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The amyloidoses are a group of diseases characterized by the aggregation of specific proteins, which are then deposited in tissues as β-structured fibrils. Pathology is the result of displacement of normal tissue structure and loss of function. Amyloid, the substance of the tissue deposits, is defined as being composed of fibrils with 10nm diameter and indeterminate length when viewed by electron microscopy, β-structure when analyzed by X-ray diffraction, and positive staining with the histochemical dye Congo red. Amyloid deposits by definition are extracellular. While there are at least 26 different proteins which can make amyloid fibrils, only certain ones are life threatening. There are three main classifications of systemic amyloidosis: (1) Immunoglobulin light chain (AL) amyloidosis is the most common form of amyloidosis and is caused by plasma cell dyscrasia. (2) Reactive (AA) amyloidosis is the result of overproduction of serum amyloid A, an acute phase protein produced by the liver as a response to inflammation. (3) Hereditary (familial) amyloidosis is really a group of diseases in which mutations in normal proteins lead to aggregation and fibril formation. The most common form is transthyretin (TTR) amyloidosis, caused by mutations in TTR, a plasma transport protein for thyroxin and vitamin A. Other forms of hereditary amyloidosis are caused by mutations in apolipoprotein A-I (apo A-I), apolipoprotein A-II (apo A-II), fibrinogen Aα-chain, lysozyme, cystatin C and gelsolin. All forms of amyloidosis are inherited as autosomal dominant traits with varying disease phenotypes depending on the protein involved or the specific mutation, and other as yet undisclosed factors. Protein deposition diseases, which do not meet the pathology definition of amyloidosis, may be characterized by tissue deposits that do not show β-structure or may be deposited intracellularly. Pathogenic mechanisms may be similar to those of the amyloidoses and, therefore, deserve discussion.

BACKGROUND Sepsis is a significant cause of morbidity and mortality in neonatal foals, especially during the first 7 days of life. Diagnosing sepsis in neonatal foals can be challenging because initial clinical signs are often ambiguous and non-specific. OBJECTIVES To determine if the major acute phase protein serum amyloid A (SAA) as measured by a point-of-care SAA testing device can be used as an evidence-based biomarker of sepsis. STUDY DESIGN Retrospective cohort. METHODS Clinical diagnosis of sepsis based on positive bacterial blood culture or a positive sepsis score was obtained and compared to SAA values in a population of neonatal foals on a breeding farm and referral hospital during four consecutive foaling seasons. A rapid, point-of-care blood test was used to measure SAA concentrations in neonatal foals

Objectives Indeed, serum amyloid A (SAA) and C-reactive protein (CRP) reportedly seem to have moderate correlation, but discrepancies between CRP and SAA levels have often been reported in patients with early rheumatoid arthritis (ERA). This study aimed to determine the reasons for this discrepancy. Methods ERA patients (n = 206) were enrolled and treated with anti-RA drugs. Clinical features and disease activities were estimated. CRP and SAA levels were monitored, and the SAA/CRP ratio was compared. Correlations between CRP and SAA levels in individuals and between individuals and disease activity scores were examined. Results In a follow-up study, the SAA/CRP ratio remained almost constant over time in the same patients. However, SAA/CRP ratios differed widely between patients (0.233–106.3). In patients with high SAA/CRP ratios (>6.52), many (26.2%) had abnormal SAA values only. In patients with low SAA/CRP ratios ( Conclusions The SAA/CRP ratio remained virtually constant in the same patients but differed dramatically between patients, which clarifies the discrepancy between CRP and SAA levels. CRP is the better marker in low-ratio patients but not in high-ratio patients; the SAA/CRP ratio is critical for its interpretation.

Rapid, accurate detection of serum amyloid A (SAA) is needed in equine practice. We validated a patient-side point-of-care (POC) assay (Stablelab; Zoetis) compared to the turbidimetric immunoassays LZ-SAA (TIA-Hum) and VET-SAA (TIA-Vet; both Eiken Chemical). Analytical performance was assessed at 3 different concentration ranges and with interferences. Inter-method comparison using 49 equine serum samples revealed a significant difference between median SAA results ( p s = 0.77 and 0.69) and excellent between both TIAs (rs = 0.93). Bias between POC/TIA-Hum, POC/TIA-Vet, and TIA-Hum/TIA-Vet was −56.7%, –80.9%, and −28.2%, respectively. POC intra- and inter-assay CVs (16.1–30% and 19.8–35.5%) were higher than TIA CVs (generally 2 = 0.92). A hook effect was present at SAA >3,000 mg/L for the POC assay. Equine serum SAA was stable over a median period of 2.5 y when stored at −80°C. Overall, there was excellent-to-moderate correlation between tests, but imprecision and hook effect of the POC, as well as bias between the methods, must be considered.

Shunxin Zhu,1 Caixiu Zeng,2 Yan Zou,1 Yanjiao Hu,1 Canfang Tang,1 Chunmei Liu2 1Clinical Laboratory, The Maternity & Child Health Care Hospital of Xiangtan City, Xiangtan City, Hunan Province, 411100, People’s Republic of China; 2Department of Pediatrics, The Maternity & Child Health Care Hospital of Xiangtan City, Xiangtan City, Hunan Province, 411100, People’s Republic of ChinaCorrespondence: Shunxin ZhuClinical Laboratory, The Maternity & Child Health Care Hospital of Xiangtan City, Xiangtan City, Hunan Province, 411100, People’s Republic of ChinaTel +86- 18975221633Email zhushunxin349@126.comBackground: Bacterial, viral, and bacterial and viral co-infections generally lead to inflammatory-related diseases. The aim of this study is to assess the clinical diagnostic values of serum amyloid A (SAA), procalcitonin (PCT), C-reactive protein (CRP), and interleukin (IL)-6 in children with bacterial, viral, or co-infections.Methods: A total of 181 children with infection symptoms (bacterial infection (Bac group), n = 46; viral infection (Vir group), n = 7; co-infections (Bac + Vir group), n = 128) were enrolled in our hospital from December 2019 to April 2020. Meanwhile, 42 healthy children without any infections were used as the controls. Venous blood samples were collected and the levels of serum SAA, PCT, CRP, and IL-6 were determined by immunoluminometric assay under an IMMAGE® analyzer. The diagnostic values of these biomarkers were assessed using the receiver operating characteristic (ROC) curves.Results: The results indicated that IL-6 level was increased in three infection groups compared to the controls. Both SAA and CRP were significantly elevated in Vir and Bac + Vir groups. High level of PCT was observed in Bac and Bac + Vir goups. In addition, PCT (0.9281, 95% CI = 0.8645– 0.9916) alone is an effective method for identifying bacterial infections. SAA in combination with CRP may distinguish co-infection from bacterial infection. Simultaneous positive of SAA, PCT, IL-6, and CRP can discriminate co-infection from the healthy controls.Conclusion: In a word, the levels of serum SAA, PCT, CRP, and IL-6 are increased to varying degrees in different infection situations. Our findings may provide early diagnosis for patients with different infections.Keywords: bacterial infection, viral infection, co-infection, combined biomarkers, diagnostic accuracy

Sepsis is a potentially fatal condition caused by infection. It is frequently difficult to distinguish sepsis from systemic inflammatory response syndrome (SIRS), often resulting in poor prognoses and the misuse of antibiotics. Hence, highly sensitive and specific biomarkers are needed to differentiate sepsis from SIRS. Urine samples were collected and segregated by group (a sepsis group, a SIRS group, and a healthy control group). iTRAQ was used to identify the differentially expressed proteins among the three groups. The identified proteins were measured by ELISA in urine samples. Finally, all the acquired data were analyzed in SPSS. C-reactive protein, leucine-rich alpha glycoprotein-1 and serum amyloid A (SAA) protein were differentially expressed among the three groups. The adjusted median concentrations of urinary C-reactive protein were 1337.6, 358.7, and 2.4 in the sepsis, SIRS, and healthy control groups, respectively. The urinary leucine-rich alpha glycoprotein-1 levels in these three groups were 1614.4, 644.5, and 13.6, respectively, and the levels of SAA were 6.3, 2.9, and 0.07, respectively. For all three of these measures, the sepsis group had higher levels than the SIRS group (P

Objectives To evaluate the long-term efficacy and safety of canakinumab in patients with mevalonate kinase deficiency during the open label extension (weeks 41–113) of the randomized controlled CLUSTER trial. Methods During a 72-week period, patients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks. The disease activity was evaluated every 8 weeks using physician global assessment and counting the number of flares. Concentrations of CRP and serum amyloid A protein were measured. The safety was studied by determination and classification of observed adverse events. The safety and efficacy were analysed separately in three subgroups of patients receiving a cumulative dose of less than Results Of the 74 patients who started the CLUSTER study, 66 entered Epoch 4 and 65 completed it. During the 72-week period, 42 (64%) patients experienced no flares, while 13 (20%) had one flare, as compared with a median of 12 flares per year reported at baseline. Low physician global assessment scores were seen at the end of the study for all groups with >90% reporting minimal disease activity or none at all. Median CRP concentrations were consistently equal or lower than 10 mg/l, while median serum amyloid A concentrations remained only slightly above the normal range of 10 mg/l. The study showed no new or unexpected adverse events. Conclusion Canakinumab proved effective to control disease activity and prevent flares in mevalonate kinase deficiency during the 72-week study period. No new safety concerns were reported. Trial registration NCT02059291. https://clinicaltrials.gov.

