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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.

PURPOSE: Physical inactivity and obesity increase risk for breast cancer recurrence and cardiovascular death; inflammation is hypothesized to mediate these associations. METHODS: In a four-arm randomized controlled trial, 318 breast cancer survivors with overweight or obesity were randomized to exercise alone, weight loss alone, exercise plus weight loss, or control for 12 months. Inflammation outcomes included C-reactive protein (CRP), serum amyloid A (SAA), intracellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). RESULTS: Compared with control, exercise alone increased ICAM-1 (9.3%; 95% confidence interval [CI] = 1.6-16.9) and VCAM-1 (8.6%; 95% CI = 2.6-14.5) but did not change CRP or SAA. Compared with control, weight loss alone reduced CRP (-35.2%; 95% CI = -49.9 to -20.7), and SAA (-25.6%; 95% CI = -39.8 to -11.9) but did not change ICAM-1 or VCAM-1. Compared with control, exercise plus weight loss reduced CRP (-44.1%; 95% CI = -57.1 to -31.1) and SAA (-26.6%; 95% CI = -40.5 to -12.6) but did not change ICAM-1 or VCAM-1. Among 194 participants with elevated CRP at baseline (e.g., >3 mg·L -1 ), compared with control, weight loss alone (0.17; 95% CI = 0.04-0.30) and exercise plus weight loss (0.31; 95% CI = 0.16-0.46) increased the probability of achieving normal CRP at month 12. In analyses that consolidated randomized groups, body weight and adiposity reductions, but not change in fitness level, correlated with decreased CRP, SAA, and ICAM-1 levels. CONCLUSIONS: In breast cancer survivors with overweight or obesity, weight loss or exercise plus weight loss reduced measures of inflammation that are associated with breast cancer recurrence and cardiovascular death.

AbstractThere are reports of AA amyloidosis associated with intravenous and/or subcutaneous injection of street drugs, such as heroin and cocaine. Most reports describe patients with substance use disorder, renal amyloidosis and concurrent viral infections, such as hepatitis and/or human immunodeficiency virus. Herein, we present a case of systemic AA amyloidosis and sepsis in a 34-year-old woman with a history of intravenous injection of oral prescription medications (as evidenced by excipient lung disease) who had no known history of human immunodeficiency virus nor of hepatitis B or C. Our case shows the broader spectrum of pathology that can occur with the misuse of prescription medications.

BackgroundCognitive dysfunction in schizophrenia is the key predictor of functional disability and drives economic burden. Inflammation has been increasingly implicated in the pathogenesis of schizophrenia, yet its role in cognitive decline has not been evaluated. This study explores the association between inflammation and cognitive functioning in persons with schizophrenia.MethodsParticipants included 143 persons with schizophrenia (PwS) and 139 non-psychiatric comparison subjects (NCs) from an ongoing study of aging. Cognitive assessments included validated measures for executive functioning, processing speed, and visuospatial skills. Plasma levels of nine biomarkers associated with inflammation (high sensitivity C-reactive protein, intercellular adhesion molecule 1, serum amyloid A, interleukin-6, interleukin-8, interferon gamma-induced protein-10, monocyte chemotactic protein-1, fractalkine, and brain-derived neurotrophic factor) were quantified using commercially available, enzyme-linked immunosorbent assays. Partial least squares regression was used to develop a composite "inflammatory profile" to maximize correlations with the cognitive outcomes. We then constructed a best-fit model using these composites and their interactions with diagnosis and sex as the predictors, controlling for covariates.ResultsThe biomarker composite, which best correlated with scores on cognitive testing, included high sensitivity C-reactive protein, intercellular adhesion molecule 1, serum amyloid A, interleukin-6, and brain-derived neurotrophic factor, for a 5-biomarker "inflammatory profile." The best-fit model showed a significant biomarker composite by diagnosis by sex three-way interaction, for executive function and processing speed, but not visuospatial skill.ConclusionsThis approach to building an "inflammatory profile" may provide insight into inflammatory pathways affecting brain function and potential targets for anti-inflammatory interventions to improve cognition in schizophrenia.

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]

[Figure: see text].

