D-dimer Levels Research Articles

Predictive models for secondary epilepsy in patients with acute ischemic stroke within one year.

Post-stroke epilepsy (PSE) is a critical complication that worsens both prognosis and quality of life in patients with ischemic stroke. An interpretable machine learning model was developed to predict PSE using medical records from four hospitals in Chongqing. Medical records, imaging reports, and laboratory test results from 21,459 ischemic stroke patients were collected and analyzed. Univariable and multivariable statistical analyses identified key predictive factors. The dataset was split into a 70% training set and a 30% testing set. To address the class imbalance, the Synthetic Minority Oversampling Technique combined with Edited Nearest Neighbors was employed. Nine widely used machine learning algorithms were evaluated using relevant prediction metrics, with SHAP (SHapley Additive exPlanations) used to interpret the model and assess the contributions of different features. Regression analyses revealed that complications such as hydrocephalus, cerebral hernia, and deep vein thrombosis, as well as specific brain regions (frontal, parietal, and temporal lobes), significantly contributed to PSE. Factors such as age, gender, NIH Stroke Scale (NIHSS) scores, and laboratory results like WBC count and D-dimer levels were associated with increased PSE risk. Tree-based methods like Random Forest, XGBoost, and LightGBM showed strong predictive performance, achieving an AUC of 0.99. The model accurately predicts PSE risk, with tree-based models demonstrating superior performance. NIHSS score, WBC count, and D-dimer were identified as the most crucial predictors. The research is funded by Central University basic research young teachers and students research ability promotion sub-projec t(2023CDJYGRH-ZD06), and by Emergency Medicine Chongqing Key Laboratory Talent Innovation and development joint fund project (2024RCCX10).

Relation of CXCL10 and CXCR3 Gene Polymorphisms with COVID-19 Severity and its Serum Biochemical Markers

CXCL10 (rs201830102) is a chemokine involved in immune cell recruitment, while its receptor, CXCR3 (rs779120264), mediates immune responses through the activation of T cells. These genes are critical in the immune response to viral infections, including COVID-19. The study aimed to explore the relationship between polymorphisms in the CXCL10 gene and CXCR3 receptor with disease severity in COVID-19 patients. In this cross-sectional analytical study, 100 COVID-19 patients were enrolled after ethical approval, and written informed consent was obtained from each participant. Polymorphisms in CXCL10 and CXCR3 were analyzed by sequencing, while biochemical and hematological parameters were assessed using appropriate methods. Descriptive and inferential statistics were employed to analyze continuous and categorical data. Significant associations were observed between severe COVID-19 cases and elevated levels of serum D-dimer, ferritin, random blood sugar (RBS), neutrophils, and erythrocyte sedimentation rate (ESR), along with reduced hemoglobin levels. Lymphocyte and platelet counts were significantly lower with increased disease severity. The wild genotype of CXCL10 was notably associated with elevated ferritin levels, suggesting that certain gene variants may offer protective effects. However, no significant correlation was found between CXCR3 and CXCL10 polymorphisms and other serum biomarkers. Our study confirmed a significant rise in serum D-dimer, ferritin, RBS, neutrophils, and ESR, along with a reduction in hemoglobin, lymphocyte, and platelet counts in severe COVID-19 cases compared to mild ones. Notably, mutations in the CXCL10 gene were linked to less severe COVID-19 outcomes.

Changes to inflammatory markers during 5 years of viral suppression and during viral blips in people with HIV initiating different integrase inhibitor based regimens

BackgroundHeightened levels of inflammatory markers are linked to increased morbidity/mortality in people with HIV (PWH) and often remain elevated after virologic suppression by antiretroviral therapy (ART). As new combinations of ART become available, an evaluation of their effects on immune activation and inflammation is warranted. Additionally, it remains unknown whether transient increases in viral load (“blips”) during ART are associated with increases in inflammation.MethodsWe utilized cryopreserved samples from treatment-naïve PWH enrolled in two Phase 3 clinical trials investigating the efficacy and safety of bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) or dolutegravir, abacavir, and lamivudine (DTG/ABC/3TC) or DTG + F/TAF over a 5-year window (GS-US-380-1489/1490). At week 144, participants were offered the option to switch to open label B/F/TAF for an additional 96 weeks. We measured levels of interleukin-6 (IL-6), C-reactive protein (hsCRP), D-dimer, soluble CD14 (sCD14), and tumor necrosis factor-α receptor 1 (TNFR1) from available baseline, week 24, 48, 144, and 240 samples (B/F/TAF, N=123; DTG/ABC/3TC, N=62; DTG+F/TAF, N=58). Additional samples from PWH who experienced a viral blip (n=44, defined as a single HIV-1 RNA >50c/mL) were also analyzed and paired with the most recent available suppressed sample before the blip. Longitudinal biomarker changes were assessed using a constrained mixed effects linear regression model adjusting for covariates.ResultsBaseline demographics and selected laboratory characteristics were similar across groups. Levels of D-dimer, sCD14, and TNFR1 decreased significantly from baseline in all treatment arms, with no significant differences between arms at any timepoint. Biomarker levels also remained stable following ART-switch at week 144. No significant changes in hsCRP or IL-6 were observed versus baseline in any arm at any timepoint. A significant association was observed between sCD14 and increasing viral load (p=0.022) in viral blips; D-dimer also increased with blips in the B/F/TAF arm.ConclusionsViral suppression was associated with reductions in most inflammatory markers in PWH, with no significant differences among the three ART regimens during the 144-week randomized period. These decreases were sustained after the open label switch to B/F/TAF. Viral blips were associated with increases in monocyte activation (sCD14). Further analysis is needed to confirm these findings and determine the potential impact on clinical outcomes.

