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AbstractWe investigated serum concentrations of specific inflammatory parameters in patients with significant carotid artery stenosis (CAS) of 50–99%, with an additional focus on patients with moderate stenosis (50–69%), in terms of both symptomatic status and plaque morphology, to determine whether there are certain parameters that can be associated with plaque instability before the progression of CAS to a high degree. The study included 119 CAS patients, 29 of whom had moderate stenosis, and 46 controls. Ultrasonography of the carotid arteries was performed using color flow Doppler and B-mode duplex ultrasound, and serum inflammatory parameters were measured using commercially available enzyme immunoassays. When comparing patients with 50–99% stenosis, only serum amyloid A (SAA) was higher in symptomatic patients, while in the group of patients with 50–69% stenosis, myeloperoxidase (MPO) was higher and pentraxin-3 (PTX-3) was lower in symptomatic compared to asymptomatic patients, and soluble urokinase plasminogen activator receptor (suPAR) was higher in patients with carotid plaque of unstable compared to stable morphology. Our results suggest that the importance of different inflammatory parameters in patients with moderate CAS is not the same as in CAS patients in general, and therefore their separate investigation in patients with high and moderate stenosis may be beneficial. SAA has the potential to be further considered in research to predict CAS symptom risk. There is a possibility that MPO and PTX-3 play a role in the development of CAS symptoms originating from less stenotic plaques and that suPAR is involved in the destabilisation of such plaques. [ABSTRACT FROM AUTHOR]

Background: AA amyloidosis is a multisystem disease characterized by the deposition of serum amyloid A protein, which is secondary to chronic inflammation. Tocilizumab (an interleukin-6 inhibitor monoclonal antibody) was effective in suppressing inflammation, normalizing serum amyloid A protein levels, and inducing remission in patients with amyloidosis. Recently, tocilizumab treatment has been associated with the disappearance of amyloid deposits. Case presentation: A 61-year-old woman was referred to our hospital in 2011 due to oligoarthritis of both knees and elevation of acute-phase reactants. Corticosteroids and methotrexate were prescribed for the possibility of polymyalgia rheumatica, without clinical response. Two years later, the patient presented with foamy urine, nocturia, sweating, and dizziness. An elevated C-reactive protein (CRP), erythrocyte sedimentation rate, and nephrotic-range proteinuria were found. Autoantibodies and complements levels were normal. No signs of acute infections or cardiovascular disease were evidenced and amyloidosis was suspected. Rectal and oral mucosa biopsies were performed and amyloid AA deposits were detected in both. Magnetic resonance imaging (MRI) of the right knee showed arthropathy due to amyloid deposition. Intravenous monthly tocilizumab was prescribed with rapid improvement of CRP, proteinuria, and nephrotic syndrome symptoms. Arthritis also improved significantly. Two years later, a new biopsy of the rectal mucosa did not show amyloid deposits and the right knee MRI was normal, without evidence of amyloid synovitis. In 2017, isotopic synoviorthesis of both knees was performed due to repeated episodes of arthritis. Eight years after the start of Tocilizumab, the patient continues treatment and remains clinically stable, with no evidence of recurrence. Conclusions: Tocilizumab treatment controls chronic inflammatory disease and improves symptoms of AA amyloidosis. According to the latest evidence, long-term treatment with tocilizumab may remove amyloid deposits from tissues, leading to a definitive cure for this disease. To our knowledge, this is the first case of regression of amyloid deposits both in biopsy and magnetic resonance after treatment with tocilizumab. [ABSTRACT FROM AUTHOR]

Abstract Background AA amyloidosis is a multisystem disease characterized by the deposition of serum amyloid A protein, which is secondary to chronic inflammation. Tocilizumab (an interleukin-6 inhibitor monoclonal antibody) was effective in suppressing inflammation, normalizing serum amyloid A protein levels, and inducing remission in patients with amyloidosis. Recently, tocilizumab treatment has been associated with the disappearance of amyloid deposits. Case presentation A 61-year-old woman was referred to our hospital in 2011 due to oligoarthritis of both knees and elevation of acute-phase reactants. Corticosteroids and methotrexate were prescribed for the possibility of polymyalgia rheumatica, without clinical response. Two years later, the patient presented with foamy urine, nocturia, sweating, and dizziness. An elevated C-reactive protein (CRP), erythrocyte sedimentation rate, and nephrotic-range proteinuria were found. Autoantibodies and complements levels were normal. No signs of acute infections or cardiovascular disease were evidenced and amyloidosis was suspected. Rectal and oral mucosa biopsies were performed and amyloid AA deposits were detected in both. Magnetic resonance imaging (MRI) of the right knee showed arthropathy due to amyloid deposition. Intravenous monthly tocilizumab was prescribed with rapid improvement of CRP, proteinuria, and nephrotic syndrome symptoms. Arthritis also improved significantly. Two years later, a new biopsy of the rectal mucosa did not show amyloid deposits and the right knee MRI was normal, without evidence of amyloid synovitis. In 2017, isotopic synoviorthesis of both knees was performed due to repeated episodes of arthritis. Eight years after the start of Tocilizumab, the patient continues treatment and remains clinically stable, with no evidence of recurrence. Conclusions Tocilizumab treatment controls chronic inflammatory disease and improves symptoms of AA amyloidosis. According to the latest evidence, long-term treatment with tocilizumab may remove amyloid deposits from tissues, leading to a definitive cure for this disease. To our knowledge, this is the first case of regression of amyloid deposits both in biopsy and magnetic resonance after treatment with tocilizumab.

Background 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.

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 2–3 days 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. [ABSTRACT FROM AUTHOR]

Background and Aim: In December 2019, human-to-human transmission of respiratory illness (pneumonia) with fever and sputum was discovered in the respiratory tract, called COVID-19. Serum amyloid A (SAA) is an acute-phase plasma protein that is considered to be diagnostically superior to CRP in pathological conditions such as viral diseases. Therefore, the study question in this review is whether SAA as an indicator is involved in the early diagnosis of COVID disease Materials and Methods: To identify related studies, we systematically searched international databases, including PubMed, Scopus, Science Direct, Cochrane, Embase, Web of Science, and Google Scholar search engine, without restriction on time until June 2021. Also, the Reference list of relevant studies was reviewed separately to find all existing articles in this field. Summary standardized mean difference (SMD) was estimated using random effects meta-analysis. Results: A total of 394 potentially relevant articles were identified from the initial search. After removing the duplicates and reading the title, abstract and full-text review, six studies were entered into the meta-analysis. There was a significant difference between the means of SSA among patients with a severe form of the disease compared to non-sever groups (SMD=-0.91, 95% CI: 1.18-1.59, -0.23) and with the control group (SMD=4.68, 95% CI: 1.18, 8.18). The Beggs and egger test results indicated no evidence of publication bias in the reported SMD. Conclusion: The result of our work indicates that SAA might potentially be used for the early diagnosis of COVID disease, but more studies are needed. [ABSTRACT FROM AUTHOR]

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.

