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Neurodevelopmental hypothesis suggested that schizophrenia is a disorder of early brain development, in which the brain structural abnormalities are present. The causes of the abnormal processes remains unclear however, Genetics vulnerability, obstetric complications and viral infections have been shown to play a role in this disorder. Several studies have shown a greater incidence of winter or spring births in patients. Prenatal and perinatal infections, especially in the second trimester of pregnancy, have been considered a plausible risk factor for schizophrenia. Maternal exposure to influenza, herpes viruses, varicella zoster virus, Epstein-Barr virus, cytomegalovirus and rarely rubella virus infections confers an increased risk of schizophrenia to the developing offspring. As clinicians, we observed that our patients with psychotic disorder were not exposed to the viral infections even during epidemic. We hypothesized that perinatal viral infections have been associated with lifelong immunity to this infectious diseases which on the other hand cause an increased risk of developing schizophrenia. If we could determine antibodies against these viruses among patients with schizophrenia, perhaps we will be able to identify accurate markers heralding psychotic illness as well as can use these markers in a large population-based sample.

Objective: Cerebrovascular diseases have a high rate in emergency services. We investigated the value of MMX in plasma for early diagnosis among the patients with suspected cerebrovascular disease and the correlation between the emergency, triage and neurology physician diagnoses. Material and Methods: It is a prospective study carried out with 83 patients. Pre-prepared forms were filled with the data about the patients. Samples of 1cc venous blood were measured for MMX and the results classified as normal or pathologic. The correlation between the results and physician diagnosis was investigated. Results: 44 (53%) of 83 patients were male, 39 (47%) were female. The average age was 69.1 (37-90) years. Neurology physician diagnosis, accepted as the gold standard, was compared with the triage, emergency physician diagnosis and MMX results by ROC curve analysis, and the difference was not significiant (p>0.05). When the diagnoses of the emergency physician were compared with the MMX results, the compatiblity for definite and probable strokes were 100% and 92.1%. The rates for triage physician were 100% and 96.4%. Conclusion: As a result of this study we can say that the stroke probablity is high if MMX is high in patients with suspected cerebrovascular disease, but more studies with large population groups are needed for specifity assessment.

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder referred to gastroenterologists. Although the pathophysiology remains unclear, accumulating evidence points to the presence of low-level immune activation both in the gut and systemically. Circulating polyunsaturated fatty acids (PUFA) have recently attracted attention as being altered in a variety of disease states. Arachidonic acid (AA), in particular, has been implicated in the development of a pro-inflammatory profile in a number of immune-related disorders. AA is the precursor of a number of important immunomodulatory eicosanoids, including prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). We investigated the hypothesis that elevated plasma AA concentrations in plasma contribute to the proposed pro-inflammatory profile in IBS. Plasma AA and related PUFA were quantified by gas chromatography analysis in IBS patients and controls. Both PGE2 and LTB4 were measured in serum using commercially available ELISA assays. AA concentrations were elevated in our patient cohort compared with healthy controls. Moreover, we demonstrated that this disturbance in plasma AA concentrations leads to downstream elevations in eicosanoids. Together, our data identifies a novel proinflammatory mechanism in irritable bowel syndrome and also suggests that elevated arachidonic acid levels in plasma may serve as putative biological markers in this condition.

Passive exposure to the aerosols of electronic cigarettes (e-cigarettes) has been little studied. We assessed this exposure in late pregnancy in a woman and her 3-year-old child, exposed through e-cigarette use by another household member. This prospective longitudinal case study involved a family unit consisting of an e-cigarette user, a pregnant woman who delivered an infant during the study, and the couple's older 3-year-old son. At 31, 36, and 40 weeks of the pregnancy, we measured biomarkers (nicotine metabolites, tobacco-specific nitrosamines, propanediols, glycerol, and metals) in the urine and hair of all three participants and in the saliva of the adults, in cord blood at delivery, and in the breast milk at the postpartum period. Samples from the e-cigarette user showed quantifiable concentrations of all analytes assessed (maximum urinary cotinine concentration, 4.9 ng/mL). Among samples taken from the mother, nicotine and its metabolites were found mainly in urine and also in saliva and hair, but not in cord blood. During the postpartum period, we found cotinine concentrations of 2.2 ng/mL in the mother's urine and 0.22 ng/mL in breast milk; 1,2-propanediol was generally detected in urine and saliva, but not in cord blood or breast milk. The maximum urinary cotinine concentration in the 3-year-old child was 2.6 ng/mL and propanediols also were detected in his urine. Nitrosamines were not detected in samples taken from the mother or the 3-year-old. Metals found in the refill liquid were detected at low levels in both the mother and the 3-year-old. We detected low but not negligible concentrations of e-cigarette–related analytes (including cord blood and breast milk) in an exposed pregnant non-user and in a 3-year-old child also living in the home. Passive exposure to e-cigarette aerosols cannot be disregarded and should be assessed in larger observational studies. • No studies exist on passive exposure to e-cigarettes during pregnancy and childhood. • We detected e-cigarette pollutants in both the pregnant woman and the child. • The only pollutants we found in breast milk were nicotine metabolites. • Neither nicotine metabolites nor any other pollutants were detected in cord blood. • Passive exposure is not irrelevant in the pregnant woman, child, or newborn. [ABSTRACT FROM AUTHOR]

