OBJECTIVE: Fibromyalgia syndrome (FMS) is a disease of unknown pathophysiology, with the diagnosis being based on a set of clinical criteria. Proteomic analysis can provide significant biological information for the pathophysiology of the disease but may also reveal biomarkers for diagnosis or therapeutic targets. The present systematic review aims to synthesize the evidence regarding the proteome of adult patients with FMS using data from observational studies.
RESULTS: An extensive literature search was conducted in MEDLINE/PubMed, CENTRAL, and clinicaltrials.gov from inception until November 2022. The study protocol was published in OSF. Two independent reviewers evaluated the studies and extracted data. The quality of studies was assessed using the modified Newcastle-Ottawa scale adjusted for proteomic research. Ten studies fulfilled the protocol criteria, identifying 3328 proteins, 145 of which were differentially expressed among patients with FMS against controls. The proteins were identified in plasma, serum, cerebrospinal fluid, and saliva samples. The control groups included healthy individuals and patients with pain (inflammatory and non-inflammatory). The most important proteins identified involved transferrin, α-, β-, and γ-fibrinogen chains, profilin-1, transaldolase, PGAM1, apolipoprotein-C3, complement C4A and C1QC, immunoglobin parts, and acute phase reactants. Weak correlations were observed between proteins and pain sensation, or quality of life scales, apart from the association of transferrin and a2-macroglobulin with moderate-to-severe pain sensation. The quality of included studies was moderate-to-good. FMS appears to be related to protein dysregulation in the complement and coagulation cascades and the metabolism of iron. Several proteins may be dysregulated due to the excessive oxidative stress response.

OBJECTIVE: This meta-analysis aimed to investigate the correlation between plasma biomarkers, such as albumin and fibrinogen, and their ratio with postoperative delirium (POD) in patients undergoing non-cardiac surgery.
METHODS: Relevant observational cohort studies were systematically searched in PubMed, EMBASE, CINAHL, and the Cochrane Library databases as of March 2023. This meta-analysis was conducted using RevMan 5.4.1 and Stata 15.0 software. For continuous variables with non-uniform units, the standardized mean difference (SMD) and 95% confidence intervals (CIs) were used; otherwise, the mean difference (MD) and 95% CIs were employed. The Newcastle-Ottawa Scale (NOS) was applied to assess the quality of included literature.
RESULTS: Eighteen studies encompassing 7,011 patients were included. The meta-analysis revealed significantly lower albumin levels (sixteen studies, 5,813 patients, SMD = -0.45, 95% CI = -0.64 to -0.26, P < 0.00001, I2 = 80%) and albumin-fibrinogen ratio (AFR) (four studies, 824 patients, MD = -0.62, 95% CI = -0.76 to -0.48, P = 0.56, I2 = 0%) in the delirious group. Conversely, higher fibrinogen concentrations (two studies, 441 patients, MD = 0.13, 95% CI = 0.02 to 0.24, P = 0.69, I2 = 0%) were observed in the delirious group. Due to high heterogeneity in albumin levels (P < 0.00001, I2 = 80%), we conducted a subgroup and sensitivity analysis, and confirmed that the association of albumin levels was not influenced by surgery type, design or delirium evaluation instruments.
CONCLUSIONS: Preoperative albumin, fibrinogen and AFR levels were associated with POD, potentially aiding in identifying high-risk patients and playing a key role in preventing POD.

BACKGROUND: Hormone replacement therapy is associated with an increased thromboembolic risk. The effects of testosterone (T) on coagulation markers in people assigned female at birth (AFAB) under gender affirming hormone therapy (GAHT) are not well described.
METHODS: Systematic review and meta-analysis on English-language articles retrieved from PubMed, Scopus and Cochrane Library up to April 2023 investigating T therapy in AFAB people. Coagulation parameters included international normalized ratio (INR), fibrinogen, activated partial thromboplastin clotting time (aPTT), plasminogen activator inhibitor-1 (PAI-1); hematological variables included hemoglobin (Hb) and hematocrit (HCT). We also reported the rate of thromboembolic events. Data were combined as mean differences (MD) with a 95 % confidence interval (CI) of pre- vs post-follow-up values, using random-effects models.
RESULTS: We included 7 studies (6 prospective and 1 retrospective) providing information on 312 subjects (mean age: 23 to 30 years) who underwent GAHT with variable T preparation. T therapy was associated with a significant increase in INR values [MD: 0.02, 95 % confidence interval (CI): 0.01-0.03; p = 0.0001], with negligible heterogeneity (I2 = 4 %). T therapy was associated with increased Hb (MD: 1.48 g/dL, 95%CI: 1.17 to 1.78; I2 = 9 %) and HCT (4.39 %, 95%CI: 3.52 to 5.26; I2 = 23 %) values. No effect on fibrinogen, aPTT and PAI-1 was found. None of the study reported thromboembolic events during the follow-up.
CONCLUSIONS: Therapy with T increased blood viscosity in AFAB men. A slight increase in INR values was also found, but the clinical relevance and mechanism(s) of this finding needs to be clarified.

