Higher Fibrinogen Levels Research Articles

The interest of inflammatory biomarkers in the diagnostic approach in an internal medicine department: A cross-sectional study

Background The role of inflammatory biomarkers in etiological orientation is increasingly under study, and their potential significance is recognized. Given the diversity of diseases managed in internal medicine and the delayed results of microbiological tests, clinicians often face challenges in the diagnostic approach. This study aimed to describe the biomarkers’ role in distinguishing between infectious and noninfectious diseases and define their thresholds for infections. Methods Procalcitonin (PCT), neutrophil-to-lymphocyte-ratio (NLR), C-reactive-protein (CRP), fibrinogen, ferritinemia and lactate were measured on admission in all patients admitted to the Internal Medicine Department of Sahloul Hospital, over a 7-month period. The optimal cut-off values for the sensitivities and specificities to the infectious diseases were determined using receiver operating characteristic (ROC) curve analysis and Youden’s index. The diagnostic accuracy of biomarkers for predicting infectious etiologies was calculated by area under the curve (AUC). Results Overall, 164 patients were included of whom 32.3% had infectious diseases. The high mean levels of leukocytes (12,047 cells/mm3), NLR (9.7), CRP (152.5 mg/L), PCT (3.28 ng/ml) and fibrinogen (5.37g/L) were significantly linked to infectious etiologies. We identified cut-offs of NLR (6.1), CRP (123mg/L), PCT (0.24ng/mL) and fibrinogen (4.9g/L) to discriminate infectious etiologies in our population. For diagnosing infectious diseases, the CRP showed higher AUC (Sp:89.7%, Se:64.3%, AUC=0.9, 95% CI: 0.83, 0.96; p<10-3) than PCT (Sp:86.1%, Se:62.3%, AUC=0,87, 95% CI: 0.80, 0.93; p<10-3), NLR (Sp:87.1%, Se:61%, AUC=0.81, 95% CI: 0.731, 0.902; p<10-3) and fibrinogen (Sp:84.7%, Se:68.3%, AUC=0.77, 95% CI: 0.65, 0.98; p<10-3). The combination of CRP and NLR levels improved the diagnostic accuracy (AUC=0.93, 95% CI: 0.84, 0.96; p<10-3) for distinguishing between infectious and non-infectious diseases. Conclusions Our study showed the usefulness of inflammatory biomarkers, particularly the NLR and its combination with CRP, which are low cost and easy to assess, in promoting the diagnostic accuracy to distinguish infections among other diagnoses.

Prognostic Factors in Children with Acute Kidney Injury Requiring Continuous Renal Replacement Therapy

Introduction: This study aimed to evaluate prognostic factors and outcomes in a single-center PICU cohort that received continuous renal replacement therapy (CRRT). Methods: This retrospective study analyzed clinical characteristics, laboratory data, and outcomes. Ninety-day mortality and advanced chronic kidney disease (CKD) (eGFR <60 mL/min/1.73 m2) were defined as primary and secondary outcomes, respectively. Results: Seventy-five patients were enrolled, all of whom received CRRT for indications including acute kidney injury with complicated refractory metabolic acidosis, electrolyte derangement, and existed or impending fluid overload. The 90-day mortality and advanced CKD were 53% and 29%, respectively. Multivariate Cox regression analysis demonstrated that only underlying bone marrow transplantation (BMT) (HR 4.58; 95% CI: 2.04–10.27) and a high pSOFA score (HR 1.12; 95% CI: 1.01–1.23) were independent risk factors for 90-day mortality. Among survivors, ten developed advanced CKD on the 90th day, and this group had a higher serum fibrinogen level (OR 1.01; 95% CI: 1.01–1.03) at the start of CRRT. Conclusion: In critically ill children with AKI requiring CRRT, post-BMT and high pSOFA scores are independent risk factors for 90-day mortality. Additionally, a high serum fibrinogen level at the initiation of CRRT is associated with the development of advanced CKD.

Correlation between bradykinin concentration and blood pressure during Rheocarna therapy: A single-center case series.

A novel LDL (low-density lipoprotein) apheresis therapeutic option, Rheocarna, has garnered attention as an alternative therapy for chronic limb-threating ischemia (CLTI). Bradykinin-mediated vasodilation is involved in the effects of LDL apheresis and a decrease in blood pressure (BP), but the changes in bradykinin concentration during Rheocarna therapy are unknown. The study involved patients with CLTI treated with Rheocarna at our hospital, from April 2022 to August 2023. After Rheocarna therapy, skin ulcers improved in 80% of the patients. Circuit coagulation was observed in two patients with high fibrinogen levels. A decrease in BP was observed at approximately the same time when the bradykinin concentration peaked. The peak bradykinin concentration in a patient undergoing hemodialysis at the same time was considerably lower than that in the other patients. This is the first report on the changes in bradykinin concentration under Rheocarna therapy.