Objective: Radiotherapy (RT) against head and neck squamous cell carcinomas (HNSCC) may lead to severe toxicity in 30-40% of patients. The normal tissue complication probability (NTCP) models, based on dosimetric data refined the normal tissue dose/volume tolerance guidelines. In parallel, the radiation-induced nucleoshuttling (RIANS) of the Ataxia-Telangiectasia Mutated protein (pATM) is a predictive approach of individual intrinsic radiosensitivity. Here, we combined NTCP with RADIODTECT©, a blood assay derived from the RIANS model, to predict RT toxicity in HNSCC patients., Methods: RADIODTECT© cutoff values (i.e. 57.8 ng/mL for grade⩾2 toxicity and 46 ng/mL for grade⩾3 toxicity) have been previously assessed. Validation was performed on a prospective cohort of 36 HNSCC patients treated with postoperative RT. Toxicity was graded with the Common Terminology Criteria for Adverse Events (CTCAE) scale and two criteria were considered: grade⩾2 oral mucositis (OM2), grade⩾3 mucositis (OM3) and grade⩾2 dysphagia (DY2), grade⩾3 dysphagia (DY3). pATM quantification was assessed in lymphocytes of HNSCC patients. The discrimination power of the pATM assay was evaluated through the Area Under the Receiver Operator Characteristics Curve (AUC-ROC). Two previously described NTCP models were considered, including the dose to the oral cavity and the mean dose to the parotid glands (OM2 and OM3) and the dose to the oral cavity, to the larynx and the volume of pharyngeal constrictor muscles (DY2 and DY3)., Results: Combining NTCP models with RADIODTECT© blood test improved the AUC-ROC. Considering the prediction of mucositis, AUC-ROC NTCP+RADIODTECT© =0.80 was for OM2, and AUC-ROC NTCP+RADIODTECT© =0.78 for OM3. Considering the prediction of acute dysphagia, AUC-ROC NTCP+RADIODTECT© =0.71 for DY2 and for DY3., Conclusions: Combining NTCP models with a radiosensitivity biomarker might significantly improve the prediction of toxicities for HNSCC patients.

Recently, there has been growing interest in exosomal biomarkers for their active targeting and specificity for delivering their cargos (proteins, lipids, nucleic acids) from the parent cell to the recipient cell. Currently, the clinical diagnosis of Parkinson's disease (PD) is mainly based on a clinician's neuropsychological examination and motor symptoms (e.g., bradykinesia, rigidity, postural instability, and resting tremor). However, this diagnosis method is not accurate due to overlapping criteria of other neurodegenerative diseases. Exosomes are differentially expressed in PD and a combination of types and contents of exosomes might be used as a biomarker in PD. Here, we systematically reviewed and meta-analyzed exosomal contents, types and sources of exosomes, method of isolation, and protein quantification tools to determine the optimum exosome-related attributes for PD diagnosis. Pubmed, Embase, and ISI Web of Science were searched for relevant studies. 25 studies were included in the meta-analysis. The Ratio of Mean (RoM) with 95% confidence intervals (CI) was calculated to estimate the effect size. Biomarker performances were rated by random-effects meta-analysis with the Restricted Maximum Likelihood (REML) method. The study protocol is available at PROSPERO (CRD42022331885). Exosomal α-synuclein (α-Syn) was significantly altered in PD patients from healthy controls [RoM = 1.67, 95% CI (0.99 to 2.35); p = 0.00] followed by tau [RoM = 1.33, 95% CI (0.79 to 1.87); p = 0.00], PS-129 [RoM = 0.97, 95% CI (0.54 to 1.40); p = 0.00], and DJ-1/PARK7 [RoM = 0.93, 95% CI (0.64 to 1.21); p = 0.00]. Central nervous system derived L1CAM exosome [RoM = 1.24, 95% CI (1.04 to 1.45); p = 0.00] from either plasma [RoM = 1.35, 95% CI (1.09 to 1.61); p = 0.00]; or serum [RoM = 1.47, 95% CI (1.05 to 1.90); p = 0.00] has been found the optimum type of exosome. The exosome isolation by ExoQuick [RoM = 1.16, 95% CI (0.89 to 1.43); p = 0.00] and protein quantification method by ELISA [RoM = 1.28, 95% CI (1.15 to 1.41); p = 0.00] has been found the optimum isolation and quantification method, respectively for PD diagnosis. This meta-analysis suggests that α-Syn in L1CAM exosome derived from blood, isolated by ExoQuick kit, and quantified by ELISA can be used for PD diagnosis. [Display omitted] • A workflow is carved for optimum exosome-based Parkinson's disease (PD) diagnosis. • Blood L1CAM exosomes containing α-synuclein (α-Syn) are the best exosomal biomarker for PD. • ExoQuick kit offers optimum isolation of exosomes for PD diagnosis. • Quantification of α-Syn by ELISA shows the best results for PD diagnosis. [ABSTRACT FROM AUTHOR]

