Acute Phase Reactants Research Articles

Dynamic Correlation between Platelet Aggregation and Inflammatory-like State in Athlete Horses

This study aimed to assess the effect of exercise on serum electrophoretic protein pattern, C-reactive protein (CRP) and platelet aggregation in horses subjected to a jumping exercise. The possible relationship between acute-phase reactions and platelet reactivity in the context of exercise was investigated. Blood samples were collected from 10 jumper horses at rest (TREST), within 5 min from the end of exercise (TPE5), and 30 min (TPE30) and 60 min after exercise (TPE60). The serum values of total proteins; CRP; albumin; α1-, α-2, β1-, β2- and γ-globulins; and the maximum degree of aggregation and the initial velocity of aggregation (slope) were evaluated. According to one-way analysis of variance, CRP and α1-, α-2, β1- and β2-globulins increased after exercise compared with rest condition (p < 0.001), whereas albumin and platelet aggregation showed lower values after exercise than at rest (p < 0.001). CRP and α1-globulin values were negatively correlated with both platelet aggregation indices at TPE5, whereas no significant correlation among these parameters was found at TREST, TPE30 and TPE60. This study provides evidence that an acute-phase response occurred in horses after the jumping exercise and suggests a linkage between the inflammatory status and the platelet responsiveness in horses during exercise.

Characterization of the Pro-Inflammatory and Pruritogenic Transcriptome in Skin Lesions of the Experimental Canine Atopic Acute IgE-Mediated Late Phase Reactions Model and Correlation to Acute Skin Lesions of Human Atopic Dermatitis.

Intradermal injection of anti-immunoglobulin E (IgE) antibodies in dogs grossly and histologically resemble naturally occurring atopic dermatitis (AD). However, the activated inflammatory and pruritic pathways have not been characterized. The objectives of this study were to characterize the inflammatory transcriptome of experimental acute canine IgE-induced lesions and to determine how these correlate to the transcriptome of naturally occurring human and canine acute atopic dermatitis. Biopsies were collected at 6 and 24 h after intradermal injections of anticanine-IgE antibodies to eight healthy male castrated Beagles; healthy and saline-injected skin served as controls. We extracted total RNA from skin biopsies and analyzed transcriptome using RNA-sequencing. Gene expressions of IgE-induced biopsies were compared to that of controls from the same subject (1.5-fold change, p-adjusted value ≤ 0.05). Acute IgE-mediated lesions had a significant upregulation of pro-inflammatory (e.g., LTB, IL-1B, PTX3, CCL2, IL6, IL8, IL18), T helper-(Th)1/IFNγ signal (e.g., STAT-1, OASL, MX-1, CXCL10, IL-12A) and Th2 (e.g., IL4R, IL5, IL13, IL33 and POSTN) genes, as well as Th2 chemokines (CCL17, CCL24). Pathway analysis revealed strong significant upregulation of JAK-STAT, histamine, IL-4 and IL13 signaling. Spearman correlation coefficient for the shared DEGs between canine anti-canine-IgE and human AD samples revealed a significant moderate positive correlation for anti-canine-IgE 6-h samples (r = 0.53) and 24-h samples (r = 0.47). In conclusion, acute canine IgE-mediated skin lesions exhibit a multipolar immunological axis upregulation (Th1, Th2 and Th17) in healthy dogs, resembling acute spontaneous human AD lesions.

Tocilizumab treatment in COVID-19 patients: therapy's side effects and effect on mortality.

This study aimed to determine the effect of tocilizumab use on mortality and the potential side effects in COVID-19 patients. The intensive care patients were divided into the tocilizumab group and the control group. Hemogram, biochemistry, acute phase reactant values, age, gender, comorbidity, and culture results were recorded on the 0th, 3rd, 7th, and 14th days. Factors affecting mortality between and within the groups and side effects were examined. 32.14% of the patients were female, and 67.85% were male. The tocilizumab group had high alanine aminotransferase and potassium on day 3. On day 7, low levels of platelet, glucose, international normalized ratio, prothrombin time, and active partial thromboplastin time levels were observed. Procalcitonin, C-reactive protein, and fibrinogen levels were low on days 3 and 7. The relationship between the tocilizumab treatment and mortality was statistically not significant, although the APACHE score was low. In the tocilizumab group, the presence of additional disease and reproduction in culture significantly increased mortality. Despite the risks of side effects, tocilizumab was used in COVID-19 treatment since it is an interleukin-6 blocker. Although the first publications stated that the treatment could decrease the mortality rate, later meta-analyses did not support these results. Our study also found that using tocilizumab did not make a difference in long-term mortality. We also observed that the known side effects were seen in short-term use.

