Amyloid pathology mediates the associations between plasma fibrinogen and cognition in non-demented adults.

Though previous studies revealed the potential associations of elevated levels of plasma fibrinogen with dementia, there is still limited understanding regarding the influence of Alzheimer's disease (AD) biomarkers on these associations. We sought to investigate the interrelationships among fibrinogen, cerebrospinal fluid (CSF) AD biomarkers, and cognition in non-demented adults. We included 1996 non-demented adults from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study and 337 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The associations of fibrinogen with AD biomarkers and cognition were explored using multiple linear regression models. The mediation analyses with 10 000 bootstrapped iterations were conducted to explore the mediating effects of AD biomarkers on cognition. In addition, interaction analyses and subgroup analyses were conducted to assess the influence of covariates on the relationships between fibrinogen and AD biomarkers. Participants exhibiting low Aß42 were designated as A+, while those demonstrating high phosphorylated tau (P-tau) and total tau (Tau) were labeled as T+ and N+, respectively. Individuals with normal measures of Aß42 and P-tau were categorized as the A-T- group, and those with abnormal levels of both Aß42 and P-tau were grouped under A+T+. Fibrinogen was higher in the A+ subgroup compared to that in the A- subgroup (p = 0.026). Fibrinogen was higher in the A+T+ subgroup compared to that in the A-T- subgroup (p = 0.011). Higher fibrinogen was associated with worse cognition and Aß pathology (all p < 0.05). Additionally, the associations between fibrinogen and cognition were partially mediated by Aß pathology (mediation proportion range 8%-28%). Interaction analyses and subgroup analyses showed that age and ApoE ε4 affect the relationships between fibrinogen and Aß pathology. Fibrinogen was associated with both cognition and Aß pathology. Aß pathology may be a critical mediator for impacts of fibrinogen on cognition.

Prognostic value of preoperative platelet-related parameters and plasma fibrinogen in patients with non-muscle invasive bladder cancer after transurethral resection of bladder tumor.

Aim: To investigate the prognostic value of preoperative mean platelet volume (MPV), MPV/lymphocyte ratio (MPVLR), MPV/platelet count ratio and plasma fibrinogen in patients with non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). Methods: A total of 371 patients who underwent TURBT were enrolled. The main end points were disease-free survival (DFS) and overall survival (OS). Results: MPVLR, tumor size, tumor number and pathological grade were independent risk factors for postoperative DFS. Age and pathological grade were independent risk factors for postoperative OS. Conclusion: MPVLR is an independent risk factor for DFS in NMIBC patients and could be used as a parameter to predict postoperative tumor recurrence in patients after TURBT.

The current study investigated the prognostic value of preoperative mean platelet volume (MPV), MPV/lymphocyte ratio (MPVLR), MPV/platelet count ratio (MPVPCR) and plasma fibrinogen (PF) in peripheral blood of patients with non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). Included were 371 patients who underwent TURBT and were followed up. A high level of PF indicated worse survival and age and pathological grade were independent risk factors for postoperative survival. High levels of MPV, MPVLR and MPVPCR were associated with recurrence. MPVLR, tumor size, tumor number and pathological grade were independent risk factors for postoperative recurrence. MPVLR could be used as a parameter to predict postoperative tumor recurrence in patients after TURBT.

Plasma fibrinogen: a sensitive biomarker for the screening of periprosthetic joint infection in patients undergoing re-revision arthroplasty.

