Acute Phase Parameters Research Articles

Effectiveness of the quercetin use in patients with COVID-19 with concomitant type 2 diabetes mellitus

AimTo conduct a comparative analysis of the effectiveness of basic therapy and basic therapy with the inclusion of quercetin in patients with COVID-19 with concomitant type 2 diabetes.Material and methodsThere were examined 60 patients with COVID-19 with concomitant T2DM. Upon admission into the hospital and again after 10 days, serum levels of interleukin-6, C-reactive protein, procalcitonin, ferritin, endothelin-1 were determined, and capillaroscopy of the nail plate was performed. Patients of the group I (30) against the background of protocol therapy received 0.5 g of quercetin intravenously once a day for 10 days. Patients of the group II (30) received to basic therapy.ResultsAfter the treatment in patients of the group I general weakness decreased, body temperature normalized, improved saturation indicators, the level of acute-phase parameters (interleukin-6, CRP and ferritin) significantly decreased, a positive effect of quercetin on the level of D-dimer in blood serum was noted, indices of pericapillary edema and hemosiderin deposition significantly decreased, indices diameter of the arterial part of the capillary and capillary network density significantly increased.ConclusionsThe use of quercetin against the background of basic therapy in patients with COVID-19 and concomitant T2DM reliably reduces the level of acute-phase indices, has an important clinical significance for reducing endothelial dysfunction and for preventing thrombotic complications.

Postoperative monitoring of ovariohysterectomy carried out with two types of surgical sutures in shelter cats and differences in selected blood parameters between shelter and pet cats

BackgroundReduction of inflammation and early detection of complications after surgical procedures are important objectives for proper veterinary practice. This study aimed to evaluate the differences between shelter and pet female cats in selected acute-phase parameters scheduled to ovariohysterectomy. Postoperative monitoring after ovariohysterectomy with the same laboratory parameters was performed in shelter cats, in which two different types of surgical sutures were used for the entire procedure. The experimental group comprised 40 female cats from animal shelters (‘shelter cats,’ n = 40). These cats were divided into two subgroups: group A (n = 20) operated on with absorbable sutures and group NA (n = 20) operated on with non-absorbable sutures. In addition, the same parameters were evaluated in pet female cats (n = 19). Blood was collected from shelter cats immediately before surgery (term 0), at 24 and 72 h (terms 1 and 3, respectively), and at 7 and 14 days (terms 7 and 14, respectively) after ovariohysterectomy. Blood samples from the pet cat group were collected only once.ResultThe mean haptoglobin concentration before ovariohysterectomy in pet cats was significantly lower than that in shelter cats. Fibrinogen concentration was significantly lower in pet cats than in cats from group A. Serum albumin, beta-1, beta-2, and gamma-globulin concentrations were significantly higher in the shelter cats than in the pet cats. Subcutaneous tissue thickening at the site of the postoperative wound was observed in five patients cats (25%) in group A, and two (10%) cats in the NA group.ConclusionThese results indicate that ovariohysterectomy leads to local and general inflammatory responses. The majority of cats from animal shelters suffered from subclinical inflammation.

Non-invasive methods for analysing pig welfare biomarkers.

Atpresent, the assessment ofpig welfare quality has gained significant importance, prompting theexploration ofnovel biomarkers for this purpose. Traditionally, these biomarkers have been monitored inthe blood; however, blood sampling isconsidered aninvasive procedure. Currently, non-invasive methods for collecting samples are emerging asviable alternatives for assessing these biomarkers. This article aims topresent the current knowledge regarding the use ofnon-invasive methods for analysing pig welfare biomarkers, specifically focusing onthe saliva, hair, faeces, and urine asmatrices todetermine these biomarkers. The saliva analysis encompasses various biomarkers, such ascortisol, alpha-amylase, chromogranin A, the total esterase, oxytocin, acute phase proteins, adenosine deaminase, immunoglobulins and parameters ofredox homeostasis. Cortisol, aspecific biomarker, can bedetermined inthe hair, urine and faeces, while urine samples allow for the analysis ofcatecholamines asnon-invasive markers ofpig welfare.