Dissociation Phenomenon of Erythrocyte Agglutination and Its Application to Assay of Functional Activity of the Complement System in Clinical Laboratory.

The objective of the study was to validate the dissociation phenomenon of erythrocyte agglutination which is based on erythrocyte fragments and to apply it in the functional activity assay of the complement system. The dissociation-agglutination effect of erythrocyte fragments was validated by detecting the number of free erythrocytes after the action of erythrocyte fragments on agglutinated erythrocytes. The number of free erythrocytes produced after hemolysis of agglutinated erythrocytes caused by complements and complement activators(CAs) was detected by auto hematology analyzer and the results were indicated by mean hemoglobin concentration of erythrocytes (MCHC). We optimized the test conditions and validated the inter-batch stability, explored the resolution of the assay method, and assayed for the total complement activity (AC) and the CAs activated complement activity (ACA) in serum from patients and healthy individual groups. Erythrocyte fragments have a dissociative effect on agglutinated erythrocytes. The auto hematology analyzer was able to detect AC and ACA, where AC showed an inverse correlation with MCHC, and ACA demonstrated a positive correlation with MCHC. The inter-batch CV of AC, ACA, and ACA/AC was found to be 5%, 9%, and 11.7%, respectively, with good stability. The study found that serum samples from acute phase reaction patients showed significant differences in ACA compared with healthy individuals, with a p value of 0.018; serum samples from patients with nephrotic syndrome showed significant differences in AC, ACA, and ACA/AC compared with healthy individuals, with p values of 0.014, 0.002, and 0.041, respectively. Erythrocyte fragments have dissociation-agglutination effect. The complement system immunological functional detection method, based on this effect, has potential clinical application value due to its sensitivity and accuracy.

The relationship between albumin level and the development of acute kidney injury and mortality in critically COVID-19 patients

Aims: The impact of the Coronavirus Pandemic, which began in 2019, has considerably diminished; however, its effects still persist. While respiratory symptoms have been prominent during the pandemic, acute kidney disease has emerged as a significant contributor to morbidity and mortality. This study aims to demonstrate that serum albumin levels can serve as a predictor for acute kidney injury (AKI) and mortality, owing to their cost- effectiveness and feasibility for use across various healthcare centers. The goal is to contribute to the reduction of AKI development and mortality rates. Methods: The study was conducted by analyzing data from a total of 350 patients admitted to intensive care units of a training and research hospital due to COVID-19 between March 1, 2020, and April 30, 2021. Of these patients, 179 (51%) were male, and 171 (49%) were female. The data were examined retrospectively. Patients were categorized into two groups based on serum albumin levels: ?2.5 mg/dl (severe hypoalbuminemia) and 2.5-3.5 mg/dl (mild hypoalbuminemia). Subsequently, the patients were further categorized into groups based on the presence or absence of AKI, and these groups were statistically compared. Demographic data, clinical information, and laboratory values of the patients were assessed. The diagnosis of acute kidney injury (AKI) was made according to KDIGO criteria. Data were compared using the SPSS version 24 software. Results: Among the 350 patients included in the study, 115 had serum albumin levels ?2.5 mg/dl (severe hypoalbuminemia), and 235 had levels in the range of 2.5-3.5 mg/dl (mild hypoalbuminemia). Among those who developed AKI, the average albumin level was found to be 2.68 mg/dl, whereas in the group without AKI, the average albumin level was 2.76 mg/dl. Out of the total, 201 (57%) patients developed AKI, and 82% of them experienced mortality. In contrast, among the 149 (43%) patients who did not develop AKI, the mortality rate was 42%. Further subgroup analysis revealed the highest mortality rate of 88% among patients with severe hypoalbuminemia and AKI development. Conversely, the lowest mortality rate of 40% was observed in patients with mild hypoalbuminemia and no AKI. Conclusion: This study aims to establish that low serum albumin levels should be regarded not only as a negative acute-phase reactant but also as a predictive factor for complications including acute kidney disease development and mortality. Lower albumin values are correlated with higher complication rates and increased mortality. Additionally, due to its widespread availability and low cost, serum albumin is a cost-effective diagnostic tool that can be utilized in almost any healthcare setting.

On-Arrival Lumbar Epidural Analgesia for Lower Limb Trauma Pain in Emergency Care: A Superiority Randomized Controlled Trial.

