Fibrinogen Values Research Articles

Prognostic value of pretreatment serum fibrinogen in young patients with small cell lung cancer: A cross-sectional study.

To explored the prognostic value of pretreatment serum fibrinogen level in young patients with small cell lung cancer (SCLC). The concentrations of serum fibrinogen of 183 young (<50 years old) SCLC patients were measured. The association of baseline serum fibrinogen level and clinical outcome was analyzed by survival analysis. Hyperfibrinogenemia was significantly associated with American Veterans Administration Lung Study Group stage and surgery treatment. The survival analysis indicated that patients with hypefibrinogenemia had worse outcome than patients with normal fibrinogen. Pretreatment serum fibrinogen level was identified as a worse independent survival predictor in young SCLC. The hazard ratio was 1.420 (95% confidence interval: 1.035-1.947). Pretreatment serum fibrinogen is independent associated with overall survival in patients with young SCLC.

Prognostic Markers in COVID-19 Patients in Intensive Care: Can Hemostatic Parameters Predict Mortality?

Objective: Our study aimed to investigate whether primarily hemostasis parameters and secondarily demographic, clinical, and laboratory values could predict the mortality of critically ill Coronavirus Disease 2019 (COVID-19) patients. Methods: We retrospectively examined 180 laboratory-confirmed adult intensive care unit (ICU) patients with COVID-19. A total of 145 patients with complete records were included in the study. The patients were divided into two groups: deceased (n=58) and discharged (n=87). The demographic and clinical characteristics of the two groups, use of vasopressor therapy, requirement for invasive mechanical ventilation (IMV), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, duration of ICU stay, and the relationship between laboratory values on ICU admission and mortality were evaluated using cutoff values. Results: Among hemostatic parameters, only D-dimer&gt;1.08 mg L-1 was found to be a significant predictor of mortality (p=0.04), while platelet, prothrombin time (PT), activated partial thromboplastin time (aPTT), International Normalized Ratio (INR) and fibrinogen values were not significantly associated with mortality (p&gt;0.05). In addition, age &gt;76 years, hypertension (HT), need for IMV, APACHE II score &gt;23, procalcitonin (PCT) &gt;0.21 μg L-1, lymphocytes &lt;0.4 109 L-1, interleukin 6 (IL-6) &gt;93 pg mL-1 were found to be predictors of mortality (p&lt;0.05). Neutrophil and C-reactive protein (CRP) values were not significantly associated with mortality (p&gt;0.05). ABSTRACT Conclusion: Our study determined that advanced age, HT, high APACHE II score, requirement for IMV, vasopressor therapy, PCT, lymphocyte count, IL-6, and D-dimer levels could serve as predictors of mortality. Identifying predictors of mortality in COVID-19 is valuable for early recognition of disease progression and management of potential complications. Keywords: COVID-19, mortality, hemostasis, clinical markers, laboratory markers

Comparison of circulating lipid profiles, D-dimer and fibrinogen levels between hypertensive patients with and without stroke

BackgroundStroke is one of the leading causes of global mortality and disability, particularly in hypertensive patients. This study aimed to compare lipid profile, fibrinogen, and D-dimer levels between hypertensive patient with and without stroke. MethodsThis was a facility-based cross-sectional study conducted from November 2022 to January 2023 among 115 hypertensive patients (70 patients without stroke and 45 with stroke) who had follow-up at Yikatit 12 Hospital Medical College, Ethiopia. All data analyses were done using SPSS version 25.0 and comparisons of variables between groups were made using the Chi-square test, independent sample t-test, and Mann-Whitney U test. Multiple logistic regression analysis was done to identify predictors of stroke among hypertensive patients. A p-value <0.05 was assumed to be statistically significant for all statistical tests. ResultsSignificantly elevated levels of TC, LDL-C, D-DI, and fibrinogen were observed in the stroke group than in the non-stroke group (p-value<0.05). The mean values of TC, D-DI, and fibrinogen were significantly higher in patients with ischemic stroke compared to those with hemorrhagic stroke. Duration of hypertension (AOR: 1.21; CI: 1.10, 2.09), TC (AOR:1.07; CI: 1.01, 1.22), D-DI (AOR: 1.15; CI: 1.05, 1.69) and fibrinogen (AOR:1.19; CI: 1.10, 2.89) were identified to be independent predictors of stroke in hypertensive patients. ConclusionThe circulating levels of TC, LDL-C, D-DI and fibrinogen in hypertensive patients with stroke were significantly higher than in those without stroke. But only TC, D-DI, and fibrinogen were found to be predictors of stroke in hypertensives. Considerably higher TC, D-DI, and fibrinogen levels were also seen in patients with ischemic stroke than in those with hemorrhagic stroke. This confirms the key roles of dyslipidemia (hypercholesterolemia) and aberrant hemostatic activation to stroke development, notably ischemic stroke.

Changes in coagulation indices and D-dimer levels in hypertriglyceridemic acute pancreatitis and their value in predicting disease severity.