Складність діагностики рефрактерної хвороби Кавасакі під «маскою» гемобластозу: клінічний випадок із досвіду гематолога

Kawasaki disease (KD) is an acute systemic vasculitis that is the most common cause of acquired heart disease in children under 5 years of age with hyperthermia. Diagnosis of KD is a clinical challenge, given the wide range of clinical manifestations and similarities with many viral and bacterial diseases. Purpose - to describe a clinical case of refractory КD in a three-month-old girl with an emphasis on the importance of echocardiography and coronary angiography for the final verification of the disease, urgent initiation of treatment with minimal suspicion of КD. Clinical case. The article reports on a three-month-old patient with a difficult diagnosis of refractory form of КD. The disease debuted with hyperthermia, enterocolitis, obstructive bronchitis, and hepatoliver syndrome. The manifestations of skin exanthema were initially considered as an allergic dermatitis to the use of a cephalosporin antibiotic. Multisystemic inflammatory syndrome associated with SARS-CoV-2 infection was suspected. After the use of immunosuppressive therapy with mega-doses of dexamethasone and intravenous human immunoglobulin 2 g/kg/day for 3 days, clinical improvement was achieved. Subsequently, the haemogram showed an increase in neutrophilic hyperleukocytosis to the appearance of blast cells, hyperthrombocytosis and severe anaemia. A differentiation was made between a leukemic reaction, the debut of myeloproliferative disease, juvenile myelomonocytic leukaemia. Against the background of a rapid decrease in the number of leukocytes, the girl developed hyperthermia, migratory intermittent maculopapular rash, and foots edema. Laboratory findings included thrombocytosis and an increase in acute-phase parameters. Echocardiography revealed left ventricular dilation, a small amount of excess fluid in the pericardium, dilatation of the left coronary artery evenly to the bifurcation. Computed tomography revealed giant coronary artery aneurysms, which gave grounds to diagnose KD. The study was performed in accordance with the principles of the Declaration of Helsinki. Informed consent of the parents of child was obtained for the study. No conflict of interests was declared by the authors.

Hereditary periodic fevers in children

Fevers in children is a pressing challenge in paediatrics, as they are one of the most common symptoms people seek medical help. Autoinflammatory diseases (AIDs) constitute a group of diseases, where fever is one of the main symptoms, and fever attacks have a certain frequency and duration. Autoinflammatory diseases are rooted in the systemic aseptic inflammation associated with activation of the innate immune system, without elevated levels of autoantibodies. The most common autoinflammatory diseases include hereditary periodic fevers, among which are familial Mediterranean fever (FMF), HIDS/MKD, CAPS-, TRAPS-syndromes and rarer diseases (deficiency of natural interleukin receptor antagonists). The pathogenesis of this group of diseases is based on the process of accelerated formation of a supramolecular protein complex (inflammasome), which subsequently leads to the transition of the inactive form of IL1β into its active form. The clinical presentations of these diseases may be similar and include episodes of fever, abdominal pain, arthralgia, various rashes, etc., as well as an increase in acute phase parameters. These diseases are characterized by symptoms at certain intervals; they usually have intervals without showing any symptoms. Familial Mediterranean fever is characterized by a certain ethnic background (Armenians, Turks, Arabs, Jews). Today, molecular genetic testing is the most accurate method for diagnosing familial Mediterranean fever. Current therapy aims to prevent attacks of the disease, but it is also important to use symptomatic therapy to relieve the child’s condition when an attack has already developed. Modern treatment strategies include both drugs that have long been used in paediatric practice (colchicine, non-steroidal anti-inflammatory drugs (ibuprofen), glucocorticosteroids) and novel genetically engineered biological drugs (interleukin antagonists and tumour necrosis factor inhibitors, etc.).