BackgroundWe sought to determine whether circulating inflammatory biomarkers were associated with the frequent exacerbator phenotype in stable COPD patients ie, those with two or more exacerbations in the previous year.MethodsEighty-eight stable, severe, COPD patients (4 females) were assessed for exacerbation frequency, pulmonary function, fraction of expired nitric oxide (FENO); inflammatory variables were measured in venous blood. Logistic regression assessed associations between the frequent exacerbator phenotype and systemic inflammation.ResultsCompared with infrequent exacerbators, frequent exacerbators (n=10; 11.4%) had greater serum concentration (median (25th-75th quartile)) of serum amyloid A (SAA; 134 (84-178) vs 71 (38-116) ng/mL; P=0.024), surfactant protein D (SP-D; 15.6 (9.0-19.3) vs 8.5 (3.6-14.9) ng/mL; P=0.049) and interleukin-4 (IL-4; 0.12 (0.08-1.44) vs 0.03 (0.01-0.10) pg/mL; P=0.001). SAA, SP-D and IL-4 were not significantly correlated with FEV1%predicted or FVC %predicted. After adjusting for sex, age, BMI, FEV1/FVC and smoking pack-years, only SAA remained independently associated with the frequent exacerbator phenotype (OR 1.49[1.09-2.04]; P=0.012). The odds of being a frequent exacerbator was 18-times greater in the highest SAA quartile (≥124.1 ng/mL) than the lowest SAA quartile (≤44.1 ng/mL) (OR 18.34[1.30-258.81]; P=0.031), and there was a significant positive trend of increasing OR with increasing SAA quartile (P=0.008). For SAA, the area under the receiver operating characteristic curve was 0.721 for identification of frequent exacerbators; an SAA cut-off of 87.0 ng/mL yielded an 80% sensitivity and 61.5% specificity.ConclusionIn stable COPD patients, SAA was independently associated with the frequent exacerbator phenotype, suggesting that SAA may be a useful serum biomarker to inform progression or management in COPD.

Mammalian serum amyloid A (SAA) is a major acute phase protein that shows a massive increase in plasma concentration during inflammation. In the present study, we demonstrate that the expression of mouse SAA1 in serum was increased when infected with Candida albicans, a major human fungal pathogen, in a systemic infection model. We then set out to investigate the antifungal activity of SAA proteins against C. albicans Recombinant human and mouse SAA1 (rhSAA1 and rmSAA1) were expressed and purified in Escherichia coli Both rhSAA1 and rmSAA1 exhibited a potent antifungal activity against C. albicans We further demonstrate that rhSAA1 binds to the cell surface of C. albicans, disrupts cell membrane integrity, and induces rapid fungal cell death in C. albicans Our finding expands the known functions of SAA1 and provides new insight into host-Candida interactions during fungal infection.

Objective To evaluate the predictive value of acute phase proteins serum amyloid A protein (SAA) and Creactive protein (CRP) for non-response to intravenous immunoglobulin (IVIG) in children with Kawasaki disease (KD). Methods According to the IVIG resistant definition, a total of 358 KD patients were assigned into the IVIG resistant group (n=41) and the IVIG responsive group (n=317). Serum levels of SAA and CRP were tested, and SAA/CRP ratio was calculated. Clinical and laboratory data before and after treatment were compared between the two groups. Binary Logistic regression analysis was used to identify influencing factors for resistance to IVIG. The diagnostic value of SAA and CRP in predicting IVIG resistance in KD was investigated by the receiver operating characteristic (ROC) curve. Results The levels of CRP, SAA, total bilirubin, alanine aminotransferase and asparate aminotransferase were significantly higher in the IVIG resistant group than those of the IVIG responsive group (P＜0.05), whereas levels of lymphocyte count, platelet count, serum sodium and duration of fever before IVIG were significantly lower in the IVIG resistant group (P＜0.05). The binary Logistic regression analysis showed that CRP (OR=1.008, 95%CI: 1.001-1.015), SAA (OR=1.002, 95%CI: 1.001-1.003), total bilirubin (OR=1.030, 95%CI: 1.009-1.051), serum sodium (OR=0.862, 95%CI: 0.762-0.975), lymphocyte count (OR=0.733, 95%CI: 0.567-0.947) and duration of fever before IVIG (OR=0.688, 95%CI: 0.513-0.922) were the independent influencing factors for IVIG resistance (P＜0.05). The incidence of coronary artery lesion was significantly higher after therapy in the IVIG resistant group than that in the IVIG responsive group (P＜0.05). ROC curve showed that the Youden index of SAA (cut-off value 252.45 mg/L), CRP (cut-off value 82.80 mg/L) and combined SAA and CRP were 0.325, 0.382 and 0.423. The area under the ROC curve of SAA, CRP and two items were 0.681, 0.703 and 0.761, respectively. The predictive efficiency of combined application was larger. Conclusion The increased SAA and CRP levels are independent risk factors of IVIG resistance, which can be utilized as combined biomarkers for the prediction of IVIG resistance in KD patients. [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.