The literature review provides up-to-date data on the frequency, developmental mechanisms, clinical manifestations, diagnosis and treatment of secondary renal amyloidosis (AA amyloidosis) in children with juvenile rheumatoid arthritis (JRA). The incidence of AA amyloidosis in children with JRA is from 0.8 to 2 %, in adults with JRA duration of 28.3 years — 8.9 %. In recent years, on the background of immunobiological therapy, the frequency of AA amyloidosis in adults has decreased to 2 %. To date, the main mechanism for the development of AA amyloidosis has been established, which consists in a constant or periodic increase in the concentration of serum amyloid A (SAA). It has been established that the synthesis of SAA is influenced by proinflammatory cytokines: interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha, IL-2, IL-11 and others. To realize the amyloidogenic potential of SAA, it is necessary to influence not only the inflammatory process in the body, but also its duration. The role of genetic factors in the deve­lopment of AA amyloidosis in patients with JRA is discussed. AA amyloidosis most often develops in children with a systemic form, in adults — with systemic and polyarticular forms of JRA. The first symptom of AA amyloidosis is isolated proteinuria, which transforms into nephrotic syndrome. The peculiarity of the nephrotic syndrome is the absence of hypercholesterolemia in most cases, and combination with arterial hypertension, hematuria, and impaired renal function in some patients. The main method confirming the diagnosis of AA amyloidosis is a morphological study of the kidneys biopsy specimens with Congo red. An increase in blood SAA in children with JRA reflects the degree of the inflammatory process and is considered as a risk factor for the development of AA amyloidosis. The use of immunobiological preparations (tocilizumab, anakinra) in children with JRA and AA amyloidosis has therapeutic efficacy., В обзоре литературы изложены современные данные о частоте, механизмах развития, клинических проявлениях, диагностике и лечении вторичного амилоидоза (АА-амилоидоза) почек у детей с ювенильным ревматоидным артритом (ЮРА). Частота встречаемости АА-амилоидоза почек при ЮРА у детей составляет от 0,8 до 2 %, у взрослых с длительностью ЮРА 28,3 года — 8,9 %. В последние годы на фоне иммунобиологической терапии частота АА-амилоидоза почек у взрослых уменьшилась до 2 %. На сегодняшний день установлен основной механизм развития АА-амилоидоза, который заключается в постоянном или периодическом повышении концентрации сывороточного амилоида А (SAA). Установлено, что на синтез SAA влияют провоспалительные цитокины: интерлейкин-1 (ИЛ-1), ИЛ-6, фактор некроза опухоли альфа (ФНО-α), ИЛ-2, ИЛ-11 и другие. Для реализации амилоидогенного потенциала SAA необходимо не только воздействие воспалительного процесса в организме, но и его продолжительность. Обсуждается роль генетических факторов в развитии АА-амилоидоза почек при ЮРА. АА-амилоидоз почек чаще всего развивается у детей при системной форме, у взрослых — при системной и полиартикулярной формах ЮРА. Первым симптомом АА-амилоидоза почек является изолированная протеинурия, которая трансформируется в нефротический синдром. Особенности нефротического синдрома заключаются в отсутствии в большинстве случаев гиперхолестеринемии, сочетании у некоторых больных с артериальной гипертензией, гематурией, нарушением функции почек. Основным методом, подтверждающим диагноз АА-амилоидоза почек, является прижизненное морфологическое исследование почек с окраской биоптатов конго красным. Повышение уровня SAA в крови у детей с ЮРА отражает степень воспалительного процесса и рассматривается как фактор риска развития АА-амилоидоза почек. Применение иммунобиологических препаратов (тоцилизумаб, анакинра) при АА-амилоидозе почек у детей с ЮРА имеет терапевтическую эффективность., В огляді літератури викладені сучасні дані щодо частоти, механізмів розвитку, клінічних проявів, діагностики та лікування вторинного амілоїдозу (АА-амілоїдозу) нирок у дітей з ювенільним ревматоїдним артритом (ЮРА). Частота розвитку АА-амілоїдозу нирок при ЮРА у дітей становить від 0,8 до 2 %, у дорослих з тривалістю ЮРА 28,3 року — 8,9 %. Останнім часом на тлі імунобіологічної терапії частота АА-амілоїдозу нирок у дорослих зменшилася до 2 %. На сьогодні встановлений основний механізм розвитку АА-амілоїдозу, що полягає в постійному або періодичному підвищенні концентрації сироваткового амілоїду А (SAA). Встановлено, що на синтез SAA впливають прозапальні цитокіни: інтерлейкін-1 (ІЛ-1), ІЛ-6, фактор некрозу пухлини альфа (ФНП-α), ІЛ-2, ІЛ-11 та ін. Для реалізації амілоїдогенного потенціалу SAA необхідний не тільки вплив запального процесу в організмі, але і його тривалість. Обговорюється роль генетичних факторів у розвитку АА-амілоїдозу нирок при ЮРА. АА-амілоїдоз нирок найчастіше розвивається у дітей при системній формі, у дорослих — при системній і поліартикулярній формах ЮРА. Першим симптомом АА-амілоїдозу нирок є ізольована протеїнурія, що трансформується в нефротичний синдром. Особливості нефротичного синдрому полягають у відсутності в більшості випадків гіперхолестеринемії, поєднанні у деяких хворих з артеріальною гіпертензією, гематурією, порушенням функції нирок. Основним методом, що підтверджує діагноз АА-амілоїдозу нирок, є прижиттєве морфологічне дослідження нирок із забарвленням біоптатів конго червоним. Підвищення рівня SAA в крові у дітей з ЮРА відображає ступінь запального процесу і розглядається як фактор ризику розвитку АА-амілоїдозу нирок. Застосування імунобіологічних препаратів (тоцилізумаб, анакінра) при АА-амілоїдозі нирок у дітей з ЮРА має терапевтичну ефективність.

Systemic inflammation plays an important role in carcinogenesis and is associated with overall survival in patients with different cancer types, including those treated with immune checkpoint blockade (ICB). Serum Amyloid A (SAA) is an acute-phase protein and a marker of persistent inflammation. We hypothesized that circulating SAA may predict outcomes in advanced non-small cell lung (aNSCLC) patients treated with PD-1/PD-L1 ICB.This retrospective study included 91 aNSCLC patients who received anti-PD-(L)1 monotherapy in Sun Yat-sen University Cancer Center (Guangzhou, China) between August 2016 and June 2018. We examined the impact of circulating SAA at baseline and 8 (±2) weeks later on overall survival (OS). X-tile program was used to determine the cut-off values which optimized the significance of the split between Kaplan-Meier survival curves. Kaplan-Meier methodology and Cox regression analyses were conducted for survival analyses.The optimal cut-off value of baseline SAA for OS stratification was 137.6 mg/L. In univariate analysis, both high level of baseline SAA (hazard ratio [HR], 2.76; 95% confidence interval [CI], 1.47-5.18; P = 0.002) and lack of early SAA descent (HR, 1.51; 95% CI, 1.11-2.06; P = 0.009) were significantly associated with inferior OS. In multivariate analysis, gender, smoking status, performance status, liver metastasis, neutrophil-to-lymphocyte ratio, baseline SAA and early changes in SAA independently predicted OS (all with P0.05). A combined baseline SAA ≥ 137.6 mg/L and without early SAA descent identified a small cohort with remarkably worse OS (median, 3.2 months).Both high baseline and lack of early decline in circulating SAA are significantly associated with inferior outcomes in aNSCLC patients treated with PD-1/PD-L1 ICB. Combined these two SAA indexes provided improved risk stratification. The prognostic value of this simple, readily-available, and cost-effective biomarker warrants larger, prospective validation before definitive recommendation can be made.