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 intimamedia 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • 97.9 % of patients over the age of 50 were positive for SAA. • 94 % of patients with SAA ≤50 were recovered from COVID-19 infection. • COVID-19 patients hospitalized in the ICU department had the highest level of SAA. • The sensitivity rate of SAA compared to PCR and CT scan was 93 % and 99 %, respectively. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cardiac involvement is the most important factor determining prognosis in patients with systemic amyloidosis. This retrospective observational study of 98 patients with amyloidosis was undertaken to assess the amyloid types that are most likely to affect the heart, describe histopathological and clinical features of cardiac amyloidosis, and estimate the number of cases not diagnosed clinically prior to death. All cases were divided into two groups based on the method of examination. The first group included 46 patients with cardiac amyloidosis revealed via endomyocardial biopsies (EMBs), and the second group included 52 amyloidosis patients who did not undergo EMBs, in whom cardiac involvement was identified only at autopsy. The EMBs demonstrated that AL amyloidosis was detected in 21 (46%) specimens, ATTR amyloid in 24 cases (52%), and AA amyloid in 1 case (2%). The autopsy reports defined 15 (46%) cases of AL amyloidosis, 21 (40%) of ATTR and 16 (31%) of AA amyloidosis. It should be noted that a clinical diagnosis of ATTR amyloidosis was made only in 9.5% of patients from the autopsy group, suggesting that ATTR may be an underdiagnosed cause of heart failure in elderly patients. The most intense amyloid deposits were determined in biopsy and autopsy specimens of patients with AL kappa amyloidosis, underlying a poorer prognosis.

Objective: Cryopyrin-associated periodic syndrome (CAPS) is characterized by excessive IL-1β release resulting in systemic and organ inflammation. As an anti-IL-1 agent, canakinumab has been approved with all CAPS phenotypes in USA and European countries. However, the use of canakinumab in CAPS in Chinese patients was rarely reported. In this study, we aimed to assess the effectiveness and safety of canakinumab in Chinese patients with CAPS., Methods: Patients with CAPS treated with canakinumab were included. Clinical data were collected retrospectively from medical records. Treatment response was evaluated by CAPS disease activity score, C-reactive protein (CRP), and/or serum amyloid A (SAA) levels. Data was analyzed at canakinumab initiation, at months 1, 3, 6, 9, and 12, or the last follow-up., Results: A total of 10 CAPS patients were included. 40% of patients were males, the median age at disease onset was 2.5 (2.5, 6) days and the median duration of follow-up while on canakinumab was 22.5 (8.5, 27.5) months. 80% (8/10) of CAPS patients presented with moderate-severe disease activity before the canakinumab treatment. 30% (3/10) of patients required canakinumab dose increase to control disease activity. After treatments, 60% (6/10) of CAPS patients achieved complete remission without relapse and the rest showed minimal disease activity. Clinical symptoms such as fever and rash were improved significantly in most patients (80%). Although abnormal imaging in brain MRI remained in over half of those patients, neurological manifestations were all relieved. 60% (6/10) of patients received prednisone before starting canakinumab therapy and five of them discontinued prednisone later. The most common adverse event was infection (40%). No serious adverse events occurred during the treatment of canakinumab., Conclusions: Canakinumab may be effective and tolerable for Chinese CAPS patients, helping to reduce the dosage of corticosteroids. However, additional trials on large samples are required to further evaluate its efficacy and safety in China., (© 2024. The Author(s).)

Amyloidosis is a localized or systemic disease caused by deposition of proteins in the extracellular space of various organs and tissues. As part of the disease, proteins that were originally soluble misfold and acquire a fibrillar conformation that renders them insoluble and resistant to proteolysis. Systemic amyloidosis is a rare, often underdiagnosed condition. In recent years, the incidence of newly diagnosed cases of amyloidosis has been increasing in association with the aging of the population and greater access to diagnostic tests. From a clinical perspective, systemic amyloidosis is frequently associated with involvement of the kidneys (causing nephrotic syndrome), heart (cardiac failure and arrhythmia), and peripheral nervous system (sensorimotor polyneuropathy and autonomic dysfunction). This condition is important to the rheumatologist for several reasons, such as its systemic involvement that mimics autoimmune rheumatic diseases, its musculoskeletal manifestations, which when recognized can allow the diagnosis of amyloidosis, and also because reactive or secondary AA amyloidosis is a complication of rheumatic inflammatory diseases. The treatment of amyloidosis depends on the type of amyloid protein involved. Early recognition of this rare disease is fundamental for improved clinical outcomes., (© 2024. The Author(s).)

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.

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

Abstract Background Psoriasis is a chronic systemic inflammatory disease frequently associated with serious comorbidities. Objectives To investigate the systemic inflammatory burden in psoriasis and to assess the correlation between traditional and novel inflammatory markers and the severity of the disease. Methods This cross-sectional study was conducted on 60 patients with psoriasis vulgaris and 50 healthy volunteers. Data including demographics, Psoriasis Area and Severity Index scores, and laboratory results were analyzed and compared. Results Compared with the control group, the psoriatic patients had significantly higher high sensitive C-reactive protein, serum amyloid A, erythrocyte sedimentation rate, leukocyte, neutrophil, neutrophil-to-lymphocyte ratio, monocyte to high density lipoprotein (HDL) cholesterol ratio, and aspartate aminotransferase levels, and significantly lower HDL cholesterol levels (p < 0.05). No significant difference was found in procalcitonin, lymphocyte, monocyte, hemoglobin, red blood cell distribution width, platelet, mean platelet volume, platelet distribution width, lymphocyte-to-monocyte ratio, anti-cyclic citrullinated peptide, glucose, alanine aminotransaminase, blood urea nitrogen, creatinine, triglyceride, total cholesterol, and LDL cholesterol levels between the two groups (p > 0.05). The Psoriasis Area and Severity Index score was positively correlated with high-sensitivity C-reactive protein, serum amyloid A, and monocyte to HDL cholesterol ratio, and negatively correlated with lymphocyte-to-monocyte ratio (p < 0.05). Study limitations This was a single-center study with relatively limited numbers of patients and controls. Conclusions The data show that high sensitivity C-reactive protein, serum amyloid A, erythrocyte sedimentation rate, neutrophil-to-lymphocyte ratio, and monocyte to HDL cholesterol ratio can be used as markers of systemic inflammation in patients with psoriasis. Moreover, high sensitivity C-reactive protein, serum amyloid A, monocyte to HDL cholesterol ratio and lymphocyte-to-monocyte ratio are closely related to the Psoriasis Area and Severity Index score, and they may be regarded as objective indicators in determining the disease severity.