Background and Purpose: The aim of this study was to investigate the effect of combined exercise on resting levels of pentraxin3 (PTX3) and serum amyloid A (SAA) in the plasma of men with type-2 diabetes.Materials and Methods: Twenty oen-athlete men with type-2 diabetes were randomly divided into control and training groups. Combined training was performed for six weeks. Training including 25-35 minutes of aerobic exercise with an intensity of 55-75% of maximum heart rate and five resistance movements involving large muscles in the upper and lower body Includes five movements: chest press, army press, squat, dead lift, dumbbell rowing with an intensity of 55-75% of a maximum repetition with a frequency of three times a week with the periorizing of resistance training on aerobic training . The intensity of aerobic exercise was measured with heart rate monitor and the intensity of resistance training was measured every two weeks with a maximum repetition test. For data analysis, dependent and independent t-test was used at the significant level of P ≤ 0.05.Results: Examining the results of the study, it was found that the training contract reduced the SAA index (16.7%) and significantly changed it in the training group compared to the control group (P = 0.047 . However, there was no effect on resting SAA in the control group and a 2.2% increase in PTX3 in the training group was not significant (P = 0.474).Conclusion: According to the results of the study and a significant decrease in inflammatory factor SAA and increase in PTX3, it can be concluded that six weeks of combined training affects the levels of these factors in men with type-2 diabetes and can probably reduce inflammation in these patients.

BackgroundSkin and soft tissue infections (SSTIs) are a leading cause of morbidity and mortality among people who inject drugs (PWID). International data indicate up to one third of PWID have experienced an SSTI within the past month. Complications include sepsis, endocarditis and amyloid A (AA) amyloidosis. AA amyloidosis is a serious sequela of chronic SSTI among PWID. Though there is a paucity of literature reporting on AA amyloidosis among PWID, what has been published suggests there is likely a causal relationship between AA amyloidosis and injecting-related SSTI. If left untreated, AA amyloidosis can lead to renal failure; premature mortality among diagnosed PWID is high. Early intervention may reverse disease. Despite the high societal and individual burden of SSTI among PWID, empirical evidence on the barriers and facilitators to injecting-related SSTI prevention and care or the feasibility and acceptability of AA amyloidosis screening and treatment referral are limited. This study aims to fill these gaps and assess the prevalence of AA amyloidosis among PWID.MethodsCare and Prevent is a UK National Institute for Health Research-funded mixed-methods study. In five phases (P1-P5), we aim to assess the evidence for AA amyloidosis among PWID (P1); assess the feasibility of AA amyloidosis screening, diagnostic and treatment referral among PWID in London (P2); investigate the barriers and facilitators to AA amyloidosis care (P3); explore SSTI protection and risk (P4); and co-create harm reduction resources with the affected community (P5). This paper describes the conceptual framework, methodological design and proposed analysis for the mixed-methods multi-phase study.ResultsWe are implementing the Care and Prevent protocol in London. The systematic review component of the study has been completed and published. Care and Prevent will generate an estimate of AA amyloidosis prevalence among community recruited PWID in London, with implications for the development of screening recommendations and intervention implementation. We aim to recruit 400 PWID from drug treatment services in London, UK.ConclusionsCare and Prevent is the first study to assess screening feasibility and the prevalence of positive proteinuria, as a marker for AA amyloidosis, among PWID accessing drug treatment services. AA amyloidosis is a serious, yet under-recognised condition for which early intervention is available but not employed.