High Fibrinogen Levels with Diabetes Mellitus are Associated with All-Cause and Cardiovascular Mortality in Patients with End-Stage Renal Disease and Acute Coronary Syndrome.

As a biomarker of inflammation and a core component in the coagulation pathway, fibrinogen contributes to atherosclerosis and subsequent adverse cardiovascular events and is modified by the occurrence of diabetes mellitus. However, the association between fibrinogen, diabetes status, and mortality in patients with end-stage renal disease (ESRD) and acute coronary syndrome (ACS) remains scarce. A multi-center cohort study enrolled 1079 patients with ESRD and ACS between January 2015 and June 2021. Patients were classified into three groups based on fibrinogen tertiles and were further categorized by diabetes status. The primary outcome was all-cause mortality, while the secondary outcome was cardiovascular mortality. During a median 21.5 months of follow-up, 386 cases of all-cause mortality were recorded, including 262 cases of cardiovascular mortality. Multivariable Cox regression model revealed that patients with the third tertile of fibrinogen and those with diabetes experienced a significantly increased risk of all-cause mortality (fibrinogen: hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.32-2.19; diabetes: HR, 1.36; 95% CI, 1.10-1.68). When patients were stratified by both fibrinogen levels and diabetes status, patients in the third fibrinogen tertile with diabetes had the highest risk of all-cause mortality (HR 2.43, 95% CI 1.69-3.48) compared to those in the first fibrinogen tertile without diabetes. Similar associations were observed for cardiovascular mortality. Notably, incorporating the combined fibrinogen and diabetes status into the Global Registry of Acute Coronary Events (GRACE) score or baseline risk model led to significant improvements in the C-statistics for predicting mortality, surpassing the advancements achieved with any single biomarker. In patients with ESRD and ACS, elevated fibrinogen and diabetes were associated with an increased risk of all-cause and cardiovascular mortality. Categorizing patients based on fibrinogen levels and diabetes status could provide valuable information for risk stratification of these patients.

The differences of fibrinogen levels in various types of hemorrhagic transformations.

Hemorrhagic transformation (HT) is a serious complication that can occur spontaneously after an acute ischemic stroke (AIS) or after a thrombolytic/mechanical thrombectomy. Our study aims to explore the potential correlations between fibrinogen levels and the occurrence of spontaneous HT (sHT) and HT after mechanical thrombectomy (tHT). A total of 423 consecutive AIS patients diagnosed HT who did not undergone thrombolysis and 423 age- and sex-matched patients without HT (non-HT) were enrolled. Fibrinogen levels were measured within 24 h of admission after stroke. The cohorts were trisected according to fibrinogen levels. The HT were further categorized into hemorrhagic infarction (HI) or parenchymal hematoma (PH) based on their imaging characteristics. In sHT cohort, fibrinogen levels were higher in HT patients than non-HT patients (p < 0.001 versus p = 0.002). High fibrinogen levels were associated with the severity of HT. HT patients without atrial fibrillation (AF) had higher levels of fibrinogen compared to non-HT (median 3.805 vs. 3.160, p < 0.001). This relationship did not differ among AF patients. In tHT cohort, fibrinogen levels were lower in HT patients than non-HT patients (p = 0.002). Lower fibrinogen levels were associated with the severity of HT (p = 0.004). The highest trisection of fibrinogen both in two cohorts were associated with HT [sHT cohort: OR = 2.515 (1.339-4.725), p = 0.016; that cohort: OR = 0.238 (0.108-0.523), p = 0.003]. Our study suggests that lower fibrinogen level in sHT without AF and higher fibrinogen level in tHT are associated with more severe HT.

Incidence of and risk factors for venous thrombosis in hospitalized patients with hematologic malignancies: A single-center, prospective cohort study.

