Plasma D-dimer Research Articles

L-arginine, aminoguanidine and mesenchymal stem cells reduce the level of endoplasmic reticulum stress markers and D-dimer in the lungs of mice with antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by damage to the intima of the microcirculatory blood vessels as a result of the formation of autoimmune antibodies to phospholipids of cell membranes. Recent data indicate a possible link between the occurrence of autoimmune diseases and endoplasmic reticulum stress, impaired nitric oxide availability, high plasma D-dimer level. The aim of the study was to estimate the effect of nitric oxide synthesis modulators L-arginine and aminoguanidine, and mesenchymal stem cells on the level of inositol-requiring enzyme-1a (IRE-1a), glucose-regulated protein 78 (GRP-78) as ER stress markers, and the level of D-dimer in the lung tissue of female BALB/c line mice with experimental APS induced with cardiolipin administration. 30 experimental animals were divided into five groups: 1 – control animals; 2 – mice with APS; 3 – mice with APS, injected intraperitoneally with L-arginine hydrochloride (25 mg/kg) and aminoguanidine (10 mg/kg); 4 – mice with APS, injected intraperitoneally with stem cells (5×106/kg); 5 – mice with APS, injected with L-arginine hydrochloride, aminoguanidine and stem cells in combination. After 10 days post APS formation animals were removed from the experiment, proteins were extracted from the lung tissue and their level was determined with Western blotting. It was established that in group with APS the levels of IRE-1, GRP-78 and D-dimer were substantially increased as compared to the control group. After separate administration of both arginine with aminoguanidine and MSC, as well as with their combined use, the level of IRE-1, GRP-78 and D-dimer decreased compared to the indices in animals with induced APS. The obtained data indicated that this effect is probably due to the reduction of ER stress through iNOS inhibition and the anti-inflammatory action of MSCs. Keywords: aminoguanidine, antiphospholipid syndrome, D-dimer, endoplasmic reticulume stress, GRP-78, IRE-1, L-arginine, lung, mesenchymal stem cells

Construction of a coagulation prediction model of the extracorporeal circulation circuit during hemodialysis with regional citrate anticoagulant (RCA).

To construct a prediction model of coagulation in the extracorporeal circulation circuit during hemodialysis with regional citrate anticoagulant(RCA) conditions. This was a single-center, retrospective study. The clinical data of patients who received hemodialysis with RCA from February 2021 to March 2022 were collected. The risk predictors of coagulation in the extracorporeal circulation circuit were screened by LASSO regression. On this basis, we used multivariate logistic regression analysis to establish a nomogram prediction model. A total of 98 patients received RCA hemodialysis for 362 times. Among them, 155 treatments with complete data were included in the study. Among the 155 treatments, coagulation of the extracorporeal circulation circuit occurred 12 times. The use of arteriovenous fistulas(AVF), the venous pressure at 4 h after hemodialysis initiation, blood flow velocity, dialyzer manufacturer, Systemic iCa2+ at 1 h after hemodialysis initiation, plasma albumin level, and plasma d-dimer level were influencing factors of coagulation in the extracorporeal circuit during hemodialysis with RCA (p < 0.05). A nomogram model was made out of the above indicators. The area under the receiver operating characteristic (ROC) curve for predicting coagulation in the circuit was 0.967 (95% CI: 0.935-0.998). The internal validation result of the memory testing (bootstrap method) showed that the area under the ROC curve was 0.967 (95% CI: 0.918-0.991). The nomogram model has good discrimination and calibration and can intuitively and succinctly predict the risk of coagulation in the extracorporeal circulation circuit during hemodialysis with RCA.