Background : The high social significance of cervical cancer, the shortcomings of the performed cervical screening is prerequisites for research in the field of mproving the diagnosis of this disease. We hypothesized that the systemic level of some inflammatory proteins could be used as a diagnostic criterion for cervical cancer. The aim of the study was to study the level of some vascular-inflammatory markers in the blood serum in patients with precancerous diseases and cervical cancer in order to improve their diagnosis and also to identify markers for predicting an unfavorable outcome in patients with cervical cancer. Materials and methods. A non-randomized prospective controlled study was carried out, the participants of which were patients with the diagnosis of cervical cancer (n = 49) and cervical intraepithelial neoplasia of the III degree (n = 13). The control group included 15 relatively healthy women. The following spectrum of inflammatory proteins was determined in blood serum by flow cytometry using the Human Vascular Inflammation Panel 1: myoglobin, calprotectin, lipocalin A, matrix metal peroxidase 2, osteopontin, myeloperoxidase, serum amyloid A, protein 4, which binds insulin-like growth factor cell-cell adhesion 1, vascular cell adhesion molecule, matrix metalloperoxidase 9, cystatin C. Statistical analysis was carried out by calculating the Mann-Whitney test with Bonferroni’s correction. The model was created using binary logistic regression to diagnose cervical cancer. Results. In the intergroup comparison of the protein`s spectrum in the blood serum, no significant differences were obtained. However, using the binary logistic regression method, an equation was drawn up to calculate the diagnostic coefficient of cervical cancer, which allows diagnosing cervical cancer with an accuracy of 82%, and in terms of information content is not inferior to cytological diagnostics. The developed coefficient can be used to predict an unfavorable outcome of cervical cancer after 1 year from the moment of diagnosis. Conclusion . The developed diagnostic coefficient makes it possible to diagnose cervical cancer with high accuracy and can be used to predict cervical cancer.

Objectives The aim of this study was to investigate the impact of radioiodine treatment (RIT) on the acute phase proteins (APPs) serum amyloid A (SAA), alpha-1-acid glycoprotein (AGP) and haptoglobin (Hp) in hyperthyroid cats. Methods Between June 2013 and November 2014, 33 hyperthyroid cats without clinical or laboratory signs of inflammatory or neoplastic disease and a body weight >2.5 kg were enrolled. Immediately before, and 12, 36, 72 h and 6 days after RIT, serum samples were obtained for determination of APP concentrations. Results Both SAA and AGP concentrations changed significantly after RIT. The concentration of AGP increased gradually after treatment with a maximum concentration at the end of the study period (median baseline 398 μg/ml; median 6 days post-RIT 562 μg/ml [ P = 0.001]). A relevant >two-fold increase in AGP was seen in 8/33 (24%) cats. SAA concentration increased significantly within 12 h (baseline 9.2 μg/ml; 12 h post-RIT 22.5 μg/ml [ P = 0.012]). In 7/33 (21%) cats, a clinically relevant >10-fold increase in SAA was observed. Hp concentration showed no significant change ( P = 0.12). Conclusions and relevance RIT induced a mild, mainly not clinically relevant acute phase reaction (APR). AGP and SAA were useful APPs to determine RIT-induced APR.

OBJECTIVE To investigate the, equine inflammatory response to ventral midline celiotomy in the absence of gastrointestinal disease in horses of varying body condition scores primarily using serial measurements of serum amyloid A (SAA). DESIGN Experimental clinical study. SETTING University teaching hospital. ANIMALS Ten adult light breed horses free of any clinical disease, 5 with body condition score (BCS) 3-4/9 and 5 with BCS 7-8/9. INTERVENTIONS Horses had a ventral midline celiotomy performed under general anesthesia, including manual decompression of the small intestine. SAA, semiquantitative fibrinogen, plasma lactate, and WBC count were measured in the blood preoperatively and at 12, 24, 48, 72, 120, and 168 hours postoperatively. Complete serum biochemistry was performed preoperatively and 24 and 72 hours postoperatively. Serial abdominocentesis was also performed with peritoneal fluid analysis of SAA, total protein, lactate, WBC count, and cytology. MEASUREMENTS AND MAIN RESULTS Significant (P

Yin-Jiang Lv, Qi-Lei Hu, Rong Huang, Liang Zhang, Li-Feng Wu, Shui Fu Department of Clinical Laboratory, The First People’s Hospital of Yuhang District, Hangzhou, Hangzhou, Zhejiang, 311100, People’s Republic of ChinaCorrespondence: Shui FuDepartment of Clinical Laboratory, The First People’s Hospital of Yuhang District, Hangzhou, No. 369 Yingbin Road of Nanyuan Street, Yuhang District, Hangzhou, 311100, People’s Republic of ChinaTel +86 571 89369404Email fushuiolo@163.comObjective: This study explores the significance of serum amyloid A (SAA), C-reactive protein (CRP), and white blood cell (WBC) in the diagnosis and treatment of diarrhea in infants.Methods: Specimens were collected from 126 children with diarrhea and 66 healthy children undergoing health examination. According to the results of stool culture and rotavirus (RV) antigen, these children were divided into three groups: rotavirus group (70 cases), bacterial infection (56 cases), and control groups (66 cases). On the fourth day of admission, children in the RV group underwent stool culture again. Based on the subsequent results, they were further divided into two groups, ie, no secondary bacterial infection and secondary bacterial infection groups. The levels of RV antigen, bacterial antigen, SAA, CRP, and WBC were detected in all children. Then, ROC curve analysis was performed to determine the diagnostic efficacy of SAA, CRP and WBC.Results: The levels of SAA, CRP, and WBC for the RV group were lower than those of the bacterial infection group, but higher compared with the control group (P< 0.05). The diagnostic efficacy of SAA was higher than that of CRP and WBC, with the area under the curve of 0.876, 0.803, and 0.765, respectively. The positive and negative predictive values, specificity, and sensitivity of SAA were slightly better compared with CRP and WBC. The SAA, CRP, and WBC levels of children with a bacterial infection in the RV group on the fourth and seventh days after admission were also significantly higher compared with children without bacterial infection.Conclusion: Serum amyloid A, CRP, and WBC levels had a high value in the differential diagnosis of infantile diarrhea. As such, they can be used in the early diagnosis and curative efficacy assessment of children with diarrhea.Keywords: group A rotavirus, serum amyloid A, C-reactive protein, white blood cell, diagnostic efficacy

Polycystic ovary syndrome (PCOS), i.e., anovulation, hyperandrogenemia and polycystic ovary, is an endocrine-metabolic disease affecting reproductive aged women. Women with PCOS are likely to develop obesity, dyslipidemia, type 2 diabetes mellitus (T2DM) and cardiovascular diseases at a younger age. Despite high frequency and severe disease burden, the pathophysiological mechanisms of PCOS remain poorly defined and correspondingly have no therapeutic options. Emerging evidence has demonstrated that PCOS is accompanied with low-grade chronic inflammation and biomarkers thereof. Interestingly, serum amyloid A (SAA) has recently been identified as a potential marker of infection and inflammation and a number of studies have reported an association with PCOS. In this review, we explore the relationship between SAA and hyperandrogenemia, inflammation, obesity and insulin resistance, and provide convincing evidence for SAA as a potential inflammatory biomarker in PCOS.

Background/aim Familial Mediterranean fever (FMF), the most common autoinflammatory disease in children, is characterized by recurrent febrile episodes. FMF is known to progress with chronic inflammation, particularly during attack periods. This study aimed to investigate the relationship of S100A12, an inflammatory marker, with attacks and inflammatory events in FMF patients. Materials and methods The study included 57 patients diagnosed with FMF, 43 in an attack-free period and 14 in an attack period, and 31 healthy children as the control group. Only white blood cell (WBC) count, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and S100A12 level were analyzed in the control group. In addition, serum amyloid A (SAA), and fibrinogen levels were measured, and a mutation analysis was performed in the patient group. The results were compared among the attack-free period, acute attack FMF and control groups. Results The mean age of patients and control group was 10 (2.5–18) and 9.5 (2.5–16) years, respectively. The CRP (p = 0.001), S100A12 (p = 0.003) and ESR (p= 0.001) values differed significantly between the FMF and control groups. S100A12 level (p = 0.027), WBC count (p = 0.003), CRP level (p = 0.0001), ESR (p = 0.004), and fibrinogen level (p = 0.001) differed significantly between the acute attack and attack-free period groups. SAA level (p = 0.05), ESR (p = 0.001), fibrinogen level (p = 0.001), WBC count (p = 0.001), and S100A12 level (p = 0.027) were higher in M694V homozygous FMF patients than in other FMF patients. Conclusion Patients with FMF had higher S100A12 levels than the control group, while the mean S100A12 concentration was higher in acute attack period patients than in attack-free period patients. S100A12 level might be an important indicator in the monitoring of chronic inflammation in patients with FMF.

