Previous research indicates an association between sleep traits and venous thromboembolism (VTE) risk, though causal relationships remain uncertain. This study evaluated combined and independent associations between sleep traits and VTE risk using UK Biobank data and explored the causal associations between sleep traits and VTE through two-sample Mendelian randomization (MR) analyses. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations between the healthy sleep score, as well as individual sleep traits (including sleep duration, insomnia, daytime sleepiness, snoring, and chronotype), and VTE risk were calculated using Cox proportional hazards regression models. Additionally, the two-sample MR analyses used the inverse-variance weighted method to determine odds ratios (ORs) and 95% CIs for causal associations. In the cohort analysis, 314 077 VTE-free participants were followed for a median of 12.3 years, during which 7176 VTE cases occurred. In comparison to those with a sleep score of 0-1, participants with a score of 5 were associated with a 30% lower risk of VTE (HR: 0.70; 95% CI: 0.61-0.80). A U-shaped association was noted between sleep duration and VTE risk. Both short (≤ 6 h) and long (≥ 9 h) sleep durations increased VTE risk. Excessive daytime sleepiness, snoring, and evening chronotype also elevated VTE risk. MR analyses supported a causal relationship for short sleep duration (OR: 1.24; 95% CI: 1.04-1.47) with VTE risk, while other sleep traits showed no causal association. These findings underscore the importance of optimal sleep in reducing VTE risk.

Lemierre's syndrome (LS) represents a rare yet potentially life-threatening systemic infection, characterized by thrombophlebitis of the internal jugular vein and abscess formation in distant organs. It typically follows episodes of tonsillitis or other infections of the oropharyngeal region. Pulmonary complications, including septic pulmonary emboli, are common. Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) sometimes associated with the JAK2V617F mutation, which predisposes patients to thrombotic events. A 66-year-old male with JAK2V617F-positive ET presented with severe pulsatile pain radiating from the right temporal region to the occipital area following a recent dental infection. Although pain management was administered, the pain continued to persist. Computed tomography of the chest revealed multiple subpleural nodules, raising suspicion for septic pulmonary emboli. Further investigation with gadolinium-enhanced magnetic resonance imaging identified a thrombus extending from the right sigmoid sinus into the internal jugular vein, consistent with cerebral venous thrombosis. The patient was diagnosed with　LS, complicated by septic thrombosis. Blood cultures yielded alpha-hemolytic streptococcus. Empirical antimicrobial therapy combined with anticoagulation was initiated, resulting in a gradual improvement of symptoms, including the resolution of fever and pain. Follow-up imaging confirmed the resolution of both the infection and thrombosis. This is the first reported case of LS in a patient with JAK2V617F-positive ET. The coexistence of LS and JAK2V617F-positive MPN highlights the potential interplay between proinflammatory and prothrombotic conditions associated with the JAK2V617F mutation.

Coagulation is related to inflammation, but the key pathway, especially innate immune system and coagulation regulation, is not well understood and need to be further explored. Here, we demonstrated that neutrophil gelatinase-associated lipocalin (NGAL), an innate immune inflammatory mediator, is upregulated in patients with thrombosis. Furthermore, it contributes to the initiation and amplification of coagulation, hemostasis, and thrombosis. This occurs by enhancing tissue factor expression on the cell surface, potentiating various clotting factors such as thrombin, kallikrein, factor XIa (FXIa), and FVIIa, promoting thrombin-induced platelet aggregation, and inhibiting antithrombin. NGAL knockout led to strikingly prolonged clot reaction time and kinetic time in thromboelastography analysis, along with reduced thrombus generation angle and lower thrombus maximum amplitude, which were in line with remarkably prolonged activated partial thromboplastin time and prothrombin time. In several mouse hemostasis and thrombosis models, NGAL overexpression or IV administration promoted coagulation and hemostasis and aggravated thrombosis, whereas NGAL knockout or treatment with anti-NGAL monoclonal antibody significantly prolonged bleeding time and alleviated thrombus formation. Notably, NGAL knockout prolonged mouse tail bleeding time or artery occlusion time to over 40 or 60 minutes, respectively, resembling uncontrollable bleeding and clotting disorder seen in hemophilic mice. Furthermore, anti-NGAL monoclonal antibody treatment markedly reduced the formation of blood clots in inflammation-induced thrombosis models. Collectively, these findings unveil a previously unidentified role of NGAL in the processes of coagulation, hemostasis, and thrombosis, as well as the cross talk between innate immunity, inflammation, and coagulation. Thus, modulating NGAL levels could potentially help balance thrombotic and hemorrhagic risks.

Gender-affirming surgery (GAS) is a complex process that often requires multiple surgical operations and carries a complication risk that could be exacerbated by connective tissue disorders (CTDs). This study aims to investigate the association between CTD diagnosis and GAS outcomes.

Using the Merative MarketScan Research Databases, patients with gender dysphoria diagnoses who underwent GAS between 2007 and 2022 were identified. Among these, patients with diagnosed CTDs were identified. Demographics, comorbidities, and postoperative complications were recorded. Chi-squared, Shapiro-Wilk, Wilcoxon-Mann-Whitney, and multivariate logistic regression testing was used for statistical analysis.

Of 7575 patients meeting criteria (mean age 29 ±10 years), 300 (4%) had CTD diagnoses. One or more postoperative complications were recorded in 9.8% of patients, without statistically significant difference between CTD and non-CTD patients. Additional simultaneous GAS procedures [odds ratio (OR) 2.02; P < 0.01], Elixhauser index scores of 3+ (OR 1.36; P = 0.010), and age >45 years (OR 1.47; P = 0.02) increased odds of experiencing complications following the index GAS procedure, while CTD diagnoses (P = 0.52) did not affect odds of experiencing complications. However, CTD diagnoses did elevate odds of readmission (OR 1.47; P = 0.046), as did multiple simultaneous GAS procedures (OR 2.66), Elixhauser index scores of 3+ (OR 3.72), and smoking (OR 2.18) (P < 0.01).

These findings suggest CTDs may impact some gender-affirming surgical outcomes, and careful preoperative evaluation and management of comorbidities is necessary to reduce the risk of complications and readmission in this population. Surgeons should continue to exercise caution when performing elective surgery on patients taking immunomodulatory medications.

Multi-trauma presents significant challenges due to the complexity of injuries and high mortality rates. Early identification and intervention are crucial for improving outcomes in these critically injured patients. This retrospective study analyzed clinical data from multi-trauma patients admitted to the emergency department of Huiyang Sanhe Hospital between January 10, 2020, and September 30, 2022. Univariate and multivariate logistic regression analyses were conducted to identify independent predictors of hospital mortality. A prediction model was developed based on these prognostic markers, visualized using a nomogram, and its discriminative ability and clinical benefit were evaluated. A total of 124 multi-trauma patients were included in the study, with a hospital mortality rate of 26.7%. Univariate and multivariate logistic regression analyses identified trauma-induced coagulopathy (TIC) (OR 4.238, 95% CI 1.46-12.28), blood urea nitrogen (BUN) (OR 1.397, 95% CI 1.09-1.78), and Glasgow Coma Scale (GCS) score (OR 0.720, 95% CI 0.61-0.85) as independent factors of hospital mortality. Therefore, a nomogram incorporating TIC, BUN, and GCS score was constructed and demonstrated excellent predictive performance and clinical impact (AUC 0.898, 95% CI 0.834-0.962). The nomogram developed in this study provided a practical tool for early prediction of hospital mortality in multi-trauma patients. By focusing on TIC, BUN, and GCS score, this model may facilitate rapid bedside assessment and timely intervention. However, further multicenter, prospective studies are required to validate its performance and applicability.