Prognostic Value of Serum D-dimer in Predicting Outcomes in COVID-19 Positive Pregnant Women

Background: Combined effects of pregnancy induced hypercoagulability and SARS-CoV-2 infection place pregnant women with COVID-19 disease at high risk of severe outcome. COVID-19 severity has also been associated with serum D-dimer, a biomarker reflecting coagulation and fibrin degradation, in general populations. Despite its prognostic value in pregnant women, the prognostic value of this finding particularly in maternal outcomes remains less understood. The aim of this study was to determine whether elevated serum D-dimer levels in pregnant COVID-19 positive women are of prognostic significance for severe maternal outcomes. Methods: This retrospective observational study included 62 third trimester COVID 19 positive pregnant women admitted to the Department of Obstetrics and Gynecology, BSMMU, Dhaka from March 2019 to February 2020. Serum D-dimer were measured at admission and day 7, 14. D-dimer levels were related to clinical outcomes and statistically evaluated using chi square tests and logistic regression at p < 0.05. Results: Significantly associated with higher risk of severe outcomes, all of which included ICU admission, respiratory complications and adverse pregnancy events is elevated D-dimer levels (≥1.5 mg/L). In logistic regression analysis, patients with D-dimer levels of ≥1.5 mg/L had 3.5-fold greater odds of severe outcomes (OR 3.486; 95% CI, 1.184 to 10.263; p = 0.023). D-dimer had a sensitivity of 64.29%, 67.55% specificity in predicting severe outcomes. Conclusion: Serum D-dimer is valuable prognostic marker of disease severity in pregnant COVID-19 positive women and may be used for early risk assessment and clinical decision making. Routine measurement may help identify early high risk cases in order to improve maternal outcomes.

Improved kidney function is associated with Colchicine treatment in COVID-19 patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) has been a major cause of significant morbidity and mortality. Acute kidney injury (AKI) has been seen in COVID-19-infected subjects, and it has frequently resulted in an abnormal estimated glomerular filtration rate. Colchicine, an immunomodulatory drug, was used in several studies in the early stages of the pandemic. Colchicine has been shown to prevent the development of renal failure in patients with Familial Mediterranean Fever (FMF). It has also been reported to reduce fibrosis, which plays a role in chronic kidney disease. We, therefore, aimed to investigate whether using Colchicine, in addition to standard care, was associated with better renal function in patients with severe COVID-19 infection. This retrospective cohort study comprised 118 out of 605 hospitalized COVID-19 subjects. Some of the subjects (n = 50) received oral Colchicine plus standard care, called the Col ( +) group. The others (n = 68) received only the standard care, called the Col (-) group. The estimated glomerular filtration rate (eGFR) and other laboratory findings, including lymphocytes, D-dimer, and CRP, were analyzed. The D-dimer and serum creatine levels were significantly reduced in both groups. The number of lymphocytes showed a significant increase in both groups at discharge. The level of C-reactive protein (CRP) was significantly higher in the Col ( +) group than in the Col (-) group at admission. The reduction of SCr was considerably higher in the Col ( +) group than in the Col (-) group. Similarly, the improvement of eGFR was higher in the Col ( +) group than in the Col (-) group at discharge and 6-12 mounts follow-up. Our findings indicated the use of Colchicine plus standard care was associated with improved renal function in hospitalized patients with severe COVID-19 infection.

