and serum amyloid A protein levels in patients with moderate and severe chronic obstructive pulmonary disease during acute exacerbation period / 中国医师进修杂志

Objective:To investigate the effects of budegforo combined with doxofylline on inflammatory indexes, monocyte chemotactic protein 1 (MCP-1) and serum amyloid A protein (SAA) levels in patients with moderate and severe chronic obstructive pulmonary disease (COPD) during exacerbation period.Methods:The method of prospective study was adopted, 80 patients with moderate and severe COPD during exacerbation period who were treated in Gongan County People′s Hospital from January 2020 to December 2021 were selected as the research objects, and they were divided into the combined group and the budegforo group by random number table method, with 40 cases in each group. The budegforo group was treated with budegforo inhalation and the conventional maintenance therapy, the combined group was treated with doxofylline on the basis treatment of the budegforo group. The patients of the two groups were treated for 12 weeks. The clinical total effective rate and pulmonary function, inflammatory indexes and MCP-1, SAA levels before and after treatment and adverse reactions of the two groups were compared.Results:The clinical total effective rate in the combined group was higher than that in the budegforo group: 95.00%(38/40) vs. 75.00%(30/40), there was statistical difference ( χ2 = 4.80, P<0.05). After 12 weeks of treatment, the forced expiratory volume in one second (FEV 1), FEV 1 and forced vital capacity (FVC) ratio (FEV 1/FVC), percentage of FEV 1 in predicted value (FEV 1% pred), maximum voluntary ventilation (MVV), percentage of predicted value of diffusing capacity of the lung for carbon monoxide (DLCO% pred) in the combined group were higher than those in the budegforo group: (2.80 ± 0.56) L vs. (2.41 ± 0.27) L, (66.35 ± 8.20)% vs. (61.84 ± 9.77)%, (72.73 ± 7.57)% vs. (65.39 ± 5.41)%, (73.56 ± 7.06) L/min vs. (68.53 ± 6.25) L/min, (71.03 ± 5.85)% vs. (66.37 ± 7.08)%; residual volume (RV) to total lung capacity (TLC) ratio (RV/TLC) level was lower than that in the budegforo group: (45.32 ± 6.64)% vs. (51.73 ± 8.45)%, there were statistical differences ( P<0.05). After 12 weeks of treatment, the levels of interleukin(IL)-17, IL-22, MCP-1, SAA in the combined group were lower than those in the budegforo group: (21.46 ± 5.86) ng/L vs. (30.55 ± 8.74) ng/L, (155.62 ± 14.39) ng/L vs. (170.81 ± 16.70) ng/L, (89.57 ± 7.41) ng/L vs. (105.25 ± 8.70) ng/L, (45.21 ± 8.86) ng/L vs. (57.67 ± 7.16) ng/L, there were statistical differences ( P<0.05). There was no statistical difference in adverse reactions between the two groups ( P>0.05). Conclusions:The application of budegforo combined with doxofylline can improve the pulmonary function and clinical efficacy of patients with moderate and severe COPD during exacerbation period, and also play a positive role in reducing MCP-1 and SAA levels.

French protocol for the diagnosis and management of familial Mediterranean fever.

Familial Mediterranean fever is the most common monogenic auto-inflammatory disease in the world. It mainly affects people originating from the Mediterranean region. The mutated gene is MEFV, which codes for pyrin. Transmission is autosomal recessive. Patients present with recurrent attacks of fever since childhood associated with abdominal and/or thoracic pain lasting an average of 2-3days and a biological inflammatory syndrome. Other symptoms include arthralgia or arthritis in large joints such as the knees and ankles, myalgia in the lower limbs and pseudo-erysipelas in the ankles. The most serious complication is inflammatory amyloidosis, which can lead to kidney failure. Treatment is based on colchicine, which helps to prevent flares and the onset of renal amyloidosis. This paper proposes national guidelines for the diagnosis, management and follow-up of familial Mediterranean fever in France, where we estimate there are between 5000 and 10,000 patients with the disease at all stages of life. The diagnosis is suspected on the basis of clinical and anamnestic factors and confirmed by genetic analysis. These guidelines also suggest a "treat-to-target" approach to disease management, particularly in case of suspected colchicine resistance - a very rare situation that should remain a diagnosis of elimination, especially after colchicine compliance has been verified. Two special situations are also addressed in these guidelines: kidney failure and pregnancy.