IgG4-related disease - a clinical case

Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease affecting one or more organs. Pathomorphologically, a dense infiltrate of lymphocytes and IgG4 plasmocytes, and subsequent fibrosis is detected. Despite the many hypotheses of genetic predisposition, molecular mimicry and autoimmune nature of the disease, the etiology still remains unclear. Both innate and acquired immunity are believed to play a key role in disease pathogenesis. The involvement of occupational risk factors is also discussed. The possible involvement of multiple organs and systems (most often lacrimal and salivary glands, kidneys, lungs, aorta, pancreas, hepatobiliary duct, lymph nodes, as well as retroperitoneal fibrosis) is the reason for the multidisciplinary approach in this disease. In pulmonary involvement, clinical manifestations are nonspecific (cough, dyspnea, chest or back pain, hemoptysis, low-grade fever, weight loss) or patients are asymptomatic and pulmonary changes are an incidental finding on imaging. Up to 60% of cases of autoimmune pancreatitis represent a pancreatic manifestation of IgG4-related disease, with the majority of patients being elderly men. The most common differential diagnosis is a malignant process due to the tumor-like changes of the affected organ. Treatment with corticosteroids, immunosuppressors and symptomatic agents in most cases has a good effect, although relapses of the disease are also observed. We present a clinical case of a 72-year-old patient whose first complaints were nonspecific, for which a chest computed tomography was performed with visualization of four solid nodules in the right lung. After antibiotic therapy, without effect and deterioration of the patient's condition, video-assisted thoracoscopy, biopsy, histology and immunohistochemistry were performed. A diagnosis of IgG4-RD with pleural and lung involvement was confirmed. Anemic syndrome, increased values ​​of amylase, lipase, and acute phase parameters were found from the laboratory tests. Through endoscopic retrograde cholangio-pancreatography, autoimmune pancreatitis was diagnosed in the course of IgG4-RD. A plastic stent was placed on the common bile duct. Treatment with Prednisolone 40 mg/day was started with a subsequent dose reduction. Follow-up computed tomography of the lung after 9 months demonstrated a reduction of the described changes in the lungs, but with persistent lymphadenopathy and fibrotic changes. Azathioprine 100 mg daily was added to prednisone therapy. Against the background of the combined treatment, an improvement of the clinical condition and laboratory parameters was established.

Different Clinical Relevance of Anti-Citrullinated Protein Antibodies in RA Patients

The objective of the study was to find a potential relationship between ACPAs and disease activity, bone destruction, and ACPA responses to various therapeutic regimens. The study included 232 patients with rheumatoid arthritis (RA); 90 patients had early RA, and 142 patients had an advanced stage of the disease. 77 (85.6%) patients with early RA were highly positive for anti-CCP, and 29 (70.7%) patients were highly positive for anti-MCV. A positive correlation was found between anti-MCV and DAS28 (r = 0.4; p = 0.04). As for advanced RA, 78 (80.4%) patients were high-positive for anti-CCP, and 70 (79.5%) were high-positive for anti-MCV. There was a positive correlation between anti-MCV concentration and SDAI (r = 0.4; p = 0.02), as well as CDAI (r = 0.4; p = 0.02). No significant correlations were found between the anti-CCP levels and activity indices, anti-CCP and acute-phase parameters in both early and advanced RA groups. Higher total Sharp scores (96.5 (65.0–122.0)) were found in pts highl-positive for anti-MCV (n = 79), compared to low-positive/negative (n = 27) patients (57.0 (31.0–88.0); p < 0.05). Anti-MCV levels dropped significantly in pts on rituximab and tocilizumab therapy at weeks 12 and 24 after initiation of treatment, while high anti-CCP concentration persisted throughout the treatment. Anti-MCV levels correlated with inflammatory activity and development of bone destruction and decreased in pts on treatment. Anti-CCP was less responsive and showed minor changes during treatment; therefore, its thorough monitoring was not feasible.

Otogenic Sinus Thrombosis and Hemophilia: A Clinical Case

Background. Patients with hemophilia are protected from thrombosis by a deficiency of one of coagulation factors, therefore thrombotic complications are rare in them. Currently, few descriptions of spontaneous venous thrombosis in adult hemophiliacs can be found in the literature. Even fewer data of thromboembolic complications are reported in pediatric practice. At present, no clear recommendations are given for the management of thrombotic complications in children with hemophilia, which requires further study of this issue to develop prevention and treatment regimens, including otogenic sinus thrombosis in this category of patients.Case description. A 7-year-old boy was transferred from the Somatic Hospital to the Intensive Care Unit of Regional Clinical Hospital No. 2 in Tyumen (Russia) with an Otorhinolaryngology Unit. He was diagnosed with non-perforative form of acute right-sided suppurative otitis media, acute right-sided mastoiditis, thrombosis of the right sigmoid sinus. The anamnesis shows that the child is diagnosed with hemophilia A, of moderate severity (factor VIII level — 5%), for which he has been receiving factor VIII replacement therapy for the last year. Upon admission, a general blood test revealed no abnormalities, with a slight increase in acute-phase parameters: C-reactive protein, fibrinogen, signs of hypocoagulation. Due to negative dynamics, the child underwent anthromastoidotomy against the background of intensive replacement therapy. Surgery revealed the presence of granulation tissue with hemorrhagic thrombi in the antrum and aditus. In the postoperative period, replacement therapy was accompanied with antibacterial and anticoagulant therapy.Conclusion. The management of patients with otogenic sinus thrombosis against the background of hereditary factor VIII deficiency is a difficult task. On the one hand, it requires surgical intervention and anticoagulant therapy in order to prevent further thrombosis, on the other hand — intensive replacement therapy in order to reduce the risks of hemorrhagic complications. The described case demonstrates the need for an interdisciplinary approach to the diagnosis and treatment of a patient with otogenic thrombosis of lateral sinus against the background of hemophilia A. The approach is to minimize the risks of intraoperative complications and insure a favorable outcome.