BACKGROUND: Although serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), plasma fibrinogen and neutrophil-lymphocyte ratio (NLR) are promising biomarkers for screening PJI in patients undergoing revision arthroplasty, their efficacy with respect to re-revision arthroplasty remains unclear. METHODS: We included patients who underwent re-revision arthroplasty at our hospital during 2008-2020, and stratified them into two groups whether they had been diagnosed with PJI (infected) or aseptic failure (non-infected) according to the 2013 International Consensus Meeting criteria. We evaluated the diagnostic performance of CRP, ESR, fibrinogen and NLR, both individually and in combinations, based on sensitivity, specificity, and area under the receiver operating characteristic curve. RESULTS: Of the 63 included patients, 32 were diagnosed with PJI. The area under the ROC curve was 0.821 for CRP, 0.794 for ESR, 0.885 for fibrinogen and 0.702 for NLR. CRP gave a sensitivity of 87.5% and specificity of 74.2% with an optimal predictive cut-off of 8.50 mg/mL. ESR gave a sensitivity of 81.3% and specificity of 71.0% with an optimal predictive cut-off of 33 mm/h. Plasma fibrinogen gave a comparatively higher sensitivity of 93.8% and specificity of 77.4% with an optimal predictive cut-off of 3.55 g/L, while NLR gave a moderate sensitivity of 84.4% but low specificity of 54.8% with an optimal predictive cut-off of 2.30. The combination of fibrinogen and CRP gave a high AUC of 0.897, an acceptable sensitivity of 75% and a high specificity 93.5%. CONCLUSIONS: Plasma fibrinogen is a cost-effective, convenient biomarker that can be used to rule out PJI in patients scheduled for re-revision arthroplasty. In combination with CRP, it may be effective in diagnosing PJI in such patients.

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model.

Background: Ischemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat. Methods: Rat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed. Results: Pre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators. Conclusion: Our result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.

Plasma fibrinogen and mortality in patients undergoing peritoneal dialysis: a prospective cohort study.

BACKGROUND: Plasma fibrinogen is significantly associated with cardiovascular (CV) events and mortality in the general population. However, the association between plasma fibrinogen and mortality in patients undergoing peritoneal dialysis (PD) is unclear. METHODS: This was a prospective cohort study. A total of 1603 incident PD patients from a single center in South China were followed for a median of 46.7 months. A Cox regression analysis was used to evaluate the independent association of plasma fibrinogen with CV and all-cause mortality. Models were adjusted for age, sex, smoking, a history of CV events, diabetes, body mass index, systolic blood pressure, hemoglobin, blood platelet count, serum potassium, serum albumin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, hypersensitive C-reactive protein, estimated glomerular filtration rate, antiplatelet agents and lipid-lowering drugs. RESULTS: The mean age was 47.4 ± 15.3 years, 955 (59.6%) patients were male, 319 (19.9%) had a history of CV events, and 410 (25.6%) had diabetes. The average plasma fibrinogen level was 4.12 ± 1.38 g/L. Of the 474 (29.6%) patients who died during follow-up, 235 (49.6%) died due to CV events. In multivariable models, the adjusted hazard ratios (HRs) for quartile 1, quartile 3, and quartile 4 versus quartile 2 were 1.18 (95% confidence interval [CI], 0.72-1.95, P = 0.51), 1.47 (95% CI, 0.93-2.33, P = 0.10), and 1.78 (95% CI, 1.15-2.77, P = 0.01) for CV mortality and 1.20 (95% CI, 0.86-1.68, P = 0.28), 1.29 (95% CI, 0.93-1.78, P = 0.13), and 1.53 (95% CI, 1.12-2.09, P = 0.007) for all-cause mortality, respectively. A nonlinear relationship between plasma fibrinogen and CV and all-cause mortality was observed. CONCLUSIONS: An elevated plasma fibrinogen level was significantly associated with an increased risk of CV and all-cause mortality in patients undergoing PD.

Prognostic value of plasma fibrinogen and D-dimer levels in patients with surgically resected non-small cell lung cancer.