Association between Serum Amyloid A Levels and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGRUOUND: To date, consistent data have not been reported on the association between serum amyloid A (SAA) levels and type 2 diabetes mellitus (T2DM). The purpose of this study was to systematically summarize their relationship. METHODS: Databases including PubMed, Cochrane Library, Embase, Web of Science, and MEDLINE were searched until August 2021. Cross-sectional and case-control studies were included. RESULTS: Twenty-one studies with 1,780 cases and 2,070 controls were identified. SAA levels were significantly higher in T2DM patients than in healthy groups (standardized mean difference [SMD], 0.68; 95% confidence interval [CI], 0.39 to 0.98). A subgroup analysis showed that the mean age of participants and the continent that participants were from were related to differences in SAA levels between cases and controls. Furthermore, in T2DM patients, SAA levels were positively associated with body mass index (r=0.34; 95% CI, 0.03 to 0.66), triglycerides (r=0.12; 95% CI, 0.01 to 0.24), fasting plasma glucose (r=0.26; 95% CI, 0.07 to 0.45), hemoglobin A1c (r=0.24; 95% CI, 0.16 to 0.33), homeostasis model assessment for insulin resistance (r=0.22; 95% CI, 0.10 to 0.34), C-reactive protein (r=0.77; 95% CI, 0.62 to 0.91), and interleukin-6 (r=0.42; 95% CI, 0.31 to 0.54), but negatively linked with highdensity lipoprotein cholesterol (r=-0.23; 95% CI, -0.44 to -0.03). CONCLUSION: The meta-analysis suggests that high SAA levels may be associated with the presence of T2DM, as well as lipid metabolism homeostasis and the inflammatory response.

French practical guidelines for the diagnosis and management of AA amyloidosis.

AA amyloidosis is secondary to the deposit of excess insoluble Serum Amyloid A (SAA) protein fibrils. AA amyloidosis complicates chronic inflammatory diseases, especially chronic inflammatory rheumatisms such as rheumatoid arthritis and spondyloarthritis; chronic infections such as tuberculosis, bronchectasia, chronic inflammatory bowel diseases such as Crohn's disease; and auto-inflammatory diseases including familial Mediterranean fever. This work consists of the French guidelines for the diagnosis workup and treatment of AA amyloidosis. We estimate in France between 500 and 700 cases in the whole French population, affecting both men and women. The most frequent organ impaired is kidney which usually manifests by oedemas of the lower extremities, proteinuria, and/or renal failure. Patients are usually tired and can display digestive features anf thyroid goiter. The diagnosis of AA amyloidosis is based on detection of amyloid deposits on a biopsy using Congo Red staining with a characteristic green birefringence in polarized light. Immunohistochemical analysis with an antibody directed against Serum Amyloid A protein is essential to confirm the diagnosis of AA amyloidosis. Peripheral inflammatory biomarkers can be measured such as C Reactive protein and SAA. We propose an algorithm to guide the etiological diagnosis of AA amyloidosis. The treatement relies on the etiologic treatment of the undelying chronic inflammatory disease to decrease and/or normalize Serum Amyloid A protein concentration in order to stabilize amyloidosis. In case of renal failure, dialysis or even a kidney transplant can be porposed. Nowadays, there is currently no specific treatment for AA amyloidosis deposits which constitutes a therapeutic challenge for the future.

Down-regulated Th17 cells in a patient with familial Mediterranean fever associated with amyloid A amyloidosis in the treatment of canakinumab.