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]

Background and Purpose: The aim of this study was to investigate the effect of combined exercise on resting levels of pentraxin3 (PTX3) and serum amyloid A (SAA) in the plasma of men with type-2 diabetes. Materials and Methods: Twenty oen-athlete men with type-2 diabetes were randomly divided into control and training groups. Combined training was performed for six weeks. Training including 25-35 minutes of aerobic exercise with an intensity of 55-75% of maximum heart rate and five resistance movements involving large muscles in the upper and lower body Includes five movements: chest press, army press, squat, dead lift, dumbbell rowing with an intensity of 55-75% of a maximum repetition with a frequency of three times a week with the periorizing of resistance training on aerobic training. The intensity of aerobic exercise was measured with heart rate monitor and the intensity of resistance training was measured every two weeks with a maximum repetition test. For data analysis, dependent and independent t-test was used at the significant level of P ≤ 0.05. Results: Examining the results of the study, it was found that the training contract reduced the SAA index (16.7%) and significantly changed it in the training group compared to the control group (P = 0.047. However, there was no effect on resting SAA in the control group and a 2.2% increase in PTX3 in the training group was not significant (P = 0.474). Conclusion: According to the results of the study and a significant decrease in inflammatory factor SAA and increase in PTX3, it can be concluded that six weeks of combined training affects the levels of these factors in men with type-2 diabetes and can probably reduce inflammation in these patients. [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]

BackgroundSerum amyloid A (SAA) is a major acute phase protein in horses. A new point-of-care (POC) test for SAA (Stablelab) is available, but studies evaluating its analytical accuracy are lacking.ObjectivesTo evaluate the analytical performance of the SAA POC test by 1) determining linearity and precision, 2) comparing results in whole blood with those in serum or plasma, and 3) comparing POC results with those obtained using a previously validated turbidimetric immunoassay (TIA).Study designAssay validation.MethodsAnalytical validation of the POC test was done in accordance with American Society of Veterinary Clinical Pathology guidelines using residual equine serum/plasma and whole blood samples from the Clinical Pathology Laboratory at the University of California-Davis. A TIA was used as the reference method. We also evaluated the effect of haematocrit (HCT).ResultsThe POC test was linear for SAA concentrations of up to at least 1000 μg/mL (r = 0.991). Intra-assay CVs were 13, 18 and 15% at high (782 μg/mL), intermediate (116 μg/mL) and low (64 μg/mL) concentrations. Inter-assay (inter-batch) CVs were 45, 14 and 15% at high (1372 μg/mL), intermediate (140 μg/mL) and low (56 μg/mL) concentrations. SAA results in whole blood were significantly lower than those in serum/plasma (P = 0.0002), but were positively correlated (r = 0.908) and not affected by HCT (P = 0.261); proportional negative bias was observed in samples with SAA>500 μg/mL. The difference between methods exceeded the 95% confidence interval of the combined imprecision of both methods (15%).Main limitationsAnalytical validation could not be performed in whole blood, the sample most likely to be used stall side.ConclusionThe POC test has acceptable accuracy and precision in equine serum/plasma with SAA concentrations of up to at least 1000 μg/mL. Low inter-batch precision at high concentrations may affect serial measurements, and the use of the same test batch and sample type (serum/plasma or whole blood) is recommended. Comparison of results between the POC test and the TIA is not recommended.

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]

The three most common varieties of systemic amyloidosis are transthyretin amyloidosis (ATTR), immunoglobulin amyloidosis (AL) and inflammatory amyloidosis (AA). There are two forms of transthyretin amyloidosis: the wild type, the most common, represents approximately 15% of heart diseases and the genetic, or "mutated" form, which is a rare disease and manifests mainly by peripheral neuropathy and heart disease. Major therapeutic advances have been made in recent years thanks to molecules that stabilize transthyretin and/or prevent its translation by destroying messenger RNA. Immunoglobulin amyloidosis (AL) is a hematological disease whose severity is due to the toxicity of immunoglobulin light chains forming amyloid deposits that are toxic to tissues, particularly the heart and kidneys. Treatments for immunoglobulin amyloidosis are increasingly effective, and target the plasma cell, leading to an overall improvement in the prognosis, with cardiac involvement being the most worrying condition. Inflammatory amyloidosis (AA) complicates chronic inflammatory diseases less often due to the effectiveness of anti-inflammatory biotherapies in inflammatory rheumatism, chronic inflammatory bowel diseases and genetic auto-inflammatory diseases. The causes of inflammatory amyloidosis are now more diverse with an increase in cases of unknown cause associated or not with obesity., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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