PURPOSE: A high plasma level of either fibrinogen or D-dimer has been shown to correlate with a poor prognosis in patients with surgically resected non-small-cell lung cancer (NSCLC). The present study aimed to identify whether or not both markers combined had a superior prognostic value to either alone. METHODS: Of the 1344 patients who underwent surgical resection for NSCLC at our institution between January 2007 and December 2016, 1065 had preoperative plasma fibrinogen and D-dimer data available and were included in the analysis. RESULTS: The recurrence-free survival (RFS) and overall survival (OS) rates were similar for patients with high plasma levels of either or both fibrinogen (> 4.0 g/L) or D-dimer (> 1.0 µg/mL); therefore, these three groups were combined for a further analysis into a single group with high plasma levels of either or both proteins. The high-level group had significantly lower 5-year RFS (53% vs. 68%, p < 0.001) and 5-year OS (65% vs. 80%, p < 0.001) rates than patients with normal plasma levels of fibrinogen and D-dimer (control group). CONCLUSIONS: Our results suggest that preoperative tests for both plasma fibrinogen and D-dimer are necessary to identify patients with surgically resected NSCLC likely to have a poor RFS and OS.

Comparison of the prognostic values of selected inflammation based scores in patients with medullary thyroid carcinoma: A pilot study.

BACKGROUND: The significance of inflammation based scores including the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and plasma fibrinogen remains unclear in medullary thyroid carcinoma (MTC). We aimed to compare the prognostic value of these scores. METHODS: Seventy-eight patients newly diagnosed as MTC with operation in our institution from May 2009 to September 2016 were retrospectively evaluated. Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses were calculated to compare the prognostic value of these scores. RESULTS: Increased PLR was predictive of lymph node metastasis (AUC = 0.644, P = 0.022), capsule invasion (AUC = 0.666, P = 0.007), advanced tumor stages (AUC = 0.657, P = 0.011), and recurrence (AUC = 0.655, P = 0.049). Increased fibrinogen was predictive of lymph node metastasis (AUC = 0.669, P = 0.006) and capsule invasion (AUC = 0.631, P = 0.038). Reduced PNI was predictive of recurrence (AUC = 0.655, P = 0.049). Kaplan-Meier analyses and Cox regression analysis revealed that PLR was a significant predictor for recurrence. CONCLUSIONS: PLR, fibrinogen, and PNI are all predictive. Specially, PLR is superior to other inflammation based scores in terms of prognostic ability.

Hyperfibrinogenemia predicts poor prognosis in patients with advanced biliary tract cancer.

Hyperfibrinogenemia reportedly predicts poor prognosis in several cancers but has not been reviewed for biliary tract cancer (BTC). The aim of the present study was to evaluate associations between baseline plasma fibrinogen concentrations, clinicopathological characteristics, and survival parameters in patients with BTC. Data for 127 patients with BTC diagnosed at the Zhongshan Affiliated Hospital of Dalian University (Liaoning, China) from January 2011 to December 2014 were retrospectively evaluated. Associations between baseline fibrinogen concentrations, selected clinicopathological characteristics, and the prognostic value were examined using SPSS software. Data for 37 patients (29.1 % of study cohort) who had undergone curative intent surgery and 90 (70.9 %) with advanced biliary tract cancer (ABTC) were analyzed. The mean plasma fibrinogen concentration 4.0 ± 0.9 g/L for the entire cohort. The percentages with hyperfibrinogenemia (>4 g/L) were 45.7, 37.8, and 48.9 % overall and in the surgical and ABTC groups, respectively. Hyperfibrinogenemia was associated with performance status (PS) and neutrophil/lymphocyte ratio in the entire cohort but not with other relevant clinicopathological factors. Log-rank test indicated that baseline hyperfibrinogenemia was associated with decreased progression-free survival (PFS) and overall survival (OS) for patients with unresectable ABTC (P > 0.05). Multivariate analysis showed that poor PS and baseline hyperfibrinogenemia were independently associated with worse survival (HR: 1.39, 95 % CI: 1.02-1.90, P = 0.04; HR: 1.75.95 %, 95 % CI: 1.01-3.01, P = 0.04, respectively). Baseline hyperfibrinogenemia is an independent predictor of poor prognosis in patients with ABTC. Baseline plasma fibrinogen concentrations may be a readily available and inexpensive prognostic biomarker in patients with ABTC; this needs further validation in large prospective clinical trials.