Autoinflammatory diseases are innate immune-mediated inflammatory disorders, unlike autoimmune diseases, which are characterised by abnormalities in adoptive immunity, although autoimmune and autoinflammatory diseases have certain similar clinical features. Familial Mediterranean fever (FMF), the most common monogenic autoinflammatory disease, is associated with mutations in the MEFV gene that encodes pyrin, which results in inflammasome activation and uncontrolled production of interleukin (IL)-1ß. Regular use of colchicine, the primary drug for FMF treatment, prevents febrile attacks and reduces the long-term risk of subsequent complications of amyloid A (AA) amyloidosis. However, a minority of FMF patients develop colchicine resistance, and anti-IL-1ß treatment with canakinumab, which is a genetically modified human IgG subclass type 1 (IgG1) monoclonal antibody specific for human IL-1ß, was beneficial in inhibiting inflammation in such patients. Here, we present a patient with FMF associated with AA amyloidosis, who was treated with canakinumab and demonstrated down-regulated Th17 cells and activated Th17 cells (from 21.4% to 12.8%, and from 1.45% to 0.83%, respectively) in peripheral blood, as shown by immunophenotyping via multicolour flow cytometry and by disease activity and improved laboratory inflammatory surrogate markers-C-reactive protein (CRP) and serum AA protein (SAA). CRP had values within normal limits, but SAA did not (Spearman's rank correlation coefficient; ρ = 0.133). We report that SAA and IL-1ß may differentiate Th17 cells from CD4+-naïve T cells, and we discuss interactions between autoinflammation and autoimmunity as a model based on this case, through modes of action with IL-1ß and SAA. This report is the first demonstrating that an IL-1ß antagonist may reduce Th17 cells in FMF as a therapeutic option.

No more tears from surgical site infections in interventional pain management.

As the field of interventional pain management (IPM) grows, the risk of surgical site infections (SSIs) is increasing. SSI is defined as an infection of the incision or organ/space that occurs within one month after operation or three months after implantation. It is also common to find patients with suspected infection in an outpatient clinic. The most frequent IPM procedures are performed in the spine. Even though primary pyogenic spondylodiscitis via hematogenous spread is the most common type among spinal infections, secondary spinal infections from direct inoculation should be monitored after IPM procedures. Various preventive guidelines for SSI have been published. Cefazolin, followed by vancomycin, is the most commonly used surgical antibiotic prophylaxis in IPM. Diagnosis of SSI is confirmed by purulent discharge, isolation of causative organisms, pain/tenderness, swelling, redness, or heat, or diagnosis by a surgeon or attending physician. Inflammatory markers include traditional (C-reactive protein, erythrocyte sedimentation rate, and white blood cell count) and novel (procalcitonin, serum amyloid A, and presepsin) markers. Empirical antibiotic therapy is defined as the initial administration of antibiotics within at least 24 hours prior to the results of blood culture and antibiotic susceptibility testing. Definitive antibiotic therapy is initiated based on the above culture and testing. Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria infections appears to be superior to monotherapy in mortality with the risk of increasing antibiotic resistance rates. The never-ending war between bacterial resistance and new antibiotics is continuing. This article reviews prevention, diagnosis, and treatment of infection in pain medicine.

Predictive value of inflammatory markers for convulsions in children infected with the severe acute respiratory syndrome coronavirus 2 Omicron variant / 中华传染病杂志