Aims/Introduction Type 2 diabetes is a worldwide disease that is associated with increased rates of obesity and reduced physical activity. Obesity-associated insulin resistance in type 2 diabetes is a disorder in the balance between pro-inflammatory and anti-inflammatory signals. T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) has been reported as an important regulatory inflammation molecule, and plays a pivotal role in several inflammation-related diseases. Materials and Methods Peripheral blood mononuclear cells were obtained from type 2 diabetes patients ( n = 31) and healthy donors ( n = 18), and Tim-3 expression on peripheral blood mononuclear cells was evaluated by flow cytometry. Results We showed the downregulated expression of Tim-3 on CD14+ monocytes from type 2 diabetes patients. In addition, the upregulated expression of Tim-3 on peripheral CD4+ T cells and CD8+ T cells was observed in the present study. The correlation analysis between Tim-3 expression on CD14+ monocytes and diabetes duration showed the longer diabetes duration time, the lower Tim-3 expression on CD14 monocytes. Conclusions The present results suggest that Tim-3 might participate in the progression of type 2 diabetes by its negative regulation on these immune cells, and Tim-3 on CD14+ monocytes serves as a novel biological marker for diabetes duration in type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Animal models of experimental branch retinal vein occlusion (BRVO) provide a unique opportunity to study protein changes directly in retinal tissue. Results from these experimental models suggest that experimental BRVO is associated with an upregulation of extracellular matrix remodeling and adhesion signaling processes. To study whether these processes could be blocked by inhibition of VEGF-A, a porcine model of experimental BRVO was combined with proteomic analyses. In six Danish Landrace pigs experimental BRVO was induced with argon laser in both eyes. After 24 h an injection of 0.05 mL ranibizumab was given in the right eyes of the animals while left eyes received an injection of 0.05 mL 9 mg/mL sodium chloride water. Retinas were dissected three days after BRVO and the retinal samples were analyzed with label-free quantification as well as tandem mass tag based proteomics. In retinas treated with ranibizumab five proteins exhibited statistically significant changes in content with both proteomic techniques. These five proteins, which were all decreased in content, included integrin β-1, peroxisomal 3-ketoacyl-CoA thiolase, OCIA domain-containing protein 1, calnexin and 40S ribosomal protein S5. As anti-integrin therapies are under development for inhibition of angiogenesis in retinal diseases it is interesting that inhibition of VEGF-A in itself resulted in a small decrease in the content of integrin β-1. The decreased content of integrin β-1 indicates that extracellular matrix remodeling and adhesion processes associated with BRVO are at least partly reversed through inhibition of VEGF-A. [ABSTRACT FROM AUTHOR]

Accompanied with the broad application of interventional therapy, the incidence of acute kidney injury (AKI) has been recently increasing in clinical renal medicine. The pathogenesis of AKI is diverse and complex. In the context of the requirements for the diagnosis and treatment of a renal disorder, a large number of studies have explored biological markers and their usefulness to the early diagnosis and treatment of AKI, including glomerular injury, renal tubular injury, and others. These biomarkers provide an important basis for early monitoring of AKI, but are still not quite sufficient. More ideal biomarkers are needed to be identified. Therefore, future studies are necessary to explore more effective biomarkers for AKI clinical practice, which would play an important role in the early diagnosis and intervention treatment of AKI. This review summarizes the important biomarkers identified by previous studies and aims to highlight the advancements that might provide new methods for early clinical diagnosis and effective therapeutic options, along with prediction of response to treatment for AKI. [ABSTRACT FROM AUTHOR]