Hypertriglyceridemic acute pancreatitis (HTG-AP) is one of the common acute and severe cases of digestive system. Incidence of HTG-AP is increasing year by year, and there is a trend of younger and severe cases. Early identification of severe patients and timely intervention are conducive to improve the prognosis. Dysfunction of coagulation and fibrinolysis systems plays an important role in the development of HTG-AP. Prothrombin time (PT) and activated partial thromboplastin time (APTT) are sensitive indicators of exogenous and endogenous coagulation system, respectively. Fibrinogen (FIB) is an acute reactive protein with coagulation function. D-dimer is a sensitive index to judge the abnormality of coagulation and fibrinolysis system. This study aims to investigate the changes of coagulation parameters and D-dimer level in patients with HTG-AP and their value in predicting the severity of the disease. The clinical data of 189 HTG-AP patients admitted to Jiangjin Hospital Affiliated to Chongqing University (Jiangjin District Central Hospital of Chongqing) from January 2019 to December 2020 were collected, including gender, age, medical history, complications, causes, and acute physiology and chronic health evaluation II (APACHE II) scores. According to the severity of the disease, the patients were divided into a mild HTG-AP group and a severe HTG-AP group. The changes of coagulation indexes (PT, APTT and FIB), D-dimer and C-reactive protein (CRP) levels were detected. Coagulation indexes, D-dimer level and disease severity (CRP level, APACHE II scores) were compared between the 2 groups. Spearman correlation analysis was used to analyze the correlation between the above indexes. Univariate and multivariate binary logistic regression analysis were used to identify the independent risk factors for severe HTG-AP. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the predictive value of PT, FIB, and D-dimer for the severity of HTG-AP. There were significant differences in gender between the mild HTG-AP group and the severe HTG-AP group (P<0.05). There was no significant difference in age, recurrence rate and incidence of complications between the 2 groups (all P>0.05). The basic conditions of the 2 groups were similar and comparable. PT, FIB and D-dimer levels in the severe HTG-AP group were significantly higher than those in the mild HTG-AP group (all P<0.001). There was no significant difference in APTT between the 2 groups (P>0.05). The CRP level and APACHE II scores in the severe HTG-AP group were significantly higher than those in the mild HTG-AP group (all P<0.05). Spearman correlation analysis showed that PT, FIB and D-dimer were positively correlated with CRP and APACHE II scores (all P<0.05), while APTT was not correlated with CRP and APACHE II scores (all P>0.05). Logistic regression analysis showed that prolonged PT and elevated D-dimer level were independent risk factors for severe HTG-AP (both P<0.05). ROC curve analysis showed that the AUC of PT for predicting severe HTG-AP was 0.764 (95% CI 0.690 to 0.837, P<0.001), when PT>14.40 s, the sensitivity, specificity, positive predictive value, and negative predictive value were 63.07%, 79.03%, 59.42%, and 80.00%, respectively. TheAUC of FIB for predicting severe HTG-AP was 0.669 (95% CI 0.588 to 0.751, P<0.001), when FIB>4.18 g/L, the sensitivity, specificity, positive predictive value, and negative predictive value were 61.53%, 70.17%, 49.38%, and 76.85%, respectively. The AUC of D-dimer for predicting severe HTG-AP was 0.753 (95% CI 0.680 to 0.826, P<0.001), when D-dimer>1.28 μg/mL, the sensitivity, specificity, positive predictive value, and negative predictive value were 73.84%, 66.12%, 53.33%, and 82.82%, respectively. The AUC of PT combined with D-dimer for predicting severe HTG-AP was 0.797. There are abnormalities in coagulation and fibrinolytic system in patients with HTG-AP in the early stage. PT, FIB and D-dimer levels are increased with the aggravation of the AP, and have a positively correlation with it. Elevated PT and D-dimer level are independent risk factors for severe HTG-AP. PT combined with D-dimer may be a sensitive indicator for prediction of the severity of HTG-AP in early phase.

Overestimation of fibrinogen concentration in cryoprecipitate by repeated freeze-thawing with long thawing period as used in the Clauss method.

Cryoprecipitate (CRY) is widely used for treating acquired hypofibrinogenemia. During our study to determine an optimal preparation method, we noticed that the measurement of fibrinogen concentration in CRY had a risk of overestimation. We analyzed this condition and mechanism. CRY was prepared from fresh frozen plasma (FFP) under four conditions: A, 30 h thawing time, 2 cycles; B, 24 h thawing time, 2 cycles; C, 30 h thawing time, 1 cycle; and D, 24 h thawing time, 1 cycle. Then, fibrinogen concentrations in CRY and cryosupernatant (CS) were measured by the Clauss method. Purification (CRY/CRY+CS) and recovery (CRY/FFP) rates in CRY prepared under 2-cycle conditions were higher than those under 1 cycle. However, recovery rates often exceeded 100%, particularly in the case of CRY prepared under A condition, and fibrinogen concentrations calculated by direct measurement were higher than those indirectly calculated from FFP and CS, suggesting an overestimation of fibrinogen values. The level of soluble fibrin monomer complex was considerably higher in CRY prepared under A than under D condition, indicating that CRY adopted a hypercoagulated state. We further found that repeated thawing/freezing increased fibrinogen values as measured by the Clauss method while mechanical vortexing did not. Our findings suggest that direct assessment of fibrinogen contents in CRY prepared by repeated freeze-thawing with a longer thawing period presents a higher risk of overestimation. For the purpose of quality control, we propose an alternative method to indirectly estimate fibrinogen concentrations in CRY from those of CS and FFP.