Multi-factor early monitoring method based on D-dimer for iliac crest flap loss

BackgroundIn recent years, the utilization of autogenous vascularized iliac crest flap for repairing jaw defects has seen a significant rise. However, the visual monitoring of iliac bone flaps present challenges, frequently leading to delayed detection of flap loss. Consequently, there’s a urgent need to develop effective indicators for monitoring postoperative complications in iliac crest flaps.MethodsA retrospective analysis was conducted on 160 patients who underwent vascularized iliac crest flap transplantation for jawbone reconstruction from January 2020 to December 2022. We investigated the changes in D-dimer levels among patients with or without postoperative complications. Additionally, multivariable logistic regression analysis was performed to explore potential individual risk factors, including surgical duration, age, pathology type, absolute and relative D-dimer levels, and gender, culminating in the development of a nomogram.ResultsOn the first day following surgery, patients who experienced thrombosis exhibited a substantial increase in plasma D-dimer levels, reaching 3.75 mg/L, 13.84 times higher than the baseline. This difference was statistically significant (P < 0.05) compared to patients without postoperative complications. Furthermore, the nomogram we have developed and validated effectively predicts venous thrombosis, assigning individual risk scores to patients. This predictive tool was assessed in both training and validation cohorts, achieving areas under the curve (AUC) of 0.630 and 0.600, with the 95% confidence intervals of 0.452–0.807 and 0.243–0.957, respectively.ConclusionsOur study illustrates that postoperative plasma D-dimer levels can serve as a sensitive biomarker for monitoring thrombosis-induced flap loss. Moreover, we have developed a novel prediction model that integrates multiple factors, thereby enhancing the accuracy of early identification of patients at risk of thrombosis-associated flap loss. This advancement contributes to improving the overall management and outcomes of such procedures.

High Plasma D-Dimer Levels Correlate with Ictal Infarction and Poor Outcomes in Spontaneous Subarachnoid Hemorrhage

Early brain injury is the leading cause of poor outcomes in spontaneous subarachnoid hemorrhage (sSAH). Plasma D-dimer levels and acute cerebral ischemia have been highlighted as relevant findings in early brain injury; however, their correlation has not been substantially investigated. This retrospective, single-center cohort study was conducted at a tertiary emergency medical center from January 2004 to June 2022. Consecutive patients with sSAH who presented within 12hours of ictus and underwent magnetic resonance imaging within 3days were included. We assessed the correlation of plasma D-dimer levels with acute ischemic lesions detected on the diffusion-weighted imageing and the clinical characteristics. Among 402 eligible patients (mean age, 63.5years; 62.7% women; median time from onset to arrival, 45.5minutes), 140 (34.8%) had acute ischemic lesions. Higher plasma D-dimer levels linearly correlated with worse neurological grades, more severe SAH on initial computed tomography, acute ischemic lesions, and poor outcomes, except for patients with neurogenic stunned myocardium. In the multivariate analysis, acute ischemic lesions were significantly associated with worse neurological grades, higher plasma D-dimer levels, bilateral loss of light reaction, and advanced age. The receiver operating characteristic curve analysis showed D-dimer levels as excellent predictors for acute ischemic lesions (area under the curve, 0.897; cut-off value, 5.7μg/mL; P<0.0001) and unfavorable outcomes (area under the curve, 0.786; cut-off value, 4.0μg/mL; P<0.0001). High plasma D-dimer levels correlated with the appearance of acute ischemic lesions on diffusion-weighted imaging and were dose-dependently associated with worse neurological grades, more severe hemorrhage, and worse outcomes.

Higher Incidence of Venous Thromboembolism in Anterolateral Approach in Lateral Position Compared to Anterolateral Supine and Direct Anterior Approaches in Minimally Invasive Total Hip Arthroplasty.

Venous thromboembolism (VTE) remains a major complication after total hip arthroplasty (THA), irrespective of the surgical approach. This study investigated the incidence of VTE in patients undergoing THA through intermuscular minimally invasive surgical techniques, which included a direct anterior approach (DAA), an anterolateral approach (AL), and an anterolateral supine approach (ALS), at a single institution. A hundred consecutive patients treated with each surgical approach were evaluated. Plasma D-dimer levels one month preoperatively and one day postoperatively, operative time, and intraoperative blood loss were recorded, and the presence of VTE was evaluated based on multidetector-row computed tomography performed the day after surgery. Student's t-test and Pearson's chi-square test or one-way analysis of variance were used in statistical analysis. No differences among the groups in terms of age, height, weight, operative time, intraoperative bleeding, and preoperative and postoperative D-dimer levels were observed. The overall incidence of VTE was 21%. The incidences of VTE were 30% in AL, 17% in ALS, and 16% in DAA, representing a significantly higher rate in AL than in ALS and DAA (P=0.025). The incidences of VTE on the operated side were 19% in AL, 13% in ALS, and 12% in DAA, with no statistically significant differences. The incidences of VTE on the non-operated side were 22% in AL, 9% in ALS, and 8% in DAA; these differences were statistically significant (P=0.0045). Results showed that the incidence of VTE was significantly higher in AL than in ALS and DAA, especially for the non-operated side.