Introduction: The hormonal fingerprint is the ratio between 2nd and 4th digit lengths. It was evidenced in the medical scenario that it can be used as an indirect marker in many diseases like Coronary Heart Disease (CHD) and metabolic syndromes. As far as dentistry is concerned very few studies in the literature have been done to evaluate the influence of hormonal fingerprint on oral health, thus provoking us to formulate new method for predicting dental caries and malocclusion and its association with Body Mass Index (BMI). Aim: The purpose of this retrospective study was to highlight the role of new biological marker-Hormonal fingerprints in the early detection of malocclusion, caries, the influence of BMI on malocclusion and caries. We also attempted to study the correlation of BMI with hormonal fingerprints. Materials and Methods: A total of 300 children were randomly selected from both sexes of age group 10-15 years. The hormonal fingerprint was made by measuring the length ratio of the index and ring finger with the help of digital Vernier caliper. Anthropometric measures (weight in kilograms and height in metres) for the calculation of BMI were recorded. Caries assessment was done using standard mouth mirrors and Community Periodontal Index probes. DMFT index was followed for assessment of caries according to the WHO assessment form, 1997. Occlusal characteristics of the children evaluated were molar relation, anterior and posterior cross bite, open bite, deep bite, lower anterior crowding. All the factors were recorded by two investigators. Results: The results of the study showed that majority of the children among study population were having 2D:4D <1. The rate of occurrence of malocclusion was increasing with increase in the value of 2D:4D ratio with a statistically significant p-value of <0.001. Higher BMI values were associated with normal occlusal conditions (p= 0.041) and lower 2D:4D ratio (p= 0.037). High caries experience was noticed in children with malocclusion (p= 0.027) which further influences the caries susceptibility. Pearson's correlation test, t-test and ANOVA were used in the study for statistical analysis using SPSS software. Conclusion: This study confirms the impact of hormones on incidence of malocclusion, BMI which in turn influences the caries index and could be used as an early predictor. [ABSTRACT FROM AUTHOR]

Objective We previously reported that decrement of compound muscle action potential (CMAP) by repetitive nerve stimulation (RNS) was greater in the median nerves than in the ulnar nerves of patients with amyotrophic lateral sclerosis (ALS). The aim of this study was to evaluate whether CMAP decrement by RNS is a feasible marker for the differentiation of ALS from other diseases. Materials & methods We performed RNS in the median and ulnar nerves of 51 patients with ALS and 40 patients with other diseases. Results The CMAP decrement was significantly greater in the median nerves of patients with ALS, compared to the disease control patients. In the median nerves of patients with ALS, CMAP decrement was significantly greater in the cervical region-onset group than in the other region-onset group. Conclusions The finding of CMAP decrement in the median nerves can be useful for differentiating ALS patients with cervical region onset from other controls with active neuropathic diseases. [ABSTRACT FROM AUTHOR]

Objective This study was conducted to assess whether serum homocysteine concentration was associated with the severity of primary chronic venous disease. Design Cross-sectional study. Methods A total of 282 primary chronic venous disease patients were enrolled from outpatient vascular services. The severity of venous disease was graded using the Clinical Etiology Anatomy Pathophysiology classification system. The association of serum homocysteine concentration with advanced primary chronic venous disease (C4-6) was assessed using the Mann Whitney U test and logistic regression analysis. Results Median (interquartile range) serum homocysteine concentrations were 9.10 µM (7.55–10.75) and 10.40 µM (8.85–13.10) in patients with primary chronic venous disease classified by C1-3 (n = 209) and C4-6 (n = 73) grades, respectively, p < 0.001. Serum homocysteine concentration was positively associated with clinical grade 4–6 after adjusting for other risk factors including age, diabetes, male sex, hypertension, recurrent varicose veins and stroke. Patients with serum homocysteine in the third (odds ratio, 2.76, 95% confidence interval, 1.01–7.54) and fourth (odds ratio 3.29, 95% confidence interval 1.15–9.43) quartiles were more likely to have grade C4-6 chronic venous disease than subjects with serum homocysteine in the first quartile. Conclusions Serum homocysteine is positively associated with the severity of primary chronic venous disease and therefore could play a role in promoting chronic venous disease complications. [ABSTRACT FROM AUTHOR]