Objective:To explore the predictive value of inflammatory markers for convulsions in children infected with the severe acute respiratory syndrome coronavirus 2 Omicron variant.Methods:A total of 263 children infected with the Omicron variant admitted to various wards of Fujian Children′s Hospital from December 2022 to January 2023 were included in this study. Based on the presence or absence of convulsions, the children were divided into convulsions group (93 cases) and non-convulsions group (170 cases). Chi-square test and independent samples t-test were used to compare the clinical characteristics and laboratory indicators of the two groups. Binary logistic regression analysis was conducted to determine the relationship between inflammatory markers and convulsions, and receiver operator characteristic (ROC) curve was used to evaluate the efficacy of serum amyloid A (SAA) and interleukin-6 (IL-6) for predicting convulsions occurrence in children. Results:The convulsions group had proportions of 29.03%(27/93) with underlying medical conditions and 40.86%(38/93) with a history of febrile convulsions, which were both higher than the non-convulsions group′s proportions of 18.24%(31/170) and 5.29%(9/170), respectively. These differences were both statistically significant ( χ2=8.71 and 16.92, respectively, both P<0.05). In the convulsions group, levels of procalcitonin, serum ferritin, IL-6, SAA, aspartate aminotransferase, creatine kinase, creatine kinase-isoenzymes and fibrinogen were all significantly higher than those in the non-convulsions group. These differences were all statistically significant ( t=-2.00, -1.54, -2.71, -5.04, -1.30, -2.03, -1.38 and 1.57, respectively, all P<0.05). Erythrocyte sedimentation rate, C-reactive protein, lymphocyte count, blood urea nitrogen and serum creatinine in the convulsions group were all lower than those in the non-convulsions group, with statistically significant differences ( t=3.31, 2.05, 4.21, 2.37 and 1.85, respectively, all P<0.05). SAA and IL-6 were identified as independent risk factors for convulsions in children infected with Omicron variant (both P<0.01). The ROC curve analysis showed that the area under the curve of predictive value of combined SAA and IL-6 was 0.833 ( P<0.01), with a sensitivity of 0.724 and specificity of 0.843. The optimal cutoff values for SAA and IL-6 in predicting convulsions in children infected with the Omicron variant were 141.40 mg/L and 85.05 ng/L, respectively. Conclusions:The combination of SAA and IL-6 could serve as early predictive indicators for convulsions in children infected with the Omicron variant, which could provide valuable insights for timely clinical diagnosis and treatment.

Correlation between sputum culture results and serum levels of C-reactive protein, amyloid A and procalcitonin in patients with acute exacerbations of chronic obstructive pulmonary disease / 中国基层医药

Objective:To investigate the correlation between sputum culture results and serum levels of C-reactive protein, amyloid A, and procalcitonin in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).Methods:The clinical data of 131 older adult patients with AECOPD who received treatment in the Affiliated Hospital of Shaoxing University between January 2019 and January 2021 were retrospectively analyzed. According to sputum culture results, these patients were divided into a sputum culture positive group ( n = 52) and a sputum culture negative group ( n = 79). The sputum of patients was collected aseptically for isolation and identification of pathogens. The general data [age, gender, history of smoking, underlying diseases (hypertension, diabetes mellitus, coronary heart disease), albumin level, mechanical ventilation, method of sputum suction, duration of antibiotics medication, length of hospital stay] were recorded for each group. The risk factors for positive sputum culture were analyzed using binary logistic regression techniques. The efficiency of serum levels of C-reactive protein, amyloid A, and procalcitonin for predicting positive sputum culture was analyzed using the receiver operating characteristic curve. Results:There were 67 strains of pathogens isolated from 52 older adult patients with positive sputum culture of AECOPD. The main pathogens were Gram-negative bacteria (67.16%) [Klebsiella pneumonia (31.34%)], followed by Gram-positive bacteria (25.37%) and fungi (7.47%). Logistic regression analysis showed that mechanical ventilation ( OR = 2.75, P = 0.020), usage of broad-spectrum antibiotics ( OR = 2.95, P = 0.012), serum C-reactive protein level ≥ 20.96 mg/L ( OR = 2.44, P = 0.007), serum amyloid A level ≥ 18.03 mg/L ( OR = 2.67, P = 0.016) and serum procalcitonin level ≥ 2.08 μg/L ( OR = 2.51, P = 0.013) were independent risk factors of positive sputum culture in older adult patients with AECOPD. The receiver operating characteristic curve analysis showed that the area under the receiver operating characteristic curve depicting serum levels of C-reactive protein, amyloid A, and procalcitonin in combination for predicting AECOPD was 0.896, which is of predictive efficiency for positive sputum culture ( P < 0.05). Conclusion:The sputum culture pathogens in older adult patients with AECOPD are mainly Gram-negative bacteria. Increased serum levels of C-reactive protein, amyloid A, and procalcitonin are independent risk factors for Gram-positive bacteria. Combined detection of serum levels of C-reactive protein, amyloid A, and procalcitonin is highly efficient in the diagnosis of AECOPD and can be used to evaluate the sputum culture results in older adult patients with AECOPD.