Incidence of venous thromboembolism (VTE) is higher than the expected in patients with hematologic malignancies and duration of hospitalization period increases the risk of thrombosis. The objective of this study was to investigate the incidence of and risk factors for venous thrombosis in hospitalized patients with hematologic malignancies. We designed a prospective cohort study and enrolled patients with hematologic malignancies, who had been hospitalized between 2020 and 2021. Thromboprophylaxis was given to all patients, other than those under a high risk of hemorrhage. 94 patients were enrolled. The incidence of superficial vein thrombosis was 11.7% and the incidence of deep vein thrombosis (including pulmonary embolism and catheter thrombosis) was 7.4%. Patients, who developed thrombosis, had statistically significantly longer hospital stays (21 vs. 11.5 days, p=0.023) and a higher number of hospitalizations (1 vs. 3, p=0.015) compared to those, who did not develop thrombosis. Patients, who had 3 or more risk factors for thrombosis, were found to be under the highest risk. (p=0.017, OR=4.32; 95% CI: 1.3-14.35). Furthermore, patients with recurrent hospitalizations (p=0.024, OR=1.49; 95% CI: 1.05-2.11) and higher fibrinogen levels (p=0.028, OR=1; 95% CI: 1-1.006) were under an increased risk of thrombosis. Venous thrombosis is frequently seen in hospitalized patients with hematologic malignancies. A universally accepted risk scoring system is required for detection of patients, under a high risk for thrombosis.

Association between fibrinogen-to-albumin ratio and functional prognosis of 3 months in patients with acute ischemic stroke after intravenous thrombolysis.

The presence of high fibrinogen and low albumin levels in serum is associated with a negative prognosis in acute ischemic stroke (AIS). Fibrinogen-to-albumin ratio (FAR), a new inflammatory biomarker, may provide better prognostic insights in patients with AIS than separate evaluation of fibrinogen or albumin. The objective of this investigation is to examine the correlation between FAR and 3-month functional prognosis after intravenous thrombolysis (IVT) in AIS patients. The retrospective study recruited AIS patients who received IVT from June 2014 to December 2021. The 3-month functional prognosis was assessed using the Modified Rankin Scale (mRS). A mRS score of ≤2 indicated a good outcome, whereas a mRS score of >2 suggested a poor outcome. A total of 591 AIS patients who underwent IVT were included and 147 patients (24.9 %) had a poor outcome. Among the 102 pairs of patients after propensity score matching, there was a significant association between FAR and 3-month prognosis (adjusted OR, 1.19; 95% CI, 1.03-1.38; p=.020). The optimal FAR cutoff value was found to be 7.57, and even after stratifying patients based on this value, we still observed a significant correlation between high FAR level and poor outcome (adjusted OR, 2.08; 95% CI, 1.28-3.40; p=.003). FAR may serve as a prospective biomarker of predicting 3-month prognosis in AIS patients after IVT.

NEUROLOGIC COMPLICATION IN LUNG ADENOCARCINOMA EFGR MUTATION WITH A CONSOLIDATION-TO-TUMOR-RATIO (CTR) &gt;75%

Lung adenocarcinoma (LAC) accounts for a large proportion of lung cancer subtypes and causes various neurologic complications. This calls for extensive use of CT scans for detecting lung cancer which contains ground glass opacity (GGO). A Consolidation-to-tumor-ratio (CTR) &gt;75% has a worse prognosis in LAC. A male 50-years-old came with paraplegia, complaining suddenly that his legs could not be moved. The patient performed a spine MRI with the result indicating a spinal metastatic process. Furthermore, the Chest X-ray only showed consolidation in the right paracardial area but the chest CT confirmed as lung mass followed by histopathology examination result of LAC with EFGR mutation. After three months, the patient also had multiple cerebral infarcts. We reported one case of LAC EFGR mutation with a CTR of 83%. higher CTR has more invasive adenocarcinomas and also correlated with immunosuppressive conditions compared with a low CTR. The patient was diagnosed lately after a complication of spinal compression. The other neurological complication is multiple cerebral infarcts. The pathogenesis of cancer-associated stroke has not been fully clarified. The pathophysiological mechanisms of these cerebrovascular complications are multifactorial. Other biological markers may also be of interest, including high levels of C-reactive protein (CRP), high levels of fibrinogen, decreased hemoglobin, and hypoalbuminemia. Retrospective studies on acute stroke detected significantly higher levels of fibrinogen and CRP in patients with cryptogenic stroke and occult malignancy. LAC with a CTR &gt;75% is more invasive due to neurologic complications such as spinal metastases and stroke infarction. Keywords: Lung adenocarcinoma, CTR, Stroke, Metastase