An Exciting Performance of Established and Novel Biomarkers in Diagnosing Periprosthetic Joint Infections: A Single-center Retrospective Cohort Study.

Significant progress has been made in recent years in the diagnosis of periprosthetic joint infections (PJI). However, the lack of a gold standard test for the diagnosis of PJI remains a challenge.The aim of this study was to evaluate the diagnostic values of the albumin/fibrinogen ratio (AFR), the C-reactive protein/albumin ratio (CAR), and the levels of fibrinogen (FIB) and albumin (ALB) in the diagnosis of PJI. The medical records of 158 patients who had undergone hip or knee revisions from January 2018 to May 2022 were retrospectively analyzed. Of these patients, 79 were diagnosed with PJI, while 79 were diagnosed with aseptic loosening (AL). PJI was defined using the Musculoskeletal Infection Society criteria. The plasma levels of C-reactive protein (CRP), ALB, and FIB; the erythrocyte sedimentation rate (ESR); and the AFR and CAR in the two groups were recorded and analyzed. The receiver operating characteristic curve was used to calculate the sensitivity and specificity of each indicator; the diagnostic value for each indicator was calculated as the area under the curve (AUC). The ESR, CRP, FIB, and CAR values in the PJI group were significantly higher than those in the AL group, and the ALB and AFR values were significantly lower than those in the AL group (p < 0.001). The AUC values of AFR and fibrinogen were 0.851 and 0.848, respectively, which were slightly higher than those of CRP (0.826) and ESR (0.846). The AUC of CAR was 0.831 which was slightly lower than that of CRP (0.846). ALB had an AUC of 0.727. The optimal threshold, sensitivity, and specificity, respectively, were 10.05, 84.81%, and 82.28% for AFR; 4.03 μg/mL, 77.22%, and 86.08% for FIB; 0.23, 72.15%, and 82.28% for CAR; and 37.30 g/L, 65.82%, and 73.42% for ALB. AFR, CAR, and FIB are good new auxiliary diagnostic indicators of PJI, while ALB is of fair value for the diagnosis of PJI.

Recurrent Bleeding in a Healthy Child-A Case of Lupus Anticoagulant-Hypoprothrombinemia Syndrome

Background: Although lupus anticoagulant (LA) is known to be associated with an increased risk of thrombosis and obstetric complications, typically seen in antiphospholipid syndrome, the presentation of LA-hypoprothrombinemia syndrome (LA-HPS) is different with bleeding manifestations more common than thrombosis. We report such a rare disorder in an otherwise healthy boy, who presented with subcutaneous bleeding and was treated successfully. Clinical Description: A 9-year-old boy presented with acute-onset swelling in the popliteal fossa region of the left leg and left great toe. History of fever, trauma, drug intake, joint pain, epistaxis, or melena was absent. Since 6 months of age, he had recurrent episodes of multiple, painful joint, and soft-tissue swellings and ecchymotic patches which subsided spontaneously. Examination showed a tense, shiny bluish patch over the left popliteal fossa and a swollen tender left great toe, without any lymphadenopathy, hepatosplenomegaly, or arthritis. Management and Outcome: Routine hemogram and liver function tests were normal. Furthermore, antinuclear antibody and rheumatoid factor were within normal limits. Coagulation studies showed prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), though bleeding and coagulation times were normal. Administration of Vitamin K and fresh frozen plasma (FFP) showed no improvement. Further investigations revealed normal values of von Willebrand Factor collagen binding, Factor VIII, Factor XIII, and fibrinogen, whereas prothrombin levels were reduced. The partial thromboplastin time-LA specific was high (170.10), suggesting a diagnosis of LA-HPS. The symptoms responded to prednisolone therapy, and there was complete recovery. Conclusion: A recurrent bleeding disorder with increased PT/APTT, not responding clinically to FFP transfusion, should raise suspicion of LA-HPS and appropriate tests need to be done. The prognosis of this disorder is good with corticosteroid therapy.

Padua Score and Coagulopathy Parameters on Survival of COVID-19 Patients at Prof Dr. R. D. Kandou General Hospital Manado