Lower limb trauma in emergency settings often leads to pain management challenges. Traditional methods, primarily non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, have limitations. This study explores the efficacy of epidural analgesia in emergency for lower limb trauma patients (ELETRA) as an alternative for managing pain in lower limb trauma patients upon arrival in emergency care. This study primarily focuses on determining ELETRA's effectiveness in reducing pain for patients with lower limb trauma upon arrival. It also aims to evaluate ELETRA's influence on decreasing stress and shortening hospital stays compared to traditional pain management approaches. This study was executed as a prospective, parallel-design, randomized controlled trial in the emergency department of a tertiary care teaching hospital. The interventions were performed in a dedicated induction room adjacent to the emergency operating theater. The trial was registered in the Clinical Trial Registry of India with registration number CTRI/2022/08/044699 dated 16/08/2022.Participants were 18- to 50-year-old patients with lower limb injuries, classified under American Society of Anesthesiologists (ASA) class 1 or 2. Participants were randomized into two groups: one receiving ELETRA and the other standard pain control treatment. The effectiveness of pain relief was measured through a visual analogscale (VAS), and hemodynamic parameters, adverse effects, levels of acute phase reactants, and stress hormones were also measured along with patient satisfaction. The study enrolled 356 participants with lower limb injuries. After excluding participants lost following the intervention, data from 157 individuals in Group A and 160 in Group B were analyzed. Group A's success rate for analgesia (VAS < 2) was 92.35% (n = 145), significantly higher than Group B's 75.62% (n = 121) (p < 0.001). The commonest side effect was hypotension (5.73%) inGroup Aand nauseainGroup B (7.5%). C-reactive protein (CRP) levels rose to 104.71 ± 8.99 mg/dL in Group A and 192.58 ± 9.23 mg/dL in Group B; the difference was statistically significant. Serum cortisol levels were also higher in Group B (67.18 ± 9.21) compared to Group A (44.72 ± 6.14) at one week. Group B had a longer hospital stay, averaging 12.24 ± 4.81 days, against Group A's 10.19 ± 4.91 days. ELETRA is a safe and effective alternative for pain management in lower limb trauma patients in emergency settings. It reduces pain, improves patient satisfaction, and has a favorable impact on stress responses.

Patient Experiences and Challenges in the Management of Autoinflammatory Diseases-Data from the International FMF & AID Global Association Survey.

Autoinflammatory diseases (AIDs) are rare, mostly genetic diseases that affect the innate immune system and are associated with inflammatory symptoms. Both paediatric and adult patients face daily challenges related to their disease, diagnosis and subsequent treatment. For this reason, a survey was developed in collaboration between the FMF & AID Global Association and the Erlangen Center for Periodic Systemic Autoinflammatory Diseases. The aim of the survey was to collect the personal assessment of affected patients with regard to their current status in terms of diagnostic timeframes, the interpretation of genetic tests, the number of misdiagnoses, and pain and fatigue despite treatment. In total, data from 1043 AID patients (829 adults and 214 children/adolescents) from 52 countries were collected and analyzed. Familial Mediterranean fever (FMF) (521/50%) and Behçet's disease (311/30%) were the most frequently reported diseases. The average time to diagnosis was 3 years for children/adolescents and 14 years for adults. Prior to the diagnosis of autoinflammatory disease, patients received several misdiagnoses, including psychosomatic disorders. The vast majority of patients reported that genetic testing was available (92%), but only 69% were tested. A total of 217 patients reported that no increase in acute-phase reactants was detected during their disease episodes. The intensity of pain and fatigue was measured in AID patients and found to be high. A total of 88% of respondents received treatment again, while 8% reported no treatment. AID patients, particularly adults, suffer from significant delays in diagnosis, misdiagnosis, and a variety of symptoms, including pain and fatigue. Based on the results presented, raising awareness of these diseases in the wider medical community is crucial to improving patient care and quality of life.

Transferrin Saturation, Serum Ferritin, and C-Reactive Protein vs. Serum Ferritin for an optimal Iron Deficiency Diagnosis in Candidates for Bariatric Surgery.