Plasma fibrinogen level: an independent prognostic factor for disease-free survival and cancer-specific survival in patients with localised renal cell carcinoma.

OBJECTIVES: To investigate the impact of perioperative plasma fibrinogen level as a biomarker of oncological outcome in localised renal cell carcinoma (RCC). PATIENTS AND METHODS: We consecutively identified 601 patients with localised RCC who underwent curative surgery at a single institution. Subsequent disease recurrence and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic impact of plasma fibrinogen level, multivariate analysis was performed for these outcomes. RESULTS: Using the defined threshold level of preoperative plasma fibrinogen of ≥420 mg/dL as elevated, we found 56 patients (9.3%) with an elevated plasma fibrinogen level preoperatively. In Kaplan-Meier analysis, there was a significant difference in disease-free survival and CSS rates between patients with and without preoperative plasma fibrinogen levels of ≥420 mg/dL. Multivariate analysis showed that elevated preoperative plasma fibrinogen level was an independent predictor of subsequent disease recurrence and cancer-specific mortality. In a subgroup analysis of the elevated preoperative plasma fibrinogen level group, postoperative normalisation of plasma fibrinogen level was significantly associated with CSS, showing that patients with non-normalised plasma fibrinogen levels tended to have a higher incidence of cancer-specific mortality after surgery. CONCLUSION: Patients with elevated preoperative plasma fibrinogen levels could be significantly predicted to have subsequent tumour metastasis and cancer-specific mortality, while there was a significant difference in CSS between patients in the normalised and non-normalised postoperative plasma fibrinogen groups. While these are hypothesis generating results, plasma fibrinogen levels may be a useful biomarker due to its low cost and ease of assessment.

Fibrinogen in the initial resuscitation of severe trauma (FiiRST): a randomized feasibility trial.

BACKGROUND: Decreased plasma fibrinogen concentration shortly after injury is associated with higher blood transfusion needs and mortality. In North America and the UK, cryoprecipitate transfusion is the standard-of-care for fibrinogen supplementation during acute haemorrhage, which often occurs late during trauma resuscitation. Alternatively, fibrinogen concentrate (FC) can be beneficial in trauma resuscitation. However, the feasibility of its early infusion, efficacy and safety remain undetermined. The objective of this trial was to evaluate the feasibility, effect on clinical and laboratory outcomes and complications of early infusion of FC in trauma. METHODS: Fifty hypotensive (systolic arterial pressure ≤100 mm Hg) adult patients requiring blood transfusion were randomly assigned to either 6 g of FC or placebo, between Oct 2014 and Nov 2015 at a tertiary trauma centre. The primary outcome, feasibility, was assessed by the proportion of patients receiving the intervention (FC or placebo) within one h of hospital arrival. Plasma fibrinogen concentration was measured, and 28-day mortality and incidence of thromboembolic events were assessed. RESULTS: Overall, 96% (43/45) [95% CI 86-99%] of patients received the intervention within one h; 95% and 96% in the FC and placebo groups, respectively (P=1.00). Plasma fibrinogen concentrations remained higher in the FC group up to 12 h after admission with the largest difference at three h (2.9 mg dL - 1 vs. 1.8 mg dL - 1; P<0.01). The 28-day mortality and thromboembolic complications were similar between groups. CONCLUSIONS: Early infusion of FC is feasible and increases plasma fibrinogen concentration during trauma resuscitation. Larger trials are justified.

Hyperfibrinogenemia is associated with inflammatory mediators and poor prognosis in patients with gastric cancer.