Coagulation factors are intrinsically expressed in various brain cells, including astrocytes and microglia. Their interaction with the inflammatory system is important for the well-being of the brain, but they are also crucial in the development of many diseases in the brain such as stroke and traumatic brain injury. The cellular effects of coagulation are mediated mainly by protease-activated receptors. In this review, we sum up the role of the coagulation cascade in the development of different diseases including psychiatric disorders. In inflammatory diseases such as multiple sclerosis, fibrinogen activates microglia and suppresses the differentiation of oligodendrocytes, leading to axonal damage and suppression of remyelination. In ischemic stroke, thrombin activity is associated with the size of infarction, and the inhibition of either thrombin- or protease-activated receptor 1 promotes neuronal survival and reduces the size of infarction. Patients suffering from Alzheimer's disease express higher levels of thrombin, which in turn damages the endothelium, increases blood-brain barrier permeability, and induces cell apoptosis. In major depressive disorder, a positive correlation is present between prothrombotic states and suicidality. Moreover, both protein S deficiency and antiphospholipid antibodies are associated with schizophrenia and there is an effect of warfarin on psychosis-free intervals. Studying the coagulation in the brain could open a new door in understanding and treating neurological and psychiatric disorders, and extensive research should be conducted in this field.

Disseminated intravascular coagulation (DIC) is a severe complication in septic patients. The Japanese Ministry of Health and Welfare (JMHW)-DIC criteria, the first DIC criteria, were established in 1983, and several other criteria have been proposed since then, including the International Society on Thrombosis and Haemostasis (ISTH)-overt DIC criteria and the Japanese Association for Acute Medicine (JAAM) DIC criteria. This study aimed to look into the transition of DIC criteria used in randomized controlled trials (RCTs) for sepsis-induced DIC.

We searched PubMed, Scopus, and the Cochrane Central Register of Controlled Trials for English-language studies published through September 30, 2023. Two reviewers looked through citations that assessed the DIC criteria used in RCTs and their secondary analyses. Data on DIC diagnostic criteria, patient characteristics, interventions, and results were gathered.

Twenty-one studies (thirteen RCTs: JMHW-DIC in 5, JAAM-DIC in 4, the sepsis-induced coagulopathy (SIC) in 2; and eight secondary analyses: ISTH-overt DIC in 3, single parameter in 5) were eligible for inclusion. Most RCTs were conducted in Japan, using the criteria of JMHW-DIC, which were followed by JAAM-DIC. Recently, SIC has been used in international RCTs. Meanwhile, other countries tended to conduct RCTs that focused on sepsis, with secondary analyses for DIC using the ISTH-overt DIC criteria.

The criteria used in RCTs have changed over decades, from the JMHW-DIC to the JAAM-DIC criteria, and the ISTH-overt DIC criteria were retained in the secondary analysis. Based on these findings, additional research is needed to determine the best criterion for diagnosing septic patients.

Background: Blunt thoracic trauma possesses unique physiopathological traits due to the complex interaction of immune and coagulation systems in the lung tissue. Hemogram-based ratios such as neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), neutrophil-to-lymphocyte × platelet (NLPR) ratios have been studied as proxies for immune dysregulation and survival in trauma. We hypothesized that blunt thoracic trauma patients exhibit distinct patterns of coagulation and inflammation abnormalities identifiable by the use of readily available hemogram-derived markers. Methods: The present study represents a retrospective observational analysis that included 86 patients with blunt thoracic trauma from a single high-volume level one trauma center. The primary outcome was mortality prediction in blunt thoracic trauma patients using these derived biomarkers. Secondary outcomes included phenotypes of the immune response and coagulopathy and the prediction of non-fatal adverse events. Results: A U-shaped distribution of mortality was found, with high rates of early deaths in patients with an NLPR value of <3.1 and high rates of late deaths in patients with NLPR > 9.5. A subgroup of blunt thoracic trauma patients expressing moderate inflammation and inflammation-induced hypercoagulation objectified as NLPR between 3.1 and 9.5 may have a survival benefit (p < 0.0001). The NLPR cut-off for predicting early deaths and the need for massive transfusion was 3.1 (sensitivity = 80.00% and specificity = 71.05%). Conclusions: These findings suggest that blunt thoracic trauma patients exhibit distinct phenotypes of the immune response and coagulopathy from the early stages. A controlled, balanced interaction of immune, coagulation, and fibrinolytic systems might effectively achieve tissue repair and increase survival in thoracic trauma patients and should be subject to further research.

Idiopathic pulmonary fibrosis (IPF) is associated with a significantly increased risk of thrombotic events and mortality. This review explores the complex bidirectional relationship between pulmonary fibrosis and thrombosis, discussing epidemiological evidence, pathogenetic mechanisms, and therapeutic implications, with a particular focus on the emerging role of extracellular vesicles (EVs) as crucial mediators linking fibrosis and coagulation. Coagulation factors directly promote fibrosis, while fibrosis itself activates thrombotic pathways. Retrospective studies suggest the benefits of anticoagulants in IPF, but prospective trials have faced challenges. Novel anticoagulants, profibrinolytic therapies, and agents targeting protease-activated receptors (PARs) show promise in preclinical studies and early clinical trials. EVs have emerged as key players in the pathogenesis of interstitial lung diseases (ILDs), serving as vehicles for intercellular communication and contributing to both fibrosis and coagulation. EV-based approaches, such as EV modulation, engineered EVs as drug delivery vehicles, and mesenchymal stem cell-derived EVs, represent promising therapeutic strategies. Ongoing research should focus on optimizing risk-benefit profiles, identifying predictive biomarkers, evaluating combination strategies targeting thrombotic, fibrotic, and inflammatory pathways, and advancing the understanding of EVs in ILDs to develop targeted interventions.

Uterine corpus endometrial carcinoma (UCEC), derived from the endometrium, is the most common type of endometrial malignasis. This gynecological malignancy is very common all over the world, especially in developed countries and shows a potentially rising trend correlated with the increase in obese women.

Differentially Expressed Genes (DEGs) analysis was conducted on GSE7305 and GSE25628 datasets from the Gene Expression Omnibus (GEO). DEGs were identified using GEO2R (adjusted p-value <0.05, |logFC| > 1). Pathway analysis employed KEGG and Gene Ontology databases, while protein-protein interactions were analyzed using Cytoscape and Gephi. GEPIA was used for target gene validation.