Coagulation parameters and prognosis analysis in COVID-19 patients

Aims: There are many factors that affect morbidity and mortality in COVID-19. Coagulopathy is thought to be one of the important mechanisms in COVID-19 mortality. In this study, it was aimed to investigate coagulation factors and their relationship with prognosis in COVID-19. Methods: Patients diagnosed with COVID-19 were retrospectively reviewed in our hospital. The patients' demographic data, laboratory data on admission to the hospital, intensive care admissions, and surveillance were recorded. Patients were divided into two groups; Group 1 is non-critical patients followed up in the clinic, Group 2 is critical patients who need treatment in the intensive care unit. Results: 403 patients followed up for COVID-19 were analyzed. It was determined that the average age of the patients in Group 1 was statistically significantly lower than those in Group 2. (1: 45.28 ± 15.31 vs. 2: 60.15 ± 15.72, respectively, p &lt;0.001). It was observed that the rates of HT, DM, CHD, and COPD in Group 2 were statistically significantly higher than Group 1 (p &lt;0.05). While APTT values were similar in both groups, D-Dimer values were significantly higher in Group 2. As QSOFA, SIC, DIC, and coagulation marker scores increased, the percentage of patients with death increased significantly (p &lt;0.05). Age, HT, COPD, PT, and high fibrinogen levels were found to increase the mortality risk rates statistically (p &lt;0.05). Conclusion: It was determined that the most important factors determining mortality in COVID-19 are COPD and HT. APTT and D-dimer values were not found to be a prognostic factor in terms of mortality. However, PT, fibrinogen, and age are poor prognostic factors and can be used to predict mortality requiring intensive care.

Clinical Significance of Stiffness during Endoscopic Surgery for Intracerebral Hemorrhage: A Retrospective Study.

Studies regarding hematoma stiffness and removal difficulty are scarce. This study explored the association between hematoma stiffness and surgical results of endoscopic hematoma removal for intracerebral hemorrhage. It also aimed to clarify factors associated with hematoma stiffness. We classified intracerebral hematoma as either soft or firm stiffness by retrospectively evaluating operative videos by two neurosurgeons. The interobserver reliability of the classification was assessed by calculating the κ values. We investigated the relationship between hematoma stiffness and surgical results. Favorable hematoma removal (FHR) was defined as a residual hematoma volume of ≤15 mL or removal rate of ≥70%. Furthermore, we compared the background characteristics, imaging findings, and laboratory data between the two groups. Forty patients were included in this study. The mean baseline hematoma volume was 69.9 mL (range, 41.3-97.6 mL). FHR was accomplished in 35 cases (87.5%). Thirty-four patients (85%) were in the soft hematoma group (group S). Six patients (15%) were in the firm hematoma group (group F). Classification of hematoma stiffness demonstrated an excellent degree of interobserver agreement (κ score = 0.91). Patients in group S had a high FHR rate (p = 0.018) and short endoscopic procedure times (p = 0.00034). The island sign was present in group S (p = 0.030). Patients in group F had significantly high fibrinogen levels (p = 0.049) and low serum total calcium (p = 0.032), hemoglobin (p = 0.041), and hematocrit (p = 0.011) levels. Hematoma stiffness during endoscopic surgery for intracerebral hemorrhage correlates with surgical results, including the endoscopic procedure time and accomplishing rate of FHR.

Residual serum fibrinogen as a universal biomarker for all serotypes of Myasthenia gravis

Myasthenia Gravis (MG) is an autoimmune disease associated with severe neuromuscular weakness. Diagnostic confirmation of MG is typically delayed and secured in about 85% and 50% of patients with generalized and ocular MG, respectively with serum antibodies. We have identified a sensitive and specific diagnostic biomarker for various MG serotypes with quantitative proteomics. Serum proteomes of 18 individuals (MG patients, healthy controls (HC), Rheumatoid Arthritis (RA) were quantified in a pilot study and occurrence of high residual fibrinogen was validated by immunoblotting and further investigated by targeted mass spectrometry on the sera of 79 individuals (31 MG of various serotypes, 30 HC, 18 RA). Initial proteomic analysis identified high residual fibrinogen in MG patient sera which was then validated by antibody-based testing. Subsequently, a blinded study of independent samples showed 100% differentiation of MG patients from controls. A final serological quantification of 14 surrogate peptides derived from α-, β-, and γ-subunits of fibrinogen in 79 individuals revealed fibrinogen to be highly specific and 100% sensitive for MG (p < 0.00001), with a remarkable average higher abundance of > 1000-fold over control groups. Our unanticipated discovery of high levels of residual serum fibrinogen in all MG patients can secure rapid bedside diagnosis of MG.