PURPOSE: Hyperfibrinogenemia is associated with poor prognosis in various cancers; however, its clinical relevance in gastric cancer has not been well analyzed. We conducted this study to assess the clinicopathological significance and prognostic value of hyperfibrinogenemia in patients with gastric cancer. METHODS: Plasma fibrinogen levels were measured preoperatively in 315 patients undergoing surgery for gastric cancer. We then evaluated the clinicopathological significance of hyperfibrinogenemia and its relationship with several biomarkers, including white blood cell (WBC), C-reactive protein (CRP), platelet count, prothrombin time (PT) and activated partial thromboplastin time (APTT). Postoperative plasma levels were compared with preoperative levels. The multivariate prognostic value of hyperfibrinogenemia was calculated using the Cox proportional hazards model. RESULTS: Tumor progression was significantly associated with hyperfibrinogenemia, as were the CRP level and platelet counts. Plasma fibrinogen levels decreased significantly after radical surgery. Adjusting for TNM factors, multivariate analysis indicated that hyperfibrinogenemia was an independent prognostic factor for poor survival (hazard ratio = 2.607, 95 % confidence interval = 1.180-5.761, P = 0.018). CONCLUSION: Preoperative hyperfibrinogenemia was associated with tumor progression, inflammatory mediators, and poor overall survival in patients with gastric cancer.

Plasma fibrinogen levels in patients with benign and malignant ovarian tumors.

OBJECTIVE: Plasma fibrinogen is a key acute phase protein and known to be elevated in ovarian cancer. We aimed to investigate the association between plasma fibrinogen and malignant and benign ovarian tumors. METHODS: In a retrospective, single-center study, we evaluated preoperative plasma fibrinogen levels in 471 patients with benign and in 224 patients with malignant (borderline ovarian tumor [BOT]: n=36, epithelial ovarian cancer [EOC]: n=188) ovarian tumors. The association between preoperative plasma fibrinogen levels and clinico-pathological parameters was investigated. A multivariate logistic regression model was performed to identify an independent association. RESULTS: Mean (standard deviation) preoperative plasma fibrinogen levels in patients with benign ovarian tumors, BOT, and invasive ovarian cancers were 346.7 (99.7), 372.8 (114), and 472.6 (148.4) mg/dL, respectively (p<0.001). Within the EOC cohort, patients with advanced stage disease had higher plasma fibrinogen levels (485.5 [151.3] mg/dL) than patients with early stage disease (430.9 [130.3] mg/dL; p=0.03). In a multivariate model plasma fibrinogen was identified to be independently associated with the presence of BOT and EOC. In the subgroup of patients <50 years, plasma fibrinogen levels remained independently associated with malignant ovarian tumors in CA 125 positive and negative patients. CONCLUSION: Plasma fibrinogen levels are independently associated with malignant ovarian tumors. Plasma fibrinogen levels showed an independent association with malignant ovarian tumors in the subgroup of patients <50 years, in whom differential diagnosis of ovarian tumors is particularly challenging.

The elevated pre-operative plasma fibrinogen level is an independent negative prognostic factor for cancer-specific, disease-free and overall survival in soft-tissue sarcoma patients.

BACKGROUND AND OBJECTIVES: Accumulating evidence indicates an important pathophysiological role of fibrinogen on tumor cell progression and metastases in different types of cancer. The aim of the present study was to evaluate the prognostic relevance of pre-operative fibrinogen levels on clinical outcome in a large cohort of STS patients. METHODS: Two hundred ninety-four consecutive STS patients were retrospectively evaluated. Cancer-specific survival (CSS), disease-free survival (DFS), and overall survival (OS) were assessed using the Kaplan-Meier curves and Cox regression models. Finally, we supplemented the well-established Kattan nomogram by the fibrinogen level and evaluated the gain of predictive accuracy of this novel nomogram by Harrell's concordance index (c-index). RESULTS: An elevated plasma fibrinogen level was significantly associated with established prognostic factors, including age, tumor grade, size, and depth (P<0.05). Furthermore, in multivariate analysis, increased fibrinogen levels were significantly associated with a poor outcome for CSS (HR=2.48; 95% CI=1.28-4.78; P=0.007), DFS (HR=2.00; 95% CI=1.11-3.60; P=0.021), and OS (HR=2.20; 95% CI=1.39-3.47; P<0.001). The estimated c-index was 0.747 using the original Kattan nomogram and 0.779 when the fibrinogen levels was added. CONCLUSION: The pre-operative plasma fibrinogen level may represent a strong and independent unfavorable prognostic factor for CSS, DFS and OS in STS patients.