We have identified 304 common DEGs and 78 hub genes using GEO and PPI analysis, respectively. The GO and KEGG pathways analysis revealed enrichment of DEGs in extracellular matrix structural constituent, extracellular space, cell adhesion, and ECM-receptor interaction. GEPIA analysis identified three genes, ENG, GNG4, and ECT2, whose expression significantly differed between normal and tumor samples.

This analysis study identified the hub genes and associated pathways involved in the pathogenesis of UCEC. The identified hub genes exhibit remarkable potential as diagnostic biomarkers, providing a significant opportunity for early diagnosis and more effective therapeutic approaches for UCEC.

Cerebral cavernous malformation (CCM) is a neurovascular disease with symptoms such as strokes, hemorrhages and neurological deficits. With surgery being the only treatment strategy, understanding the molecular mechanisms of CCM is crucial in finding alternative therapeutic options for CCM. Neutrophil extracellular traps (NETs) were recently reported in CCM, and NETs were shown to have positive or negative effects in different disease contexts. In this study, we investigated the roles of NETs in CCM by pharmacologically inhibiting NET formation using Cl-amidine (a peptidyl arginine deiminase inhibitor). We show here that Cl-amidine treatment reduced lesion burden, coagulation and endothelial-to-mesenchymal transition. Furthermore, NETs promoted the activation of microglia and fibroblasts, leading to increased neuroinflammation and a chronic wound microenvironment in CCM. The inhibition of NET formation caused endothelial quiescence and promoted a healthier microenvironment. Our study suggests the inhibition of NETs as a potential therapeutic strategy in CCM.

Drugs blocking the renin-angiotensin-aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We have shown antithrombin effects by treatment with the angiotensin converting enzyme (ACE) inhibitor ramipril. As thrombin is a key inducer of platelet aggregation, we hypothesized that treatment with ramipril could modulate platelet reactivity and endothelial glycocalyx (eGCX) function. This study assessed platelet activity (CD40 ligand and P-selectin) and eGCX markers (E-selectin, hyaluronan, syndecan-1, and thrombomodulin) in 59 individuals with mild-to-moderate hypertension, randomized double-blind to ramipril 10 mg or doxazosin 8 mg od for 12 weeks. Ramipril and doxazosin similarly reduced blood pressure. Antihypertensive treatment reduced CD40 ligand (p < .001) with no interaction (p = .405) by treatment group (reductions by ramipril and doxazosin were 8.7 ± 30.8 ng/L, p = .044, and 13.4 ± 25.5 ng/L, p = .002, respectively). There were no changes in P-selectin by treatment within (p = .556) or between (p = .256) treatment groups. No changes were observed in E-selectin, hyaluronan, syndecan-1, or thrombomodulin by antihypertensive treatment (p = .091-.991), or between ramipril and doxazosin (p = .223-.999). Our results show a potential reduction of platelet activity by ACE inhibitor treatment. Also, the alpha 1-adrenoceptor antagonist doxazosin may reduce platelet activation. Neither drug influenced eGCX markers.

Recombinant human fibroblast growth factor-2 (rhFGF-2) has demonstrated positive effects on wound healing at 2 weeks after periodontal surgery relative to enamel matrix derivative (EMD). However, the effects at earlier postoperative stages have not been reported. This retrospective study compared the early wound healing outcomes 1 week after surgery using the modified papilla preservation technique (mPPT) with either EMD or rhFGF-2 therapy.

We compiled a list of all mPPT sites treated with EMD or rhFGF-2 during the survey period (September 2011 to March 2022). Early wound healing was assessed using the early wound healing score (EHS) and the modified early wound healing index (mEHI). Inter-rater reliability for the EHS and mEHI was established using intraclass correlation coefficients. Factors influencing mPPT were identified by analyzing the correlation coefficients between the EHS items, mEHI items, and potential influencing factors. After adjusting for factors impacting EHS, mEHI, and mPPT, we compared the EHS and mEHI between EMD and rhFGF-2 groups.

In total, 72 sites were evaluated. The scores for incision line, step, and dehiscence were significantly higher in those receiving rhFGF-2 (n=42) compared to those treated with EMD (n=30). The EHS item scores did not differ significantly between groups. Among patients aged ≥50 years, but not those <50 years, significantly higher step and dehiscence scores were found in the rhFGF-2 group than the EMD group (P<0.01). Additionally, for patients exhibiting a clinical attachment level (CAL) ≥8 mm, the step score was significantly higher in the rhFGF-2 group than in the EMD group (P<0.05), but this trend was not reflected in those with a CAL <8 mm.

In this study, early wound closure at mPPT sites was more effectively achieved with rhFGF-2 than with EMD. Nevertheless, biochemical assessments are required to compare the re-epithelialization effects of these therapies.

Hospitalized COVID-19 patients exhibit diverse immune responses during acute infection, which are associated with a wide range of clinical outcomes. However, understanding these immune heterogeneities and their links to various clinical complications, especially long COVID, remains a challenge. In this study, we performed unsupervised subtyping of longitudinal multi-omics immunophenotyping in over 1,000 hospitalized patients, identifying two critical subtypes linked to mortality or mechanical ventilation with prolonged hospital stay and three severe subtypes associated with timely acute recovery. We confirmed that unresolved systemic inflammation and T-cell dysfunctions were hallmarks of increased severity and further distinguished patients with similar acute respiratory severity by their distinct immune profiles, which correlated with differences in demographic and clinical complications. Notably, one critical subtype (SubF) was uniquely characterized by early excessive inflammation, insufficient anticoagulation, and fatty acid dysregulation, alongside higher incidences of hematologic, cardiac, and renal complications, and an elevated risk of long COVID. Among the severe subtypes, significant differences in viral clearance and early antiviral responses were observed, with one subtype (SubC) showing strong early T-cell cytotoxicity but a poor humoral response, slower viral clearance, and greater risks of chronic organ dysfunction and long COVID. These findings provide crucial insights into the complex and context-dependent nature of COVID-19 immune responses, highlighting the importance of personalized therapeutic strategies to improve both acute and long-term outcomes.

Recent studies of children with inflammatory bowel disease (IBD) demonstrate an increased venous thromboembolism (VTE) risk. However, estimates of risk are variable and case numbers are limited. The aim of this study was to provide national estimates of the risk of VTE in children with IBD.

Hospital Episode Statistics was used to identify patients diagnosed with either IBD or VTE before reaching 18 years of age between 2001 and 2019. Populations and subgroups are described, and the risks of developing VTE in the general and IBD populations were calculated.

Children with VTE following a diagnosis of IBD or in the previous 6 months (n = 85) and with VTE without IBD (n = 4160) were studied. The absolute risk in children with IBD was 9.42 (95% confidence interval [CI], 7.4-11.4) per 10 000 patient-years, compared with 0.18 (95% CI, 18-0.19) in children without IBD. Between 6 months prior to and 1 year following IBD diagnosis was the highest absolute risk period for VTE (18.0; 95% CI, 13.7-22.4). The relative risk of VTE in children with IBD vs children without IBD was greatest in younger patient groups: the relative risk for the age band 0 to 8 years was 96.5 (95% CI, 51.8-179.9) and for 9 to 11 years was 153.1 (95% CI, 81.2-288.8) vs 14.3 (95% CI, 10.3-20.0) for 15 to 17 years. Cerebral venous sinus thrombosis represented 17.6% of pediatric VTE events in IBD patients compared with 4.2% in children without IBD (P = .001).