Aims  In this systematic review, we assessed the literature on the association between fibrinogen levels and stroke in patients with type 2 diabetes (T2D). Methods  MEDLINE and Ovid searches of English reports were performed on the relation between fibrinogen, stroke, and T2D in humans. The search was completed on May 4, 2023. Studies were eligible when T2D patients ≥18 years had stroke confirmed by computed tomography or magnetic resonance imaging, plasma fibrinogen was measured, and a relation between fibrinogen and stroke in T2D patients was reported. Screening of reports and extraction of data were done independently by two authors, and study quality was assessed by predefined issues. Results  Five studies of different designs were included. Three studies reported on significantly increased fibrinogen levels in T2D patients with stroke compared with T2D patients without stroke. Two studies did not observe a significant association between fibrinogen levels and stroke risk. Conclusion  No consistent association was observed between fibrinogen levels and risk of stroke in T2D patients. Due to differences in study design, low sample size, and poorly defined study participants, larger and better-defined studies are needed to elucidate the role of fibrinogen as a stroke risk marker in T2D patients.

BACKGROUND: Abnormal bleeding due to low fibrinogen (Fib) and coagulation factor XIII (FXIII) levels after lumbar vertebral surgery is exceedingly rare. Excessive bleeding is also associated with secondary hyperfibrinolysis. This report presents a case of abnormal incision bleeding caused by coagulation factor XIII deficiency (FXIIID) and secondary hyperfibrinolysis in a state of low fibrinogen after lumbar vertebral surgery.
METHODS: A middle-aged woman experienced prolonged incision and excessive bleeding after lumbar vertebral surgery.
METHODS: Combined with coagulation factors, coagulation function tests, and thromboelastography, the patient clinical presentation supported the diagnosis of FXIIID and secondary hyperfibrinolysis in a hypofibrinogenemic state.
METHODS: Cryoprecipitat, Fresh Frozen Plasma, Fibrinogen Concentrate, Leukocyte-depleted Red Blood Cells, Hemostatic (Carbazochrome Sodium Sulfonate; Hemocoagulase Bothrops Atrox for Injection; Tranexamic Acid).
RESULTS: After approximately a month of replacement therapy and symptom treatment, the patient coagulation function significantly improved, and the incision healed without any hemorrhage during follow-up.
CONCLUSIONS: Abnormal postoperative bleeding may indicate coagulation and fibrinolysis disorders that require a full set of coagulation tests, particularly coagulation factors. Given the current lack of a comprehensive approach to detect coagulation and fibrinolysis functions, a more comprehensive understanding of hematology is imperative. The current treatment for FXIIID involves replacement therapy, which requires supplementation with both Fib and FXIII to achieve effective hemostasis.

UNASSIGNED: Patients suffering from cancer are reported to have an increased risk of ischemic stroke (IS). We aimed to identify cancer-associated biomarkers found to differentiate between IS associated with cancer from those not associated with cancer.
UNASSIGNED: We performed a systematic search of PubMed and EMBASE databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study is reported in PROSPERO (#CRD42022355129). In total, 5563 papers were screened, of which 49 papers were included. Seven biomarkers were identified which had the potential to differentiate between patients who had cancer or stroke or both conditions. D-dimer was the most frequently monitored biomarker, and high levels were significantly associated with cancer-related strokes in (42/44) studies. Fibrinogen was significantly associated with cancer-related strokes in 11/27 studies. A higher level of C-reactive protein, investigated in 19 studies, was associated with cancer-related strokes, but conclusive multivariate analysis was not performed. Finally, the four cancer-associated antigens CA125, CA153, CA199, and carcinoembryonic antigen were only reported on in three to six studies, respectively. These studies all originated from the Guangxi province in China. CA125 was associated with an increased risk of IS in four of six studies.
UNASSIGNED: Increased D-dimer seems associated with cancer-related IS. CRP may also be a candidate as a cancer-associated stroke biomarker, but this requires further verification. Fibrinogen and the more specific cancer biomarkers have not yet been proven helpful for detecting cancer-related strokes.