Preoperative plasma fibrinogen and C-reactive protein/albumin ratio as prognostic biomarkers for pancreatic carcinoma.

Objective: Pancreatic carcinoma is characterised by high aggressiveness and a bleak prognosis; optimising related treatment decisions depends on the availability of reliable prognostic markers. This study was designed to compare various blood biomarkers, such as neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP), albumin (Alb), plasma fibrinogen (PF), and CRP/Alb in patients with pancreatic carcinoma. Methods: Our study retrospectively reviewed 250 patients with pancreatic carcinoma diagnosed between July 2007 and December 2018. The Cutoff Finder application was used to calculate the optimal values of CRP/Alb and PF. The Chi-square test or Fisher's exact test was used to analyse the correlation of CRP/Alb and PF with other clinicopathological factors. Conducting univariate and multivariate analyses allowed further survival analysis of these prognostic factors. Results: Multivariate analysis revealed that, in a cohort of 232 patients with pancreatic ductal adenocarcinoma (PDAC), the PF level exhibited statistical significance for overall survival (hazard ratio (HR) = 0.464; p = 0.023); however, this correlation was not found in the entire group of 250 patients with pancreatic carcinoma. Contrastingly, the CRP/Alb ratio was demonstrated statistical significance in both the entire pancreatic carcinoma cohort (HR = 0.471; p = 0.026) and the PDAC subgroup (HR = 0.484; p = 0.034). CRP/Alb and PF demonstrated a positive association (r=0.489, p<0.001) as indicated by Spearman's rank correlation analysis. Additionally, in 232 PDAC patients, the combination of the CRP/Alb ratio and PF had synergistic effects on prognosis when compared with either the CRP/Alb ratio or the PF concentration alone. Conclusion: PF concentration is a convenient, rapid, and noninvasive biomarker, and its combination with the CRP/Alb ratio could significantly enhance the accuracy of prognosis prediction in pancreatic carcinoma patients, especially those with the most common histological subtype of PDAC.

The plasma fibrinogen levels in the nitroglycerin-induced chronic migraine rat model and its association between migraine-associated vestibular dysfunction.

The purpose of this study was to measure the vestibular function and plasma fibrinogen level in the nitroglycerin (NTG)-induced chronic migraine rats, and explore the effect of defibrinogenation on migraine and associated vestibular dysfunction. The chronic migraine rat model was built by recurrent NTG injection. Batroxobin was administrated as a defibrinogenating drug. We measured the mechanical withdrawal threshold, vestibular function, and fibrinogen level of the rats 30 min before and 2 h following the model establishment, as well as 1 h after batroxobin administration. The results showed that vestibular function was impaired in NTG-induced chronic migraine rats. The fibrinogen levels were increased following repeated NTG injections. However, defibrinogenation did not affect either aggravating or alleviating mechanical hyperalgesia or vestibular dysfunction in the migraine model rats. These findings suggest that the NTG-induced chronic migraine rat model can be used for research on migraine-associated vestibular symptoms. Albeit the association between elevated fibrinogen levels and migraine attacks can be observed, the role of excessive fibrinogen in the pathogenesis of chronic migraine is yet to be determined.

Risk factors for high CAD-RADS scoring in CAD patients revealed by machine learning methods: a retrospective study.