Prevention of complications from the laparotomy wound in abdominal gunshot injury

The OBJECTIVE was to evaluate the effectiveness of the original technique for assessing the reparative potential of the anterior abdominal wall in the prevention of complications from the laparotomic wound in abdominal gunshot injury.METHODS AND MATERIALS. The comparative assessment of the results of surgical treatment of 145 victims with abdominal gunshot injury, which were divided into 2 groups, was made. The retrospective group included 92 patients who underwent a standard approach to the prevention of infectious complications in the surgical area: perioperative administration of antibiotics, daily dressings, as well as laboratory monitoring of acute phase parameters and instrumental assessment of tissue condition (ultrasound). The prospective group was formed from 53 patients in whom, as part of the prevention of the infectious process, the original method for assessing the reparative potential of the tissues of the anterior abdominal wall was used (priority certificate for the invention ¹ 2023109198 dated 04/12/2023). The studied groups were comparable in terms of the main clinical criteria: the age of the victims, the severity of injuries, and the structure of surgical interventions.RESULTS. Suppuration of the laparotomic wound was noted in 22 patients in the retrospective group and in 4 in the prospective group, which accounted for 23.9 % and 7.5 % of their number (p=0.014). Eventration was observed in 11 patients in the retrospective group and in one patient in the prospective group (11.9 % and 1.9 %, p=0.05).CONCLUSION. The use of the original technique for assessing the reparative potential of the tissues of the anterior abdominal wall makes it possible to reduce the incidence of complications from the laparotomic wound in abdominal gunshot injury.

Neurointensive Care of Traumatic Brain Injury Patients Based on Coagulation and Fibrinolytic Parameter Monitoring.

Coagulopathy, a common complication of traumatic brain injury (TBI), is characterized by a hypercoagulable state developing immediately after injury, with hyperfibrinolysis and bleeding tendency peaking 3 h after injury, followed by fibrinolysis shutdown. Reflecting this timeframe, the coagulation factor fibrinogen is first consumed and then degraded after TBI, its concentration rapidly decreasing by 3 h post-TBI. The fibrinolytic marker D-dimer reaches its maximum concentration at the same time. Hyperfibrinolysis in the acute phase of TBI is associated with poor prognosis via hematoma expansion. In the acute phase, the coagulation and fibrinolysis parameters must be monitored to determine the treatment strategy. The combination of D-dimer plasma level at admission and the level of consciousness upon arrival at the hospital can be used to predict the patients who will "talk and deteriorate." Fibrinogen and D-dimer levels should determine case selection and the amount of fresh frozen plasma required for transfusion. Surgery around 3 h after injury, when fibrinolysis and bleeding diathesis peak, should be avoided if possible. In recent years, attempts have been made to estimate the time of injury from the time course of coagulation and fibrinolysis parameter levels, which has been particularly useful in some cases of pediatric abusive head trauma patients.

Predictors of Mortality in Patients of Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Prospective Observational Study