Machine learning-based model to predict composite thromboembolic events among Chinese elderly patients with atrial fibrillation

ObjectiveAccurate prediction of survival prognosis is helpful to guide clinical decision-making. The aim of this study was to develop a model using machine learning techniques to predict the occurrence of composite thromboembolic events (CTEs) in elderly patients with atrial fibrillation(AF). These events encompass newly diagnosed cerebral ischemia events, cardiovascular events, pulmonary embolism, and lower extremity arterial embolism.MethodsThis retrospective study included 6,079 elderly hospitalized patients (≥ 75 years old) with AF admitted to the People’s Liberation Army General Hospital in China from January 2010 to June 2022. Random forest imputation was used for handling missing data. In the descriptive statistics section, patients were divided into two groups based on the occurrence of CTEs, and differences between the two groups were analyzed using chi-square tests for categorical variables and rank-sum tests for continuous variables. In the machine learning section, the patients were randomly divided into a training dataset (n = 4,225) and a validation dataset (n = 1,824) in a 7:3 ratio. Four machine learning models (logistic regression, decision tree, random forest, XGBoost) were trained on the training dataset and validated on the validation dataset.ResultsThe incidence of composite thromboembolic events was 19.53%. The Least Absolute Shrinkage and Selection Operator (LASSO) method, using 5-fold cross-validation, was applied to the training dataset and identified a total of 18 features that exhibited a significant association with the occurrence of CTEs. The random forest model outperformed other models in terms of area under the curve (ACC: 0.9144, SEN: 0.7725, SPE: 0.9489, AUC: 0.927, 95% CI: 0.9105–0.9443). The random forest model also showed good clinical validity based on the clinical decision curve. The Shapley Additive exPlanations (SHAP) showed that the top five features associated with the model were history of ischemic stroke, high triglyceride (TG), high total cholesterol (TC), high plasma D-dimer, age.ConclusionsThis study proposes an accurate model to stratify patients with a high risk of CTEs. The random forest model has good performance. History of ischemic stroke, age, high TG, high TC and high plasma D-Dimer may be correlated with CTEs.

Relationship between D-dimer levels and survival in a sample of Iraqi patients with COVID-19

Coronavirus disease 2019 was discovered in December 2019, Wuhan, China. It was transmitted globally producing the COVID-19 pandemic. Coagulopathy is one of the most common complications characterized by an increased D-dimer level. Objective: The aim of this study were to assessment the relationship between the levels of D-dimer and other biomarkers with survival in a sample of Iraqi patients with COVID-19. Methods: A cross section study included 103 patients affected by COVID-19, diagnosed by PCR and chest CT scan, (18 to 70 years old), and admitted at the isolation centers of the Khalis General Hospital and the Shifa Center in Baquba Teaching Hospital Diyala\ Iraq between November 2020 to end January 2021. The patients were divided into two groups: Group 1:(63) survivors patients, Group 2: (40) non survivors patients. Results: The patients divided into groups: 61.2% survivors patients ,38.8% non-survivors adult COVID-19 patients. The results include several biomarkers, each biomarker (mean± SE) was calculated in survivors and non-survivors patients. Serum ferritin, plasma D-dimer showed statistical significant increasing in non-survivors group (1777.8 ± 126.02, 3985.42 ± 1224.95) than survivors patients group (1182.7 ± 142.45, 1857.50 ± 291.21) with p-value ≥ 0.05.

Elevated preoperative plasma D-dimer level is an independent prognostic factor for pediatric patients with Wilms tumor.

Elevated plasma D-dimer levels are an unfavorable prognostic indicator for various tumors. However, its predictive value for prognosis in pediatric patients with Wilms tumor (WT) remains unknown. We aimed to investigate the clinical and prognostic value of preoperative plasma D-dimer levels and other clinicopathological characteristics in patients with favorable histology WT (FHWT). The clinical data of 74 children with FHWT from January 2010 to January 2022 were retrospectively analyzed. The clinicopathologic characteristics, preoperative laboratory parameter results, including D-dimer level, and follow-up data were collected. Based on the postoperative recovery status, the patients were divided into tumor-free survival and disease progression groups. The risk factors affecting disease progression in pediatric patients with WT and the impact of plasma D-dimer levels on overall survival (OS) were evaluated. Over a median follow-up of 33 months (range: 2-145 months), 56 patients survived without progression. Relapses and metastases occurred in 18 patients, of which four survived and 14 died. Higher preoperative plasma D-dimer levels (>0.865) (Odds ratio [OR] = 7.240, 95% confidence interval (CI) = 1.276-33.272, P = 0.011) and tumor rupture (OR = 19.984, 95% CI = 1.182-338.013, P = 0.038) were independent prognostic factors for disease progression. Additionally, patients with elevated D-dimer levels demonstrated a worse 5-year OS than those with low D-dimer levels (Hazard ratio (HR) =4.278, 95% CI = 1.074-17.035, P = 0.039). Elevated D-dimer levels are a prognostic factor for a poorer outcome in pediatric patients with WT and are expected to become a clinical biomarker for predicting the prognosis of WT.