Background and Aim: Ketosis is a common disease occurring during the first stage of lactation in highly productive dairy cows. The aim of the present study was the comparative assessment of selected pro-inflammatory cytokines (including tumor necrosis factor-α [TNF-α] and interleukin 6 [IL-6]), anti-inflammatory cytokines (including IL-10), and acute-phase proteins (APPs) (including haptoglobin [Hp] and serum amyloid A [SAA]), in the sera of cows with subclinical ketosis (SCK), in those with clinical ketosis (CK), and in healthy cows. Materials and Methods: Thirty dairy cows of Holstein-Friesian breed were investigated. The cows were divided into three groups depending on the serum β-hydroxybutyric acid (BHBA) level. The control, SCK, and CK groups included healthy cows, cows with SCK, and cows with CK, respectively. BHBA concentration in blood serum was determined using colorimetric method. The blood serum was used for proper tests. Cytokine (TNF-α, IL-6, and IL-10) and APPs (SAA and Hp) concentrations in the investigated samples were determined by enzyme-linked immunosorbent assay method. Results: The SCK group had significantly higher TNF-α, IL-6; IL-10, and SAA values than had the CK group (p

Shangzhi Gao,1 Corbin Quick,2 Marta Guasch-Ferre,3 Zhu Zhuo,2 John M Hutchinson,2 Li Su,1 Frank Hu,3 Xihong Lin,2 David Christiani1,4 1Environmental Health, Harvard University T H Chan School of Public Health, Boston, MA, USA; 2Biostatistics, Harvard University T H Chan School of Public Health, Boston, MA, USA; 3Nutrition, Harvard University T H Chan School of Public Health, Boston, MA, USA; 4Pulmonary and Critical Care Division, Department of Medicine, MA General Hospital, Boston, Massachusetts, USACorrespondence: David ChristianiEnvironmental Health, Harvard University T H Chan School of Public Health, Boston, MA, 02115, USAEmail dchris@hsph.harvard.eduIntroduction: Human metabolism and inflammation are closely related modulators of homeostasis and immunity. Metabolic profiling is a useful tool to understand the association between metabolism and inflammation at a systemic level.Objective: To investigate the longitudinal associations between the concentration of plasma metabolites and biomarkers related to inflammation and oxidative stress.Methods: We conducted a repeated cross-sectional analysis consisting of 8 short-term panels that included 88 healthy adult male welders in Massachusetts, USA. In each panel, we collected 1– 6 repeated measurements of blood and urine. We used a human vascular injury panel assay and custom cytokine/chemokine assay to quantify inflammatory biomarker plasma levels, liquid chromatography-mass spectrometry to quantify the concentrations of 665 plasma metabolites, and a competitive enzyme-linked immunoassay to quantify urinary 8-OHdG and 8-isoprostane levels. We used linear mixed effects models to estimate the longitudinal association between each inflammatory and oxidative stress biomarker and each metabolite.Results: At a 5% FDR threshold, we detected ≥ 1metabolite association for 8 unique inflammatory and oxidative stress biomarkers: urinary 8-isoprostane, plasma C-reactive protein (CRP), serum amyloid A (SAA), intercellular adhesion molecule 1, circulating vascular cell adhesion molecule-1, interleukin 8 (IL-8), interleukin 10 (IL-10) and vascular endothelial growth factor. Specifically, 3 metabolites in the androgenic steroids pathway were negatively associated with SAA; 3 dihydrosphingomyelins metabolites were positively associated with 1 or more of CRP, SAA, IL-8 and IL-10; 4 metabolites in acyl choline metabolism pathways were negatively associated with IL-8; 7 lysophospholipid metabolites were negatively associated with 1 or more of CRP, SAA and IL-8; 4 sphingomyelins were positively associated with CRP and/or SAA; and 10 metabolites in the xanthine pathway were positively associated with urinary 8-isoprostane.Conclusion: We found that metabolites in phospholipid groups had strong associations with multiple inflammatory biomarkers, especially CRP, SAA and IL-8. The mechanism of these associations warrants further investigation.Keywords: metabolism, inflammation, phospholipids, metals, particulates, metabolomics, occupational health

BACKGROUND: Atherosclerosis causes acute myocardial necrosis and inflammation characterized by increased mean platelet volume (MPV) and serum amyloid A (SAA). Creatine Kinase Myocardial Band (CKMB) is known as myocardial necrosis marker commonly used in daily practice to help diagnosing acute coronary syndrome. AIM: The purpose of this study was to determine the correlation between MPV, SAA, and CKMB in patients with acute coronary syndrome. METHODS: An analytic observational study with a cross-sectional approach was conducted from May to July 2019. This study involved 32 patients with ACS at the Emergency Department of Dr Kariadi Public Hospital. The inclusion criteria of this study were patients with chest pain, aged 30–75 years, and normal body temperature while the exclusion criteria were malignancy, undergoing chemotherapy/radiation, renal failure, hypertension, and liver disease. Examination of CKMB was done using the spectrophotometry method, MPV value was measured using a hematology analyzer, and SAA level was measured using the ELISA method. Statistical test was done using Spearman correlation. RESULTS: The median (min-max) of MPV and SAA values was 9.85 (2.78-11.7) fL and 40.454 (5.879–66.059) μg/ml, while the mean ± SD (min-max) value of CKMB was 115.47 ± 155.97 (10–608) U/L. The correlation coefficient between CKMB level with MPV and SAA levels were r = −0.244 (p = 0.179) and r = 0.442 (p = 0.011), respectively. CONCLUSION: There was a significant positive moderate correlation between CKMB and SAA levels which could be used as a marker of acute inflammation in ACS, whereas inflammatory marker of MPV did not have a significant correlation.

We hypothesized that the serum iron (Fe) concentration in cows with respiratory diseases is a satisfactory substitute for major inflammatory markers such as haptoglobin (HPT) and serum amyloid A (SAA). Twenty Japanese Black cows aged 279.6 ± 120.0 days were enrolled, and divided into respiratory diseases and control groups based on the presence of clinical findings of respiratory diseases. As a result, area under the receiver operating characteristic curves for plasma HPT, SAA and serum Fe concentrations for respiratory disease-associated systemic inflammation were excellent, at 1.00, 0.96 and 0.97, respectively. Therefore we confirmed that the serum Fe concentration is a satisfactory substitute for HPT and SAA in beef cows with respiratory diseases.

Objective Valve disease progression in rheumatic heart disease(RHD) is generally attributed to recurrent attacks of acute rheumatic fever(ARF). However, persistence of chronic sub-clinical inflammation remains a plausible but unproven cause. Non-invasive means to identify sub-clinical inflammation may facilitate research efforts towards understanding its contribution to disease progression. Methods Patients with chronic RHD, without clinical evidence of ARF, undergoing elective valve surgery were enrolled. Sub-clinical inflammation was ascertained by histological evaluation of left atrial appendage and valve tissue excised during surgery. We assessed the diagnostic utility of Gallium-67 scintigraphy imaging, and inflammatory biomarkers, hsCRP, IL-2, IL-6, Tumor Necrosis Factor-Alpha(TNF-α), Interferon-gamma(IFN-γ), and Serum Amyloid A(SAA), in identifying patients with sub-clinical inflammation. Results Of the 93 RHD patients enrolled(mean age 34 ± 11 years, 45% females), 86 were included in final analysis. Sub-clinical inflammation was present in 27 patients(31.4%). Patients with dominant regurgitant lesions were more likely to have sub-clinical inflammation compared to those with stenotic lesions, though this association was not statistically significant(dominant regurgitant lesions vs isolated mitral stenosis: OR 3.5, 95%CI 0.68–17.96, p = 0.133). Inflammatory biomarkers were elevated in the majority of patients: hsCRP, IL-2, IL-6, TNF-α, and IFN-γ in 44%, 89%, 90%, 79%, and 81% patients, respectively. However, there was no significant association between biomarker elevation and histologically ascertained sub-clinical inflammation. Ga-67 imaging was unable to identify inflammation in the 15 patients in whom it was performed. Conclusion Sub-clinical inflammation is common in RHD patients. Conventional inflammatory markers are elevated in the majority, but aren’t discriminatory enough to identify the presence of histologic inflammation., Graphical abstract Correlation of inflammatory biomarkers with histological inflammation. (The green horizontal line represents the proportion of patients who had inflammation on histological examination. The vertical bars represent the proportion of patients in whom the inflammatory markers were elevated. These biomarkers were elevated in a non-discriminatory fashion). Image 1

Background Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19. Methods We prospectively enrolled 171 ICU patients, including 78 (46%) patients positive and 93 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 h and 3 days after ICU admission. Results In critically ill COVID-19 and non-COVID-19 patients, the most common ICU admission diagnoses were respiratory failure or pneumonia, followed by sepsis and other diagnoses. Similar proportions of patients in both groups received invasive mechanical ventilation at the time of study enrollment. COVID-19 and non-COVID-19 patients had similar rates of acute respiratory distress syndrome, severe acute kidney injury, and in-hospital mortality. While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores. In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (p Conclusions These studies demonstrate that, unlike other well-studied causes of critical illness, endothelial dysfunction may not be characteristic of severe COVID-19 early after ICU admission. Pathways resulting in elaboration of acute phase proteins and inducing epithelial cell injury may be promising targets for therapeutics in COVID-19.

Amyloid A (AA) amyloidosis is a lethal disease characterized by systemic AA amyloid deposition, and is reported in many animal species. Despite experiments have shown that AA amyloidosis can be transmitted orally, horizontal transmission and cross-species transmission are concerns, the transmission mechanism has been unknown. In this study, we examined the oral transmission efficiency of AA amyloidosis using oxazolone-induced gastrointestinal disorder mice. As a result, the upper or lower gastrointestinal disorder groups developed more severe amyloid deposition in systemic tissues than the group without gastrointestinal disorders. The results of this study suggest that gastrointestinal damage promotes the oral transmission of AA amyloidosis.