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in increased morbidity, mortality and tremendous socioeconomic burden. Predicting inhospital mortality may aid prognostication, planning for the site of care, i.e., ward versus intensive care units, and better individualization of treatment. Aim of Study: This study aims in predicting inhospital mortality in patients of AECOPD based on the parameters measured at the time of admission. Methods: Known COPD patients in acute exacerbations admitted in a tertiary care hospital were interrogated for clinical history and examination. All relevant laboratory tests including arterial blood gas analysis, complete blood count, liver and renal function tests, and random blood sugar were done. Based on outcome, patients were grouped into survivors and nonsurvivors. Parameters recorded were then subjected for univariate analysis to get their statistical significance. All significant variables on univariate analysis were then analyzed further with multivariate analysis. Results: Out of the total 140 patients included in the study, 24 (17%) died during their hospital stay. Of the various acute-phase parameters recorded at the time of the admission, only five qualified to be predictors of inhospital mortality based on univariate and multivariate analyses. These were partial pressure of carbon dioxide in arterial blood (PaCO2) (odds ratio [OR], 95% confidence interval [CI] =1.067, 0.993–1.146), pH (OR, 95% CI = 0.001, 0.001–0.584), serum glutamic pyruvate transaminase (SGPT) (OR, 95% CI = 1.032, 1.006–1.059), sodium (OR, 95% CI = 0.779, 0.689–0.881), and random blood sugar (OR, 95% CI = 1.018, 1.007–1.029). With these five factors combined, area under receiver operating characteristic (ROC) curve was 0.9684, sensitivity 79.18%, specificity 96.55%, positive predictive value 82.61%, negative predictive value 95.73%, and correctly classify acute exacerbation in 93.57%. Good survival can be expected if these parameters are within normal limits. Conclusion: pH, PaCO2, SGPT, serum sodium, and random blood sugar at the time of admission are independent predictors of mortality in patients of AECOPD. These can be helpful in developing a prediction tool of inhospital mortality in such patients.

α2-fraction and haptoglobin as biomarkers for disease activity in oligo- and polyarticular juvenile idiopathic arthritis

ObjectivesUnlike in adult rheumatology, for most forms of juvenile idiopathic arthritis (JIA) no reliable biomarkers currently exist to assess joint and disease activity. However, electrophoresis is frequently found changed in active juvenile arthritis. The objective of this study was to evaluate the α2-fraction of serum electrophoresis and its main components as biomarkers for JIA, categories extended/persistent oligoarthritis and seronegative polyarthritis, in comparison with the conventionally used erythrocyte sedimentation rate and C-reactive protein.MethodsSerum samples and clinical data from 181 patients with JIA were collected. Serum electrophoresis and α2-fraction and its components were determined using standard methods. Relationship between calculated α2-fraction of serum electrophoresis (CA2F) and its components, acute-phase parameters and cJADAS27 was assessed using Pearson’s correlation coefficient and linear regression modelling, adjusting for confounding effects. Results were confirmed in a second cohort with 223 serum samples from 37 patients, using a mixed model to account for repeated measures.ResultsCompared to ESR and CRP, CA2F showed higher correlation to cJADAS27, in particular for persistent oligoarthritis. Of the three components of the α2-fraction, haptoglobin showed the highest correlation to cJADAS27. Regression analysis demonstrated higher ability to predict cJADAS27 for CA2F, and especially for haptoglobin as a component thereof, than for CRP and ESR.ConclusionCompared to conventional methods, α2-fraction of serum electrophoresis and specifically, haptoglobin show higher correlations with disease activity in common subtypes of JIA, representing excellent candidates as biomarkers for disease activity. Further studies are necessary to determine diagnostic value and correlations in other subtypes.

A clinical case of successful treatment with an interleukin 6 receptor blocker of a systemic variant of juvenile arthritis associated with spinal injury

The article presents a clinical case of systemic juvenile idiopathic arthritis that began after a spinal injury in a 9-year-old child. The authors noted the importance of dysregulation of the innate immune system in the pathogenesis of systemic juvenile idiopathic arthritis that entitled this variant of the disease to be regarded as autoinflammatory, and not “classical” autoimmune diseases. The article emphasized the leading role played by interleukin 6 in the development of extra-articular manifestations of the disease (fever and thrombocytosis, stimulation of hepatic production of acute-phase proteins of inflammation, anaemia, inhibition of the production of adrenocorticotropic hormone and cortisol, production of growth hormone and procalcitonin, development of amyloidosis), highlighting the need for inhibition of interleukin 6 activity in patients receiving therapy for systemic juvenile rheumatoid arthritis. It stressed the importance of early initiation of therapy from the standpoint of modern understanding of the pathogenesis of this disease: the use of new biological agents, which action is directed at interleukins 1 and 6. This approach is associated with inefficiency of such drugs as corticosteroids, methotrexate, tumour necrosis factor inhibitors. Of no less importance is the fact that the use of these biological agents can significantly reduce the effect of corticosteroids. The course of the presented disease caused some difficulties in its diagnosis and selection of therapy. This is largely due to the fact that the pathology of the sacroiliac joint is extremely difficult to diagnose clinically. Inflammatory immune response associated with trauma may be accompanied by cytokine release, free radical accumulation and apoptosis, pointing to the need to exclude juvenile spondyloarthritis and other juvenile arthritis with a view to administer adequate therapy. In this case, an attempt to treat sacroiliitis as an inflammatory disease was unsuccessful. The focus on persisting fever, arthralgia, anemia, lymphadenopathy, high values of acute phase parameters in the patient, who received courses of antibiotic therapy, allowed the doctors of the surgical department to refer the patient to a specialized pediatric rheumatology department. Resistance to glucocorticoids and a tumour necrosis factor inhibitor (etanercept) was also noted. The successful result of the use of tocilizumab (interleukin 6 receptor blocker) includes: relief of visceral manifestations, normalization of laboratory activity indicators of the disease that persisted for 1.5 years.