The identification of reliable biomarkers for Alzheimer's disease (AD) remains challenging. Recently, abnormal levels of microRNAs (miRNAs) miR-27a, miR-29a, miR-29b, and miR-125b in cerebrospinal fluid (CSF) of AD patients were reported. We aimed to confirm the biomarker potential of these miRNAs for AD diagnosis. Additionally, we examined the influence of blood contamination on CSF miRNA levels as potential confounding factor. We studied expression levels of the four miRNAs by quantitative PCR in CSF samples of AD patients and non-demented controls, and in blood-spiked CSF. Levels of miR-29a, but not of the other three miRNAs, were increased by a factor of 2.2 in CSF of AD patients. Spiking of small amounts of blood into CSF revealed that miR-27a and miR-29a, but not miR-125b levels were strongly influenced by the number of blood cells in the sample. In conclusion, miR-29a may be a candidate biomarker for AD, but only when used in cell-free CSF. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) are heterogeneous group of hematologic disorders of mostly elderly and based on distinct clinical phenotypes. Current paradigm of their pathogenesis relies on somatic gene mutations combined with the predisposing defective osteohematopoietic niche, but due to the breakout in epigenetic research scientific focus has steered toward two most common epigenetic modifications: methylation mechanisms and histone modification. At the same time, relatively few studies have been undertaken regarding the third epigenetic pathway - microRNAs - in MDS. The main aim of this review is to provide the basics of microRNA biology and function in oncogenesis, showing the complexity of mechanisms behind this single-stranded 22 nucleotides long RNA molecule, with further focus on its implication in MDS pathology and clinical context. By extensive literature search, we have shown enough evidence for their deregulation in MDS. However, few studies have addressed the issue on pathogenic events in MDS and its association with specific microRNAs. Preliminary research in clinical setting has shown the possible utility of microRNAs in terms of prognosis and therapy, although we are only beginning to understand various implications of microRNAs in MDS and further extensive research is warranted to answer multiple questions arising from interconnection of this epigenetic mechanism in MDS. [ABSTRACT FROM AUTHOR]

The aim of this study is to assess neuron-specific enolase (NSE) levels and clinical features in subjects with major depressive disorder (MDD). This is a cross-sectional study with drug-naïve young adults with MDD (aged 18–29 years). Serum levels of NSE were assessed using the electrochemiluminescence method. MDD diagnosis, suicidal ideation, and time of disease were assessed using the Structured Clinical Interview for DSM-IV (SCID). The Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were used to assess depressive and anxiety symptoms. No relationship was observed between NSE levels and severity of depressive and anxiety symptoms, time of disease, and suicidal ideation. These results suggest that NSE serum levels were not associated with clinical features of MDD among drug-naïve young adults. [ABSTRACT FROM AUTHOR]

Adenosine deaminase (ADA) activity measurement in pleural fluid is a relevant test to diagnose pleural tuberculosis (pTB) in high tuberculosis prevalence settings. We investigated the diagnostic utility of pleural ADA using a retrospective analysis of patients admitted with newly diagnosed pleural effusion without identified etiology between 2001 and 2008 in Paris suburb, a low to medium tuberculosis prevalence area. 104 adults (mean age 55 years; 34 with pTB, 70 with other diagnoses) were analyzed. Median follow-up was 15.6 months. Mean [interquartile range] pleural ADA was 119 U/L [IQR: 83–143] in pTB and 24 U/L [IQR: 15–31] in non-tuberculous effusions ( P < 0.001). With an optimal pleural ADA cut-off value of 41.5 U/L for pTB diagnosis, sensitivity and specificity were 97.1% and 92.9%, while positive and negative predictive values were 86.8% and 98.5%, respectively. We conclude that pleural ADA activity could be integrated in the diagnostic procedures of pTB in low to medium tuberculosis prevalence settings. [ABSTRACT FROM AUTHOR]