OBJECTIVE P. AERUGINOSA: (PA), the major pathogen of lung cystic fibrosis (CF), polarizes macrophages into hyperinflammatory tissue damaging phenotype. The main aim of this study was to verify whether training of macrophages with β-glucan might improve their response to P. aeruginosa infections., Methods: To perform this task C57BL/6 mice sensitive to infections with P. aeruginosa were used. Peritoneal macrophages were trained with Saccharomyces cerevisiae β-glucan and exposed to PA57, the strong biofilm-forming bacterial strain isolated from the patient with severe lung CF. The release of cytokines and the expression of macrophage phenotypic markers were measured. A quantitative proteomic approach was used for the characterization of proteome-wide changes in macrophages. The effect of in vivo β-glucan-trained macrophages in the air pouch model of PA57 infection was investigated. In all experiments the effect of trained and naïve macrophages was compared., Results: Trained macrophages acquired a specific phenotype with mixed pro-inflammatory and pro-resolution characteristics, however they retained anti-bacterial properties. Most importantly, transfer of trained macrophages into infected air pouches markedly ameliorated the course of infection. PA57 bacterial growth and formation of biofilm were significantly suppressed. The level of serum amyloid A (SAA), a systemic inflammation biomarker, was reduced., Conclusions: Training of murine macrophages with S. cerevisiae β-glucan improved macrophage defense properties along with inhibition of secretion of some detrimental inflammatory agents. We suggest that training of macrophages with such β-glucans might be a new therapeutic strategy in P. aeruginosa biofilm infections, including CF, to promote eradication of pathogens and resolution of inflammation., (© 2024. The Author(s).)

Amyloidosis is a complex group of rare disorders characterized by the deposition of misfolded proteins in the extracellular space of various tissues and organs, leading to progressive organ dysfunction. The kidneys constitute a very common site affected, most notably by immunoglobulin-mediated (light chain, heavy chain, and light and heavy chain amyloidosis), but other types that include serum amyloid A (AA) amyloidosis and leukocyte chemotactic factor 2 amyloidosis, along with mutant proteins in several hereditary forms of amyloidosis such as transthyretin, fibrinogen α-chain, gelsolin, lysozyme, and apolipoproteins AI/AII/AIV/CII/CIII amyloidosis have been incriminated as well. The clinical presentation is variable and can range from minimal proteinuria for leukocyte chemotactic factor 2 amyloidosis to a full-blown nephrotic syndrome for AA amyloidosis. Clinical correlation, genetic analysis, and adequate tissue typing through a kidney biopsy are essential to make the correct diagnosis, especially when a family history of amyloidosis is absent. Except for AA and transthyretin amyloidosis, the treatment is usually purely supportive. Kidney transplantation is an acceptable form of treatment for end-stage kidney disease in all types of non-Ig-mediated renal amyloidosis., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Amyloid A (AA) amyloidosis is an organ- or life-threatening complication of chronic inflammatory disorders. Here, we review the epidemiology, causes, pathogenesis, clinical features, and diagnostic and therapeutic strategies of AA amyloidosis., Recent Findings: The incidence of AA amyloidosis has declined due to better treatment of the underlying diseases. Histopathological examination is the gold standard of diagnosis, but magnetic resonance imaging can be used to detect cardiac involvement. There is yet no treatment option for the clearance of amyloid fibril deposits; therefore, the management strategy primarily aims to reduce serum amyloid A protein. Anti-inflammatory biologic agents have drastically expanded our therapeutic armamentarium. Kidney transplantation is preferred in patients with kidney failure, and the recurrence of amyloidosis in the allograft has become rare as transplant recipients have started to benefit from the new agents. The management of AA amyloidosis has been considerably changed over the recent years due to the novel therapeutic options aiming to control inflammatory activity. New agents capable of clearing amyloid deposits from the tissues are still needed., (© 2024. The Author(s).)

Objective: We assessed and compared immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)-23p19 subunit inhibitor, in participants with active psoriatic arthritis (PsA) who were biologic-naive or had inadequate response to tumor necrosis factor inhibitors (TNFi-IR)., Methods: Serum biomarker levels at baseline and after treatment with guselkumab 100 mg every 8 weeks were compared between biologic-naive (n = 251) and TNFi-IR (n = 93) subgroups identified in the pooled DISCOVER-1/DISCOVER-2/COSMOS data set. Baseline biomarker levels determined by achievement of week 24 clinical responses (≥75%/90% improvement in Psoriasis Area and Severity Index [PASI 75/90], Investigator's Global Assessment [IGA] of psoriasis score 0/1 and ≥2-point improvement], ≥20% improvement in American College of Rheumatology criteria [ACR20]) were compared between prior treatment subgroups., Results: Baseline IL-22, TNFα, and beta defensin-2 (BD-2) levels were significantly lower in biologic-naive than in TNFi-IR participants. With guselkumab, week 24 IL-17A, IL-17F, IL-22, serum amyloid A, C-reactive protein, IL-6, and BD-2 levels were significantly reduced from baseline in biologic-naive and TNFi-IR participants (≥1.4-fold difference, nominal P < 0.05). Clinical responders to guselkumab exhibited significantly higher baseline levels of several biomarkers than nonresponders (IL-17A, IL-17F, BD-2 in biologic-naive PASI 90 responders; IL-17A, BD-2 in TNFi-IR IGA 0/1 responders; IL-22, BD-2 in TNFi-IR PASI 90 responders [nominal P < 0.05]) and trended higher in TNFi-IR ACR20 responders., Conclusion: Guselkumab modulates IL-23 signaling and provides consistent pharmacodynamic effects in both biologic-naive and TNFi-IR PsA patients. Significantly elevated baseline IL-22, TNFα, and BD-2 levels and associations between baseline IL-22, IL-17A, and BD-2 levels and skin responses to guselkumab suggest greater dysregulation of IL-23/Th17 signaling in patients with TNFi-IR., (© 2024 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Abstract: Background: Serum amyloid A is an acute-phase protein. There is no available data regarding serum amyloid A levels in patients with acute (AU) and chronic urticaria (CU). Objective: To investigate the association between serum amyloid A and urticaria. Methods: This was a case-control study of 81 patients who visited our Hospital between June and December 2016 with a diagnosis of urticaria. Eighty healthy controls (HC) who visited for routine health examination and physical checkups were recruited. Serum amyloid A and C-reactive protein levels were measured by automated methods. Results: Serum amyloid A and C-reactive protein levels were significantly higher in AU (Serum amyloid A: 207.1 (6.7-439.0) mg/L; C-reactive protein: 16.0 (0.2-90.0) mg/L) and CU (Serum amyloid A: 6.5 (2.5-35.8) mg/L; C-reactive protein: 1.0 (0.1-16.0) mg/L) compared with HC (Serum amyloid A: 5.04 (2.0-9.1) mg/L; C-reactive protein: 1.2 (0.1-5.6) mg/L), and in AU compared with CU (all P