Objective: This study aimed to investigate a variety of machine learning (ML) methods to predict the association between cardiovascular risk factors and coronary artery disease-reporting and data system (CAD-RADS) scores. Methods: This is a retrospective cohort study. Demographical, cardiovascular risk factors and coronary CT angiography (CCTA) characteristics of the patients were obtained. Coronary artery disease (CAD) was evaluated using CAD-RADS score. The stenosis severity component of the CAD-RADS was stratified into two groups: CAD-RADS score 0-2 group and CAD-RADS score 3-5 group. CAD-RADS scores were predicted with random forest (RF), k-nearest neighbors (KNN), support vector machines (SVM), neural network (NN), decision tree classification (DTC) and linear discriminant analysis (LDA). Prediction sensitivity, specificity, accuracy and area under the curve (AUC) were calculated. Feature importance analysis was utilized to find the most important predictors. Results: A total of 442 CAD patients with CCTA examinations were included in this study. 234 (52.9%) subjects were CAD-RADS score 0-2 group and 208 (47.1%) were CAD-RADS score 3-5 group. CAD-RADS score 3-5 group had a high prevalence of hypertension (66.8%), hyperlipidemia (50%) and diabetes mellitus (DM) (35.1%). Age, systolic blood pressure (SBP), mean arterial pressure, pulse pressure, pulse pressure index, plasma fibrinogen, uric acid and blood urea nitrogen were significantly higher (p < 0.001), and high-density lipoprotein (HDL-C) lower (p < 0.001) in CAD-RADS score 3-5 group compared to the CAD-RADS score 0-2 group. Nineteen features were chosen to train the models. RF (AUC = 0.832) and LDA (AUC = 0.81) outperformed SVM (AUC = 0.772), NN (AUC = 0.773), DTC (AUC = 0.682), KNN (AUC = 0.707). Feature importance analysis indicated that plasma fibrinogen, age and DM contributed most to CAD-RADS scores. Conclusion: ML algorithms are capable of predicting the correlation between cardiovascular risk factors and CAD-RADS scores with high accuracy.

Pre-operative Plasma Fibrinogen Level as a Potential Predictor of Pathological T3 Upstaging in Clinically Localized Renal Cell Carcinoma.

BACKGROUND/AIM: We investigated pre-operative factors for predicting pathological T3 (pT3) upstaging in clinical T1 renal cell carcinoma (RCC). PATIENTS AND METHODS: We evaluated 181 patients with renal tumors suspected to be clinical T1 RCC. All patients had undergone a partial or radical nephrectomy. Pre-operative parameters, including patient characteristics, RENAL nephrometry score and blood tests were analyzed to determine factors predicting pT3 upstaging. RESULTS: Eight (4.4%) tumors were diagnosed as pT3. Large tumor diameter, less than 4 mm distance between the tumor and the renal collecting system and a high level of preoperative plasma fibrinogen were associated with pT3 stage. Multivariate analysis showed that a preoperative plasma fibrinogen level >330 mg/dl was a significant independent factor predicting upstage (p=0.041). Furthermore, among patients diagnosed with RCC (n=162), a preoperative plasma fibrinogen level >330 mg/dl was related to poor overall survival (p<0.001) and poor recurrence-free survival (p=0.002). CONCLUSION: A high preoperative plasma fibrinogen level may be a predictor of pT3 upstaging and may suggest the need for radical nephrectomy rather than partial nephrectomy because of the associated poor oncological outcomes.

Comparative Evaluation of Plasma Fibrinogen Degradation Product and Salivary Fibrin Precipitating Factor in Oral Submucous Fibrosis Patients and Betel Quid Chewers.

Aim and Objectives: Estimation and correlation of plasma fibrinogen degradation product (FDP) and salivary fibrin precipitating factor (FPF) in oral sub mucous fibrosis (OSMF) patients, betel quid chewers without OSMF and healthy individuals. The study aims to evaluate whether FDP and FPF can be used as a marker for development and progression of OSMF and whether there is any correlation between the two. Methodology: The study included 163 subjects grouped into three categories, Group 1, which included 54 control patients, Group 2, which included 55 betel quid chewers, and Group 3, which included 54 clinically confirmed OSMF patients. All of them were subjected to the estimation of plasma FDP and salivary FPF. Results: FDP was present in 52 (96.3%) patients in Group 3, 2 (3.6%) patients in Group 2, and 1 patient in Group 1 (1.9%). FPF was positive in eight patients. The correlation of FDP and FPF was done by Fisher's exact test and was found to be statistically nonsignificant. Conclusion: In the present study, FDP was positive in 52 (96.3%) OSMF patients; hence, FDP may be used as an early indicator of OSMF. FDP was found to be positive in two patients with a habit of chewing betel quid without OSMF. It may be hypothesized that these patients are more likely to develop OSMF. Hence, the estimation of FDP may be used as a diagnostic test to predict an impending OSMF before it could manifest itself clinically. FPF was negative in some OSMF patients, may be because it is below the detectable range.