The correlation between Plasma Fibrinogen Levels and Glycemic Status in type 2 Diabetes Mellitus

Abstract Introduction/Objective Background: Fibrinogen is considered a well-known contributor to the progression of atherosclerotic lesions and a predictor of cardiovascular events. Patients with diabetes mellitus (DM) have higher levels of fibrinogen, which may raise their thromboembolic risk for cardiovascular disease (CVD). Plasma fibrinogen is an indicator of inflammation, and endothelial dysfunction has been described as an independent risk factor for cardiovascular morbidity in type-2 diabetes mellitus (T2DM) patients. Poor glycemic control has been reported to be associated with hyperfibrinogenemia. Aim This study aims to estimate the levels of fibrinogen in patients with type-2 diabetes mellitus and determine its correlation with glycated hemoglobin levels. Methods/Case Report Subjects and methods: It is a cross-sectional analytic study conducted in the Benghazi Diabetic Clinic, Libya. Patients who were diagnosed with type 2 diabetes mellitus, either newly detected or already on diet or treatments, were included in the study during the period between May 2022 to December 2022. A total of 231 adult subjects were selected, with ages ranging from 20-80 years. Random blood sugar levels were assessed. Plasma fibrinogen levels (mg/dl) were estimated by the "Clauss method" and glycosylated hemoglobin (%) by the "immunoturbidimetric method." Patients were categorized into three groups depending upon the HbA1c values, i.e., into &amp;lt;5.7% (good control), 5.7-6.5% (fair control), and &amp;gt;6.5% (poor control). Results (if a Case Study enter NA) Result: Out of 231 subjects, (40.6%) were males and (59.4%) were females, with a mean±SD of age was (47.03±15.54) years. There was a significant positive correlation between fibrinogen and HbA1c in the fair control group (r=0.424, p=0.003) and the poor control group (r=0.369, P=0.000). Moreover, the difference between fibrinogen and age in the good control group was significant (p&amp;gt;0.05), whereas no significance was recognized in other groups. Conclusions Plasma fibrinogen levels are elevated in type 2 DM, and this elevation was associated with poor glycemic control; increased HbA1c levels. The other parameters which correlated with plasma fibrinogen levels were age. Lowering plasma fibrinogen levels could be an integral approach to cardiovascular complications reduction in type-2 DM.

The association between fibrinogen levels and severity of coronary artery disease and long-term prognosis following percutaneous coronary intervention in patients with type 2 diabetes mellitus.

Fibrinogen is a potential risk factor for the prognosis of CAD and is associated with the complexity of CAD. There is limited research specifically investigating the predictive role of fibrinogen in determining the severity of CAD among patients with T2DM, as well as its impact on the prognosis following PCI. The study included 675 T2DM patients who underwent PCI at the Third People's Hospital of Chengdu between April 27, 2018, and February 5, 2021, with 540 of them remaining after exclusions. The complexity of CAD was assessed using the SYNTAX score. The primary endpoint of the study was the incidence of MACCEs. After adjusting for multiple confounding factors, fibrinogen remained a significant independent risk factor for mid/high SYNTAX scores (SYNTAX score > 22, OR 1.184, 95% CI 1.022-1.373, P = 0.025). Additionally, a dose-response relationship between fibrinogen and the risk of complicated CAD was observed (SYNTAX score > 22; nonlinear P = 0.0043). The area under the receiver operating characteristic curve(AUROC) of fibrinogen for predicting mid/high SYNTAX score was 0.610 (95% CI 0.567-0.651, P = 0.0002). The high fibrinogen group (fibrinogen > 3.79 g/L) had a higher incidence of calcified lesions and an elevated trend of more multivessel disease and chronic total occlusion. A total of 116 patients (21.5%) experienced MACCEs during the median follow-up time of 18.5 months. After adjustment, multivariate Cox regression analysis confirmed that fibrinogen (HR, 1.138; 95% CI 1.010-1.284, P = 0.034) remained a significant independent risk factor for MACCEs. The AUROC of fibrinogen for predicting MACCEs was 0.609 (95% CI 0.566-0.650, P = 0.0002). Individuals with high fibrinogen levels (fibrinogen > 4.28 g/L) had a higher incidence of acute myocardial infarction (P < 0.001), MACCEs (P < 0.001), all-cause death (P < 0.001), stroke (P = 0.030), and cardiac death (P = 0.002). Kaplan-Meier analysis revealed a higher incidence of MACCEs in the high fibrinogen group (Log-Rank test: P < 0.001). Elevated fibrinogen levels were associated with increased coronary anatomical complexity (as quantified by the SYNTAX score) and a higher incidence of MACCEs after PCI in patients with T2DM.