AimsTo determine if serum levels of serum amyloid A (SAA) predict death and end-stage renal disease in a cohort of people with diabetic kidney disease.MethodsIn a longitudinal cohort study of 135 participants with type 2 diabetes and diabetic kidney disease, serum samples were assayed for SAA. Censored time-to-event analyses in Cox-proportional hazard models were utilized to assess SAA as a predictor of the primary outcome of death and end-stage renal disease.ResultsParticipants were 73% Mexican-American (99/135) and 55% men (75/135), with a mean±SD age of 57±7.5years. At baseline, participants had hemoglobin A1c of 8.6±2.3%, systolic blood pressure of 153±27mm Hg, body mass index of 31±9kg/m2, median urine-albumin-to-creatinine ratio of 1861mg/g (interquartile range 720-3912mg/g), and estimated glomerular filtration rate of 55.7±22.3ml/min/1.73m2. Over a median duration of follow-up of 3.5years, 44% (60/135) of participants experienced a primary outcome event. The hazards ratio for the primary outcome was 3.03 (95% CI 1.43-6.40, p=0.003) in the highest (>1.0 μg/ml) compared to the lowest (

Background and purposeAmong children with arterial ischemic stroke (AIS), those with arteriopathy have the highest recurrence risk. We hypothesized that arteriopathy progression is an inflammatory process and that inflammatory biomarkers would predict recurrent AIS.MethodsIn an international study of childhood AIS, we selected cases classified into 1 of the 3 most common childhood AIS causes: definite arteriopathic (n=103), cardioembolic (n=55), or idiopathic (n=78). We measured serum concentrations of high-sensitivity C-reactive protein, serum amyloid A, myeloperoxidase, and tumor necrosis factor-α. We used linear regression to compare analyte concentrations across the subtypes and Cox proportional hazards models to determine predictors of recurrent AIS.ResultsMedian age at index stroke was 8.2 years (interquartile range, 3.6-14.3); serum samples were collected at median 5.5 days post stroke (interquartile range, 3-10 days). In adjusted models (including age, infarct volume, and time to sample collection) with idiopathic as the reference, the cardioembolic (but not arteriopathic) group had higher concentrations of high-sensitivity C-reactive protein and myeloperoxidase, whereas both cardioembolic and arteriopathic groups had higher serum amyloid A. In the arteriopathic (but not cardioembolic) group, higher high-sensitivity C-reactive protein and serum amyloid A predicted recurrent AIS. Children with progressive arteriopathies on follow-up imaging had higher recurrence rates, and a trend toward higher high-sensitivity C-reactive protein and serum amyloid A, compared with children with stable or improved arteriopathies.ConclusionsAmong children with AIS, specific inflammatory biomarkers correlate with cause and-in the arteriopathy group-risk of stroke recurrence. Interventions targeting inflammation should be considered for pediatric secondary stroke prevention trials.

Systemic amyloid A (AA) amyloidosis is highly prevalent (34%) in endangered island foxes (Urocyon littoralis) and poses a risk to species recovery. Although elevated serum AA (SAA) from prolonged or recurrent inflammation predisposes to AA amyloidosis, additional risk factors are poorly understood. Here we define the severity of glomerular and medullary renal amyloid and identify risk factors for AA amyloidosis in 321 island foxes necropsied from 1987 through 2010. In affected kidneys, amyloid more commonly accumulated in the medullary interstitium than in the glomeruli (98% [n= 78 of 80] vs 56% [n= 45], respectively;P< .0001), and medullary deposition was more commonly severe (19% [n= 20 of 105]) as compared with glomeruli (7% [n= 7];P= .01). Univariate odds ratios (ORs) of severe renal AA amyloidosis were greater for short- and long-term captive foxes as compared with free-ranging foxes (ORs = 3.2, 3.7, respectively; overall P= .05) and for females as compared with males (OR = 2.9;P= .05). Multivariable logistic regression revealed that independent risk factors for amyloid development were increasing age class (OR = 3.8;P< .0001), San Clemente Island subspecies versus San Nicolas Island subspecies (OR = 5.3;P= .0003), captivity (OR = 5.1;P= .0001), and nephritis (OR = 2.3;P= .01). The increased risk associated with the San Clemente subspecies or captivity suggests roles for genetic as well as exogenous risk factors in the development of AA amyloidosis.