Iron has different physiological processes and is regulated by hepcidin that is also an acute phase reactant, which increases with inflammation. Obesity produces a pro-inflammatory state, affecting directly the normal regulation of iron, causing ferritin (FER) deficiency. FER is used as the only indicator of the status of iron in patients with obesity, so the majority of them would be underdiagnosed, leading to a high prevalence of iron deficiency (ID) and anemia. The aim of this study is to evaluate the diagnostic tests: transferrin saturation (TS), FER, and C-reactive protein (CRP) vs. FER with the objective of analyzing the most accurate variable for the diagnosis of ID. We present a cross-sectional, analytical, and retrospective study, evaluating the diagnostic tests in 96 patients, to whom two methods were applied for the diagnosis of ID: method 1 (FER < 30ng/mL) and method 2 divided into 2A (FER < 30ng/mL), 2B (FER 30-100ng/mL + CRP ≥ 5mg/L), 2C (FER 100-300ng/mL + CRP ≥ 5mg/L + TS < 20%), and 2D (TS < 20%). The prevalence of ID obtained using method 1 was 30.2% while 69.8% presented ID using total method 2, confirming an underdiagnosis of 39.6%. The inflammatory state in patients with obesity must be considered in the diagnosis of ID. The use of TS, FER, and CRP has greater validity than the use of serum FER for the diagnosis of ID in patients with obesity.

Reticulocyte Response in Paired Blood Samples of Babesia canis Infected Young and Adult Dogs

Abstract Acute B. canis infection can lead to an acute phase reaction (APR) in dogs. The parasite invades red blood cells causing anemia through immune-mediated hemolysis and possible erythropoietic suppression. A regenerative response of the erythroid lineage during the babesiosis has not been described in extension. This research examines hematologic parameters focusing on the absolute reticulocyte count and apolipoprotein A I (ApoA I) level on the day of admission and 14 days after treatment with imidocarb-dipropionate in young (n=11) and adult (n=11) dogs naturally infected with B. canis. Metabolic and inflammatory processes were characterized by analyzing protein and lipid profiles, as well as ApoA I at specified time points. Automated analyzers were used to determine complete blood count and biochemical parameters, while ApoA I was assessed using radioimmunoassay. The reticulocyte count was determined using a manual method by means of supravital staining. Both young and adult dogs with acute B. canis infection showed non-regenerative anemia without difference. Fourteen days after successful treatment with imidocarb-dipropionate, the anemia was corrected and a high reticulocyte count was observed (p&lt;0.05). This indicates that the erythroid regenerative response was efficient in young and adult dogs, although vital signs, leukocyte count and triglyceride concentration suggest a more intense APR in young dogs. A decrease in ApoA I in both groups 14 days after treatment (p&lt;0.01) confirmed that this lipoprotein acts as a positive acute-phase protein in acute B. canis infection in dogs, but further studies are needed to connect its role in erythroid lineage regeneration.

Comparison of Eosinophil Counts in Inflammatory Conditions: Multisystem Inflammatory Syndrome in Children, Kawasaki Disease, and Infectious Mononucleosis.

This study examined the distinctions between multisystem inflammatory syndrome associated with coronavirus disease 2019, Kawasaki disease, and infectious mononucleosis. These three inflammatory disorders have commonalities according to clinical and laboratory results, particularly in relation to eosinophil levels. In this retrospective, single-center study, we documented the examination records (acute phase reactants and complete blood count) and clinical and cardiological findings of 130 patients diagnosed with multisystem inflammatory syndrome, Kawasaki disease, and infectious mononucleosis. These patients were treated and received follow-up care in our hospital from March 12, 2020, to September 13, 2022, as per the hospital records. Statistical analyses were performed using NCSS 2007, version 1 software. Eosinopenia was more prevalent in children with multisystem inflammatory syndrome than in those with Kawasaki disease, who showed normal or elevated eosinophil counts. The eosinophil counts in patients with infectious mononucleosis typically fell within the normal range. Our study found no correlation between the eosinophil counts and cardiac involvement in pediatric patients with either condition. These findings indicate a higher prevalence of eosinopenia in patients with multisystem inflammatory syndrome, irrespective of cardiac involvement, than in those with Kawasaki disease. Despite similarities in clinical findings, Kawasaki disease and multisystem inflammatory syndrome in children necessitate further studies for distinct characteristic elucidation.