A novel prognostic system based on clinical and laboratory parameters for childhood Guillain-Barre syndrome.

To develop a score based on clinical and laboratory parameters in acute-phase of GBS to predict outcome at 6months. Clinical and laboratory assessment at admission including blood neutrophil-to-lymphocyte ratio (NLR), pre and post-immunotherapy serum albumin was prospectively performed in pediatric-GBS cases at a tertiary-care hospital over 1year. Clinical features and laboratory test results were compared between children with complete (Hughes Disability Score; HDS ≤ 1) and incomplete recovery (HDS > 1) at 6months from onset, using univariate and multivariate analysis. Area-under-receiver-operating-characteristic-curve (AUC) of predictors of prognosisand their optimal cutoffs were assessed. Forty-six patients were enrolled (mean age 69.1 ± 35.2months; male 57.6%). Factors on admission that independently predicted poor-outcome at 6months were older age, feeble voice, lower NLR and lower post-immunotherapy serum albumin. AUCs and optimal cutoffs of NLR and post-immunotherapy serum albumin for predicting disability at 6 monthswere 0.729, 0.781 and ≤ 1.65, ≤ 34.5 g/L, respectively. AUCs of clinical parameters such as older age and feeble voice were 0.749 and 0.713 respectively. King GBS outcomescore including all predictors had maximum AUC of 0.971 (95% CI 0.921-1.02). The score at cutoff ≥ 3 demonstrated excellent sensitivity (92.3%) and specificity (96.7%) to determine poor outcome. This new prognostic system may be beneficial in recognising children-at-risk of poor prognosis who may benefit from additional treatment.

Different clinical relevance of anti-citrullinated proteins antibodies in RA patients

Objective – to find a potential relationship between ACPA and disease activity, bone destruction, and ACPAs responses to various therapeutic regimens.Materials and methods. The study included 232 patients with rheumatoid arthritis (RA); 90 patients had early RA; 142 patients had advanced stage of the disease.Results. 77 (85.6%) patients with early RA were high positive for anti-CCP, and 29 (70.7%) patients – high positive for anti-MCV. A positive correlation was found between anti-MCV and DAS28 (r=0.4; p=0.04). As for advanced RA, 78 (80.4%) patients were high positive for anti-CCP, and 70 (79.5%) – for anti-MCV. There was a positive correlation between anti-MCV concentration and SDAI (r=0.4; p=0.02), as well as CDAI (r=0.4; p=0.02). No significant correlations were found between the anti-CCP levels and activity indices, anti-CCP and acute-phase parameters in both early and advanced RA groups. Higher total Sharp scores (96.5 (65.0–122.0)) were found in pts high positive for anti-MCV (n=79), compared to low-positive/negative (n=27) patients (57.0 (31.0–88.0); p&lt;0.05). Anti-MCV levels dropped significantly in pts on rituximab and tocilizumab therapy at weeks 12 and 24 after initiation of treatment, while high anti-CCP concentration persisted throughout the treatment.Conclusion. Anti-MCV levels correlated with inflammatory activity and development of bone destruction, and were decreasing in pts on treatment. Anti-CCP was less responsive, showed minor changes during treatment, therefore its’ thorough monitoring was not feasible.

Erythropoietin in children with hemolytic uremic syndrome: a pilot randomized controlled trial.