The serum concentration of certain acute phase proteins significantly increases during various pathological conditions in cattle. The aim of this study was to determine the influence of claw disorders etiology on the concentrations of two major acute phase proteins in dairy cattle: haptoglobin (Hp) and serum amyloid protein A (SAA). Fifty dairy cows with claw pathology were included. Fourteen clinically healthy heifers served as controls. The animals were subdivided in 5 groups according to the pathological findings on their claws: 1. Heel horn erosion (HE), 2. Acute laminitis (AL), 3. Sole ulcer (SU), 4. Digital dermatitis (DD) and 5. White line separation (WLS). Hp and SAA concentrations were measured in serum samples using commercial ELISA kits. Higher concentrations of both Hp and SAA were found in the AL and SU groups (p

Objective: The clinical value of Serum amyloid A (SAA) and Lactoferrin (LTF) has received significant attention, but their detection methods are inadequate, which limits their application. This study aims to develop a dual detection method based on stable element labeling strategies and inductively coupled plasma mass spectrometry (ICP-MS) for SAA/LTF and to assess whether it can be widely used in clinical practice., Methods: A duplex immunoassay system based on sandwich method was constructed. After optimization, methodological evaluation was performed with the guidelines of Clinical Laboratory Standards Institute (CLSI). Finally, 131 plasma samples were collected to analyze whether the new method is suitable for clinical detection., Results: The LoB, LLoQ, ULoQ, and linear range of the assay were 1.09 ng/mL, 3 ng/mL, 1500 ng/mL, 3-1500 ng/mL for SAA and 0.85 ng/mL, 2 ng/mL, 1200 ng/mL, 2-1200 ng/mL for LTF respectively. The recovery rates were 95.01% to 106.26%, the intra-batch precision of low, intermediate, and high-level samples was <8%, and the inter-batch of them was <11%, the deviation of interference test results was less than±10%. The Area Under the Curve (AUC) was 0.9809 for SAA, 0.8599 for LTF, and 0.9986 for combination., Conclusion: The quantitative duplex immunoassay for SAA/LTF has high accuracy, good precision, and high specificity, which meets the clinical testing requirements and can be widely used in clinical practice., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Objective: The purpose of this study is to analyze the changes in inflammatory markers and efficacy in the treatment of senior patients with type 2 diabetes mellitus (T2DM) and community-acquired pneumonia with continuous subcutaneous insulin infusion (CSII)., Methods: A total of 105 senior patients with T2DM and community-acquired pneumonia, were randomly divided into two groups, viz., treatment group and control group-52 patients in the treatment group were treated with CSII, and 53 patients in the control group with multiple daily insulin injections (MDI). The changes in fasting blood glucose, postprandial blood glucose, total number of white blood cells, neutrophils, percentage of neutrophils, lymphocytes, percentage of lymphocytes, C-reactive protein, serum amyloid A, procalcitonin, interleukin-6 indexes, and the improvement in clinical outcome between the two groups were compared on the 5th and the 10th day of treatment., Results: In the treatment group, there were 52 patients with an average age of (73.7 ± 8.5) years, which included 28 males and 24 females. In the control group, there were 53 patients, with 27 males and 26 females, with an average age of (74.8 ± 8.8) years. On the 5th and the 10th day of the treatment, the fasting blood glucose, postprandial blood glucose, total number of white blood cells, neutrophils, percentage of neutrophils, lymphocytes, percentage of lymphocytes, C-reactive protein, serum amyloid A, procalcitonin and interleukin-6 of the treatment group were better than that of the control group (P < 0.05). The use of CSII was associated with a higher probability of a prompt recovery (P < 0.05)., Conclusion: The administration of CSII in the treatment of senior patients with T2DM and community-acquired pneumonia can effectively control fasting and postprandial blood glucose, significantly reduce the levels of inflammatory markers, and improve infection treatment efficacy., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Ulcerative colitis is a chronic immune-mediated inflammatory condition of large intestine that is frequently associated with inflammation of the rectum but often extends proximally to involve other areas of the colon. The ultimate target of therapy is complete healing in the form of clinical remission, complete endoscopic and histological healing, and transmural healing for which endoscopy is mandatory. Colonoscopy may not always be applicable due to possible complications in active ulcerative colitis. Therefore, non-invasive biomarkers are needed to avoid the disadvantageous complications of invasive diagnostic procedures. The aim of this study was to evaluate the role of serum Amyloid-A (SAA) as a non-invasive predictive biomarker of mucosal healing in comparison to different laboratory biomarkers, and endoscopic activity scores. The study included 100 ulcerative colitis patients classified into two groups: 50 patients in clinical, and biochemical remission and 50 patients in activity. Complete blood picture, C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and SAA were measured and recorded, colonoscopies with histopathological examination were done for all patients. SAA levels were significantly higher in patients with active ulcerative colitis than in clinical remission patients (p < 0.001). In clinical, remission patients without full mucosal healing, SAA was positively correlated with endoscopic disease activity represented with Mayo score, Mayo endoscopic sub-score and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) (p < 0.001). However, there was no significant correlation between SAA and endoscopic scores among the activity patients' group. The cut off value of SAA for determining disease activity was > 5.199 µg/ml with 100 % sensitivity, specificity of 92 %, and accuracy of 99.6%. In conclusion, SAA can be used for prediction of mucosal healing in ulcerative colitis remission patients despite not being superior to fecal calprotectin. However, it was unable to differentiate between the different disease activities or extents., (Copyright© by the Egyptian Association of Immunologists.)