Amyloidosis is diagnosed by the histologic detection of amyloid deposits; however, this method has limitations such as a prolonged diagnosis time and the need for histologic proficiency. We aimed to develop a rapid and simple method for diagnosing amyloidosis by targeting amyloid-specific endogenous fluorescence, which has not been reported previously, to our knowledge. Fluorescence fingerprint analysis of amyloid extracts and tissue homogenates derived from amyloid A (AA) amyloidosis-affected cattle exhibited a specific intrinsic fluorescence pattern. Furthermore, principal component analysis using analytical data revealed that AA could be identified by peaks near λex 350 nm and λem 430 nm. Fluorescence spectrometry analysis using tissue homogenates, which does not require special histochemical staining, enables the rapid detection of bovine AA.

Background Lately, monoclonal gammopathy of renal significance (MGRS) has been defined as a group of renal disorders that are strongly associated with monoclonal protein, including amyloid immunoglobulin light chain (AL) amyloidosis. Amyloid myopathy is rare (1.5% of all patients with amyloidosis) and the prognosis is poor. Furthermore, only approximately 20% of patients with amyloid myopathy are reported to have renal involvement, indicating a lack of data in the literature. Case presentation Here, we report a rare case of MGRS-related AL amyloidosis complicated by amyloid myopathy that presented with muscle weakness in the upper and lower limbs, neck and fingers, and nephrotic syndrome. Blood, urine, and bone marrow examination revealed monoclonal gammopathy of undetermined significance (MGUS) (Bence Jones protein-lambda). Muscle biopsy of the vastus lateralis muscle demonstrated amyloid proteins in the sarcolemma and in the blood vessel walls on Congo red staining, suggesting amyloid myopathy, and tiny inclusions in fibers on modified Gomori trichrome stain. Although we thought they were reminiscent of nemaline bodies, we could not confirm the nature of this structure. Renal biopsy demonstrated amyloid proteins in the mesangial region, part of the capillary walls, and the blood vessel walls on direct fast scarlet staining. As these amyloid proteins were positive for p-component staining and negative for amyloid A staining, β2-microglobulin, and pre-albumin, and as lambda light chains were positive in the mesangial region, we diagnosed the patient with MGRS-related AL amyloidosis. Although he was treated with melphalan and dexamethasone, his symptoms did not improve. Conclusions AL amyloidosis involving the kidneys and muscles has a poor prognosis, and a delayed diagnosis of amyloid myopathy is common because of its rarity and frequent misdiagnosis, which increases organ function deterioration. Therefore, early detection, therapeutic intervention, and careful follow-up are crucial.

The list of approved indications for anakinra (Kineret®), an anti-interleukin (IL)-1 biological, has been expanded in the EU to include Familial Mediterranean fever (FMF). The pathology of FMF is associated with excess production of IL-1, thus IL-1 blockade with anakinra was investigated as a treatment for FMF. Results from a phase 3 clinical trial and real-world experience in patients with FMF demonstrated reductions in FMF attack frequency, improvements in quality of life and reductions in serum amyloid A (SAA) and C-reactive protein (CRP) levels. Efficacy was also observed in patients with FMF and amyloidosis in the real-world setting; nevertheless, concurrent use of colchicine with anti-IL-1 biologicals is recommended to prevent and/or halt the progression of amyloidosis. Anakinra was generally well tolerated during the phase 3 clinical trial, with comparable proportions of patients with adverse reactions in the anakinra and placebo groups. Furthermore, the safety profile of anakinra in FMF was consistent with that established in other indications, based on all available evidence.

BackgroundOutcomes after renal transplantation have traditionally been poor in systemic amyloid A (AA) amyloidosis and systemic light chain (AL) amyloidosis, with high mortality and frequent recurrent disease. We sought to compare outcomes with matched transplant recipients with autosomal dominant polycystic kidney disease (ADPKD) and diabetic nephropathy (DN), and identify factors predictive of outcomes.MethodsWe performed a retrospective cohort study of 51 systemic AL and 48 systemic AA amyloidosis patients undergoing renal transplantation. Matched groups were generated by propensity score matching. Patient and death-censored allograft survival were compared via Kaplan–Meier survival analyses, and assessment of clinicopathological features predicting outcomes via Cox proportional hazard analyses.ResultsOne-, 5- and 10-year death-censored unadjusted graft survival was, respectively, 94, 91 and 78% for AA amyloidosis, and 98, 93 and 93% for AL amyloidosis; median patient survival was 13.1 and 7.9 years, respectively. Patient survival in AL and AA amyloidosis was comparable to DN, but poorer than ADPKD [hazard ratio (HR) = 3.12 and 3.09, respectively; P 12 mm (HR = 26.58; P = 0.03), while survival was predicted by haematologic response (very good partial or complete response; HR = 0.07; P = 0.018). In AA amyloidosis, recurrent amyloid was associated with elevated serum amyloid A concentration but not with outcomes.ConclusionsRenal transplantation outcomes for selected patients with AA and AL amyloidosis are comparable to those with DN. In AL amyloidosis, IVSd thickness and achievement of deep haematologic response pre-transplant profoundly impact patient survival.

Serum amyloid A (SAA) is one of the acute phase proteins synthesized in hepatocytes and secreted by various inflammation or infectious stimuli. We investigated the clinical implication of measuring SAA in patients with antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV). Seventy-five patients who had been classified as AAV and enrolled in our prospective observational cohort for AAV patients were included. Clinical and laboratory data were obtained on the day of blood sampling, and SAA was measured by ELISA kits. Birmingham Vasculitis Activity Score (BVAS) and Short-Form 36-Item Health Survey (SF-36) were assessed for disease activity and health-related quality-of-life (HRQoL) measures. We stratified patients into having high BVAS when the BVAS was over the median values, and those with either low SF-36 PCS or low SF-36 MCS were defined as having poor HRQoL. Multivariate logistic regression analysis was conducted to estimate independent predictors of high BVAS. The relative risk (RR) was analyzed using the contingency tables and the chi-squared test. SAA was positively correlated with BVAS ( r = 0.642 ) and FFS ( r = 0.367 ) and was inversely correlated with both the SF-36 physical component summary ( r = − 0.456 ) and mental component summary scores ( r = − 0.394 ). Furthermore, SAA was significantly correlated with acute phase reactants ESR ( r = 0.611 ) and CRP ( r = 0.629 ). Patients with high BVAS exhibited significantly higher SAA than those with low BVAS (1317.1 ng/mL vs. 423.1 ng/mL). In multivariable logistic regression analysis, serum albumin (odds ratio (OR) 0.132) and SAA > 1173.6 ng / mL (OR 15.132) were independently associated with high BVAS. The risk of having high BVAS and poor HRQoL in patients with SAA > 1173.6 ng / mL was higher than in those with SAA ≤ 1173.6 ng / mL (RR 3.419 and 1.493). Our results suggest that SAA might be a useful biomarker in assessing disease activity and HRQoL in AAV.

Peripheral immune activation can influence neurodevelopment and is increased in autism, but is less explored in attention deficit hyperactivity disorder (ADHD). Patients with ADHD often display comorbid autism traits and gastrointestinal (GI) symptoms. Plasma protein levels of two acute phase reactants, C-reactive protein (CRP) and serum amyloid A (SAA), and two endothelial adhesion molecules, soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1), which share important roles in inflammation, were analyzed in 154 patients with ADHD and 61 healthy controls. Their associations with ADHD diagnosis, severity, medication and comorbid autistic symptoms, emotion dysregulation and GI symptoms were explored. The ADHD patients had increased levels of sICAM-1 and sVCAM-1 compared to healthy controls (p = 8.6e–05, p = 6.9e–07, respectively). In children with ADHD, the sICAM-1 and sVCAM-1 levels were higher among those with ADHD medication than among children (p = 0.0037, p = 0.0053, respectively) and adults (p = 3.5e–09, p = 1.9e–09, respectively) without ADHD medication. Among the adult ADHD patients, higher sICAM-1 levels were associated with increased comorbid autistic symptoms in the domains attention to detail and imagination (p = 0.0081, p = 0.00028, respectively), and higher CRP levels were associated with more GI symptoms (p = 0.014). sICAM-1 and sVCAM-1 levels were highly correlated with each other, and so were CRP and SAA levels. To conclude, vascular inflammatory activity may be overrepresented in ADHD, with elevated sICAM-1 and sVCAM-1 levels and this may in children be a consequence of current ADHD medication, and in adults relate to increased comorbid autistic symptoms. Replication is warranted.

Serum amyloid A (SAA) is an apo-lipoprotein produced by the liver in response to proinflammatory cytokines. Few data are available on SAA levels in patients with idiopathic pulmonary fibrosis (IPF), the most common idiopathic form of interstitial pneumonitis (ILD). This study compared SAA concentration in IPF patients to other ILD groups to explore its potential use as a clinical biomarker.