The level and significance of CD64 index, matrix metalloproteinase-9 and serum amyloid A in peripheral blood of patients with severe carbapenem resistant Enterobacteriaceae infection / 中国医师杂志

Objective:To investigate the level and significance of CD64 index, matrix metalloproteinase-9 (MMP-9) and serum amyloid A (SAA) in peripheral blood of patients with severe carbapenem resistant Enterobacteriaceae (CRE) infection.Methods:A total of 61 patients with severe CRE infection who were admitted to the neurosurgery department of Kashgar First People′s Hospital from January 2019 to January 2022 were selected as the CRE group, and 100 patients with severe carbapenem sensitive Enterobacteriaceae (CSE) infection were selected as the CSE group. The difference in clinical data between the two groups was compared, and the difference in clinical data between the dead and surviving patients in the CRE group was compared. The value of CD64 index, MMP-9 and SAA in differential diagnosis of CRE was analyzed. Logistic regression was used to analyze the influencing factors of prognosis in patients with CRE infection.Results:The age, hypertension, lung disease, liver and kidney disease, comorbidities≥2, antibiotic use≥2 combinations, antibiotic use time>10 days, proportion of carbapenem use, CD64 index, MMP-9, and SAA of the CRE group patients were significantly higher than those of the CSE group patients (all P<0.05). The area under the receiver operating characteristic (ROC) curve for CD64 index, MMP-9, and SAA differential diagnosis of CRE was 0.857, 0.701, and 0.655, respectively (all P<0.05). In the CRE group, the age , the score of Acute Physiological and Chronic Health Status Ⅱ (APACHE Ⅱ) score at admission, diabetes, liver and kidney diseases, comorbidities≥2, the proportion of carbapenems, CD64 index, MMP-9 and SAA of dead patients were significantly higher than those of survivors (all P<0.05). Logistic regression analysis showed that age, APACHE Ⅱ score at admission, comorbidities≥2, CD64 index, MMP-9, and SAA were influencing factors for the prognosis of severe CRE patients (all P<0.05). Conclusions:The peripheral blood CD64 index, MMP-9, and SAA have certain application value in the diagnosis of neurological severe CRE infection, and are also influencing factors for the prognosis of CRE infected patients.

Serum amyloid A in children and adolescents: association with overweight and carotid intima-media thickness

ABSTRACT Objective To compare serum amyloid A concentrations between overweight and eutrophic children and adolescents and to relate it to lipid profiles, glucose tolerance, and carotid intima-media thickness. Methods One hundred children and adolescents (mean age: 10.8±3.16 years) were included and divided into two groups: overweight and non-overweight. The following were evaluated: Z-score body mass index, carotid intima-media thickness, lipid metabolism biomarkers (lipid profile and apolipoproteins A1 and B), inflammatory biomarkers (ultra-sensitive C-reactive protein and serum amyloid A), and glucose homeostasis model assessment of insulin resistance. Results The groups were homogeneous in age, sex, and pubertal stage. Higher levels of triglycerides, apolipoprotein B, homeostasis model assessment of insulin resistance, ultrasensitive C-reactive protein, serum amyloid A, and carotid intima-media thickness were observed in the overweight group. In the multivariate analysis, age (OR=1.73; 95%CI: 1.16-2.60, p=0.007), Z-score body mass index (OR=3.76; 95%CI: 1.64-8.59, p=0.002), apolipoprotein-B (OR=1.1; 95%CI: 1.01-1.2, p=0.030), and carotid intima-media thickness (OR=5.00; 95%CI: 1.38-18.04, p=0.014) were independently associated with serum amyloid A levels above the fourth quartile of the studied sample (>9.4mg/dL). Conclusion Overweight children and adolescents had higher serum amyloid A concentrations than eutrophic children. There was an independent association between higher concentrations of serum amyloid A and Z-score, body mass index, apolipoprotein B, and carotid intima-media thickness, indicating the importance of this inflammatory biomarker in identifying the early risk of atherosclerosis.