Ovarian Torsion: A Review of the Evidence.

Ovarian torsion is a gynecological emergency caused by the twisting of the ovary and/or fallopian tube, further resulting in ischemic changes of the adnexa. Early diagnosis is likely to preserve ovarian function. The purpose of this review is to review the current findings of ovarian torsion including clinical presentations, diagnostic criteria, surgical procedures, and prognosis. The literature search is mainly available in PubMed and Web of Science platforms by searching "ovarian torsion" combined with one or several terms including "diagnosis" "risk factors" "surgery" and "torsion recurrence." Abdominal pain, nausea, and vomiting were normal clinical presentations. In order to increase the accuracy of diagnosis, it is necessary to integrate clinical presentation and the findings of imaging and laboratory examinations. Computed tomography findings, plasma d-dimer level, and the time from pain onset play a critical role in distinguishing ovarian necrosis. The efficiency of oophoropexy on preventing recurrent ovarian torsion is controversial. Most patients with early diagnosis of ovarian torsion may have a better prognosis with conservative surgery. Better understanding of ovarian torsion is critical for gynecologists to promote accuracy of diagnosis and select the optimal surgical procedure.

Laboratory blood markers in COVID-19 and their connection to Viral variant

Morality rates in COVID-19 are dependent on timely diagnosis. Therefore, studying the relationship between laboratory markers and the severity of disease is important. The first wave of COVID-19 associated with the spread of the original strain of SARS-CoV-2, showed higher mortality rates caused by cytokine storm. As the viral variant changed, a change in the disease course towards a less pronounced inflammatory reaction was observed. These changes affected major players of inflammation, cytokines. However, cytokines are not the only markers in the inflammatory response. The purpose of this work was to determine the significance of laboratory markers in inflammation: WBC, C-reactive protein, ferritin, fibrinogen, and D-dimer. The study included 227 patients with acute COVID-19 in the first 5–7 days from the onset of the disease from January 2021 to March 2022. When compared with reference, all groups were characterized by reduced absolute values of lymphocytes. Correlation analysis between the absolute value of lymphocytes and plasma cytokine concentrations also revealed statistically significant strong relationships with the level of the chemokine CCL22/MDC. Given that CCL22/MDC is an important component of lymphopoiesis, its low concentrations may indicate dysregulation of this process in COVID-19. In addition, we noted a positive correlation between the level of C-reactive protein and IL-6 in peripheral blood. IL-6 is a proinflammatory cytokine, and its elevated levels have been associated with the development of severe COVID-19. One of its functions is the induction of C-reactive protein, and this trend persists regardless of which variant causes COVID-19. We also noted positive correlations between the concentrations of fibrinogen and IL-18, ferritin and IL-6, IL-18. Both of these proteins are involved in inflammation along with cytokines. The literature provides data on the significance of these markers for determining the severity of COVID-19. There is evidence of a synergistic effect of ferritin and IL-18 against viral pathogens. Of interest was the negative correlation between plasma D-dimer levels and IFNα. At the same time, data on the role of the latter in thrombus formation processes are increasingly appearing in the literature.

An important diagnostic marker of acute myocardial infarction patients: Plasma miRNA133 levels.