This study confirms the increased risk of VTE in children with IBD compared with children without IBD. The time of greatest VTE risk was around diagnosis. Cerebral venous sinus thrombosis was significantly more common in children with IBD than other children.

Inflammatory dermatologic diseases have long been viewed as a "skin limited" disease process. Current literature on inflammatory dermatologic diseases investigates their relationship and influence on thromboembolic states and thromboembolic complications and the understanding of their pathophysiology and molecular mechanisms.Studies specifically discuss known inflammatory skin diseases including alopecia areata, vitiligo, psoriasis, hidradenitis suppurativa, atopic dermatitis, chronic spontaneous urticaria, and autoimmune bullous diseases, and their effects on systemic inflammation, associated cardiovascular comorbidities, and thromboembolic or hypercoagulable states. The limited current literature shows potential for links between inflammatory skin diseases and hypercoagulable states. Biomarkers such as F1 + 2, D-dimer, eosinophilic cationic protein, and PAI-1 are currently being studied to outline the mechanisms connecting inflammatory skin disease to the coagulation system. Further study and larger amounts of data are needed to draw definitive conclusions, especially when interpreting biomarkers alone such as PAI-1.The mechanisms, rates of systemic inflammation, and clinical outcomes of traditionally "skin limited" inflammatory diseases remain chronically understudied in dermatology. Many organ systems have well established connections between inflammatory disease and hypercoagulable states, but there are significant gaps in the literature regarding skin diseases. There is a significant need for comprehensive investigation of molecular mechanisms behind inflammatory dermatologic disease and hypercoagulability, how hypercoagulability effects clinical outcomes, and proper intervention to optimize patient outcomes.

Factor V (FV) is a key molecular player in the coagulation cascade. FV plasma levels have been associated with several human diseases, including thrombosis, bleeding, and diabetic complications. So far, 2 genes have been robustly found through genome-wide association analyses to contribute to the inter-individual variability of plasma FV levels: structural F5 gene and PLXDC2.

The authors used the underestimated Brown-Forsythe methodology implemented in the QuickTest software to search for non-additive genetic effects that could contribute to the inter-individual variability of FV plasma activity. QUICKTEST was applied to 4 independent genome-wide association studies studies (LURIC [Ludwigshafen RIsk and Cardiovascular Health Study], MARTHA [Marseille Thrombosis Association], MEGA [Multiple Environmental and Genetic Assessment], and RETROVE [Riesgo de Enfermedad Tromboembolica Venosa]) totaling 4505 participants of European ancestry with measured FV plasma levels. Results obtained in the 4 cohorts were meta-analyzed using a fixed-effect model. Additional analyses involved exploring haplotype and gene×gene interactions in downstream investigations. A genome-wide significant signal at the PSKH2 locus on chr8q21.3 with lead variant rs75463553 with no evidence for heterogeneity across cohorts was observed (P=0.518). Although rs75463553 did not show an association with mean FV levels (P=0.49), it demonstrated a robust significant (P=3.38x10-9) association with the variance of FV plasma levels. Further analyses confirmed the reported association of PSKH2 with neutrophil biology and revealed that rs75463553 likely interacts with two loci, GRIN2A and POM121L12, known for their involvement in smoking biology.

This comprehensive approach identifies the role of PSKH2 as a novel molecular player in the genetic regulation of FV, shedding light on the contribution of neutrophils to FV biology.

Acute infectious purpura fulminans (AIPF) is a rare but potentially fatal postoperative complication characterised by rapidly progressing disseminated intravascular coagulation (DIC), widespread purpura, and multi-organ dysfunction. Despite its severe and critical outcomes, the literature on this condition in the postoperative context is limited.

This study aimed to analyse and evaluate the incidence, clinical presentation, laboratory findings, management strategies, and outcomes of postoperative AIPF in patients who underwent various surgical procedures.

A retrospective case series was conducted, identifying adult patients diagnosed with AIPF within 30 days post surgery from January 2017 to December 2022. Inclusion was based on the International Classification of Diseases, Tenth Revision (ICD-10) coding for purpura fulminans and DIC. Clinical data, including demographic details, type and duration of surgery, onset of symptoms, laboratory findings, microbiology results, treatment strategies, and outcomes, were collected from electronic medical records. Data analysis included descriptive statistics and differences in survival among surgical subgroups were assessed using Kaplan-Meier survival analysis and the log-rank test.

Seven cases of AIPF were identified, with a mean patient age of 57.1 ± 12.5 years, out of which 71.4% (n = 5) were male. Surgical procedures included vascular (42.9%, n = 3), abdominal (28.6%, n = 2), thoracic (14.3%, n = 1), and orthopaedic (14.3%, n = 1) surgeries. The average surgical duration was 5.2 ± 2.7 hours and the mean onset of AIPF was 3.9 ± 1.9 days postoperatively. Clinically, all patients presented with widespread purpura, fever, hypotension, and multi-organ dysfunction, including renal, hepatic, and respiratory failure. Laboratory findings revealed severe coagulopathy, with a low platelet count, higher levels of D-dimer, prolonged prothrombin time, and activated partial thromboplastin time. Gram-negative bacteria were the most prevalent pathogens, particularly Klebsiella pneumoniae and Escherichia coli (28.6% each), while gram-positive Staphylococcus aureus was isolated in one case (14.3%). Despite comprehensive ICU management, including mechanical ventilation, fluid resuscitation, broad-spectrum antibiotics, and administration of fresh frozen plasma/cryoprecipitate (71.4%, n = 5), the mortality rate was 57.1% (n = 4). The median time to death was 48 hours (IQR = 36-72). The highest mortality was observed in vascular (33.3% survival) and thoracic (0% survival) surgery subgroups. Orthopaedic surgery demonstrated a 100% survival rate.

AIPF after surgery is associated with significant morbidity and mortality, particularly following vascular and thoracic procedures. The findings underscore the need for heightened postoperative vigilance, early detection, and aggressive management to improve patient outcomes. Future studies should focus on identifying strategies for risk mitigation and early intervention protocols.

Dexamethasone (DEX) has demonstrated promise with respect to decreasing postoperative thromboembolic complications following total joint arthroplasty (TJA). Therefore, the aim of this study was to investigate the effects of perioperative intravenous DEX on rates of pulmonary embolism (PE) and deep vein thrombosis (DVT) after primary TJA in patients who have a history of venous thromboembolism (VTE).

Patients who have a history of VTE who underwent primary elective TJA from 2015 to 2021 were identified using a commercial health care database. Patients were divided based on receipt of perioperative intravenous DEX [DEX(+) versus DEX(-)] on the day of index TJA. Patient demographics and hospital factors were collected. The 90-day risk of postoperative complications, readmission, and in-hospital mortality were compared.