BACKGROUND: Coagulopathy in coronavirus disease 2019 (COVID-19) patients causes a prothrombotic state that increases the risk of thromboembolism. The Padua score and coagulopathy parameter including D-dimer values, fibrinogen, prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet counts are very important parameters to determine risk of thrombosis and mortality in hospitalized COVID-19 patients. AIM: This study aimed to assess the prognosis of COVID-19 patients with Padua score and coagulopathy parameters. METHODS: This retrospective cohort study was conducted in tertiary university hospital, Prof. Dr. R. D. Kandou Hospital Manado, Indonesia from October 2020 to July 2021. Patients admitted with final diagnosis of COVID-19 confirmed with positive reverse transcriptase-polymer chain reaction test were included in the study. The data were refined by excluding the patients under 18 years old and the patients with no blood test results, D-dimer values, fibrinogen values, PT values, aPTT values, and platelet counts. The association of Padua score and coagulopathy parameters with survival of COVID-19 patients was analyzed by multivariate cox regression and Kaplan–Meier analysis. RESULTS: The probability of survival on day 14 in patients with Padua score &lt;4, D-dimer &lt;0.5 mg/dl, PT ≤16 s, aPTT ≤39 s, and platelets &gt;150,000/μL was 100%, 100%, 84.6%, 81.5%, and 81.4%, respectively. COVID-19 survival was influenced by Padua score ≥4 (heart rate [HR] = 4.199; CI 95% 2.221–7.936), D-dimer ≥0.5 mg/L (HR = 4.772; CI 95% 2.244–10.147), PT &gt;16 s (HR = 2.124; CI 95% 1.608–2.805), aPTT &gt;39 s (HR = 1.449; CI 95% 1.080–1.943), and platelet count &lt;150000/μL (HR = 2.056; CI 95% 1.489–2.840). Padua score has the highest probability of mortality compared to the other coagulopathy parameters (p &lt; 0.001; HR = 3.655; CI 95% 1.927–6.932). CONCLUSION: There was an association of Padua score, D-dimer value, PT value, aPTT value, and platelet count on survival of COVID-19 patients. Padua score being the most influential variable on survivals.

Features of disorders and methods of correction of the hemostasis system in women with antenatal fetal death

The improvement of the providing medical services quality to pregnant women remains an urgent issue in modern obstetrics. Women with perinatal losses deserve special attention, especially in the second half of pregnancy. Changes in the hemostasis system are an integral part of the development of pregnancy. The tendency to hypercoagulation has significant pathogenetic significance and can be the cause of a number of complications – miscarriage in the I trimester of pregnancy and preeclampsia, premature birth, antenatal fetal death (AFD) – in the II and III trimesters of pregnancy. Also, pregnancy is a background process for the activation of a number of diseases, in particular hereditary thrombophilia.The objective: to evaluate the changes in the hemostasis system in women with antenatal fetal death and the effectiveness of the use of low molecular weight heparins for the correction of disorders in the hemostasis system in this category of patients during childbirth and in the postpartum period.Materials and methods. 72 women were examined, including 42 pregnant women with AFD (main group) and 30 pregnant women with a physiological course of pregnancy, childbirth and the postpartum period (control group). The state of the hemostasis system was studied using a standard coagulogram. D-dimer was determined by immunoturbometric analysis.To assess the state of the hemostasis system, the following biochemical tests were used: procoagulant link – fibrinogen content and indicators: prothrombin index, activated partial thrombin time (APTT), thrombin time (TP), ancistrone time (AT), soluble fibrinogen-monomer complex (SFMC), factor X (FX); to evaluate the antithrombin system, the content of antithrombin-III (AT-III), protein C were determined; to characterize the state of the fibrinolytic system – the amount of plasminogen, α2-antiplasmin, fibrinogen degradation products (FDC).Thrombophilia markers and antiphospholipid antibodies were also determined. The preference was given to vaginal childbirth. During childbirth, mechanical compression of the lower limbs was applied using special compression stockings (compression level 2). In 12 hours after delivery thromboprophylaxis with low molecular weight heparins was started, the drug of choice being enoxaparin sodium. After 48 hours of the postpartum period, a comparative analysis of coagulogram indicators was performed to further determine the timing of thromboprophylaxis.Results. Analysis of family thrombotic anamnesis revealed risk factors in 12 (28.6%) patients of the main group. In close relatives of the first line, the presence of peripheral vein thrombosis was found – 5 (41.7%) cases, myocardial infarction under the age of 45 – 3 (25.0%) cases, pulmonary embolism – 1 (8.3%) case, transient ischemic attack of the brain – 3 (25.0%).In the control group only 2 (6.6%) patients had a family history of venous thromboembolism in first-line relatives. The analysis of the coagulation system shows significantly higher fibrinogen values (the main group – 5.3±0.2 g/l, the control group – 4.3±0.1 g/l; p&lt;0.05), functional FX activity (the main group – 149.3±3.1%, control group – 107.3±2.7%; p&lt;0.05), SFMC (main group – 15.9±1.2 μg/ml, control group – 7.8±0.9 μg/ml; p&lt;0.05) and D-dimer (main group – 4.4±0.25 μg/ml, control group – 0.7±0.2 μg/ml; p&lt; 0.05) in pregnant women of the main group. An increase in these indicators is a predictor of thrombus formation, activation of blood coagulation by the internal pathway with a decrease in the antithrombin reserve due to FX.During the correlation analysis, a strong direct relationship (r=0.8633) was established between the indicators of SFMC and FX in the blood serum of pregnant women of the main group, the combination of which determines the tendency to clot formation. Determination of markers for the most common types of thrombophilia shows the dominance of hereditary forms (prothrombin, Leiden mutation, MTHFR) in 43% of pregnant women of the main group.The implementation of the proposed treatment approach contributed to a significant decrease in the average concentration of fibrinogen 48 hours after delivery in postpartum women of the main group (main group: before delivery – 5.3±0.2 g/l, after 48 hours after delivery – 3.9±0.3 g/l; control group: 48 hours after delivery – 3.2±0.2 g/l; p&lt;0.05) in combination with a synergistic decrease in the average indicators of SFMC (main group: before delivery – 15.9±1.2 μg/ml, 48 hours after delivery – 6.2±0.2 μg/ml; control group: 48 hours after delivery – 5.4±0.3 μg/ml; p&lt;0.05) and FX (main group: before delivery – 149.3±3.1%, after 48 hours after delivery – 103.1±3.6%; control group: after 48 hours after delivery – 117.1±4.1%; p&lt;0.05).Conclusions. Increased coagulation function was confirmed in pregnant women with antenatal fetal death (AFD). Thanks to the proposed method of correcting disorders in the hemostasis system, a decrease in the frequency of postpartum thromboembolism in women with AFD is achieved, as well as an improvement in the main indicators of the hemostasis system. This prevents the emergence of a chronic form of the syndrome of disseminated intravascular blood coagulation which is developed in the cases of AFD.