A 71-year-old Japanese woman with a history of rheumatoid arthritis of 50 years’ duration was admitted to our hospital with refractory diarrhea. Endoscopic biopsy revealed AA amyloid deposition in the large intestine. Although the patient had been prescribed 5 tumor necrosis factor inhibitors over the past 10 years, rheumatoid arthritis was poorly controlled, with a Disease Activity Score 28 using C-reactive protein score of 6.52 on admission. Treatment with tocilizumab (8 mg/kg every 2 weeks) was initiated, but this was ineffective. After 3 months, abatacept (cytotoxic T-lymphocyte–associated antigen 4 immunoglobulin) was initiated (750 mg/mo) and the patient’s diarrhea began to improve. After 3 months of abatacept treatment, serum albumin, C-reactive protein, and serum amyloid A levels had all decreased to within normal ranges. After 3 years of abatacept treatment, a repeat biopsy of the large intestine revealed a marked improvement in amyloid deposition. Interleukin 6 is a key factor in AA amyloid formation, but this case suggests that T-cell activation increases the production of cytokines (including interleukin 6) via a mechanism involving cytotoxic T-lymphocyte–associated antigen 4, resulting in a second key factor of AA amyloid formation.

Background Infectious disease is the leading cause of fever of unknown origin (FUO). Serum inflammatory markers historically used to diagnose bacterial infection have sufficient diagnostic sensitivity but low specificity. This study aimed to develop a simple scoring system for differentiating bacterial infections from other causes of early-stage FUO. Methods This study included a retrospective cohort of patients presenting with FUO at the Huashan Hospital (January 2014 to June 2017). The diagnostic utility of serum inflammatory markers for bacterial infection was evaluated using the receiver operating characteristic (ROC) curve analysis. Relevant markers were subsequently measured prospectively in a separate cohort of FUO patients (December 2017 to May 2019). A scoring system was based on inflammatory markers and other test results. Results Bacterial infection was identified in 34% of patients in the retrospective cohort. The area under the ROC curve (AUC) was 0.644 (95% confidence interval [CI], .595–.693) for C-reactive protein, 0.624 (95% CI, .573–.675) for procalcitonin, and 0.646 (95% CI, .595–.697) for serum ferritin (SF) in diagnosing bacterial infection. Bacterial infection was found in 29% of cases in the prospective cohort. A model based on serum amyloid A (SAA) and SF levels and neutrophil percentage yielded an AUC of 0.775 (95% CI, .695–.854). Validation analysis indicated lower probability ( Conclusions A scoring system based on SAA and SF levels and neutrophil percentage can help distinguish bacterial infection from other causes of FUO, potentially reducing antibiotic use.

Background Animals tend to increase in body weight and body condition score (BCS) with aging. Serum diagnostic markers related to energy metabolism may show changes even in healthy cats with aging. Materials and methods Seventy domestic cats were recruited for this study. Based upon the modified AAFP-AAHA Feline Life Stage Guidelines, animals were divided into six groups: Junior (7 months-2 years), Prime (3 -6 years), Mature (7-10 years), Senior (11-14 years), Geriatric-obese (15 years ≤) and Geriatric-thin (15 years ≤). Their body condition scores (BCS) ranged from 3/9 to 9/9. Changes in metabolites, inflammatory markers, hormone concentrations and enzyme activities related to energy metabolism were investigated in serum of 70 domestic cats of various ages. Results Serum glucose (GLU) concentrations in the Mature, Senior, and Geriatric-obese groups were significantly higher than those in the Junior group. Serum amyloid A (SAA) concentrations in the Geriatric-thin group were significantly increased compared with the Junior group. SAA concentrations in the Geriatric-obese group tended to increase although there were no statistically significant differences. In the Mature, Senior, Geriatric-obese and Geriatric-thin groups, malate dehydrogenase/lactate dehydrogenase (M/L) ratio, an energy metabolic indicator, tended to decrease compared with the Junior group. In the Senior group, triglyceride (TG) concentrations were significantly increased compared with the Junior group. In the Geriatric-obese and Geriatric-thin groups, blood urea nitrogen (BUN) concentrations were significantly increased compared with the Junior group. In the Geriatric-obese group, albumin (ALB) concentrations were decreased compared with the Junior group. Conclusion Aged domestic cats tend to increase in body weight and BCS. In addition, serum GLU, TG, SAA, and BUN concentrations increased and serum ALB concentrations and M/L ratio decreased. These diagnostic markers may be useful to detect small changes related to energy metabolism with aging that may cause obesity with light inflammation in healthy cats.

Background and Aim: Staphylococcus pyoderma is a common problem in dogs that need a novel treatment rather than antibiotic therapy. The aim of this study was to investigate the therapeutic efficacy, anti-inflammatory, and antioxidative properties of Aloe vera (Aloe barbadensis) gel ointment on dogs' Staphylococcus pyoderma compared to gentamicin ointment. Materials and Methods: The inhibition zone of A. vera extract 20% and 40% and gentamicin 1% against Staphylococcus aureus was determined on well diffusion agar. Twenty Baladi local breed dogs were used as control negative group before intradermal inoculation with 105 CFU S. aureus. The animals were classified into four equal groups, control positive group without treatment (n=5), treated groups by 20% A. vera gel ointment (n=5), 40% A. vera gel ointment (n=5), and gentamicin ointment 1% (n=5). Topical application of A. vera and gentamicin ointments was carried out twice daily for 2 weeks until complete healing of dogs' pyoderma. Clinical evaluation was recorded. Inflammatory, oxidant, and antioxidant parameters were measured in serum. Results: The inhibition zone of A. vera extracts 20% and 40% was 19 mm and 23 mm, respectively, while gentamicin 1% was 18 mm. The half maximal inhibitory concentration (of A. vera 20% and 40% were 13.70 with R2=0.98. Dogs' pyoderma treated with A. vera gel ointment 20% and 40% were more likely to have low haptoglobin and tumor necrosis factor-α concentrations than gentamicin 1% ([odds ratio [OR]=4.6; 95% confidence interval [CI]=1.31-17.40; p

Serum amyloid A (SAA) is an acute phase protein and a novel inflammatory biomarker of cardiovascular diseases. Of the four subtypes, SAA1 is the most representative biomarker. In this study, we aimed to assess the value of SAA1 as a novel biomarker for evaluating the presence and severity of acute coronary syndrome (ACS) in Chinese patients.A total of 140 ACS patients and 88 non-ACS patients (including 36 stable coronary artery disease (SCAD) patients and 52 healthy controls) who underwent coronary angiography were enrolled. The SAA1 level was significantly higher in ACS patients compared with the SCAD and healthy control subgroups (P 0.001, respectively), and was significantly higher in the high SYNTAX Score II (SS II) group compared with the medium SS II group and low SS II group (P 0.001, respectively) in ACS patients. The cutoff level of SAA1 for indicating the presence of ACS was 324.65 ng/mL (sensitivity of 77.9%, specificity of 60.2% and an area under the curve of 0.717). The increased SAA1 levels were positively associated with the presence (OR = 1.013, P 0.001) and severity (OR = 1.023, P 0.001) of ACS. Furthermore, there was a positive correlation between SAA1 levels and SS II (r = 0.467, P 0.001).Our results suggest that elevated SAA1 levels may be a novel biomarker for evaluating the presence of ACS and the severity of CAD in ACS patients. Measuring SAA1 levels makes it possible to evaluate the presence of ACS and severity of CAD in ACS patients.

Serum amyloid A (SAA) is a family of acute-phase reactants. The rise of SAA concentration in blood circulation during the acute-phase response is a clinical marker of active inflammation. Despite its practical and analytical advantages, SAA measurement by enzyme-linked immunosorbent assay (ELISA) has been used mainly as a research tool rather than for the routine laboratory testing. This may be partly explained by the lack of robust reference data in the literature for the different commercially available immunoassays. Using the recommended procedures for the production of reference intervals published by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), we developed the SAA reference interval for a well-defined Italian healthy population and investigated the correlation among SAA and C-reactive protein (CRP), the commonly used acute-phase marker. After data normalization, the reference cutoff was calculated as 225 ng/ml. A good correlation between SAA and CRP was found (

Amyloidosis is described by the deposition of misfolded proteins in the tissues. Amyloidoses are classified into two as systemic and localized. Out of the systemic forms, AL (light chain) amyloidosis is the most prevalent type; however, amyloid A (AA) amyloidosis is more frequently encountered in the rheumatology practice. AA amyloidosis stands out as a major complication of familial Mediterranean fever (FMF). Splenic and renal involvement is more likely in FMF-associated systemic amyloidosis. The involvement of thyroid and adrenal glands has also been described, although infrequently. Amyloidoses have a heterogeneous plethora of clinical manifestations, with certain phenotypes associated with specific amyloid forms. Gynecological amyloidosis is a rare condition. Uterine involvement may occur in a localized fashion or may also arise as a part of systemic involvement, albeit at a lesser ratio. Several cases of uterine AL amyloidosis have been documented so far as an organ involvement in systemic AL amyloidosis. On the other hand, uterine amyloidosis associated with AA amyloidosis has been described merely in one case with rheumatoid arthritis (RA). Here, we presented a 40-year-old female patient with FMF known for 38 years who underwent splenectomy and hysterectomy due to massive splenomegaly, deep anemia, and persistent menometrorrhagia. Histological examinations of materials revealed uterine and splenic AA amyloidosis. This case report is first-of-its-kind to describe FMF-associated uterine AA amyloidosis and also provides a discussion of possible mechanisms of amyloidosis-induced uterine bleeding.