OBJECTIVE: To study the bone marrow (BM) immunohistomorphological characteristics in adult systemic lupus erythematosus (SLE) associated macrophage activation syndrome (SLE-MAS).
METHODS: Immunohistochemical (IHC) expression of CD3, CD8, perforin (PFN), and CD163 was studied on BM trephine biopsies from 30 cytopenic adult SLE cases (male: female = 1:5, age; 24 years, range; 19-32) and compared them with ten age matched controls. Clinicopathological parameters were compared among the cases likely (L) or unlikely (U) to have MAS using probability scoring criteria. The best cut off laboratory parameters to discriminate between the two were obtained through receiver operator curve (ROC) analysis.
RESULTS: MAS occurred in 12/30 (40%) cases and was more commonly associated with prior immunosuppressive therapy (p = .07), ≥ 3 system involvement (p = .09), lower fibrinogen (p < .01), increased triglyceride (p = .002), increased BM hemophagocytosis (p = .002), and higher MAS score [185 (176-203) vs. 105 (77-119), p < .01] than MAS-U subgroup. Although PFN+CD8+ T lymphocytes significantly decreased among cases than controls (p < .05), it was comparable between MAS-L and MAS-U subgroups. Fibrinogen (< 2.4 g/L, AUC; 0.93, p < .01), hemophagocytosis score (> 1.5, AUC; 0.71, p = .03), and an MAS probability score of ≥ 164 (AUC; 1, p < .01) discriminated MAS from those without MAS.
CONCLUSIONS: We noted a decrease in perforin mediated CD8 + T cell cytotoxicity in SLE. Immunohistochemical demonstration of the same along with histiocytic hemophagocytosis on BM biopsy may be useful adjunct in early diagnosis and management of MAS in SLE.

Statins are powerful lipid-lowering drugs that inhibit cholesterol biosynthesis via downregulation of hydroxymethylglutaryl coenzyme-A reductase, which are largely used in patients with or at risk of cardiovascular disease. Available data on thromboembolic disease include primary and secondary prevention as well as bleeding and mortality rates in statin users during anticoagulation for VTE. Experimental studies indicate that statins alter blood clotting at various levels. Statins produce anticoagulant effects via downregulation of tissue factor expression and enhanced endothelial thrombomodulin expression resulting in reduced thrombin generation. Statins impair fibrinogen cleavage and reduce thrombin generation. A reduction of factor V and factor XIII activation has been observed in patients treated with statins. It is postulated that the mechanisms involved are downregulation of factor V and activated factor V, modulation of the protein C pathway and alteration of the tissue factor pathway inhibitor. Clinical and experimental studies have shown that statins exert antiplatelet effects through early and delayed inhibition of platelet activation, adhesion and aggregation. It has been postulated that statin-induced anticoagulant effects can explain, at least partially, a reduction in primary and secondary VTE and death. Evidence supporting the use of statins for prevention of arterial thrombosis-related cardiovascular events is robust, but their role in VTE remains to be further elucidated. In this review, we present biological evidence and experimental data supporting the ability of statins to directly interfere with the clotting system.

Fibrinogen and homocysteine (HCY) are molecules known to play a role in vascular homeostasis, and their blood levels are often elevated in patients with metabolic syndrome. Recent evidence suggests that sudden sensorineural hearing loss (SSHL) may have a vascular origin. This has led many authors to advocate that fibrinogen, homocysteine, and metabolic syndrome (MetS) may play a direct role in SSHL. The aim of this brief review is to examine the role and influence of these molecules and MetS on the mechanisms of SSHL. Elevated fibrinogen levels have been associated with a worse prognosis in SSHL, possibly due to increased blood viscosity and decreased blood flow. Similarly, HCY has been associated with vascular damage, particularly in hyperhomocysteinemia, although the exact association with SSHL remains controversial. MetS has been demonstrated to function both as a causative factor and as a contributor to poorer recovery in cases of SSHL. However, although some studies suggest a possible role for these biomarkers and MetS in the prognosis and treatment of SSHL, specific therapeutic and preventive strategies based solely on these factors have yet to be developed. Given their potential role in prognosis and treatment and the global epidemic of metabolic syndrome, this issue needs to be analyzed comprehensively. Thus, further quality studies need to be conducted, even though it is difficult to determine the actual impact of MetS on the development of SSHL, as it is a multifactorial disease affecting multiple organs.

Parasitic blood diseases (theileriosis, babesiosis, anaplasmosis, and trypanosomiasis) are common in regions where the distributions of the hosts, parasites, and vectors are convergent. They endanger animal production, and a few are also harmful to public health. The acute phase reaction (APR) is a complex, non-specific reaction that occurs in various events, including surgical trauma, infection, stress, inflammation, and neoplasia. To understand pathogenesis, we must study APR effects and acute phase proteins (APPs) alterations in naturally occurring and experimental infections. The elevation of haptoglobin (Hp), Serum amyloid A (SAA), and fibrinogen concentrations was markedly significant in bovine and ovine theileriosis. Hp, SAA, ceruloplasmin, and fibrinogen concentrations in anaplasmosis were dramatically elevated. A significant increase in SAA was observed in bovine babesiosis, while ovine babesiosis showed a significant rise in sialic acid levels. In cases of trypanosomiasis caused by T. vivax, there have been reports of elevated levels of Hp, complement C3, and antitrypsin. Improving our understanding of APR could result in more effective methods for diagnosis, treatment, control, and eradication of diseases. The article provides an overview of APPs alterations and other inflammation-related parameters (some cytokines, adenosine deaminase, and sialic acids) in parasitic blood diseases of ruminants.