A diagnostic model for differentiating tuberculous spondylitis from pyogenic spondylitis: a retrospective case–control study

The purpose of this study was to describe and compare the clinical data, laboratory examination and imaging examination of tuberculous spondylitis (TS) and pyogenic spondylitis (PS), and to provide ideas for diagnosis and treatment intervention. The patients with TS or PS diagnosed by pathology who first occurred in our hospital from September 2018 to November 2021 were studied retrospectively. The clinical data, laboratory results and imaging findings of the two groups were analyzed and compared. The diagnostic model was constructed by binary logistic regression. In addition, an external validation group was used to verify the effectiveness of the diagnostic model. A total of 112 patients were included, including 65 cases of TS with an average age of 49 ± 15 years, 47 cases of PS with an average of 56 ± 10 years. The PS group had a significantly older age than the TS group (P = 0.005). In laboratory examination, there were significant differences in WBC, neutrophil (N), lymphocyte (L), ESR, CRP, fibrinogen (FIB), serum albumin (A) and sodium (Na). The difference was also statistically significant in the comparison of imaging examinations at epidural abscesses, paravertebral abscesses, spinal cord compression, involvement of cervical, lumbar and thoracic vertebrae. This study constructed a diagnostic model, which was Y (value of TS > 0.5, value of PS < 0.5) = 1.251 * X1 (thoracic vertebrae involved = 1, thoracic vertebrae uninvolved = 0) + 2.021 * X2 (paravertebral abscesses = 1, no paravertebral abscess = 0) + 2.432 * X3 (spinal cord compression = 1, no spinal cord compression = 0) + 0.18 * X4 (value of serum A)−4.209 * X5 (cervical vertebrae involved = 1, cervical vertebrae uninvolved = 0)−0.02 * X6 (value of ESR)−0.806 * X7 (value of FIB)−3.36. Furthermore, the diagnostic model was validated using an external validation group, indicating a certain value in diagnosing TS and PS. This study puts forward a diagnostic model for the diagnosis of TS and PS in spinal infection for the first time, which has potential guiding value in the diagnosis of them and provides a certain reference for clinical work.

Pharmacokinetic/Pharmacodynamic Target Attainment of Tigecycline in Patients with Hepatic Impairment in a Real-World Setting.

This study aimed to investigate the pharmacokinetic/pharmacodynamic (PK/PD) target attainment of various tigecycline dosing regimens in real-world patients with impaired liver function. The clinical data and serum concentrations of tigecycline were extracted from the patients' electronic medical records. Patients were classified into Child-Pugh A, Child-Pugh B, and Child-Pugh C groups, according to the severity of liver impairment. Furthermore, the minimum inhibition concentration (MIC) distribution and PK/PD targets of tigecycline from the literature were used to obtain a proportion of PK/PD targets attainment of various tigecycline dosing regimens at different infected sites. The pharmacokinetic parameters revealed significantly higher values in moderate and severe liver failure (groups Child-Pugh B and Child-Pugh C) than those in mild impairment (Child-Pugh A). Considering the target area under the time-concentration curve (AUC 0-24 )/MIC ≥4.5 for patients with pulmonary infection, most patients with high-dose (100 mg, every 12 hours) or standard-dose (50 mg, every 12 hours) for tigecycline achieved the target in groups Child-Pugh A, B, and C. Considering the target AUC 0-24 /MIC ≥6.96 for patients with intra-abdominal infection, when MIC ≤1 mg/L, more than 80% of the patients achieved the target. For an MIC of 2-4 mg/L, only patients with high-dose tigecycline in groups Child-Pugh B and C attained the treatment target. Patients experienced a reduction in fibrinogen values after treatment with tigecycline. In group Child-Pugh C, all 6 patients developed hypofibrinogenemia. Severe hepatic impairment may attain higher PK/PD targets, but carries a high risk of adverse reactions.