Objectives Cardiac MR is widely used to diagnose cardiac amyloid, but cannot differentiate AL and ATTR subtypes: an important distinction given their differing treatments and prognoses. We used PET/MR imaging to quantify myocardial uptake of 18F-fluoride in ATTR and AL amyloid patients, as well as participants with aortic stenosis and age/sex-matched controls. Methods In this prospective multicenter study, patients were recruited in Edinburgh and New York and underwent 18F-fluoride PET/MR imaging. Standardized volumes of interest were drawn in the septum and areas of late gadolinium enhancement to derive myocardial standardized uptake values (SUV) and tissue-to-background ratio (TBRMEAN) after correction for blood pool activity in the right atrium. Results 53 patients were scanned: 18 with cardiac amyloid (10 ATTR and 8 AL), 13 controls, and 22 with aortic stenosis. No differences in myocardial TBR values were observed between participants scanned in Edinburgh and New York. Mean myocardial TBRMEAN values in ATTR amyloid (1.13 ± 0.16) were higher than controls (0.84 ± 0.11, P = .0006), aortic stenosis (0.73 ± 0.12, P < .0001), and those with AL amyloid (0.96 ± 0.08, P = .01). TBRMEAN values within areas of late gadolinium enhancement provided discrimination between patients with ATTR (1.36 ± 0.23) and all other groups (e.g., AL [1.06 ± 0.07, P = .003]). A TBRMEAN threshold >1.14 in areas of LGE demonstrated 100% sensitivity (CI 72.25 to 100%) and 100% specificity (CI 67.56 to 100%) for ATTR compared to AL amyloid (AUC 1, P = .0004). Conclusion Quantitative 18F-fluoride PET/MR imaging can distinguish ATTR amyloid from other similar phenotypes and holds promise in improving the diagnosis of this condition.

Author(s): Zhao, Dongxing; Abbasi, Asghar; Rossiter, Harry B; Su, Xiaofen; Liu, Heng; Pi, Yuhong; Sang, Li; Zhong, Weiyong; Yang, Qifeng; Guo, Xiongtian; Zhou, Yanyan; Li, Tianyang; Casaburi, Richard; Zhang, Nuofu | Abstract: 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.

Paraoxonase 1 (PON1) is an inflammation marker associated with lipid oxidation and is used as a diagnostic marker in people. There is no information about the suitable substrate and analytic performance in cats, or its biological behavior compared with other inflammation markers. Our aims were to validate a paraoxon-based method to measure PON1 activity in feline serum, to assess stability of PON1 under different storage conditions and the impact of interfering elements, to determine a reference interval (RI) for healthy cats, and to correlate PON1 activity with 2 major acute-phase proteins. Intra- and inter-assay precision, accuracy, and RI were assessed using fresh serum. The same specimens were stored at room temperature, refrigerated, or frozen, and retested at defined intervals. Hemolysis, lipemia, and icterus were simulated to study interferences. PON1 results were compared to serum amyloid A (SAA) and alpha-1-acid glycoprotein (AGP) results. Analytical validation yielded precise and accurate results. PON1 activity is stable for up to 24 h at room temperature and up to 48 h at 4°C. Freezing at −20°C results in an increase after 72 h, with return to baseline values after 1 wk, that again increases after 6 mo. Only hyperlipemia interfered with PON1 activity. The RI based on 71 healthy cats was 58–154 U/L. PON1 activity was negatively correlated with AGP, but not with SAA. Serum PON1 activity can be measured accurately in cats, and it acts as a negative acute-phase protein.

Background Niacin has modest but overall favorable effects on plasma lipids by increasing high density lipoprotein cholesterol (HDL-C) and lowering triglycerides. Clinical trials, however, evaluating niacin therapy for prevention of cardiovascular outcomes have returned mixed results. Recent evidence suggests that the HDL proteome may be a better indicator of HDL’s cardioprotective function than HDL-C. The objective of this study was to evaluate the effect of niacin monotherapy on HDL protein composition and function. Methods A 20-week investigational study was performed with 11 participants receiving extended-release niacin (target dose = 2 g/day) for 16-weeks followed by a 4-week washout period. HDL was isolated from participants at weeks: 0, 16, and 20. The HDL proteome was analyzed at each time point by mass spectrometry and relative protein quantification was performed by label-free precursor ion intensity measurement. Results In this cohort, niacin therapy had typical effects on routine clinical lipids (HDL-C + 16%, q Conclusion Extended-release niacin therapy, in the absence of other lipid-modifying medications, can increase HDL-associated SAA, an acute phase protein associated with HDL dysfunction.

The present study aimed to evaluate the value of serum amyloid A (SAA) in coronavirus disease 2019 (COVID-19) and compared the efficacy of SAA and C-reactive protein (CRP) in predicting the severity and recovery of COVID-19. A retrospective study was conducted on COVID-19 patients hospitalized in Wuhan No. 1 Hospital (Hubei, China) from January 21, 2020 to March 4, 2020. A two-way ANOVA analysis was used to compare the serum CRP and SAA levels between mild group and severe group during hospitalization days. Linear regression was used to analyze the relationship between the serum CRP, SAA levels and treatment days in recovered patients. The Logistic regression analysis and the area under curve (AUC) were calculated to determine the probability for predicting the severity and recovery of COVID-19. The severe group displayed higher CRP and SAA levels compared with the mild group during hospitalization (P

Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by frequent attacks and chronic inflammation. Subclinical inflammation continues during the attack-free period. Omentin is an anti-inflammatory adipokine, which plays important roles in the adjustments of glucose metabolism, cardiovascular homeostasis and atherosclerosis. The aim is to investigate the omentin levels in FMF patients and to assess the association with markers of subclinical inflammation in FMF patients such as serum amyloid A (SAA), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).This cross-sectional study included 54 consecutive adult FMF patients (27 male, 27 female) and 28 healthy individuals (16 male, 12 female). The FMF patients were separated into 3 groups: (1) attack-free group, (2) active-attack group and (3) colchicine-resistant group. Serum omentin levels were compared between the FMF patients and the healthy control group.A significant difference was determined between the FMF patients and healthy control subjects in terms of omentin levels (108.05 (19.97-343.22) vs. 199.5 (42.98-339.41) p 0.05). SAA values were significantly higher in the FMF patients compared with the healthy control group. When the FMF patients were examined as separate groups, serum omentin values were lower in the colchicine-resistant group than in the groups without resistance (76.64 (19.77-224.33) vs. 186.47 (28.41-343.21) p = 0.006).FMF patients with colchicine resistance are associated with decreased omentin concentrations, probably mediated by inflammation-driven mechanisms. Key Points • Omentin is a type of adipokine which has an anti-inflammatory effect by inhibiting the inflammatory cytokine network. • Decreased omentin levels are associated with increased obesity, insulin resistance and comorbidities. • We report that omentin levels fluctuate in various diseases. In addition, we have focused on the levels of omentin in patients with FMF, as it may act as a biomarker for colchicine resistance.

Aim of the work It was to estimate the carotid intima-media thickness (CIMT), lipid profile, serum amyloid A and vitamin D in Familial Mediterranean Fever (FMF) patients and to explore the relationship between CIMT and FMF. Patients and methods The study comprised forty-five FMF patients diagnosed during the attack free period and 40 healthy children with similar demographic features as control. The diagnosis of the FMF cases was confirmed by clinical, laboratory assessments and confirmed by the molecular diagnosis. The CIMT, lipid profile, complete blood picture, serum amyloid A (SAA) levels, vitamin D and the growth pattern were investigated. Results The study showed no significant difference of CIMT among patients and controls, significant decrease of vitamin D levels, while lipid profile parameters, triglyceride (TG) to HDL-Cholesterol (HDL-C) ratio, serum amyloid A were significantly increased. A significant correlation was present between the CIMT with the serum cholesterol, low density lipoprotein and triglycerides as well as between SAA and the number of attacks. In addition, vitamin D levels showed significant negative correlation with colchicine. M694I mutation was the most prevalent among FMF patients. Growth parameters were normal in FMF cases. Conclusion This study sheds light that the normal CIMT in the FMF patients makes it difficult to describe the children as having subclinical atherosclerosis although the higher TG/HDL ratio reflects their risk of atherosclerosis. Moreover, significant decrease of vitamin D in FMF patients was observed. The growth parameters of the FMF patients on regular treatment of colchicine were not affected.