The efficacy of recombinant human erythropoietin (rHuEPO) in sparing red blood cell (RBC) transfusions in children with hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) is uncertain. We conducted a pilot randomized controlled open trial between December 2018 and January 2021. Children were randomized to the intervention (subcutaneous rHuEPO 50 U/kg three times weekly until discharge + RBC transfusion if hemoglobin ≤ 7g/dL and/or hemodynamic instability) or to the control arm (RBC transfusion if hemoglobin ≤ 7g/dL and/or hemodynamic instability). Primary outcome was the number of RBC transfusions received during hospitalization. Secondary outcomes were to explore whether baseline EPO levels were adequate to the degree of anemia, to correlate selected acute phase parameters with the number of RBC transfusions, and to assess possible adverse events. Twelve patients per arm were included; they were comparable at recruitment and throughout the disease course. Median number of RBC transfusions was similar between groups (1.5, p = 0.76). Most patients had baseline EPO levels adequate to the degree of anemia, which did not correlate with the number of transfusions (r = 0.19, p = 0.44). Conversely, baseline (r = 0.73, p = 0.032) and maximum lactic dehydrogenase levels (r = 0.78, p = 0.003), creatinine peak (r = 0.71, p = 0.03) and dialysis duration (r = 0.7, p = 0.04) correlated significantly with RBC requirements. No side effects were recorded. In children with STEC-HUS, the administration of rHuEPO did not reduce the number of RBC transfusions. Larger studies addressing higher doses and similar severity of kidney failure at rHuEPO initiation (e.g. at start of dialysis) are warranted. ClinicalTrials.gov identifier: NCT03776851. A higher resolution version of the Graphical abstract is available as Supplementary information.

THE ROLE OF PEPSINOGENS IN THE FORMATION OF GERD IN PATIENTS WITH COPD

The article presents data on the role of pepsinogen-1 and -2 and bilirubin in the formation of gastroesophageal reflux disease (GERD) in patients with chronic obstructive pulmonary disease (COPD). Clinical, biochemical, immunological research methods were used in the work. The activity of pepsinogens 1 and 2 and bilirubin in saliva was determined in all patients with combined pathology. It has been established that the presence of concomitant GERD in patients is an independent aggravating factor for the function of external respiration. In patients with concomitant GERD, a significant increase in acute phase parameters in the serum, indicating active systemic inflammation. Increased activity of the cytokine IL-6 and IFNγ indicates the activation of the cellular immune system, with an unregulated immune response that supports chronic inflammation in the bronchi even in remission. Increased levels of IL-4 are compensatory in nature, as IL-4 inhibits the production of macrophages of proinflammatory cytokines, including IL-6. Detection of correlations between the concentration of total bilirubin in saliva with a decrease in external respiration, namely FVC, FEV-1, as well as the presence of shortness of breath allows us to consider bilirubin as a possible marker of reflux and respiratory inflammation in the bronchi, until obstruction. The positive correlation of pepsinogen-1 in saliva with an allergic history, and pepsinogen-2 in saliva with cough, shortness of breath and smoking, and a negative correlation of pepsinogen-1 with the value of FEV1 / FVC, allows to consider pepsinogen-1 and pepsinogen-2 as markers of non-acid reflux and respiratory inflammation with bronchoobstruction

Late onset familial Mediterranian fever: a clinical case

Familial Mediterranean fever (FMF) is a rare genetic autosomal recessive disease typical for special ethnic groups, such as Arabs, Greeks, Armenians, Jews, Turks and other ethnicities inhabiting the Mediterranean coast. The characteristic clinical signs and symptoms of the disease are recurrent episodes of fever, associated with polyserositis, in particular, with benign (aseptic) peritonitis. The disease is caused by mutation in the MEFV gene encoding the synthesis of the protein pyrine, which leads to an uncontrolled release of pro-inflammatory cytokines by granulocytes. The criterion for the severe course of the disease is AA-renal amyloidosis associated with an unfavorable prognosis. Here we present a clinical case of classic FMF with high fever and abdominal pain syndrome. A 26-year-old Armenian patient had a sudden attack of fever and severe pain in the right iliac area several months before his first hospital admission. Non-steroid anti-inflammatory drugs and antispasmodics were unable to relieve the symptoms, with the attack ceasing spontaneously after 3 days from the beginning. Thereafter, the attacks recurred 1 to 2 times per month within a year. During hospital stay at the peak of the attack, peritoneal symptoms at abdominal palpation, together with neutrophilic leukocytosis and a significant increase in acute phase parameters of inflammation (C-reactive protein, fibrinogen, erythrocyte sedimentation rate) were found. Based on the characteristics of the complaints, past history, laboratory and instrumental results, we excluded infections, autoimmune and surgical disorders and made a decision to perform genetic testing to detect the MEFV gene mutation. Confirmation of the mutation has led to the definitive diagnosis of FMF. This clinical case is remarkable for its late onset, which is not typical for FMF. As a result, the patient was prescribed continuous therapy with сolchicine. Six months of the follow up have demonstrated a positive trend with no attacks during this period.