Serum amyloid A (SAA) predominantly synthesized by hepatocytes is a classical acute phase protein and has been extensively studied in mammals. However, the studies on the structure and properties of fish SAA are limited although SAA genes have been cloned and identified from various fishes. In the present study, a cDNA of grass carp (Ctenopharyngodon idella) SAA (gcSAA) was cloned and characterized, displaying a high homology with its counterparts in vertebrates. gcSAA mRNA was expressed with highest abundance in the liver and its levels were increased by a 24-hour infection of Aeromonas hydrophila (A. hydrophila) for more than 5 folds in the intestine, 15 folds in the spleen, 75 folds in the head kidney and 100 folds in the liver, implying that it is an acute phase protein in grass carp. Subsequently, recombinant gcSAA protein (rgcSAA) was prepared from a prokaryotic expression system after codon optimization of its coding sequence. The direct antibacterial activity assay and the plate count assay disclosed that gcSAA inhibited the growth and survival of A. hydrophila but not Edwardsiella piscicida (E. piscicida) which both are common bacterial pathogens in aquaculture. The propidium iodide (PI) uptake assay confirmed the bactericidal property of gcSAA, showing that it is able to enhance the uptake of PI in A. hydrophila but not E. piscicida. These findings revealed the molecular features of gcSAA and its roles in host defense against bacterial infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Renal amyloid-associated (AA) amyloidosis is a harmful complication of familial Mediterranean fever (FMF). Its occurrence involves polymorphisms and mutations in the Serum Amyloid A1 (SAA1) and Mediterranean Fever (MEFV) genes, respectively. In Algeria, the association between SAA1 variants and FMF-related amyloidosis was not investigated, hence the aim of this case-control study. It included 60 healthy controls and 60 unrelated FMF patients (39 with amyloidosis, and 21 without amyloidosis). All were genotyped for the SAA1 alleles (SAA1.1, SAA1.5, and SAA1.3), and a subset of them for the - 13 C/T polymorphism by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Comparisons between genotype and allele frequencies were performed using Chi-square and Fisher tests. The SAA1.1/1.1 genotype was predominant in amyloid FMF patients, compared to non-amyloid FMF patients (p = 0.001) and controls (p < 0.0001). SAA1.1/1.5 was higher in non-amyloid patients (p = 0.0069) and in controls (p = 0.0082) than in patients with amyloidosis. Bivariate logistic regression revealed an increased risk of AA amyloidosis with three genotypes, SAA1.1/1.1 [odds ratio 7.589 (OR); 95% confidence interval (CI): 2.130-27.041] (p = 0.0018), SAA1.1/1.3 [OR 5.700; 95% CI: 1.435-22.644] (p = 0.0134), and M694I/M694I [OR 4.6; 95% CI: 1.400-15.117] (p = 0.0119). The SAA1.1/1.5 genotype [OR 0.152; 95% CI: 0.040-0.587] (p = 0.0062) was protective against amyloidosis. In all groups, the - 13 C/C genotype predominated, and was not related to renal complication [OR 0.88; 95% CI: 0.07-10.43] (p = 0.915). In conclusion, in contrast to the - 13 C/T polymorphism, the SAA1.1/1.1, SAA1.1/1.3 and M694I/M694I genotypes may increase the risk of developing renal AA amyloidosis in the Algerian population., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale & Objective: Outcomes of kidney transplantation for patients with renal AA amyloidosis are uncertain, with reports of poor survival and high rates of disease recurrence. However, the data are inconclusive and mostly based on studies from the early 2000s and earlier., Study Design: Retrospective multicenter cohort study., Setting & Participants: We searched the French national transplant database to identify all patients with renal AA amyloidosis who underwent kidney transplantation between 2008 and 2018., Exposures: Age, cause of amyloidosis, use of biotherapies, and C-reactive protein levels., Outcomes: Outcomes were all-cause mortality and allograft loss. We also reported amyloidosis allograft recurrence, occurrence of acute rejection episodes, as well as infectious, cardiovascular, and neoplastic disease events., Analytical Approach: Kaplan-Meier estimator for mortality and cumulative incidence function method for allograft loss. Factors associated with patient and allograft survival were investigated using a Cox proportional hazards model and a cause-specific hazards model, respectively., Results: 86 patients who received kidney transplants for AA amyloidosis at 26 French centers were included. The median age was 49.4 years (IQR, 39.7-61.1). The main cause of amyloidosis was familial Mediterranean fever (37 cases; 43%). 16 (18.6%) patients received biotherapy after transplantation. Patient survival rates were 94.0% (95% CI, 89.1-99.2) at 1 year and 85.5% (77.8-94.0) at 5 years after transplantation. Cumulative incidences of allograft loss were 10.5% (4.0-17.0) at 1 year and 13.0% (5.8-20.1) at 5 years after transplantation. Histologically proven AA amyloidosis recurrence occurred in 5 transplants (5.8%). An infection requiring hospitalization developed in 55.8% of cases, and there was a 27.9% incidence of acute allograft rejection. Multivariable analysis showed that C-reactive protein concentration at the time of transplantation was associated with patient survival (HR, 1.01; 95% CI, 1.00-1.02; P=0.01) and allograft survival (HR, 1.68; 95% CI, 1.10-2.57; P=0.02)., Limitations: The study lacked a control group, and the effect of biotherapies on transplantation outcomes could not be explored., Conclusions: This relatively contemporary cohort of patients who received a kidney transplant for AA amyloidosis experienced favorable rates of survival and lower recurrence rates than previously reported. These data support the practice of treating these patients with kidney transplantation for end-stage kidney disease., Plain-Language Summary: AA amyloidosis is a severe and rare disease. Kidney involvement is frequent and leads to end-stage kidney disease. Because of the involvement of other organs, these patients are often frail, which has raised concerns about their suitability for kidney transplantation. We reviewed all patients with AA amyloidosis nephropathy who underwent kidney transplantation in France in the recent era (2008-2018) and found that the outcomes after kidney transplantation were favorable, with 85.5% of patients still alive 5 years after transplantation, a survival rate that is comparable to the outcomes of patients receiving a transplant for other forms of kidney diseases. Recurrence of amyloidosis in the transplanted kidney was infrequent (5.8%). These data support the practice of kidney transplantation for patients with AA amyloidosis who experience kidney failure., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Serum amyloid A (SAA) is a clinically useful inflammatory marker involved in the pathogenesis of autoimmune diseases. This study aimed to explore the SAA levels in a cohort of patients with myasthenia gravis (MG) in relation to disease-related clinical parameters and myasthenic crisis (MC) and elucidate the effects of SAA on immune response. A total of 82 MG patients including 50 new-onset MG patients and 32 MC patients were enrolled in this study. Baseline data and laboratory parameters of all enrolled MG patients were routinely recorded through electronic medical systems. SAA levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. CD4 + T and CD19 + B cell subsets were analyzed by flow cytometry. In vitro, human recombinant SAA (Apo-SAA) was applied to stimulate peripheral blood mononuclear cells (PBMCs) from MG patients to observe the effect on T and B cell differentiation. Our results indicated that SAA levels in new-onset MG patients were higher than those in controls and were positively correlated with QMG score, MGFA classification, plasmablast cells, IL-6, and IL-17 levels. Subgroup analysis revealed that SAA levels were increased in generalized MG (GMG) patients than in ocular MG (OMG), as well as elevated in late-onset MG (LOMG) than in early-onset MG (EOMG) and higher in MGFA III/IV compared with MGFA I/II. The ROC curve demonstrated that SAA showed good diagnostic value for MC, especially when combined with NLR. In vitro, Apo-SAA promoted the Th1 cells, Th17 cells, plasmablast cells, and plasma cells differentiation in MG PBMCs. The present findings suggested that SAA was increased in MG patients and promoted expansion of CD4 + T cell and CD19 + B cell subsets, which implicated in the severity of MG patients., (© 2024 International Society for Neurochemistry.)