Testosterone Replacement Therapy in Klinefelter Syndrome-Follow-up Study Associating Hemostasis and RNA Expression.

Men with Klinefelter syndrome (KS) develop hypergonadotropic hypogonadism, are in need of testosterone replacement therapy (TRT), and present with a more than 4-fold increased risk of thrombosis. TRT in KS has the potential to modify thrombotic risk, but data are scarce. To assess effects of 18 months of TRT on hemostasis in KS and identify genes associated with the prothrombotic phenotype. Untreated and TRT-treated men with KS were included at baseline and matched to healthy controls. TRT was initiated in untreated KS and all groups were reassessed after 18 months of follow-up. Thrombin generation was evaluated with or without thrombomodulin, and fibrin clot lysis was evaluated by turbidity measurements. RNA expression was assessed in blood, fat, and muscle tissue of patients with TRT-treated KS and controls. Thrombin generation with thrombomodulin was slightly increased in untreated KS, but overall KS was not associated with a hypercoagulable state. KS presented with fibrinolytic impairment associated with higher body fat and higher levels of fibrinogen. Eighteen months of TRT in KS was associated with a reduction in body fat and fibrinogen, attenuating the prothrombotic profile. The expression of ENPP4 was higher in men with KS and served as a key player among a group of genes associated with impaired fibrinolysis. KS is associated with a specific expression profile contributing to fibrinolytic impairment and increased thrombotic risk in the patients. TRT in patients with KS has the potential for alleviating the prothrombotic phenotype, in particular by reducing body fat and fibrinogen.

Primary apical periodontitis correlates to elevated levels of interleukin-8 in a Swedish population: A report from the PAROKRANK study.

To explore associations between root filled teeth, primary and secondary apical periodontitis, and levels of inflammatory markers in blood from patients with a first myocardial infarction and matched controls. Between May 2010 and February 2014, 805 patients with a first myocardial infarction and 805 controls, matched for sex, age, and postal code area, were recruited to the multicentre case-control study PAROKRANK (periodontitis and its relation to coronary artery disease). All participants underwent a physical and oral examination, as well as blood sampling. Using panoramic radiography, root filled teeth, primary apical periodontitis, and secondary apical periodontitis were assessed by three independent observers. Blood samples were analysed with enzyme-linked immunosorbent assay method for the following inflammatory markers: interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12p70, tumour necrosis factor-α, and high-sensitivity C-reactive protein (hsCRP). Additionally, white blood cell count and plasma-fibrinogen were analysed. Associations between endodontic variables and the levels of inflammatory markers were statistically analysed with Mann-Whitney U-test and Spearman correlation, adjusted for confounding effects of baseline factors (sex, age, myocardial infarction, current smoking, diabetes, family history of cardiovascular disease, education, marital status, and periodontal disease). Mean age of the cohort was 62 years, and 81% were males. Root fillings were present in 8.4% of the 39 978 examined teeth and were associated with higher levels of hsCRP, fibrinogen, and leukocyte count, but lower levels of IL-2 and IL-12p70. After adjusting for confounders, root filled teeth remained associated with higher levels of fibrinogen, but lower levels of IL-1β, IL-2, IL-6, and IL-12p70. Primary apical periodontitis was found in 1.2% of non-root filled teeth and associated with higher levels of IL-8 (correlation 0.06, p = .025). Secondary apical periodontitis was found in 29.6% of root filled teeth but did not relate to the levels of any of the inflammatory markers. This study supports the notion that inflammation at the periapex is more than a local process and that systemic influences cannot be disregarded. Whether the observed alterations in plasma levels of inflammatory markers have any dismal effects on systemic health is presently unknown but, considering the present results, in demand of further investigation.