BackgroundAA amyloidosis due to subcutaneous injection of drugs of abuse has been described in the USA, but all the existing literature is from more than 20 years ago. There is more recent literature from Europe. We have observed a high incidence of AA amyloidosis in the county hospital in San Francisco.DesignHere, we describe 24 patients who had kidney biopsy-proven AA amyloidosis from our hospital from 1998 to 2013. All the patients were thought to have AA amyloidosis from skin popping of illicit drugs after having exhausted the intravenous route. These patients with biopsy-proven AA amyloidosis were analysed further.ResultsAll patients were found to have hepatitis C infection, hypertension was not common, most had advanced kidney failure, and acidosis was common as was tubulointerstitial involvement on the kidney biopsy. Other organ involvement included hepatomegaly and splenomegaly in a number of patients; direct myocardial involvement was not seen, but pulmonary hypertension, history of deep vein thrombosis and pulmonary embolism were common. The prognosis of these patients was poor. The mortality rate approached 50% 1 year after biopsy, and most of the patient needed dialysis shortly after diagnosis. Cessation of drug use seemed beneficial but rarely achievable.ConclusionAA amyloidosis from skin popping is common in San Francisco. Most patients with renal involvement end up on dialysis, and mortality rates are exceedingly high.

Serum amyloid A (SAA) is an evolutionary highly conserved acute phase protein that is predominantly secreted by hepatocytes. However, its role in liver injury and fibrogenesis has not been elucidated so far. In this study, we determined the effects of SAA on hepatic stellate cells (HSCs), the main fibrogenic cell type of the liver. Serum amyloid A potently activated IκB kinase, c-Jun N-terminal kinase (JNK), Erk and Akt and enhanced NF-κB-dependent luciferase activity in primary human and rat HSCs. Serum amyloid A induced the transcription of MCP-1, RANTES and MMP9 in an NF-κB- and JNK-dependent manner. Blockade of NF-κB revealed cytotoxic effects of SAA in primary HSCs with signs of apoptosis such as caspase 3 and PARP cleavage and Annexin V staining. Serum amyloid A induced HSC proliferation, which depended on JNK, Erk and Akt activity. In primary hepatocytes, SAA also activated MAP kinases, but did not induce relevant cell death after NF-κB inhibition. In two models of hepatic fibrogenesis, CCl4 treatment and bile duct ligation, hepatic mRNA levels of SAA1 and SAA3 were strongly increased. In conclusion, SAA may modulate fibrogenic responses in the liver in a positive and negative fashion by inducing inflammation, proliferation and cell death in HSCs.

BackgroundKawasaki disease (KD) is an acute vasculitis in children that can cause coronary artery abnormalities. Its diagnosis is challenging, and many cytokines, chemokines, acute phase reactants, and growth factors have failed evaluation as specific biomarkers to distinguish KD from other febrile illnesses. We performed protein profiling, comparing plasma from children with KD with febrile control (FC) subjects to determine if there were specific proteins or peptides that could distinguish the two clinical states.Materials and methodsPlasma from three independent cohorts from the blood of 68 KD and 61 FC subjects was fractionated by anion exchange chromatography, followed by surface-enhanced laser desorption ionization (SELDI) mass spectrometry of the fractions. The mass spectra of KD and FC plasma samples were analyzed for peaks that were statistically significantly different.ResultsA mass spectrometry peak with a mass of 7,860 Da had high intensity in acute KD subjects compared to subacute KD (p = 0.0003) and FC (p = 7.9 x 10-10) subjects. We identified this peak as a novel truncated form of serum amyloid A with N-terminal at Lys-34 of the circulating form and validated its identity using a hybrid mass spectrum immunoassay technique. The truncated form of serum amyloid A was present in plasma of KD subjects when blood was collected in tubes containing protease inhibitors. This peak disappeared when the patients were examined after their symptoms resolved. Intensities of this peptide did not correlate with KD-associated laboratory values or with other mass spectrum peaks from the plasma of these KD subjects.ConclusionsUsing SELDI mass spectrometry, we have discovered a novel truncated form of serum amyloid A that is elevated in the plasma of KD when compared with FC subjects. Future studies will evaluate its relevance as a diagnostic biomarker and its potential role in the pathophysiology of KD.

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.)