The objective of this study was to explore changes in miRNA133 levels as a basis for clinical diagnostic markers in patients with acute myocardial infarction (AMI). A total of 100 chest pain patient cases admitted to a hospital from June 2021 to December 2022 were used. The study involved the selection of 50 patients: 25 patients with unstable undetermined heart pain and 25 healthy subjects were included in the control group of 50 patients with non-AMI patients. Meanwhile, 50 patients with AMI were designated as the experimental group. Changes in miRNA133 levels in patients' plasma were analyzed for expression using quantitative fluorescence analysis. When the serum TPI, plasma NT-ProBNP, glycosylated hemoglobin, and plasma D-dimer index values were compared between the control and experimental groups, there was a statistically significant difference (P < .05). mi-RNA-133 had a mean plasma level value of 2.60 ± 1.01, the mean level value of mi-RNA-133 in patients with non-AMI was 1.34 ± 1.18, and the patients in the AMI group showed significantly high values of the mean plasma level of mi-RNA-133. The relative expression level value of cTnl in patients with AMI was 10.84 ± 12.64. Of the specificity and sensitivity diagnostics, mi-RNA-133 had the best diagnostic effect. The area under mi-RNA-133 in the regression curve was 95.4%, the specificity of the whole combination of indicators was 89.4% and the sensitivity was 100%. Finally, the correlation between mi-RNA-133 and white blood cell count (WBC) and TG was statistically significant (P < .05). In conclusion, changes in the level of mi-RNA-133 may be an important marker for diagnosing the status of patients with AMI, while a faster and more accurate method will emerge along with the improvement of the detection technology, and at the same time, due to the variability of the study cases and other limitations, further research will be carried out subsequently.

Evaluation of the Prognostic Role of D-dimer in Egyptian Hepatocellular Carcinoma Patients Undergoing Locoregional Treatment

Abstract Background The blood coagulation function is often abnormal in HCC patients due to hypercoagulatory state, hyperfibrinolytic state, and increased plasma D-dimer. HCC patients treated with locoregional treatment may show changes of D-dimer levels. Several studies explored the validity of D-dimer levels during locoregional treatment in HCC but definitive data are still lacking. Aim of the Work Determination of the efficacy of D-dimer profile as a prognostic marker regarding tumor features, and post interventional response in HCC subjects undergoing TACE or RFA. Patients and Methods The clinical data of 50HCC patients who underwent TACE or RFA in our hospital from October 2021 to June 2022 were collected, including the CBC, CRP Alfa-fetoproteins and plasma d-dimer level 1 week before TACE or RFA(D0), D-dimer level 1 month (D1) and 4 months(D2) after TACE or RFA. Contrast enhanced CT was performed within 1 week before locoregional treatment and was repeated 1month and 4 months after locoregional treatment to assess for treatment efficacy according to the mRECIST criteria based on change in tumor size as measured by CT scan. One month after TACE or RFA, these patients were divided into four groups according to the mRecist criteria: complete response, partial response, stationary disease and progressive disease. D0, D1 and D2 were compared between the 4 groups and the relation between D-dimer level and the efficacy of locoregional treatment was assessed. Results In patients with negative D-dimer before locoregional treatment (D0), there was no significant difference between D0 and D1 (P &amp;gt; 0.05), while patients with elevated pretreatment D-dimer levels (D0), D1 was significantly higher than D0 (P &amp;lt; 0.05) and the D1 is higher than that in patients with negative Do. Progressive rise of D-dimer levels 4months post locoregional treatment (D2) in HCC was associated with tumor progression suggesting aggressive tumor biology and poor outcome(P = 0.02). Conclusion The changes in plasma D-dimer level can be used as a potential prognostic biomarker in predicting the efficacy of locoregional treatment in HCC patients and thus, elevated D-dimer levels pre and post locoregional treatment may serve as predictors of adverse tumor profile and poor outcome.

Effects of dabigatran, rivaroxaban, and apixaban on fibrin network permeability, thrombin generation, and fibrinolysis

Introduction There are important pharmacological differences between direct oral anticoagulants (DOAC) and a deeper knowledge of how they influence different aspects of hemostasis in patients on treatment is desirable. Materials and methods Blood samples from patients on dabigatran (n = 23), rivaroxaban (n = 26), or apixaban (n = 20) were analyzed with a fibrin network permeability assay, a turbidimetric clotting and lysis assay, the calibrated automated thrombogram (CAT), plasma levels of thrombin-antithrombin complex (TAT) and D-dimer, as well as DOAC concentrations, PT-INR and aPTT. As a comparison, we also analyzed samples from 27 patients on treatment with warfarin. Results Patients on dabigatran had a more permeable fibrin network, longer lag time (CAT and turbidimetric assay), and lower levels of D-dimer in plasma, compared with patients on rivaroxaban- and apixaban treatment, and a more permeable fibrin network than patients on warfarin. Clot lysis time was slightly longer in patients on dabigatran than in patients on rivaroxaban. Warfarin patients formed a more permeable fibrin network than patients on apixaban, had longer lag time than patients on rivaroxaban (CAT assay), and lower peak thrombin and ETP compared to patients on treatment with both FXa-inhibitors. Conclusions Results from this study indicate dabigatran treatment is a more potent anticoagulant than apixaban and rivaroxaban. However, as these results are not supported by clinical data, they are probably more related to the assays used and highlight the difficulty of measuring and comparing the effect of anticoagulants.