The results of hemostasis assessment using thromboelastography in patients with COVID-19

All currently existing studies of the hemostasis system in COVID-19 using thromboelastography (TEG) were performed on the delta strain of SARS-CoV-2, while there is no information in the literature on conducting such studies in patients infected with the current omicron strain.Research objective. To determine the state of the hemostasis system in hospitalized patients with COVID-19 (omicron strain) using TEG. To assess the relevance of existing guidelines on anticoagulant therapy.Materials and methods. TEG was performed in 93 hospitalized patients with COVID-19 aged 1 to 88 years, of which 66 patients (group 1) on the first day and 27 patients (group 2) – on the second day. For comparison with the parameters of healthy volunteers, a sample of 30 people was formed. Data analysis was performed using the Statistica, version 12 (StatSoft, USA). To compare the independent variable in more than two samples, a multivariate ANOVA analysis of variance was performed with the calculation of the Kruskal-Wallis test. To assess the relationships between continuous variables, the Spearman direct linear correlation coefficient (r) was determined.Results. 53% of patients had hypocoagulation, 31% had normocoagulation, and 16% had hypercoagulation. Elderly patients (61 [26–72]) more often have developed hypocoagulation. Young patients (24.5 [7–37]) more often have developed hypercoagulation. Routine methods for assessing hemostasis did not reflect its true state. Higher levels of fibrinogen (4.5 [5.8–4] g/l) and D-dimer (1.28 [0.5–2.77] µg/ ml) were observed in patients from the group with normocoagulation. Was revealed a statistical tendency towards an increase in the level of amylase when there was an increase in the coagulation properties of the blood.Conclusion. With the current course of COVID-19 and early admission of non-severe patients to the hospital, normocoagulation and hypocoagulation predominate. Elderly and senile patients are not recommended to prescribe anticoagulants without TEG. It is necessary to specify the recommendations for prescribing anticoagulants to hospitalized patients. For the diagnosis of hemostasis disorders expand application of TEG.

High Plasma Fibrinogen Level Elevates the Risk of Cardiac Complications Following Spontaneous Intracerebral Hemorrhage

Cardiac complications are related to poor prognosis after spontaneous intracerebral hemorrhage (ICH). This study aims to predict the cardiac complications arising from small intracranial hematoma at ultraearly stage. The data of this work were derived from the Risk Stratification and Minimally Invasive Surgery in Acute ICH Patients study (ClinicalTrials.gov Identifier: NCT03862729). This work included patients with ICH but without brain herniation, as confirmed by a brain computed tomography scan within 48hours of symptom onset. Every Patient's information recorded at the emergent department, including clinical, laboratory, electrocardiogram, and medical records, was derived from the electronic data capture. Cardiac complications were defined as the occurrence of myocardial damage, arrhythmias, and ischemic electrocardiogram changes during hospitalization. Variables associated with cardiac complications were filtrated by univariate and multivariate regression analyses. Independent risk factors were used to form the early predictive model. The restricted cubic splines were employed to investigate the nonlinear associations in a more sophisticated and scholarly manner. A total of 587 ICH patients were enrolled in this work, including 72 patients who suffered from cardiac complications after ICH. Out of the 78 variables, 24 were found to be statistically significant in the univariate logistic regression analysis. These significant variables were then subjected to multivariate logistic regression analysis and utilized for constructing risk models. Multivariate logistic regression analysis showed high plasma fibrinogen (FIB) level [odds ratio (OR) per standard deviation (SD) 1.327, 95% confidence intervals (CI) 1.037-1.697; P=0. 024)] and older age (OR per SD 1.777, 95% CI 1.344-2.349; P ＜0.001) were associated with a higher incidence of cardiac complications after ICH. High admission pulse rate (OR 0.620, 95% CI 0.451-0.853; P=0. 003) was considered a protective factor for cardiac complications after ICH. In the restricted cubic spline regression model, FIB and cardiac complications following ICH were positively correlated and almost linearly (P for nonlinearity=0.073). The reference point for FIB in predicting cardiac complications after ICH was 2.64g/L. Emergent factors, including plasma FIB level, age, and pulse rate, might be independently associated with cardiac complications after ICH, which warrants attention in the context of treatment.

Fibrinogen Levels in Patients with Metastatic Renal Cell Carcinoma Treated with Nivolumab: Results of a Multicenter Prospective Trial