AIM:To investigate the clinical value of serum amyloid A(SAA)in the diagnosis of infectious endophthalmitis. METHODS:A total of 270 patients admitted to the Eye Hospital of Wenzhou Medical University from June 2016 to March 2019 were collected, including 116 patients with infectious endophthalmitis as the experimental group and 154 non-infectious patients as the control group. The levels of SAA was detected by colloidal gold immunochromatography. Variables were compared and diagnostic value was measured by using receiver operating characteristic(ROC)curve.RESULTS:The median levels of SAA in experimental group and control group were 14.98mg/L and 2.56mg/L, respectively,the difference between the two groups was statistically significant(PPCONCLUSION: SAA combined with CRP and WBC can improve the diagnostic efficacy of infective endophthalmitis. SAA can provide useful reference information for the assistant diagnosis of infectious endophthalmitis, which is worthy of clinical application.

Background: Acute phase protein (APP) concentrations can change due to inflammation and be used to monitor disease in the Iberian ibex (Capra pyrenaica). Objectives: This study aimed to validate Haptoglobin (Hp) and serum amyloid A (SAA) analytes, establish reference values, and characterize Hp and SAA responses in the Iberian ibex after experimentally induced inflammation and experimental bluetongue virus (BTV) infection. Methods: Sera from 40 free‐ranging box‐trapped ibexes were used to establish Hp and SAA reference values. Six healthy ibexes were subcutaneously injected with 5 mL of turpentine, then, blood samples were taken, and clinical evaluations were performed on days 0, 1, 2, 3, 4, 7, and 14 postinjection. Another seven ibexes were challenged with BTV. Serum Hp and SAA concentrations were quantified using commercial assays following the manufacturer's instructions. Results: Intra‐assay precision and linearity were acceptable for both Hp and SAA. Intra‐assay variation for high and low concentration of Hp and SAA were 9.74% and 17.31% and 16.49% and 12.89%, respectively. Inter‐assay variation was higher for the low APP concentrations. Reference values for the healthy Iberian ibexes were (median, minimum, and maximum values) 0.2 (0.12‐0.64) g/L for Hp and 4.74 (0.05‐29.54) mg/L for SAA. Both Hp and SAA acted as a moderate and a major APP, respectively, and each could distinguish animals with turpentine‐induced inflammation from those without. Hp and SAA did not change in asymptomatic BTV‐infected animals. Conclusion: This study validated Hp and SAA analytes and provided basal reference values for these analytes in the Iberian ibex. Both APPs were able to discriminate between healthy and diseased Iberian ibexes animals during turpentine‐induced inflammatory processes. [ABSTRACT FROM AUTHOR]

Urinary omics has become a powerful tool for elucidating pathophysiology of glomerular diseases. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urine proteomic and metabolomic analysis between recently diagnosed renal AA amyloidosis (AA) and membranous nephropathy (MN) patients. Urine samples of 22 (8 AA, 8 MN and 6 healthy control) patients were analyzed with nLC-MS/MS and GC/MS for proteomic and metabolomic studies, respectively. Pathological specimens were scored for glomerulosclerosis and tubulointerstitial fibrosis grades. Functional enrichment analysis between AA and control groups showed enrichment in cell adhesion related sub-domains. Uromodulin (UMOD) was lower, whereas ribonuclease 1 (RNase1) and α-1-microglobulin/bikunin precursor (AMBP) were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = -0.48, p = 0.03) and AMBP-eGFR (r = -0.69, p = 0.003) variables. Metabolomic analysis showed myo-inositol and urate were higher in AA compared to MN group. A positive correlation was detected between RNase1 and urate independent of eGFR values (r = 0.63, p = 0.01). Enrichment in cell adhesion related domains suggested a possible increased urinary shear stress due to amyloid fibrils. UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be related with systemic inflammation in AA amyloidosis. SIGNIFICANCE: Urinary omics studies have become a standard tool for biomarker studies. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urinary omics analysis between recently diagnosed renal AA amyloidosis (AA), membranous nephropathy (MN) patients and healthy controls. Pathological specimens were scored with glomerulosclerosis (G) and tubulointerstitial fibrosis (IF) grades to consolidate the results of the omics studies and correlation analyzes. Functional enrichment analysis showed enrichment in cell adhesion related sub-domains due to downregulation of cadherins; which could be related with increased urinary shear stress due to amyloid deposition and disruption of tissue micro-architecture. In comparative proteomic analyzes UMOD was lower, whereas RNase1 and AMBP were higher in AA compared to MN group. Whereas in metabolomic analyzes; myo-inositol, urate and maltose were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = -0.48, p = 0.03), AMBP-eGFR (r = -0.69, p = 0.003) and between RNase1-Urate independent of eGFR values (r = 0.63, p = 0.01). This study is the first comprehensive urinary omics analysis focusing on renal AA Amyloidosis to the best of our knowledge. Based on physiologic roles and clinicopathologic correlations of the molecules; UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be increased with systemic inflammation and endothelial damage in AA amyloidosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) is a potentially fatal tick-borne zoonotic disease, endemic to Asian regions, including western Japan. Cats appear to suffer a particularly severe form of the disease; however, feline SFTS is not clinically well characterized. Accordingly, in this study, we investigated the associations of, demographic, hematological and biochemical, immunological, and virological parameters with clinical outcome (fatal cases vs. survivors) in SFTSV-positive cats. Viral genomic analysis was also performed. Viral load in blood, total bilirubin, creatine phosphokinase, serum amyloid A, interleukin-6, tumor necrotic factor-α, and virus-specific IgM and IgG differed significantly between survivors and fatal cases, and thus may have utility as prognosticators. Furthermore, survivor profiling revealed high-level of viremia with multiple parameters (white blood cells, platelet, total bilirubin, glucose, and serum amyloid A) beyond the reference range in the 7-day acute phase, and signs of clinical recovery in the post-acute phase (parameters returning to, or tending toward, the reference range). However, SFTSV was still detectable from some survived cats even 14 days after onset of disease, indicating the risk of infection posed by close-contact exposure may persist through the post-acute phase. This study provides useful information for prognostic assessments of acute feline SFTS, and may contribute to early treatment plans for cats with SFTS. Our findings also alert pet owners and animal health professionals to the need for prolonged vigilance against animal-to-human transmission when handling cats that have been diagnosed with SFTS.