Preoperative fibrinogen is associated with the clinical survival of primary liver cancer patients and promotes hepatoma metastasis via the PTEN/AKT/mTOR pathway

AimHyperfibrinogenemia had been widely observed in various cancer patients, however, whether fibrinogen (FIB) influences the survival outcome of patients with primary liver cancer (PLC) remains unknown. This study was aimed to evaluate the predictive value of preoperative FIB in the survival outcome of PLC patients and explore the possible mechanism. MethodsRetrospective study was performed in PLC patients who underwent hepatectomy. Logistic regression analysis was used to explore the independent risk factors of the overall survival (OS) of PLC patients. The predictive value of FIB for the survival outcome was analyzed by Kaplan-Meier method, receiver operating characteristic curve and Cox proportional hazard model combined with B-splines. Hepatoma cell migration and invasion were detected by wound healing assay and Transwell assay, protein expression was measured by Western blot. mTOR inhibitor and PTEN overexpression plasmid were used to confirm the involvement of the PTEN/AKT/mTOR pathway during FIB treatment. ResultsPreoperative FIB was confirmed to be related with the OS in PLC patients, higher FIB (>2.5 g/L) indicated higher hazard ratio. Meanwhile, FIB could promote hepatoma cell migration and invasion through the activation of AKT/mTOR pathway and epithelial-mesenchymal transformation (EMT). Moreover, the promotion of FIB on cell migration and invasion could be inhibited by mTOR inhibitor and PTEN overexpression. ConclusionsPreoperative FIB could be related with the prognosis of PLC patients, the risk of death in PLC patients gradually increases along with the up-regulation of FIB. FIB may promote hepatoma metastasis by inducing EMT via the activation of PTEN/AKT/mTOR pathway.

Hematological Changes in Patients with Severe COVID-19: Systematic Review and Meta-Analysis

Aims: To produce a systematic review with meta-analysis on the hematological manifestations of COVID-19, comparing the changes among the clinical severity groups.&#x0D; Study Design: We conducted a systematic review with meta-analyses.&#x0D; Methodology: A systematic review was carried out based on the PRISMA 2020 protocol in Medline/Pubmed, Embase, LILACS and SciElo databases. A standardized mean difference was calculated to assess the differences between the groups, with a confidence interval of 95%. Heterogeneity was calculated using the Chi-square test and the I2 test. Significant heterogeneity was defined as p&lt;0.10 or I2&gt;50%.&#x0D; Results: The systematic review search identified a total of 2682 articles, and at the end of the screening, 55 were selected for review and 16 for meta-analysis. The selected articles enrolled 13,289 participants, 10,312 with a mild to moderate clinical condition and 3977 with a severe to critical clinical condition. When comparing the severe disease group with the mild disease group, it was found that the mean values of leukocytes, neutrophils, C-reactive protein (CRP), ferritin, fibrinogen, and prothrombin time (PT) were significantly higher, and the lymphocyte count was significantly lower in the severe group.&#x0D; Conclusions: Individuals with severe COVID-19 had reduced lymphocyte count and elevated leukocytes, neutrophils, CRP, ferritin, fibrinogen, and PT.

Pretreatment fibrinogen levels are associated with survival outcome in patients with cancer using immunotherapy as a second‑line treatment.

The present study aimed to investigate the predictive value of pretreatment fibrinogen (FIB) levels in patients with cancer who received immunotherapy as a second-line treatment. A total of 61 patients with stage III-IV cancer were included. The cut-off value of FIB for predicting overall survival (OS) was determined by receiver operating characteristic curve analysis. The prognostic value of pretreatment FIB on progression-free survival (PFS) and OS was determined by univariate and multivariate analyses. Based on a cut-off point of 3.47 g/l, patients were divided into low pretreatment FIB (<3.47 g/l) and high pretreatment FIB (≥3.47 g/l) groups. A high pretreatment FIB level was more common in older patients (P=0.03). Kaplan-Meier analysis showed that patients with high pretreatment FIB levels had shorter PFS and OS times than patients with low FIB levels (P<0.05). In multivariate analysis, pretreatment FIB was an independent prognostic factor for OS [hazard ratio (HR), 6.06; 95% CI, 2.01-18.28; P<0.01] and OS from the initiation of second-line treatment (HR, 3.69; 95% CI, 1.28-10.63; P=0.02). Overall, FIB is associated with survival outcome in patients with cancer who are administered immunotherapy as a second-line treatment.

DYNAMIC SURFACE PROPERTIES OF FIBRIN

Fibrin is formed via polymerization of one of the main blood proteins, fibrinogen, under the action of an enzyme, thrombin. Dynamic surface elasticity and dynamic surface tension of mixed solutions of fibrinogen and thrombin are measured as functions of surface age and enzyme concentration (50–800 U/L). The nonmonotonic pattern of the dependences for the dynamic surface elasticity indicates the multistage character of fibrin film formation and makes it possible to monitor the transition from unfolded protein to individual filamentous aggregates; a network of branched fibrils; and, finally, a continuous film. The dynamic surface elasticity of fibrin films is twofold higher than the corresponding values for fibrinogen (115 and 55 mN/m, respectively). The use of different types of microscopy makes it possible to assess the morphology of the obtained films.