Urinary C3 levels associated with sepsis and acute kidney injury-A pilot study.

Acute kidney injury (AKI) is an abrupt deterioration of renal function often caused by severe clinical disease such as sepsis, and patients require intensive care. Acute-phase parameters for systemic inflammation are well established and used in routine clinical diagnosis, but no such parameters are known for AKI and inflammation at the local site of tissue damage, namely the nephron. Therefore, we sought to investigate complement factors C3a/C3 in urine and urinary sediment cells. After the development of a C3a/C3-specific mouse monoclonal antibody (3F7E2), urine excretion from ICU sepsis patients was examined by dot blot and immunoblotting. This C3a/C3 ELISA and a C3a ELISA were used to obtain quantitative data over 24 hours for 6 consecutive days. Urine sediment cells were analyzed for topology of expression. Patients with severe infections (n = 85) showed peak levels of C3a/C3 on the second day of ICU treatment. The majority (n = 59) showed C3a/C3 levels above 20 μg/ml at least once in the first 6 days after admission. C3a was detectable on all 6 days. Peak C3a/C3 levels correlated negatively with peak C-reactive protein (CRP) levels. No relationship was found between peak C3a/C3 with peak leukocyte count, age, or AKI stage. Analysis of urine sediment cells identified C3a/C3-producing epithelial cells with reticular staining patterns and cells with large-granular staining. Opsonized bacteria were detected in patients with urinary tract infections. In critically ill sepsis patients with AKI, urinary C3a/C3 inversely correlated with serum CRP. Whether urinary C3a/C3 has a protective function through autophagy, as previously shown for cisplatin exposure, or is a by-product of sepsis caused by pathogenic stimuli to the kidney must remain open in this study. However, our data suggest that C3a/C3 may function as an inverse acute-phase parameter that originates in the kidney and is detectable in urine.

Expression of interferon-stimulated genes in patients with rheumatoid arthritis on anti-B-cell therapy (preliminary results)

Objective: to evaluate the expression of interferon-stimulated genes (ISG) – interferon (IFN) signature – in patients with rheumatoid arthritis (RA) and its dynamics during anti-B-cell therapy.Patients and methods.We examined 20 patients with RA who received two infusions of the biosimilar rituximab (RTM) Acellbia® in a total dose of 1200 mg. Five genes were selected to evaluate IFN signature: IFI44L, MX1, IFIT1, RSAD2, EPSTI1. The expression of IFI44L and IFIT1 could not be determined for technical reasons, and further analysis included three genes – MX1, EPSTI1, RSAD2. IFN signature was calculated as the average value of the expression of three selected genes (IFN-score).Results and discussion. The initial expression level of MX1 was 11.48 (5.45–19.38), EPSTI1 – 12.83 (5.62–19.64), RSAD2 – 5.16 (2.73–10.4) and IFN-score –10.3 (5.18–17.12), in patients with RA it was statistically significantly higher than in healthy donors: 1.26 (0.73–1.6); 1.06 (0.81–1.48); 0.93 (0.72–1.19) and 1.09 (0.92–1.42), respectively (p&lt;0.05). The IFN-score was high in 15 (75%) patients, low in 5 (15%). The use of RTM was accompanied by a statistically significant decrease in disease activity and the level of acute phase parameters (ESR, CRP) after 12 and 24 weeks of therapy (p&lt;0.05). In the group as a whole, as well as in patients with a moderate effect of therapy or its absence, by the 24th week of treatment, an increase in the expression of RSAD2 (p&lt;0.05) and a tendency to an increase in the IFN-score level (p=0.06) were observed.Conclusion. In patients with RA, an increased expression of ISH was found compared to healthy donors. An increase in the expression of RSAD2 and IFN-score is observed both in patients with a satisfactory effect of RTM and with no effect. The obtained results can be important for predicting the course of the disease and personalizing therapy.