The role of citicoline in the correction of cerebral blood flow disorders in patients with coronary artery disease in combination with COVID-19

OBJECTIVE. To evaluate the effect of citicoline on cerebral blood flow and microembolic signals (MES) after 6 months of treatment in patients with coronary artery disease combined with coronavirus disease (COVID-19). MATERIALS AND METHODS. A prospective study of 68 patients with coronary artery disease with confirmed COVID-19 by PCR was conducted. Group I (n=35) included patients with coronary artery disease in combination with COVID-19, who, in addition to standard therapy of cerebrovascular disease, received citicoline (500 mg twice daily) for 6 months after discharge from the hospital. The comparison group (group II; n=33) consisted of patients who did not receive citicoline. Cerebral blood flow, peak systolic velocity in extracranial and intracranial vessels were determined, and 1-hour transcranial monitoring to detect MES were performed. Patients were re-examined in 6 months. RESULTS. At the initial examination of patients, cerebral blood flow and the number of MES did not differ significantly. After 6 months, there was an increase in cerebral blood flow in the cerebral arteries, as well as a decrease in MES in patients taking citicoline, whereas in group II there was no positive dynamics of this ratio. A direct correlation between plasma C-reactive protein, D-dimer and MES was found in patients of both groups. After 6 months of treatment, C-reactive protein and D-dimer decreased in both groups equally. CONCLUSIONS. The obtained results of improvement of cerebral perfusion, blood rheology, due to the anti-inflammatory effect, stabilising function of citicoline on phospholipid membranes of cerebral vascular endothelium, neurons and glial elements allow the use of citicoline in patients with coronary artery disease in combination with COVID-19 to reduce the negative impact of COVID-19 on the central nervous system.

Clinical value of measuring plasma D-dimer levels in patients with esophageal cancer

BackgroundEsophageal cancer represents a significant public health concern; however, reliable diagnostic and prognostic markers have not been established. This study aimed to investigate the clinical value of plasma D-dimer levels in patients with esophageal cancer.MethodsOverall, 120 patients with esophageal cancer who underwent radical surgical resection at our department between January 2019 and 2020 were included (esophageal cancer group). Plasma D-dimer levels were measured preoperatively and on postoperative days 1 and 14. Additionally, 60 healthy participants (control group) with measured plasma D-dimer levels were included. The preoperative D-dimer levels and positive D-dimer test rates were compared between the groups. The 3-year survival rate in patients with esophageal cancer was calculated using the Kaplan–Meier method.ResultsPreoperative D-dimer concentration in the esophageal cancer group was (0.65 ± 0.859 µg/mL) significantly higher than that in the control group (0.32 ± 0.369 µg/mL). The positivity rate in the esophageal cancer group (35.0%, 42/120) was significantly higher than that in the control group (15%, 9/60). D-dimer concentrations were significantly higher 1 day postoperatively than preoperatively. Conversely, D-dimer concentrations were significantly lower 14 days postoperatively than preoperatively. Patients in the esophageal cancer group with plasma D-dimer concentrations ≤ 0.5 µg/mL had significantly higher 3-year survival rates than those with higher concentrations. In the logistic multivariate analysis, tumor pathological stage and preoperative plasma D-dimer levels were independent prognostic factors of 3-year survival rates in patients with esophageal cancer.ConclusionPlasma D-dimer concentrations are clinically valuable in esophageal cancer diagnosis, postoperative recurrence monitoring, and prognosis prediction.

Impact of interrupting antiretroviral therapy started during primary HIV-1 infection on plasma neurofilament light chain protein, a marker of neuronal injury: The SPARTAC trial