Overall, 70,147 patients who had a history of VTE underwent TJA, of which 40,607 (57.89%) received DEX and 29,540 (42.11%) did not. The DEX(+) patients were younger (67 ± 9.8 versus 68 ± 9.9 years, P < .001) and had a significantly shorter length of stay compared to the DEX(-) patients (1.8 ± 1.6 versus 2.2 ± 1.8 days, P < .001). The DEX(+) patients demonstrated lower rates of PE (1.37 versus 1.75%, P < .001) and DVT (2.37 versus 3.01%, P < .001) compared to DEX(-) patients. The DEX(+) patients experienced a lower risk of PE (adjusted odds ratio: 0.78, 95% confidence interval: 0.66 to 0.93, P = .006) and DVT (adjusted odds ratio: 0.84, 95% confidence interval: 0.74 to 0.95, P = .006) compared to DEX(-) patients. The DEX(+) patients demonstrated no differences in the odds of surgical site infection, periprosthetic joint infection, or sepsis compared to the DEX(-) patients (P > .05).

The administration of DEX was associated with a decreased risk of PE and DVT in patients who have a history of VTE who underwent TJA. These data warrant further study investigating the postoperative benefits of perioperative DEX administration for high-risk patients undergoing TJA.

Level III.

Early severe cerebral edema and chronic hydrocephalus are the primary cause of poor prognosis in patients with subarachnoid hemorrhage (SAH). This study investigated the role of cerebrospinal fluid (CSF) inflammatory cytokines and coagulation factors in the development of severe cerebral edema and chronic hydrocephalus in patients with SAH.

Patients with SAH enrolled in this study were categorized into mild and severe cerebral edema groups based on the Subarachnoid Hemorrhage Early Brain Edema Score at admission. During long-term follow-up, patients were further classified into hydrocephalus and non-hydrocephalus groups. CSF samples were collected within 48 h post-SAH, and levels of inflammatory cytokines and coagulation factors were measured. Univariate and multivariate logistic regression analyses were performed to identify independent factors associated with severe cerebral edema and chronic hydrocephalus. The correlation between inflammatory cytokines and coagulation factors was further investigated and validated in a mouse model of SAH.

Seventy-two patients were enrolled in the study. Factors from the extrinsic coagulation pathway and inflammatory cytokines were associated with both severe cerebral edema and chronic hydrocephalus. Coagulation products thrombin-antithrombin complexes (TAT) and fibrin, as well as inflammatory cytokines IL-1β, IL-2, IL-5, IL-7, and IL-4, were independently associated with severe cerebral edema. Additionally, Factor VII, fibrin, IL-2, IL-5, IL-12, TNF-α, and CCL-4 were independently associated with chronic hydrocephalus. A positive correlation between extrinsic coagulation factors and inflammatory cytokines was observed. In the SAH mouse model, tissue plasminogen activator was shown to alleviate neuroinflammation and cerebral edema, potentially by restoring glymphatic-meningeal lymphatic function.

Elevated levels of inflammatory cytokines and extrinsic coagulation pathway factors in the CSF are associated with the development of early severe cerebral edema and chronic hydrocephalus following SAH. These factors are interrelated and may contribute to post-SAH glymphatic-meningeal lymphatic dysfunction.

This study aimed to explore the relationship between plasma proteome and the clinical features of Major Depressive Disorder (MDD) during treatment of acute episode.

In this longitudinal observational study, 26 patients hospitalized for moderate to severe MDD were analyzed. The study utilized Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) alongside clinical metrics, including symptomatology derived from the Montgomery-Åsberg Depression Rating Scale (MADRS). Plasma protein analysis was conducted at the onset of acute depression and 6 weeks into treatment. Analytical methods comprised of Linear Models for Microarray Data (LIMMA), Weighted Correlation Network Analysis (WGCNA), Generalized Linear Models, Random Forests, and The Database for Annotation, Visualization and Integrated Discovery (DAVID).

Five distinct plasma protein modules were identified, correlating with specific biological processes, and uniquely associated with symptom presentation, the disorder's trajectory, and treatment response. A module rich in proteins related to adaptive immunity was correlated with the manifestation of somatic syndrome, treatment response, and inversely associated with achieving remission. A module associated with cell adhesion was linked to affective symptoms and avolition, and played a role in the initial episodes and treatment response. Another module, characterized by proteins involved in blood coagulation and lipid transport, exhibited negative correlations with a variety of MDD symptoms and was predominantly associated with the manifestation of psychotic symptoms.

This research points to a complex interplay between the plasma proteome and MDD's clinical presentation, suggesting that somatic, affective, and psychotic symptoms may represent distinct endophenotypic manifestations of MDD. These insights hold potential for advancing targeted therapeutic strategies and diagnostic tools.

The study's limited sample size and its naturalistic design, encompassing diverse treatment modalities, present methodological constraints. Furthermore, the analysis focused on peripheral blood proteins, with potential implications for interpretability.

Plasma proteins involved in coagulation and fibrinolysis are essential to hemostasis. Consequently, their circulating levels and functionality are critical in bleeding and thrombosis development. Well-established laboratory tests to assess these are available; however, said tests do not allow high multiplicity, require large volumes of plasma and are often costly. A novel technology to quantify plasma proteins is quantitative protein mass spectrometry (QPMS). Aided by stable isotope-labeled internal standards a large number of proteins can be quantified in one single analytical run requiring <30 μL of plasma. This provides an opportunity to improve insight in the etiology and prognosis of bleeding and thrombotic disorders, in which the balance between different proteins plays a crucial role. This manuscript aims to give an overview of the QPMS potential applications in thrombosis and hemostasis research (quantifying the 38 proteins assigned to coagulation and fibrinolysis by the KEGG database), but also to explore the potential and hurdles if designed for clinical practice. Advantages and limitations of QPMS are described and strategies for improved analysis are proposed, using as an example the test requirements for antithrombin. Application of this technology in the future could represent a step towards individualized patient care.

Approximately half of ischemic strokes (IS) in cancer patients are cryptogenic, with many presumed cardioembolic. We evaluated whether there were specific miRNA and mRNA transcriptome architectures in peripheral blood of IS patients with and without comorbid cancer, and between cardioembolic versus noncardioembolic IS etiologies in comorbid cancer.

We studied patients with cancer and IS (CS; n = 42), stroke only (SO; n = 41), and cancer only (n = 28), and vascular risk factor-matched controls (n = 30). mRNA-Seq and miRNA-Seq data, analyzed with linear regression models, identified differentially expressed genes in CS versus SO and in cardioembolic versus noncardioembolic CS, and miRNA-mRNA regulatory pairs. Network-level analyses identified stroke etiology-specific responses in CS.