Diagnostic accuracy of inflammatory markers in adults with suspected central nervous system infections

We aimed to determine diagnostic accuracy of inflammatory markers in plasma and cerebrospinal fluid (CSF) for the diagnosis of central nervous system (CNS) infections and specifically bacterial meningitis. We analyzed 12 cytokines, chemokines, and acute phase reactants in CSF and plasma of 738 patients with suspected neurological infection included in a multicenter prospective cohort. We determined diagnostic accuracy for predicting any CNS infection and bacterial meningitis. We included 738 episodes between 2017 and 2022, split into a derivation (n=450) and validation cohort (n=288). Of these patients, 224 (30%) were diagnosed with CNS infection, of which 81 (11%) with bacterial meningitis, 107 (14%) with viral meningitis or encephalitis, and 35 patients (5%) with another CNS infection. Diagnostic accuracy of CRP, IL-6, and Il-1β in CSF was high, especially for diagnosing bacterial meningitis. Combining these biomarkers in a multivariable model increased accuracy and provided excellent discrimination between bacterial meningitis and all other disorders (AUC=0.99), outperforming all individual biomarkers as well as CSF leukocytes (AUC=0.97). When applied to the population of patients with a CSF leukocyte count of 5-1000 cells/mm3, accuracy of the model also provided a high diagnostic accuracy (AUC model=0.97 vs. AUC CSF leukocytes=0.80) with 100% sensitivity and 92% specificity. These results remained robust in a temporal validation cohort. Inflammatory biomarkers in CSF are able to differentiate CNS infections and especially bacterial meningitis from other disorders. When these biomarkers are combined, their diagnostic accuracy exceeds that of CSF leukocytes alone and as such these markers have added value to current clinical practice.

Malondialdehyde Serum Levels in a Full Characterized Series of 430 Rheumatoid Arthritis Patients

Background. Oxidative stress has been involved in the pathogenesis of rheumatoid arthritis (RA). The serum malondialdehyde (MDA) level is a reliable biomarker of oxidative stress status. In the present work, we aimed to analyze how a comprehensive characterization of the disease characteristics in RA, including a lipid profile, insulin resistance, and subclinical atherosclerosis, relates to serum MDA levels. Methods. In a cross-sectional study that included 430 RA patients, serum MDA levels were evaluated. Multivariable analysis was performed to examine the relationship of MDA with disease activity scores and disease characteristics, including subclinical carotid atherosclerosis, a comprehensive lipid molecule profile, and indices of insulin resistance and beta cell function indices. Results. The erythrocyte sedimentation rate (ESR) showed a significant and positive relationship with MDA. However, this did not occur for other acute phase reactants such as C-reactive protein or interleukin-6. Although the DAS28-ESR score (Disease Activity Score in 28 joints) had a positive and significant association with MDA serum levels, other disease activity scores that do not use the erythrocyte sedimentation rate in their formula did not show a significant relationship with MDA. Other disease characteristics, such as disease duration and the existence of rheumatoid factor and antibodies against citrullinated protein, were not related to serum MDA levels. This also occurred for lipid profiles, insulin resistance indices, and subclinical carotid atherosclerosis, for which no associations with circulating MDA were found. Conclusions. The disease characteristics are not related to circulating MDA levels in patients with RA.

Limited Diagnostic and Prognostic Value of Routine Radiographs in Newly Presenting Arthritis Suspected of Rheumatoid Arthritis: A Retrospective Study.

Current recommendations suggest that patients with newly presenting arthritis suspected of rheumatoid arthritis (RA) should undergo routine radiographs of hands and feet (X-HF) as the presence of RA-associated erosions might be of diagnostic and prognostic value. Our objective was to investigate the prevalence, diagnostic, and prognostic value of RA-associated erosions seen on routine X-HF in a large, recent cohort of patients with newly presenting arthritis. A retrospective cohort study was performed between 2016 and 2019 in patients with newly presenting arthritis suspected of RA. Patients were included if arthritis was present at diagnosis, rheumatoid factor and anticitrullinated protein antibodies were measured, RA was noted in the differential diagnosis, and routine X-HF were conducted. Outcomes were the prevalence of one or more RA-associated erosion(s), and whether diagnostic or prognostic classification were changed by erosivity. Seronegative patients, patients without acute phase reactants, and patients with longer symptom duration were analyzed as subgroups. RA-associated erosions were found in 32 of 724 patients (4.4%, 95% confidence interval [95% CI] 3.1-6.2). Erosions led to a change of diagnostic classification in two patients (0.3%, 95% CI 0.01-1.1) and changed prognostic classification in three patients (0.4%, 95% CI 0.1-1.3). Seronegative patients and patients without elevated acute phase reactants had significantly lower prevalence of erosions (χ2 9.4, P = 0.002, χ2 6.5, P = 0.01). Longer symptom duration was not associated with a different prevalence of erosions (χ2 0.4, P = 0.81). The recommendation of conducting routine X-HF in patients with newly presenting arthritis suspected of RA might be reconsidered due to low prevalence of early erosive disease and lack of diagnostic and prognostic value.