ObjectiveAntiretroviral therapy (ART)-conferred suppression of HIV replication limits neuronal injury and inflammation. ART interruption tests efficacy in HIV cure trials and viral rebound after ART interruption may induce neuronal injury. We investigated the impact of protocol-defined ART interruption, commenced during primary HIV-1 infection (PHI) on a biomarker of neuro-axonal injury (neurofilament light protein (NfL)), and its associations with inflammation (D-dimer and interleukin-6 (IL-6)) and HIV-1 reservoir size (total HIV-1 DNA). DesignRetrospective study measuring plasma NfL in 83 participants enrolled in SPARTAC randomised to receive 48-weeks ART initiated during PHI, followed by ART interruption. MethodsNfL (Simoa immunoassay, Quanterix™) was measured before ART, after 48 weeks on ART, and 12 weeks after stopping ART. Plasma D-dimer and IL-6, and total HIV-1 DNA in peripheral CD4+ T-cells results were available in a subset of participants. Longitudinal NfL changes were assessed using mixed models, and associations with clinical and laboratory parameters using linear regression. ResultsNfL decreased following 48-weeks ART (geometric mean 6.9 to 5.8 pg/mL, p = 0.006) with no further significant change up to 12-weeks post-stopping ART despite viral rebound in the majority of participants (median 1.7 to 3.9 plasma HIV-1 RNA log10 copies/mL). Higher baseline NfL was independently associated with higher plasma HIV-1 RNA (p = 0.020) and older age (p = 0.002). While NfL was positively associated with D-dimer (n = 48; p = 0.002), there was no significant association with IL-6 (n = 48) or total HIV-1 DNA (n = 51). ConclusionsUsing plasma NfL as a surrogate marker, a decrease in neuro-axonal injury was observed in a cohort of participants following ART initiation during PHI, with no evidence of neuro-axonal injury rebound following ART interruption for up to 12 weeks, despite viral rebound in the majority of participants.

Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study

Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune dysregulation. We aimed to characterise biomarker trajectories and their associations with clinical outcomes. In this international, prospective cohort study, patients admitted to hospital with COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 platform trial within the Accelerating COVID-19 Therapeutic Interventions and Vaccines programme between Aug 5, 2020 and Sept 30, 2021 were included. Participants were included from 108sites in Denmark, Greece, Poland, Singapore, Spain, Switzerland, Uganda, the UK, and the USA, and randomised to placebo or one of four neutralising monoclonal antibodies: bamlanivimab (Aug 5 to Oct 13, 2020), sotrovimab (Dec16, 2020, to March 1, 2021), amubarvimab-romlusevimab (Dec 16, 2020, to March 1, 2021), and tixagevimab-cilgavimab (Feb 10 to Sept 30, 2021). This trial included an analysis of 2149 participants with plasma nucleocapsid antigen, anti-nucleocapsid antibody, C-reactive protein (CRP), IL-6, and D-dimer measured at baseline and day 1, day3, and day 5 of enrolment. Day-90 follow-up status was available for 1790 participants. Biomarker trajectories were evaluated for associations with baseline characteristics, a 7-day pulmonary ordinal outcome, 90-day mortality, and 90-day rate of sustained recovery. The study included 2149 participants. Participant median age was 57 years (IQR 46-68), 1246 (58·0%) of 2149 participants were male and 903 (42·0%) were female; 1792 (83·4%) had at least one comorbidity, and 1764 (82·1%) were unvaccinated. Mortality to day 90 was 172 (8·0%) of 2149 and 189 (8·8%) participants had sustained recovery. Apattern of less favourable trajectories of low anti-nucleocapsid antibody, high plasma nucleocapsid antigen, and high inflammatory markers over the first 5 days was observed for high-risk baseline clinical characteristics or factors related to SARS-CoV-2 infection. For example, participants with chronic kidney disease demonstrated plasma nucleocapsid antigen 424% higher (95% CI 319-559), CRP 174% higher (150-202), IL-6 173% higher (144-208), D-dimer 149% higher (134-165), and anti-nucleocapsid antibody 39% lower (60-18) to day 5 than those without chronic kidney disease. Participants in the highest quartile for plasma nucleocapsid antigen, CRP, and IL-6 at baseline and day 5 had worse clinical outcomes, including 90-day all-cause mortality (plasma nucleocapsid antigen hazard ratio (HR) 4·50 (95% CI 3·29-6·15), CRP HR 3·37 (2·30-4·94), and IL-6 HR 5·67 (4·12-7·80). This risk persisted for plasma nucleocapsid antigen and CRP after adjustment for baseline biomarker values and other baseline factors. Patients admitted to hospital with less favourable 5-day biomarker trajectories had worse prognosis, suggesting that persistent viral burden might drive inflammation in the pathogenesis of COVID-19, identifying patients that might benefit from escalation of antiviral or anti-inflammatory treatment. US National Institutes of Health.