The relation between C-reactive protein and serum amyloid A in patients with autoinflammatory diseases.

BACKGROUND: Autoinflammatory diseases are rare disorders of the innate immune system characterized by fever and other signs of inflammation. A feared complication of autoinflammatory diseases is the development of AA amyloidosis. AA amyloidosis is caused by extracellular deposition of soluble serum amyloid A (SAA) proteins as insoluble amyloid fibrils leading to organ damage. Prolonged high levels of SAA are a prerequisite to develop AA amyloidosis. Since measurement of SAA is relatively expensive and sometimes unavailable, C-reactive protein (CRP) is often used as a surrogacy marker to test for inflammation. OBJECTIVE: The aim of this research is to evaluate the possible relation between CRP and SAA. METHODS: A retrospective cohort of patients with autoinflammatory diseases (n = 99) where SAA and CRP blood testing was performed in the period between 2015 and 2021 in the University Medical Centre in Groningen was used to investigate the correlation between CRP and SAA. RESULTS: CRP and SAA have a high correlation (rho = 0.755, p < 0.001). A CRP value below 0.45 mg/L results in 100% sensitivity for SAA below 4 mg/L. CRP below 5 mg/L is a good predictor of SAA below 4 mg/L with 85.4% sensitivity and 83.6% specificity. Only prednisone and erythrocyte sedimentation rate (ESR) significantly influence the relation between CRP and log10SAA. CONCLUSION: There was a significant correlation between CRP and SAA in our retrospective cohort. CRP levels below 5 mg/L proved to be highly predictive of SAA levels below 4 mg/L. This may not be true for patients on steroids.

Serum Amyloid A Protein-Associated Kidney Disease: Presentation, Diagnosis, and Management.

Serum amyloid A protein (AA) amyloidosis, also known as secondary amyloidosis, is a known consequence of chronic inflammation and results from several conditions including inflammatory arthritis, periodic fever syndromes, and chronic infection. AA amyloidosis can lead to multiorgan dysfunction, including changes in glomerular filtration rate and proteinuria. Definitive diagnosis requires tissue biopsy, and management of AA amyloid kidney disease is primarily focused on treating the underlying inflammatory condition to stabilize glomerular filtration rate, reduce proteinuria, and slow potential progression to kidney failure. In this narrative review, we describe the causes, pathophysiology, presentation, and pathologic diagnosis of AA amyloid kidney disease using an illustrative case of biopsy-proven AA amyloid kidney disease in a patient with long-standing rheumatoid arthritis who had a favorable response to interleukin 6 inhibition. We conclude the review with a description of established and more novel therapies for AA amyloidosis including published cases of use of tocilizumab (an interleukin 6 inhibitor) in biopsy-proven AA amyloid kidney disease.

Constitutive androstane receptor (CAR) mediates pyrene-induced inflammatory responses in mouse liver, with increased serum amyloid A proteins and Th17 cells.

BACKGROUND AND PURPOSE: The constitutive androstane receptor (CAR), a known xenobiotic sensor, plays an important role in drug metabolism by regulating numerous genes. The polycyclic aromatic hydrocarbon pyrene, an environmental pollutant, is a CAR activator and induces mouse hepatotoxicity via CAR. Here, we investigate the molecular mechanisms of the inflammatory response in pyrene-caused mice liver injury. EXPERIMENTAL APPROACH: Effects of pyrene on the liver were investigated in wild-type and CAR knockout (KO) mice. Levels of pyrene and its urinary metabolite were analysed by high performance liquid chromatography (HPLC). Inflammatory responses were measured by qRT-PCR, western blotting, and ELISA for cytokines. KEY RESULTS: Serum amyloid A proteins (SAAs) were markedly increased in the liver and serum of pyrene-exposed wild-type mice. IL-17-producing helper T cells (Th17 cells) and IL-17 levels were increased in the liver of pyrene-exposed wild-type mice. Hepatic mRNA levels of inflammatory cytokines including IL-1ß, IL-6 and TNFα, and serum IL-6 levels were significantly elevated in pyrene-treated wild-type mice. However, these changes were not observed in CAR KO mice. CONCLUSION AND IMPLICATIONS: CAR plays a crucial role in pyrene-caused mice liver inflammatory response with increased SAAs and Th17 cells. Our results suggest that serum SAAs may be a convenient biomarker for early diagnosis of liver inflammatory response caused by polycyclic aromatic hydrocarbons, including pyrene. CAR and Th17 cells may be potential targets for novel therapeutic strategies for xenobiotic-induced liver inflammation.