Study of serum ferritin levels in various phases of dengue in pediatric dengue patients admitted in a tertiary hospital

Background: Dengue is a cause of public health concern with case fatality rate of 1%. Ferritin is an acute-phase reactant which is produced in response to infection and inflammation. The aim of this study is to evaluate serum ferritin levels in various phases of dengue in pediatric dengue patients. Methods: A hospital-based, prospective, and observational study was done involving 30 dengue cases diagnosed by positive NS1 antigen or dengue specific serology (capture enzyme-linked immunosorbent assay). Serum ferritin was estimated by electrochemiluminescence in all three phases of dengue. Clinical and platelet count monitoring was done daily; respectively. All children classified as dengue with or without warning signs and severe dengue according to the World Health Organization guidelines on diagnosis treatment, prevention, and control of dengue, 2009. Results: Out of total of 30 children with mean age of the children were 7 years, and 61% were male who were majority. High serum ferritin levels were noted during critical phase. Eight children with dengue shock syndrome and one with acute respiratory distress syndrome were managed in intensive care unit as compared to non-severe dengue with statistically significant difference as p&lt;0.05. Increase in serum ferritin is associated with severe thrombocytopenia. The mean hospital stay duration was found to be 5±3 days (mean ± standard deviation). Conclusion: Serum ferritin levels taken on admission can serve as a reliable and cost-effective biomarker in the assessment and in predicting the severity of dengue fever. Serum ferritin levels may help in identifying an uncomplicated dengue illness, from that of patients who may require inpatient admission/intensive critical care.

Rheumatological complaints in H syndrome: from inflammatory profiling to target treatment in a case study

BackgroundH Syndrome is a rare genetic condition caused by biallelic pathogenic variants in the SLC29A3 gene. It is characterized by a wide range of clinical manifestations, many of which are related to the immune-rheumatological field. These include scleroderma-like skin changes, deforming arthritis, and enlarged lymph nodes. The condition also features cardiac and endocrine defects, as well as hearing loss, for which the immune pathogenesis appears less clear. Immunomodulatory medications have been shown to improve many symptoms in recent experiences.Case presentationA 21-year-old girl was referred to our institute after being diagnosed with H syndrome. Her medical history was characterized by the development of finger and toe deformities, which developed since the first years of life and progressively worsened with clinodactyly. At 6 years of age, she was diagnosed with diabetes mellitus without typical autoantibodies and with bilateral sensorineural hearing loss. She also complained of frequent episodes of lymphadenopathy, sometimes with colliquation and growth retardation due to pancreatic insufficiency. It wasn’t until the genetic diagnosis of H syndrome that the continual increase in acute phase reactants was noticed, suggesting that an immunological pathogenesis may be the source of her problems. During her visit to our institute, she reported serious pain in both feet and hands and difficulty walking due to knee arthritis and muscle contractures. Conventional therapy with steroid injection in affected joints and methotrexate only led to partial improvement. After a thorough assessment of her inflammatory profile showing a high interferon score, the girl received treatment with baricitinib. Furthermore, based on recent data showing that SLC29A3 deficiency results in interferon production because of Toll-like Receptor 7 activation in lysosomes, hydroxychloroquine was also added. The combination of the two drugs resulted for the first time in a rapid and persistent normalization of inflammatory markers, paralleled by a dramatic improvement in symptoms.ConclusionsWe describe the results of inhibiting IFN inflammation in H syndrome and discuss how JAK inhibitors and antimalarials might represent a mechanistically based treatment for this orphan drug disorder.

Can rheumatologists unequivocally diagnose axial spondyloarthritis in patients with chronic back pain of less than 2 years duration? Primary outcome of the 2-year SPondyloArthritis Caught Early (SPACE) cohort

ObjectivesTo investigate the prevalence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP) of less than 2 years (2y) duration referred to the rheumatologist, the development of diagnosis...

Minor micro-rheological alterations in the presence of an artificial saphenous arteriovenous shunt, as an arteriovenous malformation model in the rat.

Arteriovenous malformations (AVMs) are vascular anomalies characterized by abnormal shunting between arteries and veins. The progression of the AVMs and their hemodynamic and rheological relations are poorly studied, and there is a lack of a feasible experimental model. To establish a model that cause only minimal micro-rheological alterations, compared to other AV models. Sixteen female Sprague Dawley rats were randomly divided into control and AVM groups. End-to-end anastomoses were created between the saphenous veins and arteries to mimic AVM nidus. Hematological and hemorheological parameters were analyzed before surgery and on the 1st, 3rd, 5th, 7th, 9th, and 12th postoperative weeks. Compared to sham-operated Control group the AVM group did not show important alterations in hematological parameters nor in erythrocyte aggregation and deformability. However, slightly increased aggregation and moderately decreased deformability values were found, without significant differences. The changes normalized by the 12th postoperative week. The presented rat model of a small-caliber AVM created on saphenous vessels does not cause significant micro-rheological changes. The alterations found were most likely related to the acute phase reactions and not to the presence of a small-caliber shunt. The model seems to be suitable for further studies of AVM progression.