BackgroundThe overall burden of chronic disease, inflammation and cardiovascular risk increases with age. Whether the relationship between age and inflammation is impacted by presence of an adverse metabolic burden is not known.MethodsWe determined inflammatory markers in humans (336 Caucasians and 224 African Americans) and in mice, representing a spectrum of age, weight and metabolic burden.ResultsIn humans, levels of inflammatory markers increased significantly with age in subjects without the metabolic syndrome, (P=0.009 and P=0.037 for C-reactive protein, P

Well-differentiated hepatocellular carcinoma in non-cirrhotic liver can show morphological features similar to hepatocellular adenoma. In rare instances, hepatocellular carcinoma can arise in the setting of hepatocellular adenoma. This study compares the immunohistochemical and cytogenetic features of the hepatocellular adenoma-like and hepatocellular carcinoma portions of these tumors. Immunohistochemistry for β-catenin, glutamine synthetase, serum amyloid A protein, glypican-3, and heat-shock protein 70 was done in 11 cases of hepatocellular carcinoma arising in hepatocellular adenoma in non-cirrhotic liver. Tumors with nuclear β-catenin and/or diffuse glutamine synthetase were considered β-catenin activated. Fluorescence in situ hybridization (FISH) was done in nine cases for gains of chromosomes 1, 8 and MYC. There were seven men (33-75 years) and four women (29-65 years). Focal atypical morphological features were seen in hepatocellular adenoma-like areas in 7 (64%) cases. Hepatocellular adenoma-like areas showed features of inflammatory hepatocellular adenoma in 7 (64%) cases; 4 of these were also serum amyloid A-positive in the hepatocellular carcinoma portion. β-Catenin activation, heat-shock protein 70 positivity, and chromosomal gains on FISH were seen in the hepatocellular adenoma portion in 55%, 40%, and 56% of cases, and 73%, 60%, and 78% of cases in the hepatocellular carcinoma portion, respectively. In conclusion, the hepatocellular adenoma-like portion of most cases of hepatocellular carcinoma arising in hepatocellular adenoma shows features typically seen in hepatocellular carcinoma such as focal morphological abnormalities, β-catenin activation, heat-shock protein 70 expression, and chromosomal gains. Hepatocellular adenoma-like areas in these tumors, especially in men and older women, may represent an extremely well-differentiated variant of hepatocellular carcinoma, whereas the morphologically recognizable hepatocellular carcinoma portion represents a relatively higher grade component of the tumor.

Folate-mediated one-carbon metabolism is essential for DNA synthesis, repair, and methylation. Perturbations in one-carbon metabolism have been implicated in increased risk of some cancers and may also affect inflammatory processes. We investigated these interrelated pathways to understand their relation. The objective was to explore associations between inflammation and biomarkers of nutritional status and one-carbon metabolism. In a cross-sectional study in 1976 women selected from the Women's Health Initiative Observational Study, plasma vitamin B-6 [pyridoxal-5'-phosphate (PLP)], plasma vitamin B-12, plasma folate, and RBC folate were measured as nutritional biomarkers; serum C-reactive protein (CRP) and serum amyloid A (SAA) were measured as biomarkers of inflammation; and homocysteine and cysteine were measured as integrated biomarkers of one-carbon metabolism. Student's t, chi-square, and Spearman rank correlations, along with multiple linear regressions, were used to explore relations between biomarkers; additionally, we tested stratification by folic acid fortification period and multivitamin use. With the use of univariate analysis, plasma PLP was the only nutritional biomarker that was modestly significantly correlated with serum CRP and SAA (ρ = -0.22 and -0.12, respectively; P < 0.0001). Homocysteine (μmol/L) showed significant inverse correlations with all nutritional biomarkers (ranging from ρ = -0.30 to ρ = -0.46; all P < 0.0001). With the use of multiple linear regression, plasma PLP, RBC folate, homocysteine, and cysteine were identified as independent predictors of CRP; and PLP, vitamin B-12, RBC folate, and homocysteine were identified as predictors of SAA. When stratified by folic acid fortification period, nutrition-homocysteine correlations were generally weaker in the postfortification period, whereas associations between plasma PLP and serum CRP increased. Biomarkers of inflammation are associated with PLP, RBC folate, and homocysteine in women. The connection between the pathways needs to be further investigated and causality established. The trial is registered at clinicaltrials.gov as NCT00000611.