Serum Amyloid A1: A Biomarker for Neutrophilic Airway Inflammation in Adult Asthmatic Patients.

PURPOSE: We evaluated the role of serum amyloid A1 (SAA1) in the pathogenesis of airway inflammation according to the phenotype of asthma. METHODS: One hundred twenty-two asthmatic patients and 60 healthy control subjects (HCs) were enrolled to measure SAA1 levels. The production of SAA1 from airway epithelial cells (AECs) and its effects on macrophages and neutrophils were investigated in vitro and in vivo. RESULTS: The SAA1 levels were significantly higher in sera of asthmatic patients than in those of HCs (P = 0.014); among asthmatics, patients with neutrophilic asthma (NA) showed significantly higher SAA1 levels than those with non-NA (P < 0.001). In vitro, polyinosinic:polycytidylic acid (Poly I-C) treatment markedly enhanced the production of SAA1 from AECs, which was further augmented by neutrophils; SAA1 could induce the production of interleukin (IL)-6, IL-8, and S100 calcium-binding protein A9 from AECs. Additionally, SAA1 activated neutrophils and macrophages isolated from peripheral blood of asthmatics, releasing neutrophil extracellular traps (NETs) and secreting proinflammatory cytokines presenting M1 phenotype, respectively. In ovalbumin-induced asthma mice, Poly I-C treatment significantly increased SAA1 levels as well as IL-17A/interferon-gamma/IL-33 levels in bronchoalveolar lavage fluid (BALF), leading to airway hyperresponsiveness and inflammation. The highest levels of SAA1 and neutrophilia were noted in the BALF and sera of the NA mouse model, followed by the mixed granulocytic asthma (MA) model. Especially, SAA1 induced IL-17/retinoic acid receptor-related orphan receptor γt expression from activated CD4+ T lymphocytes in asthmatic mice. CONCLUSIONS: The results show that SAA1 could induce neutrophilic airway inflammation by activating neutrophils along with NET formation, M1 macrophages, and Th2/Th17 predominant cells, contributing to the phenotype of NA or MA.

Predictive value of serum amyloid A/albumin level in activity and prognosis of systemic lupus erythematosus / 中国医师杂志

Objective:To investigate the predictive value of serum amyloid A/albumin (SAA/ALB) in the activity and prognosis of systemic lupus erythematosus (SLE).Methods:97 SLE patients initially diagnosed in Jincheng People′s Hospital from January 2018 to December 2020 were selected. According to whether the SLE disease activity index (SLE-DAI) was ≥5, SLE patients were divided into active and stable periods. The clinical data of active and stable SLE patients were compared. The independent influencing factors of active SLE were analyzed by logistic regression. The predictive value of SAA, ALB, SAA/ALB on active SLE and severe active SLE was analyzed by receiver operating characteristic(ROC) curve; Kaplan Meier survival curve was used to analyze the prognosis of patients with different SAA/ALB.Results:There were 97 SLE patients, including 64 in active phase and 33 in stable phase.Compared with the stable phase, the SLE-DAI, alanine aminotransferase (ALT) and α-Hydroxybutyrate dehydrogenase (α- HBDH), lactate dehydrogenase (LDH), SAA, SAA/ALB≥0.52 mg/g, urinary microalbumin/creatinine (ACR) in SLE patients of active phase were all higher, while the ALB, albumin/globulin (A/G) and complement (C3) levels were all lower, with statistically significant difference (all P<0.05). LDH, SAA/ALB ≥0.52 mg/g, A/G≥1.18 and C3≥0.60 g/L were all independent influencing factors of active SLE, and the OR were 1.321, 1.401, 0.744 and 0.663 respectively (all P<0.05). The area under the curve (AUC) of SAA and SAA/ALB in predicting active SLE were 0.755 and 0.861, respectively. AUC SAA/ALB>AUC SAA, with statistically significant difference ( P<0.05). The AUC of ALB in predicting stable SLE was 0.743. The AUC of SAA and SAA/ALB in predicting severe active SLE were 0.699 and 0.746, respectively. AUC SAA/ALB>AUC SAA, with statistically significant difference ( P<0.05). The AUC of ALB in predicting non severe active SLE was 0.671. Among the 64 active SLE patients, 21 had poor prognosis. The AUC of poor prognosis predicted by SAA/ALB was 0.736, and the best cut-off value was 0.78 mg/g. There was significant difference in the duration of remission between the high and low SAA/ALB groups (χ 2=6.507, P<0.05). Conclusions:SAA/ALB ≥0.52 mg/g was an independent factor for active SLE. SAA/ALB had a high predictive value for active SLE, severe active SLE and poor prognosis.