P-78 Life-threatening fungal infection due to long term glucocorticoid usage in amiadarone thyrotoxicosis

Abstract Introduction Amiadorone-associated thyroiditis (AIT) has 2 subtypes. In type 1, there is usually underlying thyroid disease and thyrotoxicosis occurs due to increased hormone synthesis. In type 2, thyrotoxicosis occurs as a result of T4-T3 release due to destruction(1). Steroid use is recommended in the treatment of AIT. Steroids may cause infections by affecting both innate and acquired immunity. If the patient has other comorbidities, long-term hospitalization, type 2 diabetes mellitus or lymphopenia, these factors may also predispose to infection(2). Clinical Case V.E., age 63, male. The patient was diagnosed atrial fibrillation 4 years ago and was started on amiadorone. After 3 years of amiadorone use, amiadorone was discontinued in January 2023. In April, thyrotoxicosis was detected in an external center where he went with complaint of weight loss. The patient was considered to have amiadorone-associated thyroiditis and methyl prednisolone treatment was started. He used approximately 2 grams of steroid and methimazole 2×15 mg regularly for 2 months. During the period of steroid use, TSH value was always suppressed and T4 value was always 3-4 times the reference value. With the use of methyl prednisolone, severe myopathy developed especially in the proximal muscles and steroid induced diabetes was diagnosed. The patient was admitted to our hospital on 06.07.2023.TSH value was found to be suppressed and T4&amp;gt;100 pmol/liter (reference:11-22). On admission examination, there were diffuse candida plaques in the mouth. On pulmonary examination, rales were heard in the right lung and voriconazole was started because of fungal infection in the right hilar region on tomography. Steroid was discontinued and methimazole was increased to 2×30 mg in the patient who was thought to have fungal infection and had severe myopathy. Cholestyramine was added to his treatment. Voriconazole was discontinued in the patient who had visual hallucinations after 5 days of voriconazole use. During follow-up, the patient developed hypoxia 6 days later and a newly developed cavity in the lower lobe of the right lung was observed in the tomography. The findings were evaluated in favor of fungal pneumonia in the foreground and amphotericin B was started with the recommendation of infectious diseases. Galactomannan, aspergillus and Quantiferon tests were negative. The patient was consulted to pulmonology department because of the newly developed cavity and fiberoptic bronchoscopy was planned. Bronchoscopy showed no appearance suggestive of malignancy. Tuberculosis PCR was negative. T4 values and acute phase reactants completely regressed under treatment and the patient was discharged. Conclusion Steroid treatment is used in AIT type 2 and in cases of indistinguishable AIT, but it should not be ignored that this treatment has its own side effects. Especially, not giving steroids for a long time and trying to reduce the dose as soon as possible will be important in reducing steroid-related side effects.

Synovial tissue features associated with poor prognosis in inflammatory arthritis

BackgroundInflammatory arthritis encompasses a group of immune-mediated diseases characterized by chronic joint inflammation. Despite having pathogenic mechanisms in common, the prognosis of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and undifferentiated arthritis (UA) could be different regarding progression to chronic, to erosive, or to self-limited disease. Our aim was to evaluate the potential association of synovial tissue (ST) inflammatory cell infiltrate, the presence of ectopic lymphoid neogenesis (LN +) structures, and poor prognosis factors (PPF) in patients with RA, PsA, and UA.MethodsWe conducted a retrospective study including patients with active arthritis (RA, PsA, UA) who had ST obtained by rheumatological arthroscopy or ultrasound-guided biopsy. Clinical, demographic, and immunohistochemical data of the synovium was evaluated. Patients with biological therapy at the time of synovial biopsy were excluded. PPF in patients with RA and UA were defined by the presence of anti-cyclic citrullinated peptide antibodies and/or rheumatoid factor, development of bone erosions, or requirement of biological therapy during the follow-up. PPF in patients with PsA were defined as the presence of high levels of acute-phase reactants (ESR/CRP), dactylitis or nail involvement at the time of biopsy, development of bone erosion, or requirement of biological therapy during the follow-up.ResultsA total of 88 patients were included: 26 RA, 33 PsA, and 29 UA. All patients were followed up for 5 years after the biopsy. Fourteen (53.84%) RA patients had PPF, and 17 (65.38%) had LN + . LN + was associated with PPF (p 0.038) and biologic therapy initiation (p 0.018). A total of 14 (43.75%) PsA patients had PPF. CD15 infiltrate (410.68 [SD 477.63] cells/mm2) was associated with PPF (p 0.008) in PsA patients. Sixteen (55.17%) patients with UA had PPF, and 13 (44.82%) had LN + . In this group, synovial CD68 + macrophages cells density was negatively correlated with DAS28-CRP (r = − 0.346, p 0.042).ConclusionsThe presence of LN + and higher CD15 + polymorphonuclear cells infiltrate was associated with PPF in RA and PsA, respectively. No associations were found for UA. These findings suggest a great heterogeneity of the ST features and its pathogenic implications in the subtypes of inflammatory arthritis.