The combination of systemic amyloid A (AA) amyloidosis and xanthogranulomatous pyelonephritis (XGP) resulting from a chronic urinary tract infection is extremely rare. We herein report a case of systemic AA amyloidosis secondary to XGP for which clinical remission developed after nephrectomy. To our knowledge, this is the first case report describing the clinical improvement of systemic AA amyloidosis secondary to XGP after nephrectomy in Japan. Clinicians should be aware of this uncommon combination and search for amyloid depositions in cases of XGP.

Aims of the Study: Systemic amyloidoses are rare protein-folding diseases with heterogeneous, often nonspecific clinical presentations. To better understand systemic amyloidoses and to apply state-of-the-art diagnostic pathways and treatment, the interdisciplinary Amyloidosis Network was founded in 2013 at University Hospital Zurich. In this respect, a registry was implemented to study the characteristics and life expectancy of patients with amyloidosis within the area covered by the network. Patient data were collected retrospectively for the period 2005-2014 and prospectively from 2015 onwards., Methods: Patients aged 18 years or older diagnosed with any subtype of systemic amyloidosis were eligible for inclusion if they were treated in one of the four referring centres (Zurich, Chur, St Gallen, Bellinzona). Baseline data were captured at the time of diagnosis. Follow-up data were assessed half-yearly for the first two years, then annually., Results: Between January 2005 and March 2020, 247 patients were screened, and 155 patients with confirmed systemic amyloidosis were included in the present analysis. The most common amyloidosis type was light-chain (49.7%, n = 77), followed by transthyretin amyloidosis (40%, n = 62) and amyloid A amyloidosis (5.2%, n = 8). Most patients (61.9%, n = 96) presented with multiorgan involvement. Nevertheless, single organ involvement was seen in all types of amyloidosis, most commonly in amyloid A amyloidosis (75%, n = 6). The median observation time of the surviving patients was calculated by the reverse Kaplan-Meier method and was 3.29 years (95% confidence interval [CI] 2.33-4.87); it was 4.87 years (95% CI 3.14-7.22) in light-chain amyloidosis patients and 1.85 years (95% CI 1.48-3.66) in transthyretin amyloidosis patients, respectively. The 1-, 3- and 5-year survival rates were 87.0% (95% CI 79.4-95.3%), 68.5% (95% CI 57.4-81.7%) and 66.0% (95% CI 54.6-79.9%) respectively for light-chain amyloidosis patients and 91.2% (95% CI 83.2-99.8%), 77.0% (95% CI 63.4-93.7%) and 50.6% (95% CI 31.8-80.3%) respectively for transthyretin amyloidosis patients. There was no significant difference between the two groups (p = 0.81)., Conclusion: During registry set-up, a more comprehensive work-up of our patients suffering mainly from light-chain amyloidosis and transthyretin amyloidosis was implemented. Survival rates were remarkably high and similar between light-chain amyloidosis and transthyretin amyloidosis, a finding which was noted in similar historic registries of international centres. However, further studies are needed to depict morbidity and mortality as the amyloidosis landscape is changing rapidly.

To investigate clinical symptoms and genetic variants in patients from the German anti-IL-1 registry for autoinflammatory orphan diseases (GARROD) between 2013 and 2022. Multicentre, retrospective analysis of demographic, clinical and genetic data of patients with autoinflammatory diseases (AID) who received anti-IL-1 targeted therapy. The cohort comprised 152 patients with familial Mediterranean fever (FMF; n = 71), cryopyrin-associated periodic syndromes (CAPS; n = 43), TNF-receptor associated periodic syndrome (TRAPS; n = 19), mevalonate kinase deficiency (MKD; n = 3) and unclassified AID (uAID; n = 16). Inflammatory attacks started in 61.2% of the patients before the age of 18 years. The delay between the first AID attack and anti-IL-1 therapy was 17.8 years. Monogenetic AIDs were diagnosed by clinical symptoms. Genetic analyses confirmed the diagnosis in 87.3% of patients with FMF, 65.2% with CAPS and 94.8% with TRAPS. Among this group, heterozygous MEFV variants and variants of unknown significance (VUS) were detected in 22.5% of patients with FMF, 51.2% with CAPS and 47.4% with TRAPS. Patients with VUS were older at disease onset which is consistent with a milder phenotype. Twenty-four patients had secondary AA amyloidosis (AA) at initiation of anti-IL-1 therapy. The mean age of these patients was 16.4 years at their first attack and 44.9 years at the time of AA diagnosis. Turkish-Armenian ancestry correlated with MEFV variants and higher FMF disease activity compared to German ancestry. Molecular genetic analyses should substantiate the clinical diagnosis of a monogenetic AID. Our data support the concept of variable penetrance of VUS which can be associated with late-onset AID., (© 2023. The Author(s).)