A total of 2,085 mRNAs and 31 miRNAs were differentially expressed between CS and SO. In CS, 122 and 35 miRNA-mRNA regulatory pairs, and 5 and 3 coexpressed gene modules, were associated with cardioembolic and noncardioembolic CS, respectively. Complement, growth factor, and immune/inflammatory pathways showed differences between IS etiologies in CS. A 15-gene biomarker panel assembled from a derivation cohort (n = 50) correctly classified 81% of CS and 71% of SO participants in a validation cohort (n = 33). Another 15-gene panel correctly identified etiologies for 13 of 13 CS-cardioembolic and 11 of 11 CS-noncardioembolic participants upon cross-validation; 11 of 16 CS-cryptogenic participants were predicted cardioembolic.

We discovered unique mRNA and miRNA transcriptome architecture in CS and SO, and in CS with different IS etiologies. Cardioembolic and noncardioembolic etiologies in CS showed unique coexpression networks and potential master regulators. These may help distinguish CS from SO and identify IS etiology in cryptogenic CS patients. ANN NEUROL 2024;96:565-581.

The thrombin generation assay (TGA) evaluates the potential of plasma to generate thrombin over time, providing a global picture of an individual's hemostatic balance.

This study aimed to identify novel biological determinants of thrombin generation using a multiomics approach.

Associations between TGA parameters and plasma levels of 377 antibodies targeting 236 candidate proteins for cardiovascular risk were tested using multiple linear regression analysis in 770 individuals with venous thrombosis from the Marseille Thrombosis Association (MARTHA) study. Proteins associated with at least 3 TGA parameters were selected for validation in an independent population of 536 healthy individuals (Etablissement Français du Sang Alpes-Méditerranée [EFS-AM]). Proteins with strongest associations in both groups underwent additional genetic analyses and in vitro experiments.

Eighteen proteins were associated (P < 1.33 × 10⁻4) with at least 3 TGA parameters in MARTHA, among which 13 demonstrated a similar pattern of associations in EFS-AM. Complement proteins C5 and C9 had the strongest associations in both groups. Ex vivo supplementation of platelet-poor plasma with purified C9 protein had a significant dose-dependent effect on TGA parameters. No effect was observed with purified C5. Several single nucleotide polymorphisms associated with C5 and C9 plasma levels were identified, with the strongest association for the C5 missense variant rs17611, which was associated with a decrease in C5 levels, endogenous thrombin potential, and peak in MARTHA. No association of this variant with TGA parameters was observed in EFS-AM.

This study identified complement proteins C5 and C9 as potential determinants of thrombin generation. Further studies are warranted to establish causality and elucidate the underlying mechanisms.

Extracellular histones are crucial damage-associated molecular patterns involved in the development and progression of multiple critical and inflammatory diseases, such as sepsis, pancreatitis, trauma, acute liver failure, acute respiratory distress syndrome, vasculitis and arthritis. During the past decade, the physiopathologic mechanisms of histone-mediated hyperinflammation, endothelial dysfunction, coagulation activation, neuroimmune injury and organ dysfunction in diseases have been systematically elucidated. Emerging preclinical evidence further shows that anti-histone strategies with either their neutralizers (heparin, heparinoids, nature plasma proteins, small anion molecules and nanomedicines, etc.) or extracorporeal blood purification techniques can significantly alleviate histone-induced deleterious effects, and thus improve the outcomes of histone-related critical and inflammatory animal models. However, a systemic evaluation of the efficacy and safety of these histone-targeting therapeutic strategies is currently lacking. In this review, we first update our latest understanding of the underlying molecular mechanisms of histone-induced hyperinflammation, endothelial dysfunction, coagulopathy, and organ dysfunction. Then, we summarize the latest advances in histone-targeting therapy strategies with heparin, anti-histone antibodies, histone-binding proteins or molecules, and histone-affinity hemoadsorption in pre-clinical studies. Finally, challenges and future perspectives for improving the clinical translation of histone-targeting therapeutic strategies are also discussed to promote better management of patients with histone-related diseases.

Hemorrhagic transformation (HT) is a common and serious complication in patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). This study was performed to determine the predictive factors associated with HT in stroke patients with EVT and to establish and validate a nomogram that combines with independent predictors to predict the probability of HT after EVT in patients with AIS.

All patients were randomly divided into development and validation cohorts at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) regression was used to select the optimal factors, and multivariate logistic regression analysis was used to build a clinical prediction model. Calibration plots, decision curve analysis (DCA) and receiver operating characteristic curve (ROC) were generated to assess predictive performance.

LASSO regression analysis showed that Alberta Stroke Program Early CT Scores (ASPECTS), international normalized ratio (INR), uric acid (UA), neutrophils (NEU) were the influencing factors for AIS with HT after EVT. A novel prognostic nomogram model was established to predict the possibility of HT with AIS after EVT. The calibration curve showed that the model had good consistency. The results of ROC analysis showed that the AUC of the prediction model established in this study for predicting HT was 0.797 in the development cohort and 0.786 in the validation cohort.

This study proposes a novel and practical nomogram based on ASPECTS, INR, UA, NEU, which can well predict the probability of HT after EVT in patients with AIS.

Body contouring surgery removes excess skin and fat, often after massive weight loss. Some reports suggest that patients who have previously undergone obesity (bariatric) surgery are at excess risk of subsequent bleeding, possibly due to complex nutritional and metabolic sequelae of massive weight loss.

A retrospective cohort study of intraoperative blood loss and postoperative bleeding indicators were examined for patients who had undergone abdominoplasty. Participants were categorized based on their history of previous obesity surgery, and outcome variables were compared using odds ratio, followed by subgroup comparison between a history of restrictive versus malabsorptive obesity surgery.

The study included 472 patients, of which 171 (36.2 %) had a history of obesity surgery. Mean age was 40.4 years, and 402 (85.1%) participant were women. Fifty-five (11.6%) patients were smokers whereas 65 (13.7%) were hypertensive. Mean body mass index before surgery was 30.2 kg per m2, and average time between obesity and body contouring surgery (if applicable) was 35.8 months. Patients with a history of obesity surgery exhibited greater intraoperative blood loss (162.2 mL versus 132.1 mL; P = 0.001), drainage volume at 24 h (155 mL versus 135 mL; P = 0.001), and total drainage volume (300ml versus 220 mL; P = 0.001). Postoperative hematoma requiring surgical re-exploration was almost three times higher following a history of obesity surgery (4.7% versus 1.7 %; P = 0.05).

History of obesity surgery increases intraoperative blood loss, postoperative serosanguinous drainage volumes, and the risk of postoperative hematoma requiring surgical evacuation after abdominal body contouring procedures.

The cell surface protease-activated receptor 1 (PAR1) is overexpressed in glioblastoma multiforme (GBM). We studied the function and structure of intracellular microtubule (MT) and PAR1 in a tubulin-mediated process. We found that exposure to thrombin increased the percentage of proliferative, S, and M phases cells, affected morphology, and increased process elongation. PAR1 antagonist inversely affects these measures, increases tubulin end-binding protein 3 (EB3) mRNA expression in C6 cells, and reduces EB3 comet length, track length, and duration in neuroblastoma cells. In addition, immunofluorescence staining suggests that PAR1 is in close association with the MT α-tubulin and with coagulation cascade proteins during cell division stages. Our findings support PAR1 involvement in MT dynamics.