Pretreatment Fibrinogen-Albumin Ratio (FAR) Associated with Treatment Response and Survival in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Anti-PD-1 Therapy Plus Platinum-Based Combination Chemotherapy.

PURPOSE: PD-1 inhibitors have been routinely used to treat advanced non-small cell lung cancer (NSCLC) and have significantly improved clinical outcomes. In this study, we aimed to explore the influence of pretreatment fibrinogen-albumin ratio (FAR) on treatment response and survival in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy. PATIENTS AND METHODS: A total of 91 patients with advanced NSCLC were included in the study. All patients received at least two cycles of systemic first-line anti-PD-1 therapy plus platinum-based combination chemotherapy. Receiver operating characteristics analysis was performed to determine the optimal cutoff values of FAR. Univariate and multivariate analyses were used to identify independent prognostic factors, and the Kaplan-Meier method was used to estimate survival curves. RESULTS: Multivariate logistic regression analysis showed that N stage (N2-3) and high FAR (≥0.175, optimal cutoff value) were independent predictors for objective response rate (P = 0.0002, P = 0.0005, respectively). Multivariate Cox regression analysis of progression-free survival and overall survival showed that high FAR (≥0.145) was independent prognostic factors (P = 0.0061, P = 0.0024, respectively). Progression-free survival and overall survival were significantly shorter in the high FAR (≥0.145) group than those in the low FAR (<0.145) group (P = 0.0024, P = 0.0024, respectively). CONCLUSION: Pretreatment FAR was an independent predictor for treatment response and independent prognostic factors in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy.

Combination of albumin-to-globulin ratio and plasma fibrinogen is a sensitive tool for preoperative screening of infected nonunion in patients undergoing reoperation after open reduction and internal fixation: a retrospective study.

BACKGROUND: Accurate preoperative diagnosis of infected nonunion remains a challenge. Here, we evaluated the diagnostic potential of novel biomarkers for infected nonunion. METHODS: A cohort of 275 patients who underwent surgery for suspected septic nonunion after open reduction and internal fixation were enrolled. Preoperatively analyzed clinical parameters included white blood cell (WBC) count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, globulin, albumin-to-globulin ratio (AGR), plasma D-dimer, plasma fibrinogen, platelet count (PC), monocyte-lymphocyte ratio (MLR), neutrophil-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). Receiver operating characteristic (ROC) curves, sensitivity, and specificity were utilized to compare the diagnostic potential of those biomarkers. RESULTS: The WBC count and levels of CRP, ESR, NLR, MLR, PLR, PC, plasma D-dimer, plasma fibrinogen, and globulin in infected nonunion patients were significantly higher (p < 0.05) than those in aseptic patients. The albumin and AGR levels of the infected nonunion group were significantly lower (p < 0.05) than the aseptic group. The ROC curve analysis showed that the diagnostic accuracy of AGR and plasma fibrinogen was good. The combination of AGR with plasma fibrinogen had the highest area under the curve (AUC) (0.916). The sensitivity and specificity were 70.27% and 91.04% for AGR, and 67.57% and 84.08% for plasma fibrinogen, respectively. The combination of AGR with plasma fibrinogen showed a sensitivity of 86.49% and specificity of 92.54%. In patients with comorbidities, the diagnostic accuracy of the combination of AGR with plasma fibrinogen was also good. CONCLUSIONS: AGR and plasma fibrinogen are promising biomarkers to improve the diagnosis of infected nonunion. The combination of AGR with plasma fibrinogen is a sensitive tool for screening infected nonunion.