Objectives: This study aimed to evaluate the clinical, laboratory and genetic characteristics and outcomes of patients with AA amyloidosis., Methods: Patients followed up in a tertiary referral centre in Turkey with the diagnosis of inflammatory rheumatic diseases and immunohistologically proven AA amyloidosis were included in the study and retrospectively analysed., Results: Among 184 patients with the diagnosis of AA amyloidosis, 174 (83 female, 91 male) were included in the analysis. The most common cause of AA amyloidosis was FMF (78.7%), and 91% of FMF-AA amyloidosis patients were carrying the p.M694V variant (74.1% homozygous). AA amyloidosis was identified earlier in patients with homozygous or compound heterozygous MEFV exon 10 variants compared with the heterozygous patients (27, 30 and 41 years, respectively). Patients with an estimated glomerular filtration rate <60 ml/min at admission had a higher frequency of progression to end-stage renal disease (P < 0.001). The overall mortality rate was 15.3% and it increased gradually in association with the amyloid burden (10% in patients with renal, 15% in renal + gastrointestinal and 43% in those with additional cardiac involvement). Renal findings responded completely to treatment in 31% of the patients, a partial response was observed in 4%, a stable course in 23.6% and progression in 38.5%. Amyloid storm was identified in nine patients and was found to be associated with increased mortality within 1 year., Conclusion: FMF patients still constitute the majority of AA amyloidosis patients in Turkey. The MEFV genotype and associated inflammatory load may affect the age of onset of AA amyloidosis, and earlier diagnosis and stricter follow-up and treatment may delay progression of the disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

The acute phase protein Serum Amyloid A (SAA) is synthesised by the liver in response to inflammatory stimuli. Previous studies have revealed that SAA may be a better biomarker of disease activity in inflammatory bowel disease (IBD) compared to C-reactive protein (CRP). This retrospective monocentric study evaluated whether SAA correlates with biomarkers like faecal calprotectin (FC), CRP, the Neutrophil to Lymphocyte ratio (NLR), the platelet count and clinical disease activity of IBD patients. Serum samples from the IBD outpatient clinic of the University Hospital Heidelberg were analysed for SAA concentrations if an FC concentration measurement was available from ±14 days to collection of the serum sample. Three hundred and six serum samples from 265 patients (166 with Crohn's disease, 91 with ulcerative colitis and 8 with IBD unclassified) met the inclusion criteria. There was a significant positive correlation between SAA and FC, CRP, NLR, platelet count and the Simple Clinical Colitis Activity Index (SCCAI). The cut-off for SAA serum concentration at 4.55 mg/L achieved a sensitivity of 57.5% and a specificity of 69.7% for the detection of active inflammation in IBD. SAA may be used as an additional biomarker in the disease monitoring strategy of IBD patients, especially in patients with low CRP concentrations.

Severe trauma could induce sepsis due to the loss of control of the infection, which may eventually lead to death. Accurate and timely diagnosis of sepsis with severe trauma remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis. We compared the diagnostic characteristics of routinely used biomarkers of sepsis alone and in combination, trying to define a biomarker panel to predict sepsis in severe patients. This prospective observational study included patients with severe trauma (Injury severity score, ISS = 16 or more) in the emergency intensive care unit (EICU) at a university hospital. Blood samples were collected and plasma levels of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. A total of 100 patients were eligible for analysis. Of these, 52 were diagnosed with sepsis. CRP yielded the highest discriminative value followed by PCT. In multiple logistic regression, SAA, CRP, and PCT were found to be independent predictors of sepsis. Bioscore which was composed of SAA, CRP, and PCT was shown to be far superior to that of each individual biomarker taken individually. Therefore, compared with single markers, the biomarker panel of PCT, CRP, and SAA was more predictive of sepsis in severe polytrauma patients., (© 2024. The Author(s).)

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 (r s  = 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., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Serum amyloid A (SAA) is an acute-phase protein produced in response to inflammatory proteins during infections, inflammation, trauma, surgery, cancer, and other conditions. Early and accurate detection of SAA is necessary for diagnosis and monitoring of disease progression. To meet this need, we developed a gradient lateral flow immunoassay test strip using Au nanoparticles as signal reporters. The test strip has three test (T1, T2, and T3) lines with progressively decreasing concentrations of SAA antibody, enabling the determination of high, medium, and low concentrations of SAA in serum. The test strip results were analyzed using three distinct readout methods, each with different sensitivity, accuracy, and precision for SAA concentration measurements. Qualitative judgment is based on the color of the T1 line. Semi-quantitative assessment of SAA concentration is determined by the number of colored T-lines. Specifically, color development in T1 line alone indicates a concentration range of 10-50 μg/mL, while T1 and T2 lines together indicate a range of 50-100 μg/mL, and development in all three lines (T1, T2, and T3) indicates a concentration of >100 μg/mL. Quantitative analysis was performed using either smartphone imaging or image scanning with ImageJ software. By using a five-parameter logistic function, we found a strong correlation (R 2  = 0.998) between the ratio of signal intensities of (T1 + T2 + T3) to the control (C) line and SAA concentrations ranging from 5 to 1000 μg/mL. At lower concentrations (0-100 μg/mL), we observed a proportional relationship between the value of (T1 + T2 + T3)/C and SAA concentration. The limit of detection for SAA was 9.33 ng/mL (or 6.53 μg/mL of SAA in undiluted serum samples) for the smartphone method and 3.06 ng/mL (or 2.14 μg/mL of SAA in undiluted serum samples) for the scanner method. The gradient test strip was highly consistent with a commercially available SAA immunochromatographic test strip when tested with real human serum samples. Passing-Bablok regression indicated that results obtained using the smartphone app and scanner methods of the gradient test strip were comparable to those obtained using the commercial test strip. The gradient test strip is flexible and adaptable, providing solutions for qualitative, semi-quantitative, and quantitative SAA measurements., (Copyright © 2023. Published by Elsevier B.V.)

Markers of acute inflammation are gaining broader acceptance in feline veterinary practice but the criteria of their diagnostic accuracy have mostly not been determined. The goal of this study was to compare the diagnostic accuracy of a variety of markers of inflammation that can be rapidly measured in everyday veterinary practice settings. White blood cell, as well as neutrophil and band cell count, degree of toxic neutrophilia, total proteins, albumin, albumin-to-globulin ratio, fibrinogen, and serum amyloid A protein were measured in 35 cats with acute inflammatory diseases and 16 control cats. The sensitivity, specificity, and receiver operating curves of these markers were then compared. The markers with the highest sensitivities and specificities, as well as areas-under-the-curve of the receiver operating curves > 0.9, were fibrinogen, serum amyloid A, degree of toxic neutrophilia, and albumin-to-globulin ratio. The correlations between the different markers were, with the exception of fibrinogen and SAA, low. SAA, fibrinogen, albumin-to-globulin ratio are a panel of sensitive inflammatory biochemistry biomarkers easily available for non specialist veterinarians improving the rapidity of feline patient assessment. [ABSTRACT FROM AUTHOR]