 Septic-associated disseminated intravascular coagulation (DIC) is heterogeneous regarding prognosis and responsiveness to anticoagulant therapy.

 To investigate the relationship between the timing of development and recovery of DIC, its prognosis, and the difference in response to anticoagulant therapy in sepsis-associated DIC patients.

 This study was performed with a dataset from a multicenter nationwide retrospective cohort study (J-Septic DIC registry) in Japan between 2011 and 2013 to reveal the subgroup "high risk of death in DIC" and investigate the relationship between anticoagulant use and mortality. Patients were assigned to four groups based on the International Society on Thrombosis and Haemostasis-overt DIC status at days 1 and 3: non-DIC (-/-), early-recovered DIC (+/-), late-onset DIC (-/+), and persistent DIC (+/+).

 A total of 1,922 patients were included. In-hospital mortality in persistent and late-onset DIC patients was significantly higher than in patients with non-DIC and early-recovered DIC. This finding indicates that persistent DIC and late-onset DIC were a poor-prognosis subgroup, "high-risk" DIC. Meanwhile, patients with high-risk DIC treated with anticoagulants had significantly better outcomes than those without anticoagulants after adjusting for confounding factors.

 This study showed that individuals with a high risk of death, persistent DIC, and late-onset DIC were a poor-prognostic subgroup in septic DIC; however, high-risk DIC is also a subgroup that can obtain more benefits from anticoagulant therapy.

This review examines the endothelial glycocalyx's role in inflammation and explores its involvement in coagulation. The glycocalyx, composed of proteins and glycosaminoglycans, interacts with von Willebrand Factor and could play a crucial role in anchoring it to the endothelium. In inflammatory conditions, glycocalyx degradation may leave P-selectin as the only attachment point for von Willebrand Factor, potentially leading to uncontrolled release of ultralong von Willebrand Factor in the bulk flow in a shear stress-dependent manner. Identifying specific glycocalyx glycosaminoglycan interactions with von Willebrand Factor and P-selectin can offer insights into unexplored coagulation mechanisms.

Granzymes are a family of serine proteases, composed of five human members: GA, B, H, M and K. They were first discovered in the 1980s within cytotoxic granules released during NK cell- and T cell-mediated killing. Through their various proteolytic activities, granzymes can trigger different pathways within cells, all of which ultimately lead to the same result, cell death. Over the years, the initial consideration of granzymes as mere cytotoxic mediators has changed due to surprising findings demonstrating their expression in cells other than immune effectors as well as new intracellular and extracellular activities. Additional roles have been identified in the extracellular milieu, following granzyme escape from the immunological synapse or their release by specific cell types. Outside the cell, granzyme activities mediate extracellular matrix alteration via the degradation of matrix proteins or surface receptors. In certain contexts, these processes are essential for tissue homeostasis; in others, excessive matrix degradation and extensive cell death contribute to the onset of chronic diseases, inflammation, and autoimmunity. Here, we provide an overview of both the physiological and pathological roles of granzymes, highlighting their utility while also recognizing how their unregulated presence can trigger the development and/or worsening of diseases.

This study, which included patients over the age of 18 who were diagnosed with coronavirus disease 2019 (COVID-19) in the emergency clinic, aims to determine the relationship between coagulation parameters and mortality. Epidemiologic data such as age, gender, medical history, vital parameters at emergency department admission, clinical findings, coagulation parameters such as d-dimer, prothrombin time (PT), active partial thromboplastin time (aPTT), international normalized ration (INR), fibrinogen, and platelet were evaluated. Patients with positive computerized tomography (CT) findings and positive polymerase chain reaction (PCR) together were included in the study. It was revealed that d-dimer, fibrinogen, INR, and PT values were higher in the elderly group. It was shown that there was a significant relationship between hospitalization days (ward or intensive care unit) and d-dimer levels. It was observed that d-dimer, fibrinogen elevation was significantly associated with prognosis by increasing mortality, and that platelet and aPTT values were also associated with prognosis and were lower in the mortality group. On the other hand, in receiver operating characteristic (ROC) analysis, the sensitivity and specificity data were 80.3%/80.0% for d-dimer, 70.5%/72.2% for fibrinogen, 58.2%/59.4% for aPTT, and 59.7%/59.2% for platelet, respectively. The overall classification success was 88.6% and mortality prediction success was 37.7% in the regression model of some coagulation parameters (d-dimer, fibrinogen, aPTT, and platelet) which were effective on prognosis. In conclusion, it was determined that d-dimer, fibrinogen, aPTT, and platelet parameters were directly associated with mortality and when these coagulation parameters were used together with the clinical, vital, and demographic data of the patients, the success of mortality prediction increased significantly.

Glycosylation is a crucial post-translational modification process where sugar molecules (glycans) are covalently linked to proteins, lipids, or other biomolecules. In this highly regulated and complex process, a series of enzymes are involved in adding, modifying, or removing sugar residues. This process plays a pivotal role in various biological functions, influencing the structure, stability, and functionality of the modified molecules. Glycosylation is essential in numerous biological processes, including cell adhesion, signal transduction, immune response, and biomolecular recognition. Dysregulation of glycosylation is associated with various diseases. Glycation, a post-translational modification characterized by the non-enzymatic attachment of sugar molecules to proteins, has also emerged as a crucial factor in various diseases. This review comprehensively explores the multifaceted role of glycation in disease pathogenesis, with a specific focus on its implications in osteoarthritis (OA). Glycosylation and glycation alterations wield a profound influence on OA pathogenesis, intertwining with disease onset and progression. Diverse studies underscore the multifaceted role of aberrant glycosylation in OA, particularly emphasizing its intricate relationship with joint tissue degradation and inflammatory cascades. Distinct glycosylation patterns, including N-glycans and O-glycans, showcase correlations with inflammatory cytokines, matrix metalloproteinases, and cellular senescence pathways, amplifying the degenerative processes within cartilage. Furthermore, the impact of advanced glycation end-products (AGEs) formation in OA pathophysiology unveils critical insights into glycosylation-driven chondrocyte behavior and extracellular matrix remodeling. These findings illuminate potential therapeutic targets and diagnostic markers, signaling a promising avenue for targeted interventions in OA management. In this comprehensive review, we aim to thoroughly examine the significant impact of glycosylation or AGEs in OA and explore its varied effects on other related conditions, such as liver-related diseases, immune system disorders, and cancers, among others. By emphasizing glycosylation's role beyond OA and its implications in other diseases, we uncover insights that extend beyond the immediate focus on OA, potentially revealing novel perspectives for diagnosing and treating OA.

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.

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.

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.