Aim We examined the utility of the neutrophil CD64 level as a rapid and sensitive diagnostic marker for infections in febrile aged patients. Methods The expression level of CD64 per neutrophil was quantitatively measured with flow cytometry using a QuantiBrite kit in samples from febrile (aged >65 years) patients. Information about the presence or absence of infectious disease was retrospectively obtained from each patient's medical record in which attending physicians were obliged to write down a tentative diagnosis after resolution of manifestations. Results With receiver operating characteristic curve evaluation using the results, a CD64 level >2000 molecules per neutrophil was sensitive and specific for detecting infection. Among 102 patients suspected of having infection, 72 patients were diagnosed with infectious diseases, and 30 patients had non-infectious diseases. The sensitivity and specificity of determination of the neutrophil CD64 level were 88% and 63%, respectively. However, considering the high frequency of infections in elderly patients (71% in the present study), the post-test probability reached as high as 93%. The positive likelihood ratio was 2.4, and the negative likelihood ratio was 0.2. Conclusions Considering the frequency of infectious diseases in elderly patients, determination of the neutrophil CD64 level helps detect infectious diseases. Geriatr Gerontol Int 2015; ●●: ●●-●●. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is linked to numerous brain functions. In addition, BDNF alterations contribute to neurological, mental, and addictive disorders. Cocaine dependence has received much attention recently due to its prevalence and psychological effects. Symptoms of psychosis are one of the most serious adverse events precipitated by cocaine use. It is particularly important to identify patients at risk of developing cocaine-induced psychosis (CIP). We described two cases of patients with cocaine dependence who presented with CIP and had changes in their BDNF levels during the psychotic episode. BDNF levels were initially low in both patients, and then decreased by more than 50% in association with CIP. The relationship between BDNF and psychosis is described in the literature. These cases revealed that BDNF levels decreased during a CIP episode and, thus, it is necessary to investigate BDNF and its relationship with CIP further. [ABSTRACT FROM AUTHOR]

Background: The physiological background of exercise-induced muscle fatigue(EIMUF) is only poorly understood. Thus, monitoring of EIMUF by a single or multiple biomarkers(BMs) is under debate. After a systematic literature review 91 papers were included.Results: EIMUF is mainly due to depletion of substrates, increased oxidative stress, muscle membrane depolarisation following potassium depletion, muscle hyperthermia, muscle damage, impaired oxygen supply to the muscle, activation of an inflammatory response, or impaired calcium-handling. Dehydration, hyperammonemia, mitochondrial biogenesis, and genetic responses are also discussed. Since EIMUF is dependent on age, sex, degree of fatigue, type, intensity, and duration of exercise, energy supply during exercise, climate, training status (physical fitness), and health status, BMs currently available for monitoring EIMUF have limited reliability. Generally, wet, volatile, and dry BMs are differentiated. Among dry BMs of EIMUF the most promising include power output measures, electrophysiological measures, cardiologic measures, and questionnaires. Among wet BMs of EIMUF those most applicable include markers of ATP-metabolism, of oxidative stress, muscle damage, and inflammation. VO2-kinetics are used as a volatile BM.Conclusions: Though the physiology of EIMUF remains to be fully elucidated, some promising BMs have been recently introduced, which together with other BMs, could be useful in monitoring EIMUF. The combination of biomarkers seems to be more efficient than a single biomarker to monitor EIMUF. However, it is essential that efficacy, reliability, and applicability of each BM candidate is validated in appropriate studies. [ABSTRACT FROM AUTHOR]

Background Previous studies have suggested that plasma fibrinogen contributes to tumor cell proliferation, progression and metastasis. The current study was performed to evaluate the prognostic relevance of preoperative plasma fibrinogen in breast cancer patients. Method Data of 2073 consecutive breast cancer patients, who underwent surgery between January 2002 and December 2008 at the Sun Yat-sen University Cancer Center, were retrospectively evaluated. Plasma fibrinogen levels were routinely measured before surgeries. Participants were grouped by the cutoff value estimated by the receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed using Kaplan–Meier analysis, and multivariate Cox proportional hazards regression model was performed to evaluate the independent prognostic value of plasma fibrinogen level. Results The optimal cutoff value of preoperative plasma fibrinogen was determined to be 2.83 g/L. The Kaplan–Meier analysis showed that patients with high fibrinogen levels had shorter OS than patients with low fibrinogen levels ( p < 0.001). Multivariate analysis suggested preoperative plasma fibrinogen as an independent prognostic factor for OS in breast cancer patients (HR = 1.475, 95% confidence interval (CI): 1.177–1.848, p = 0.001). Subgroup analyses revealed that plasma fibrinogen level was an unfavorable prognostic parameter in stage II–III, Luminal subtypes and triple-negative breast cancer patients. Conclusion Elevated preoperative plasma fibrinogen was independently associated with poor prognosis in breast cancer patients and may serve as a valuable parameter for risk assessment in breast cancer patients. [ABSTRACT FROM AUTHOR]