Novel biomarkers for the prediction of COVID-19 progression a retrospective, multi-center cohort study.

A pandemic designated as Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Up to date, there is no efficient biomarker for the timely prediction of the disease progression in patients. To analyze the inflammatory profiles of COVID-19 patients and demonstrate their implications for the illness progression of COVID-19. Retrospective analysis of 3,265 confirmed COVID-19 cases hospitalized between 10 January 2020, and 26 March 2020 in three medical centers in Wuhan, China. Patients were diagnosed as COVID-19 and hospitalized in Leishenshan Hospital, Zhongnan Hospital of Wuhan University and The Seventh Hospital of Wuhan, China. Univariable and multivariable logistic regression models were used to determine the possible risk factors for disease progression. Moreover, cutoff values, the sensitivity and specificity of inflammatory parameters for disease progression were determined by MedCalc Version 19.2.0. Age (95%CI, 1.017 to 1.048; P < 0.001), serum amyloid A protein (SAA) (95%CI, 1.216 to 1.396; P < 0.001) and erythrocyte sedimentation rate (ESR) (95%CI, 1.006 to 1.045; P < 0.001) were likely the risk factors for the disease progression. The Area under the curve (AUC) of SAA for the progression of COVID-19 was 0.923, with the best predictive cutoff value of SAA of 12.4 mg/L, with a sensitivity of 83.9% and a specificity of 97.67%. SAA-containing parameters are novel promising ones for predicting disease progression in COVID-19.

SAA (Serum Amyloid A): A Novel Predictor of Stroke-Associated Infections.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate and independently validate SAA (serum amyloid A)-a recently discovered blood biomarker-to predict poststroke infections. METHODS: The derivation cohort (A) was composed of 283 acute ischemic stroke patients and the independent validation cohort (B), of 367 patients. The primary outcome measure was any stroke-associated infection, defined by the criteria of the US Centers for Disease Control and Prevention, occurring during hospitalization. To determine the association of SAA levels on admission with the development of infections, logistic regression models were calculated. The discriminatory ability of SAA was assessed, by calculating the area under the receiver operating characteristic curve. RESULTS: After adjusting for all predictors that were significantly associated with any infection in the univariate analysis, SAA remained an independent predictor in study A (adjusted odds ratio, 1.44 [95% CI, 1.16-1.79]; P=0.001) and in study B (adjusted odds ratio, 1.52 [1.05-2.22]; P=0.028). Adding SAA to the best regression model without the biomarker, the discriminatory accuracy improved from 0.76 (0.69-0.83) to 0.79 (0.72-0.86; P<0.001; likelihood ratio test) in study A. These results were externally validated in study B with an improvement in the area under the receiver operating characteristic curve, from 0.75 (0.70-0.81) to 0.76 (0.71-0.82; P<0.038). CONCLUSIONS: Among patients with ischemic stroke, blood SAA measured on admission is a novel independent predictor of infection after stroke. SAA improved the discrimination between patients who developed an infection compared with those who did not in both derivation and validation cohorts. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00390962.