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.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a societal burden due to the lack of effective treatment and incomplete pathophysiology understanding. This review explores the intricate connections among liver sinusoidal endothelial cells (LSECs), platelets, neutrophil extracellular traps (NETs), and coagulation disruptions in MASLD pathogenesis. In MASLD's early stages, LSECs undergo capillarization and dysfunction due to excessive dietary macronutrients and gut-derived products. Capillarization leads to ischemic changes in hepatocytes, triggering pro-inflammatory responses in Kupffer cells (KCs) and activating hepatic stellate cells (HSCs). Capillarized LSECs show a pro-inflammatory phenotype through adhesion molecule overexpression, autophagy loss, and increased cytokines production. Platelet interaction favors leucocyte recruitment, NETs formation, and liver inflammatory foci. Liver fibrosis is facilitated by reduced nitric oxide, HSC activation, profibrogenic mediators, and increased angiogenesis. Moreover, platelet attachment, activation, α-granule cargo release, and NETs formation contribute to MASLD progression. Platelets foster fibrosis and microthrombosis, leading to parenchymal extinction and fibrotic healing. Additionally, platelets promote tumor growth, epithelial-mesenchymal transition, and tumor cell metastasis. MASLD's prothrombotic features are exacerbated by insulin resistance, diabetes, and obesity, manifesting as increased von Willebrand factor, platelet hyperaggregability, hypo-fibrinolysis, and a prothrombotic fibrin clot structure. Improving LSEC health and using antiplatelet treatment appear promising for preventing MASLD development and progression.

Orange juice is an important food source of bioactive compounds, mainly the flavanones hesperidin and narirutin. This study aimed to investigate the underlying molecular mechanisms of action of orange juice's health properties by analyzing changes in the plasma proteome of healthy Brazilian volunteers after consuming juices made from 'Bahia' (BOJ-source of flavanones) and 'Cara Cara' (CCOJ-source of flavanones and carotenoids) oranges cultivated in Brazil. We used an untargeted proteomic approach, with a particular emphasis on the juices' effects on blood coagulant activity. We identified 247 differentially expressed proteins, of which 170 significantly increased or decreased after BOJ consumption and 145 after CCOJ. These proteins are involved in 105 processes that can significantly regulate cell adhesion, cell signaling, cell metabolism, inflammation, or others. Bioinformatic analysis evidenced proteins with major cellular regulatory capacity (e.g., FN1 and GAPDH) and predicted transcription factors (TFs) (e.g., SP1 and CEBPA) and miRNAs (e.g., miR-1-3p and miR-615-3p) that could be involved in the regulation of differentially expressed proteins. In-silico docking analyses between flavanone metabolites and TFs evidenced the higher binding capacity of narirutin phase II metabolites with akt1 and p38, interactions that suggest how the expression of genes of differentially expressed proteins were activated or inhibited. Moreover, the study shed light on proteins of coagulation cascade that presented expression modulated by both juices, proposing the modulation of blood coagulant activity as a potential benefit of OJ (mainly CCOJ) consumption. Taken together, this study revealed that BOJ and CCOJ consumption affected plasma proteome in healthy individuals, suggesting potential molecular targets and mechanisms of OJ bioactive compounds in humans.

The objective of this study was to use shotgun label-free tandem mass spectrometry (LF-MS/MS) to evaluate aqueous humor (AH) from horses with uveitis (UH) compared to ophthalmologically healthy horses (HH).

Twelve horses diagnosed with uveitis based on ophthalmic examination and six ophthalmologically healthy horses (postmortem) purchased for teaching purposes.

All horses received a complete ophthalmic examination and physical exam. Aqueous paracentesis was performed on all horses and AH total protein concentrations were measured with nanodrop (TPn) and refractometry (TPr). AH samples were analyzed with shotgun LF-MS/MS and proteomic data were compared between groups using Wilcoxon rank-sum test.

A total of 147 proteins were detected, 11 proteins had higher abundance in UH, and 38 proteins had lower abundance in UH. Proteins with higher abundance included apolipoprotein E, alpha-2-macroglobulin (A2M), alpha-2-HS-glycoprotein, prothrombin, fibrinogen, complement component 4 (C4), joining chain for IgA and IgM, afamin, and amine oxidase. There were positive correlations between TPn (p = .003) and TPr (p = .0001) compared to flare scores.

Differential abundance of A2M, prothrombin, fibrinogen, and C4 indicate upregulation of the complement and coagulation cascade in equine uveitis. Proinflammatory cytokines and the complement cascade have potential as therapeutic targets for equine uveitis.

Patients with auto-antibodies neutralizing type I interferons (anti-IFN auto-Abs) are at risk of severe forms of coronavirus disease 19 (COVID-19). The chest computed tomography (CT) scan characteristics of critically ill COVID-19 patients harboring these auto-Abs have never been reported.

Bicentric ancillary study of the ANTICOV study (observational prospective cohort of severe COVID-19 patients admitted to the intensive care unit (ICU) for hypoxemic acute respiratory failure between March 2020 and May 2021) on chest CT scan characteristics (severity score, parenchymal, pleural, vascular patterns). Anti-IFN auto-Abs were detected using a luciferase neutralization reporting assay. Imaging data were collected through independent blinded reading of two thoracic radiologists of chest CT studies performed at ICU admission (± 72 h). The primary outcome measure was the evaluation of severity by the total severity score (TSS) and the CT severity score (CTSS) according to the presence or absence of anti-IFN auto-Abs.

Two hundred thirty-one critically ill COVID-19 patients were included in the study (mean age 59.5 ± 12.7 years; males 74.6%). Day 90 mortality was 29.5% (n = 72/244). There was a trend towards more severe radiological lesions in patients with anti-IFN auto-Abs than in others, not reaching statistical significance (median CTSS 27.5 (21.0-34.8) versus 24.0 (19.0-30.0), p = 0.052; median TSS 14.5 (10.2-17.0) versus 12.0 (9.0-15.0), p = 0.070). The extra-parenchymal evaluation found no difference in the proportion of patients with pleural effusion, mediastinal lymphadenopathy, or thymal abnormalities in the two populations. The prevalence of pulmonary embolism was not significantly different between groups (8.7% versus 5.3%, p = 0.623, n = 175).

There was no significant difference in disease severity as evaluated by chest CT in severe COVID-19 patients admitted to the ICU for hypoxemic acute respiratory failure with or without anti-IFN auto-Abs.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arterial, venous, and microvascular thrombosis where activated neutrophils play a determinant role. However, neutrophils are challenging to target given their short lifespan in circulation and spontaneous activation. Screening of a small library of gold nanoparticles (AuNPs) led to the discovery of a formulation capable of targeting activated neutrophil attachment and has demonstrated that star-shaped, anti-PSGL-1-antibody-coated AuNPs (aPSGL-1-AuNPs) were more efficacious compared with other shapes of AuNPs. Our findings further revealed an exciting and safe targeting mode toward activated neutrophils in the APS mouse model induced by human-patient-derived antiphospholipid IgGs. Our studies demonstrate that targeting is dependent on the specific topographical features of the highly segregated PSGL-1 on the activated neutrophil surface for which a high affinity shape-driven nanomedicine can be designed and implemented. As such, star-shaped aPSGL-1-AuNPs serve as a promising nanoimmunotherapy for immunothrombosis associated with neutrophil adhesion in APS.