This study aims to investigate the utility of digital protocols for Ki-67 immunohistochemistry quantitative analysis (“hot spot” method) in the setting of well-differentiated hepatocellular neoplasms. Resection cases of typical hepatic adenomas (HAs) (n = 40), atypical HAs (n = 9), and well-differentiated hepatocellular carcinomas (WD HCCs) (n = 56) were selected. HAs were further classified by immunohistochemistry using antibodies against liver fatty acid binding protein, glutamine synthetase, B-catenin, hepatic serum amyloid A, and C-reactive protein. Ki-67 proliferative index by immunohistochemistry was evaluated in all cases by digital analysis using a modified neuroendocrine tumor “hot spot” protocol. The proliferative rate of HAs (typical, median 1.2% (range 0–7.4%) and atypical, median 1.0% (range 0.3–3%)) was significantly lower than that of WD HCCs (median 4.5%, range 0–49.8%) (P

This study aims to observe the clinical characteristics of recovered patients from Coronavirus Disease 2019 (COVID-19) with positive in reverse transcription-polymerase chain reaction (RT-PCR) or serum antibody. The profile, clinical symptoms, laboratory outcomes, and radiologic assessments were extracted on 11 patients, who tested positive for COVID-19 with RT-PCR or serum antibody after discharged and was admitted to Hubei No. 3 People's Hospital of Jianghan University for a second treatment in March 2020. The average interval time between the first discharge and the second admission measured 16.00 ± 7.14 days, ranging from 6 to 27 days. In the second hospitalization, one patient was positive for RT-PCR and serum antibody immunoglobulin M (IgM)-immunoglobulin G (IgG), five patients were positive for both IgM and IgG but negative for RT-PCR. Three patients were positive for both RT-PCR and IgG but negative for IgM. The main symptoms were cough (54.55%), fever (27.27%), and feeble (27.27%) in the second hospitalization. Compared with the first hospitalization, there were significant decreases in gastrointestinal symptoms (5 vs 0, P = .035), elevated levels of both white blood cell count (P = .036) and lymphocyte count (P = .002), remarkedly decreases in C-reactive protein and serum amyloid A (P < .05) in the second hospitalization. Additionally, six patients' chest computed tomography (CT) exhibited notable improvements in acute exudative lesions. There could be positive results for RT-PCR analysis or serum IgM-IgG in discharged patients, even with mild clinical symptoms, however, their laboratory outcomes and chest CT images would not indicate the on-going development in those patients.

Background: Diagnosis of Spontaneous Bacterial Peritonitis (SBP) depends mainly on ascetic fluid culture which may be negative in spite of the clinical suggestion of SBP and high ascetic fluid neutrophilic count. Aim: This study aimed to evaluate the biological importance of amyloid A biomarker in both serum and ascetic fluid to diagnose SBP as early as possible and to compare it to other markers (C-reactive protein (CRP), and the neutrophil-to-lymphocyte ratio (NLR)). Methods: This study included 37 patients with hepatic ascites; twenty-two of them had SBP, and 15 patients did not have SBP. Serum and ascetic fluid amyloid A, ascetic fluid neutrophil, C-reactive protein, and neutrophil-to-lymphocyte ratio were measured in all subjects before the start of antimicrobial chemotherapy to the infected ones. Results: Both the serum and ascetic fluid amyloid and also, CRP were significantly higher in patients infected with ascetic fluid than others. The cut-off point of serum amyloid A for early detection of SBP was 9.25ug/ml with the high sensitivity and specificity. For ascetic amyloid A, the sensitivity and specificity were 90.09% and 60% at cut-off point 2.85ug/ml, respectively. Conclusion: Amyloid A in serum and ascitic fluid can be considered as a good biomarker for early diagnosis of SBP.

Summary Background To explore the significance of SAA in evaluating the severity and prognosis of COVID-19. Methods A total of 132 patients with confirmed COVID-19 who were admitted to a designated COVID-19 hospital in Wuhan, China from January 18, 2020 to February 26, 2020 were collected. The dynamic changes of blood SAA, CRP, PCT, WBC, Lymphocyte (L), PLT, CT imaging, and disease progression were studied. All patients completed at least twice laboratory data collection and clinical condition assessment at three time points indicated for this study; The length of hospital stay was longer than 14 days prior to February 26, 2020. Results COVID-19 patients had significantly increased SAA and CRP levels, while L count decreased, and PCT, WBC, and PLT were in the normal range. As disease progressed from mild to critically severe, SAA and CRP gradually increased, while L decreased, and PLT, WBC, and PCT had no significant changes; ROC curve analysis suggests that SAA/L, CRP, SAA, and L count are valuable in evaluating the severity of COVID-19 and distinguishing critically ill patients from mild ones; Patients with SAA consistently trending down during the course of disease have better prognosis, compared with the patients with SAA continuously rising; The initial SAA level is positively correlated with the dynamic changes of the serial CT scans. Patient with higher initial SAA level are more likely to have poor CT imaging. Conclusions SAA and L are sensitive indicators in evaluating the severity and prognosis of COVID-19. Monitoring dynamic changes of SAA, combined with CT imaging could be valuable in diagnosis and treatment of COVID-19.

It is well established that intravenous administration of lipopolysaccharides (LPS)—cell wall components from gram-negative bacteria—induce acute inflammatory responses in dairy calves, but the effect of oral administration of LPS to dairy calves is currently unknown. To evaluate the effects of oral administration of LPS derived from Escherichia coli (serotype O111:B4) on innate immune responses in milk-fed Holstein calves, 20 visually healthy calves (34 ± 1 d) received 4 L of milk with LPS (12 μg/kg body weight; n = 10; LPS) or without LPS (n = 10; control) at the morning feeding. Samples were collected at 0.5 h before the morning feeding and at 3, 6, 24, 48, 72, and 168 h after the morning feeding to measure rectal temperature and heart rate, as well as plasma-negative and plasma-positive acute phase proteins (i.e., haptoglobin, serum amyloid A, albumin, total protein, and fibrinogen) and immunoglobulin concentrations (IgG, IgM, and IgA). None of these measurements was affected by the oral administration of LPS. Oral administration of LPS at 12 μg/kg of body weight did not induce an acute inflammatory response in visually healthy milk-fed Holstein calves when administered in milk.

The objective of the present study was to elucidate sequential changes in mRNA abundance of serum amyloid A (SAA) isotypes in endotoxin (ETX) challenge model cattle. Ten healthy cattle were separated to 2 groups: control and ETX groups. Cattle in the ETX group were challenged by 2.5 µg/kg of O111:B4 lipopolysaccharide in 4 ml of autologous serum. Blood samples were withdrawn at pre, 0.5, 1, 2, 4, 8, 12, 24, 48, 72 and 96 hr after ETX challenge. Plasma ETX activity, serum SAA concentrations, mRNA abundance of interleukin (IL)-6, SAA2 and SAA4 in the liver and polymorphonuclear leukocytes were measured. The plasma ETX activity in the ETX group increased at 0.5 hr after the ETX challenge. The serum SAA value remained higher between 12 and 72 hr after the ETX challenge than that of the control group. Hepatic IL-6 mRNA abundance in the ETX group increased at 2 hr after the ETX challenge. Hepatic SAA2 and SAA4 mRNA abundance significantly increased from 4 hr after administration, and remained significantly higher than those pre-values up to 12 and 24 hr, respectively. The abundance ratio of hepatic SAA2 was much higher than that of SAA4. The major isotype was SAA2 in liver tissue, and it is indicating systemic inflammation in cattle.

Background and aim A novel coronavirus severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) caused pneumonia, Coronavirus Disease 2019 (COVID-19), broke out in Wuhan, China in December 2019, and spread all over the world. Patients with COVID-19 showed huge differences in the hospital stay, progression, and prognosis. As reported, the comorbidities may play an important role in COVID-19. Here, we aim to address the role of cardiovascular disease (CVD) in the progression and prognosis of COVID-19. Methods and results Eighty-three confirmed COVID-19 patients were divided into CVD (n = 42) and non-CVD (n = 41) group according to their medical history. Medical records including demographic data, medical history, clinical characteristics, laboratory examinations, chest computed tomography (CT), and treatment measures were collected, analyzed, and compared between the two groups. COVID-19 patients with CVD showed (1) more severe pathological changes in the lungs, (2) elevated injury-related enzymes including α-hydroxybutyrate dehydrogenase (HDBH), lactic dehydrogenase (LDH), γ-glutamyltransferase (GGT), creatine kinase (CK), and alanine aminotransferase (ALT), (3) significantly increased uncontrolled inflammation related markers, such as c-reactive protein (CRP), interleukin (IL)-6, serum ferritin, erythrocyte sedimentation rate (ESR), and serum amyloid A (SAA), (4) serious hypercoagulable status reflected by increased D-dimer and serum fibrinogen (FIB), and (5) higher mortality, compared to COVID-19 patients without CVD. Conclusions Our data indicated that CVD is a strong risk factor for rapid progression and bad prognosis of COVID-19. More intensive medical care should be applied to patients with CVD to prevent rapid deterioration of the disease.