Plasma D-Dimer Value Corrected with Some Physiological and Inflammatory Markers (C-Reactive Protein and Ferritin) in Iraqi Patients with COVID-19 Infection

Since the beginning of the COVID-19 pandemic it has been observed that patients have elevated plasma levels of D-dimer and some inflammatory markers (ferritin, interleukine 6, C-reactive protein (CRP) or fibrinogen). Some studies point to the existence of a certain correlation between those markers and D-dimer. CRP is a protein discovered in the 1930s by Tillett and Francis and is an acute phase reactant. It is a pentameric protein which is synthesized by the liver under the action of cytokine interleukin 6 (IL-6). D-dimers are multiple peptide fragments produced as a result of degradation of crosslinked fibrin, mediated by plasmin. A total of 60 patients were recruited and categorized into :1- group1 (controls), 2- group 2 (COVID-19 patients). 5 ml of blood was obtained from each patient by vein puncture, using 5 ml disposable syringes, then centrifuged at 3000 rpm for 10 minutes to collect the serum. D- dimer, C-reactive protein were measured by using (Roche Diagnostics GmbH, Mannheim, Germany). At the same time, the Ferritin was assessed by using a miniVIDAS analyzer for the fluorescent enzymatic detection of β2-microglobulin (β2M) using the technique. Enzyme Linked Fluorescent Assay (ELFA) (BioMerieux). Our results showed that there was a non- significant difference in the P-values between control and patients males and females. The Mean ± SE of age in control group was 45.90 ± 3.34, while the Mean ± SE of age in patients was 45.35 ± 2.52. There was a non- significant difference between the two groups, the Mean ± SE of CRP in control group was 5.04 ±0.81, while the Mean ± SE of CRP in COVID-19 patients was 37.16 ±3.24, there was a highly Significant differences between them (P≤0.01). The CRP of COVID-19 patients were compared with those of control patients, the results shows significant increased CRP in covid-19 patients group as a compression with the control group, the findings of the study is similar to Jacob Lentner, etal findings. In response to infections, the liver synthesizes significant quantities of acute-phase proteins (APPs), such as CRP. This acute inflammatory protein is a highly sensitive biomarker for inflammation, tissue damage, and infection. It has been shown that CRP levels are correlated with levels of inflammation. CRP levels can promote phagocytosis and activate the complement system. In other words, CRP binds to microorganisms and promotes their removal through phagocytosis. D-dimers are one of the fragments produced when plasmin cleaves fibrin to break down clots. Our study showed that the serum D-dimer concentrations in patients significantly higher than those in control group which is similar to Mamta Soni, etal, 2020 findings. Elevated D-dimer levels have emerged as a consistent finding in severely ill COVID-19 patients, Multiple studies have identified an association between higher D-dimer levels and an increased risk of mortality in the COVID-19 patient population. Ferritin is an iron-storing protein; its serum level reflects the normal iron level and helps the diagnosis of iron deficiency anemia. Circulation ferritin level increases during viral infections and can be a marker of viral replication. Our study showed a significant increase in ferritin level in covid-19 patients group compared to control group, which consider similar to [] results. Although the exact cause for elevated ferritin in COVID-19 infection is unknown, it could be influenced by cytokine release or cellular damage that results in the leakage of intracellular ferritin. It has been previously shown that ferritin is a direct indicator of cellular damage suggestive of an association between organ damage and ferritin production. This could later cause cell death, known as ferroptosis. It is suggested that inflammation associated with sepsis could alter iron metabolism and deficiency to facilitate the immune system, which could be an early sign of COVID.