Background: Introduction of immune checkpoint inhibitors in the standard of care for metastatic renal cell carcinoma (mRCC) requires robust but yet simple biomarkers to predict efficacy of immunotherapy. Objective: The aim of this study was to evaluate the association between fibrinogen levels and efficacy of second-line therapy with nivolumab in mRCC. Methods: This is a prospective multicenter biomarker study. Fibrinogen levels were measured one week prior to second-line nivolumab therapy and six times monthly. A high fibrinogen level was defined as ≥5 g/L. Patients were divided into two cohorts: high (H) and normal (N) fibrinogen levels. The primary endpoint was overall survival (OS). Results: The median OS was 31.5 months (95% confidence interval [CI], 27.9 to 35.1) in cohort N vs. 20.9 months (95% CI, 18.1 to 23.7) in cohort H (hazard ratio [HR], 0.39; 98.5% CI, 0.21 to 0.7; P = 0.002). The median progression-free survival was 9.4 months (95% CI, 5.5 to 14.1) in cohort N and 4.0 months (95% CI, 2.9 to 5.1) in cohort H (HR, 0.65; 95% CI, 0.51 to 0.72; P &lt; 0.001). The objective response rate was higher in N cohort (33% vs. 17% ; P = 0.012). No statistically significant changes of fibrinogen concentration during nivolumab therapy were found. Conclusion: The study demonstrated an association of hyperfibrinogenemia with worse clinical outcomes of second-line nivolumab monotherapy in patients with mRCC. Further validation of fibrinogen as a predictive biomarker for immunotherapy efficacy in patients with mRCC is warranted.

Prognostic value of neutrophil-to-lymphocyte ratio and fibrinogen levels in ovarian cancer

BACKGROUND High neutrophil-to-lymphocyte ratio (NLR) and fibrinogen levels have been associated with mortality in several malignancies. However, the studies on the association between NLR or fibrinogen levels and ovarian cancer prognosis are inconsistent. This study aimed to investigate the prognostic roles of NLR and fibrinogen in ovarian cancer.&#x0D; METHODS A systematic search of electronic databases was performed to analyze studies on the association of pre-treatment NLR and fibrinogen levels with overall survival (OS) and progression-free survival (PFS) among patients with ovarian cancer. The hazard ratio (HR) and corresponding 95% confidence intervals [CIs] were analyzed. All statistical analyses were done using RevMan version 5.4 (Cochrane, United Kingdom).&#x0D; RESULTS A total of 7,312 patients from 27 studies were included. The median cut-off for high NLR was 3.6 for OS among 17 studies and 3.23 for PFS among 11 studies reporting an NLR HR. The median cut-off for fibrinogen levels was 4.0 in 9 studies reporting fibrinogen levels HR. High NLR was associated with lower OS (HR 1.35, 95% CI 1.18 to 1.55, p&lt;0.0001, I2 = 76%) and PFS (HR 1.35, 95% CI 1.14 to 1.60, p = 0.0005, I2 = 71%). High fibrinogen levels were associated with lower OS (HR 1.44, 95% CI 1.14 to 1.82, p = 0.002, I2 = 81%) and PFS (HR 1.34, 95% CI 1.17 to 1.55, p&lt;0.0001, I2 = 15%). This association occurred in all ovarian cancer types.&#x0D; CONCLUSIONS High pre-treatment NLR and plasma fibrinogen levels were related to poor OS and PFS in ovarian cancer.

Plasma fibrinogen: a driver of left ventricular remodeling in patients undergoing peritoneal dialysis and its related risk factors

Background and aim Plasma fibrinogen has been proven to be significantly associated with cardiovascular mortality in patients undergoing peritoneal dialysis (PD). The study aimed to investigate the role of fibrinogen in left ventricular (LV) remodeling and functions in patients on PD, and explore risk factors related to high fibrinogen level. Methods From February 2008 to July 2018, adult patients on regular PD for at least 1 month were recruited and followed up for two years. Correlation analysis was performed to explore the fibrinogen level and echocardiography measurements. Pathogenic factors correlated to the left ventricular hypertrophy (LVH) progression were explored by logistic regression models and the role of fibrinogen in it was verified by receiver operating characteristic (ROC) curves. Linear regression models were conducted to identify factors associated with fibrinogen level. Results A total of 278 patients undergoing PD (168 males, 60.4%) were recruited. Patients were trisected according to fibrinogen levels at baseline. Mean wall thickness (MWT), relative wall thickness (RWT), and left ventricular mass index (LVMI) were positively associated with fibrinogen level while E/A ratio was negatively associated with it. Multivariate logistic regression and ROC curve showed that fibrinogen was an independent risk factor for LVH progression. Multivariate linear regression analysis identified age, total cholesterol (CHO), fasting blood glucose (FBG), and high-sensitivity C-reactive protein (hsCRP) were significantly related to plasma fibrinogen level. Conclusions An elevated fibrinogen level was independently associated with LVH progression in patients undergoing PD. Older age, higher level of FBG, CHO, and hsCRP were risk factors for elevated plasma fibrinogen level.