Serum amyloid A (SAA) represents an evolutionarily conserved family of inflammatory acute-phase proteins. It is also a major constituent of secondary amyloidosis. To understand its function and structural transition to amyloid, we determined a structure of human SAA1.1 in two crystal forms, representing a prototypic member of the family. Native SAA1.1 exists as a hexamer, with subunits displaying a unique four-helix bundle fold stabilized by its long C-terminal tail. Structure-based mutational studies revealed two positive-charge clusters, near the center and apex of the hexamer, that are involved in SAA association with heparin. The binding of high-density lipoprotein involves only the apex region of SAA and can be inhibited by heparin. Peptide amyloid formation assays identified the N-terminal helices 1 and 3 as amyloidogenic peptides of SAA1.1. Both peptides are secluded in the hexameric structure of SAA1.1, suggesting that the native SAA is nonpathogenic. Furthermore, dissociation of the SAA hexamer appears insufficient to initiate amyloidogenic transition, and proteolytic cleavage or removal of the C-terminal tail of SAA resulted in formation of various-sized structural aggregates containing ∼5-nm regular repeating protofibril-like units. The combined structural and functional studies provide mechanistic insights into the pathogenic contribution of glycosaminoglycan in SAA1.1-mediated AA amyloid formation.

Amyloid A (AA) amyloidosis is a debilitating, often fatal, systemic amyloid disease associated with chronic inflammation and persistently elevated serum amyloid A (SAA). Elevated SAA is necessary but not sufficient to cause disease and the risk factors for AA amyloidosis remain poorly understood. Here we identify an extraordinarily high prevalence of AA amyloidosis (34%) in a genetically isolated population of island foxes (Urocyon littoralis) with concurrent chronic inflammatory diseases. Amyloid deposits were most common in kidney (76%), spleen (58%), oral cavity (45%), and vasculature (44%) and were composed of unbranching, 10 nm in diameter fibrils. Peptide sequencing by mass spectrometry revealed that SAA peptides were dominant in amyloid-laden kidney, together with high levels of apolipoprotein E, apolipoprotein A-IV, fibrinogen-α chain, and complement C3 and C4 (false discovery rate ≤ 0.05). Reassembled peptide sequences showed island fox SAA as an 111 amino acid protein, most similar to dog and artic fox, with 5 unique amino acid variants among carnivores. SAA peptides extended to the last two C-terminal amino acids in 5 of 9 samples, indicating that near full length SAA was often present in amyloid aggregates. These studies define a remarkably prevalent AA amyloidosis in island foxes with widespread systemic amyloid deposition, a unique SAA sequence, and the co-occurrence of AA with apolipoproteins.

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

In an unbiased approach to biomarker discovery, we applied a highly multiplexed proteomic technology (SOMAscan, SomaLogic, Inc, Boulder, CO) to understand changes in proteins from paired serum samples at enrollment and after 8 weeks of TB treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in the Center for Disease Control and Preventions Tuberculosis Trials Consortium (TBTC) Study 29. This work represents the first large-scale proteomic analysis employing modified DNA aptamers in a study of active tuberculosis (TB). We identified multiple proteins that exhibit significant expression differences during the intensive phase of TB therapy. There was enrichment for proteins in conserved networks of biological processes and function including antimicrobial defense, tissue healing and remodeling, acute phase response, pattern recognition, protease/anti-proteases, complement and coagulation cascade, apoptosis, immunity and inflammation pathways. Members of cytokine pathways such as interferon-gamma, while present, were not as highly represented as might have been predicted. The top proteins that changed between baseline and 8 weeks of therapy were TSP4, TIMP-2, SEPR, MRC-2, Antithrombin III, SAA, CRP, NPS-PLA2, LEAP-1, and LBP. The novel proteins elucidated in this work may provide new insights for understanding TB disease, its treatment and subsequent healing processes that occur in response to effective therapy.

Giant magnetoresistive (GMR) nanosensors provide a novel approach for measuring protein concentrations in blood for medical diagnosis. Using an in vivo mouse radiation model, we developed protocols for measuring Flt3 ligand (Flt3lg) and serum amyloid A1 (Saa1) in small amounts of blood collected during the first week after X-ray exposures of sham, 0.1, 1, 2, 3, or 6 Gy. Flt3lg concentrations showed excellent dose discrimination at ≥ 1 Gy in the time window of 1 to 7 days after exposure except 1 Gy at day 7. Saa1 dose response was limited to the first two days after exposure. A multiplex assay with both proteins showed improved dose classification accuracy. Our magneto-nanosensor assay demonstrates the dose and time responses, low-dose sensitivity, small volume requirements, and rapid speed that have important advantages in radiation triage biodosimetry.