Оценка системы гемостаза кроликов после прижизненного экспериментального моделирования забрюшинной гематомы

The purpose of research is to study the dynamics of the hemostasis system in rabbits after intravital experimental modeling of retroperitoneal hematoma. The object of the study was 50 male rabbits of the Gray Giant breed, from which experimental and control groups of 25 individuals each were formed. Animals of the experimental group under non-inhalation anesthesia underwent intravital modeling of a retroperitoneal hematoma using a method we developed, including taking blood from the ear artery with the addition of an anticoagulant and subsequent injection of autologous blood into the retroperitoneal space. Animals in the control group were subjected to non-inhalational anesthesia only. Intravital experimental modeling of retroperitoneal hematoma in rabbits led to a number of significant changes in the hemostatic system, which were most pronounced in the first 14 days after the experiment. The international norma-lized ratio (INR) in the experimental group of animals had significantly low values compared to the control group only on the 1st, 3rd and 7th days, and the activated partial thromboplastin time (aPTT) – on the 1st, 3rd days , 7th and 14th days after the experiment. There were no significant differences in the level of fibrinogen in blood plasma between the animals of the experimental and control groups. Thrombin time (TT) in animals of the experimental group was significantly higher only on the 1st, 3rd, 7th and 14th days, and the D-dimer content was significantly higher in all studied periods after the experiment in comparison with the control group animals. The highest level of D-dimer in the blood plasma of animals in the experimental group was recorded on the 7th day and probably indicated that in retroperitoneal hematomas the most active processes of fibrinolysis occur at this time. Low values of INR in the first 7 days and aPTT in the first 14 days, as well as prolongation of TT in the first 14 days after the experiment, give reason to believe that with retroperitoneal hematomas, the threshold for the likelihood of thrombus formation increases during these periods.

Treatment strategies for patients with out-of-hospital cardiac arrest associated with traumatic brain injury: A case series

IntroductionCollapse after out-of-hospital cardiac arrest (OHCA) can cause severe traumatic brain injury (TBI). We aimed to investigate the clinical characteristics and treatment strategies for patients with OHCA and TBI. MethodsWe analyzed a consecutive cohort of patients with intrinsic OHCA retrospectively treated between January 2011 and December 2021 at a single critical care center, and presented a case series of seven patients. Patients with collapse-related TBI were examined for the causes and situations of cardiac arrest, laboratory data, radiological images, targeted temperature management (TTM), coronary angiography (CAG), percutaneous coronary intervention (PCI), and extracorporeal cardiopulmonary resuscitation (ECPR). ResultsOf the 197 patients with intrinsic OHCA, 7 (3.6%) had TBI (age range: 49–70 years; 6 men). All seven patients presented with ventricular fibrillation in the initial electrocardiograms, with four refractory cases treated with ECPR. All patients underwent CAG under heparinization, and four underwent PCI with antiplatelet administration. Initial head computed tomography indicated an intracranial hemorrhage (ICH) in three patients. ICH appeared or was exacerbated in six patients after CAG with or without PCI, except in one who underwent delayed PCI. All patients displayed elevated plasma D-dimer levels, and four underwent neurosurgical procedures. Four patients survived (three with cerebral performance category [CPC] 2, one with CPC 3) and three died; two had hypoxic-ischemic brain injury and one had severe TBI. ConclusionDelayed ICH occurred frequently. Individualized management is required based on the extent of brain and cardiac damage, including optimal TTM, PCI procedures, and antiplatelet medications. Early detection of ICH and emergency treatment are critical for multi-disciplinary collaboration.

A new surface plasmon resonance-based immunoassay for rapid and sensitive quantification of D-dimer in human plasma for thrombus screening

D-dimer is a protein fragment generated during the fibrin breakdown by plasmin, and it serves as a mature biomarker for diagnosing thrombotic disorders. A novel immunoassay method based on surface plasmon resonance (SPR) has been developed, validated, and successfully applied for the quantification of D-dimer in human plasma with high sensitivity and rapidity. In this methodological study, we investigated the activity and stability of the SPR biosensor, sample pre-processing, washing conditions, intra-day and inter-day precision and accuracy and detection parameters, including a limit of detection of 8.3 ng/mL, a detection range spanning from 31.25 to 4000 ng/mL, and a detection time of 20 min. We compared D-dimer plasma concentration determination results using SPR with a classical latex-enhanced immunoturbidimetric immunoassay in 29 healthy individuals and thrombotic patients, and both methods exhibited consistency. Furthermore, we propose a hypothesis about the relationship between the concentration of D-dimer and its molecular weight. With an increase in the D-dimer concentration in plasma, the D-dimer approaches its simplest form (190 kDa).