The clinical and prognostic role of changes in parameters of the hemostasis system and C-reactive protein in the development of thrombotic complications in oxygen-dependent patients with coronavirus disease (COVID-19)

Aim. The purpose of our work was to find out the clinical and prognostic role of changes in hemostasis parameters and C-reactive protein (CRP) in the development of thrombotic complications in oxygen-dependent patients with coronavirus disease (COVID-19). Materials and methods. 211 oxygen-dependent patients with COVID-19 were examined. To assess the prognostic role of changes in hemostasis parameters and CRP, patients were divided into groups: I group – 94 patients who recovered, II group – 117 patients who died. Subgroups: II-A subgroup – 35 patients with thrombotic complications and II-B subgroup – 82 patients without these complications. All patients were examined and received treatment according to the normative documents in force at the relevant time. Results. The frequency of thrombotic complications in oxygen-dependent patients with COVID-19 was 16.6 %, among which the most common were pulmonary embolism (6.6 %), myocardial infarction (6.2 %), and ischemic stroke (3.2 %). Lifetime diagnosis of thrombotic complications took place on the 18th [16.0; 24.0] day of illness in 45.9 % of cases. Deathtime diagnosis of thrombotic complications took place on the 24th [20.0; 28.0] day of illness in 54.1 % of cases. Lifetime pulmonary artery thromboembolism was diagnosed less frequently than ischemic stroke (p = 0.002) and myocardial infarction (p = 0.02). With the development of oxygen dependence and admission to the intensive care unit on the 9th [8.0; 11.0] day of illness, changes in the hemostasis system were characterized as prothrombotic with an increase above the reference values of fibrinogen and D-dimer in patients of all groups. CRP in patients with fatal outcomes of the disease, regardless of the development of thrombotic complications, was higher (p &lt; 0.05) than in patients who subsequently recovered, and was accordingly in patients of the I group – 67.65 [41.20; 139.95] mg/l, in the II-A group – 122.2 [61.2; 178.0] mg/l, and in patients of the II-B group – 109.8 [56.3; 180.0] mg/l. In the dynamics of complex treatment after 5–7 days, the level of fibrinogen, D-dimer and CRP had a diagnostic value in predicting the further development of thrombotic complications. With an increase in the level of fibrinogen &gt;4.6 g/l (AUC = 0.600, p = 0.042), D-dimer &gt;2.1 μg/ml (AUC = 0.704, p = 0.001) and CRP &gt;89.3 mg/l (AUC = 0.720, p &lt; 0.001) the probability of developing thrombotic complications was significant. Conclusions. In dynamics of complex treatment of oxygen-dependent patients after 5–7 days, the levels of fibrinogen, D-dimer and C-reactive protein had consistent diagnostic value in predicting further development of thrombotic complications. Increased fibrinogen &gt;4.6 g/l, D-dimer &gt;2.1 μg/ml, and CRP &gt;89.3 mg/l were important for predicting the risk of developing thrombotic complications.

Prognostic analysis of the plasma fibrinogen combined with neutrophil-to-lymphocyte ratio in patients with non-small cell lung cancer after radical resection.

To investigate the correlation between the fibrinogen combined with neutrophil-to-lymphocyte ratio (F-NLR) and the clinicopathologic features of non-small cell lung cancer (NSCLC) patients who underwent radical resection. This study reviewed the medical records of 289 patients with NSCLC who underwent radical resection. The patients were stratified into three groups based on F-NLR as follows: patients with low NLR and fibrinogen were group A, patients with high NLR or fibrinogen were group B, and patients with high NLR and fibrinogen were group C. Receiver operating characteristic curve and Youden index were used to determine the cutoff value of the NLR and fibrinogen. Survival curves were described by Kaplan-Meier method and compared by log-rank test. The univariate and multivariate analyses were performed with the Cox proportional hazard model to identify the prognostic factors. A value of 3.19 was taken as the optimal cutoff value of NLR in this study. A value of 309 was used as the optimal cutoff value of fibrinogen. Cox multivariate analysis showed that tumor, nodes, metastasis (TNM) stage and F-NLR were independent prognostic factors affecting the survival rate of patients. The first-, third-, and fifth-year survival rates in group A were 99.2%, 96.6%, and 95.0%, respectively. The first-, third-, and fifth-year survival rates in group B were 98.4%, 76.6%, and 63.2%, respectively. The first-, third-, and fifth-year survival rates in group C were 91.3%, 41.1%, and 22.8%, respectively. F-NLR was significantly correlated with overall survival in patients with NSCLC (p < 0.001). The F-NLR level is markedly related to the prognosis of patients with NSCLC undergoing radical surgery. Therefore, closer attention should be given to patients with NSCLC with a high F-NLR before surgery to provide postoperative adjuvant therapy.

Experience in the use of neutralizing monoclonal antibodies in kidney transplant recipients with COVID-19

Therapy with neutralizing monoclonal antibodies (mAbs) is particularly relevant during COVID-19 outbreaks in patients at high risk of severe disease, including kidney transplant recipients (KTRs).Objective: to evaluate the efficacy and safety of neutralizing mAbs in KTRs with mild to moderate COVID-19.Materials and methods. The retrospective study included 99 KTRs who received inpatient treatment for COVID-19 between September 1 and December 31, 2021. Patients were 52.0 ± 11.5 years old (M, 47.5%). Bamlanivimab/etesevimab combination drug at a dose of 700/1400 mg was used as mAbs. To evaluate the efficacy of mAbs therapy, two groups of patients were identified. Group 1 consisted of 33 KTRs who received mAbs as one of the therapy components, while group 2 consisted of 66 patients who received no mAbs. Discharge from the hospital or death was considered as the endpoint of follow-up.Results. In group 1, after the use of mAb, progression of pulmonary process was observed less frequently than in the control group with CT1-2 transformation to CT3-4 (9.1% vs. 30.3%, respectively, p &lt; 0.01). Group 1 KTRs differed significantly from group 2 - lower need for ICU and ventilator care (6.1% vs. 27.3% and 3% vs. 19.8%, respectively). The groups were comparable by sex, age, body mass index, Charlson Comorbidity Index (CCI) and time after kidney transplant (KTx) at the onset of the disease and by rnseline blood biochemistry parameter values at the time of hospitalization. Only C-reactive protein (CRP) and fibrinogen values were higher in the non-mAbs patients who were hospitalized later in the course of the disease (7.7 ± 3.2 days versus 4.6 ± 1.6 days in group 1, p &lt; 0 .001). The frequency of prescription of other therapies did not differ between the compared groups. Use of mAbs significantly reduced mortality from 19.7% in KTRs in group 2 to 3% in group 1 without adverse effect on graft function. Conclusion. The use of mAbs therapy in the early stages of COVID-19 in KTRs is safe, it prevents severe COVID-19, and reduces the incidence of adverse outcomes.

Role of plasma fibrinogen and D-dimer as prognostic biomarkers in patients with non-muscle invasive bladder cancer

BackgroundWe aimed to evaluate the role of plasma fibrinogen and D-dimer as prognostic biomarkers in patients with non-muscle invasive bladder cancer (NMIBC).MethodsThe prospective study included 35 patients (30 males) with newly diagnosed NMIBC with no history of thromboembolic event or anti-coagulant intake or active infection and underwent complete trans-urethral resection between September 2020 and December 2021. Patients with deranged hepato-renal functions, refractory hypertension or diagnosed with COVID-19 infection with in one-month before surgery or routine follow-up were excluded. Follow-up was done as per NCCN guidelines. Fibrinogen and D-dimer levels were measured with in seven days of surgery or follow-up and analyzed for recurrence-free survival (RFS) and progression-free survival (PFS). Cox regression analyses were adopted to assess the influence of these two parameters on RFS and PFS.ResultsThe mean age was 53.9 years with a median follow-up of 9-months. Nine had recurrence of which six had progression. The cut-off values of fibrinogen and D-dimer were 402.5 mg/dl and 0.55 µg/ml, respectively. Kaplan–Meier analysis demonstrated that high fibrinogen and D-dimer levels were significantly related to poor RFS and PFS (p < 0.001). On multivariate analysis only fibrinogen and D-dimer retained their significance for RFS (p = 0.026 and 0.014, respectively) and PFS (p = 0.027 and 0.042, respectively). High levels of fibrinogen and D-dimer were also present in patients who had recurrence or progression at follow-up visits compared to rest of the patients.ConclusionsHigh levels of fibrinogen and D-dimer may indicate worse prognosis in patients with NMIBC, suggesting that these two can be used as prognostic biomarkers.

Evaluation of prognostic inflammatory and systemic inflammatory response indices in auxiliary diagnosis of bacteria-negative pulmonary tuberculosis: A diagnostic accuracy study.

Although molecular biology has made great progress in recent years, the detection rate of mycobacterium tuberculosis (MTB) is still not ideal. This study aimed to evaluate the role of prognostic inflammatory index (PII) and systemic inflammatory response index (SIRI) in the auxiliary diagnosis of bacteria-negative pulmonary tuberculosis (TB). Sixty patients diagnosed with bacteria-negative pulmonary TB at the Affiliated Hospital of Qinghai University between October 2019 and September 2022 were randomly selected as the case group, and seventy patients with nontuberculous pulmonary infection in the same department of the same hospital during the same period were randomly selected as the control group. Baseline data and values of erythrocyte sedimentation rate (ESR), lymphocyte count (LY), neutrophil count (NE), monocyte count (MO), albumin (ALB), prealbumin (PA), C-reactive protein (CRP), fibrinogen (FIB), neutrophil-to-lymphocyte ratio (NLR), PII, and SIRI were compared between the 2 groups. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of PII and SIRI in the diagnosis of bacteria-negative pulmonary TB. No significant differences were found between the 2 groups in terms of sex and age (P > .05); however significant differences were observed in relation to body mass index (BMI), ESR, LY, NE, MO, ALB, PA, CRP, FIB, NLR, PII, and SIRI (P < .05). ROC curve analysis showed that area under curve (AUC) value {0.84 [95% CI (0.77, 0.90)]} and specificity {82.86% [95% CI (72.0, 90.8)]} of PII were the highest, while the sensitivity {86.67 [95% CI (75.4, 94.1)]} of NLR + PII was the highest. Pairwise comparison of the 7 indicators of ROC curve was performed, and only the diagnostic efficiency of NLR and NLR + PII was statistically significant (Z = 2.36, P = .02 < .05). NLR, PII, SIRI, pairwise combinations, and NLR + PII + SIRI showed auxiliary diagnostic values for bacteria-negative pulmonary TB, among which PII had the highest diagnostic value and specificity, while NLR + PII had the highest sensitivity.