Abstract 4134249: Cardiovascular Risk Factors and Associations of Chronic Inflammatory-Related Disease in the Multi-Ethnic Study of Atherosclerosis

Background: Inflammation plays a role in the development of cardiovascular disease (CVD). We have defined various non-cardiovascular and non-cancer conditions, both infectious and non-infectious, with a common basis of inflammation; collectively termed Chronic Inflammatory-Related Disease (ChrIRD). We have previously described that ChrIRD is common, associated with baseline inflammatory marker levels, associated with high mortality, and has a bidirectional association with CVD. The clinical implications of these data require further study. Aims: We hypothesize that many traditional risk factors for CVD are also associated with ChrIRD and that ChrIRD has additional unique risk factors. We also hypothesize that the treatment of traditional CVD risk factors is associated with a decreased likelihood of ChrIRD. Methods: We studied MESA participants free of overt CVD or significant illness at baseline. ChrIRD was determined based on review of ICD codes for hospitalizations and deaths. Incident CVD was adjudicated by review of medical records. We performed proportional hazards regression (time-dependent for CVD) to identify factors associated with a first diagnosis of ChrIRD. All variables were simultaneously entered into the model. Results: Participants (n=6155) had mean age 62±10 years and 47% male gender. ChrIRD was observed in 24% and CVD in 18%; including 8% with both conditions. Participants with a diagnosis of CVD, older age, higher heart rate, higher BMI, current or ever smoking status, higher HDL, higher baseline IL6 and GlycA levels, and NSAID use had increased likelihood of ChrIRD. Whereas those with female sex, higher total cholesterol, and statin use had a decreased likelihood of ChrIRD. Participant race/ethnicity, blood pressure, diabetes status, antihypertensive use, aspirin use, baseline CRP level, and baseline D-dimer level were not associated with ChrIRD. Regression results are summarized in Table 1. Conclusions: ChrIRD shares some risk factors with CVD, while other risk factors are opposite. Better understanding of ChrIRD could eventually lead to improved patient care.

Abstract 4142798: Differences in Clinical presentation in Spontaneous Coronary Artery Dissection vs. Type 1 Myocardial Infarction

Background: Spontaneous coronary artery dissection (SCAD) refers to the nontraumatic, non-iatrogenic, and nonatherosclerotic separation of the coronary artery wall leading to acute coronary syndrome. This condition predominantly affects women with minimal or no traditional cardiac risk factors. We aimed to determine the differences in clinical presentation between SCAD and Type 1 myocardial infarction (MI) in the Aurora Health Care community. Methods: A retrospective, matched cohort, multicenter community study was carried out on adult patients aged >18 years admitted to all Aurora Hospitals from January 2012 to December 2022. A total of 57 patients were diagnosed with SCAD during that period. SCAD group and Type 1 MI group were matched by age and gender at a 1:5 ratio using a propensity score-based matching. Outcomes between the SCAD and the Type 1 MI groups were compared using chi-squared tests or Fisher’s exact tests, and t-tests or nonparametric equivalents (Wilcoxon). Results: A higher percentage of Type 1 MI patients presented as NSTEMI compared to SCAD patients (70% vs. 59.6%, p=0.028). Although not statistically significant, SCAD patients had a higher occurrence of STEMI than Type 1 MI patients (42.1% vs. 32.6%, p=0.169). On admission, SCAD patients had a higher maximum troponin (12,000 vs. 3,550, p=0.012). Type 1 MI patients had higher HgbA1C (6 vs. 5.4, p=0.0008). Both patients had similar LDL levels, but Type 1 MI had lower HDL levels (44 vs. 48, p=0.024). ESR, CRP, and D-dimer levels showed no significant difference. LV ejection fraction was 53% in both groups, and the LV global longitudinal strain was similar. The Type 1 MI group exhibited higher grades of diastolic dysfunction (Grade 2 and Grade 3) and mitral valve disease. E/e was higher in Type 1 MI compared to SCAD (11.5 vs 8.8, p <0.0001). Type 2 SCAD was most prevalent at presentation, with the most frequently affected artery being LAD (47.4%) and the most frequently affected branch vessel being obtuse marginal (36.4%). The most common location was distal (59.6%), followed by mid (22.8%), with the diameter of the vessel involved mostly between 2-3.5 mm. Conclusion: This study observed that although more SCAD patients presented as STEMI with higher troponins, Type 1 MI patients were sicker overall. These differences in clinical findings can aid in diagnosis as the management of these two populations differ.

A Dynamic, D-dimer-based Thromboprophylaxis Strategy in Patients with COVID-19

Background COVID-19 pandemics increases venous thromboembolism (VTE) risk during hospitalization, despite prophylactic anticoagulation. Limited radiological diagnosis in pandemic requires a guided protocol for anticoagulant adjustment. Methods This retrospective cohort study was conducted at a single center as part of a quality improvement program evaluating the efficacy and safety of anticoagulation protocols. The study focused on implementing a guideline for anticoagulant dosing protocol based on dynamic changes in D-dimer levels in COVID-19 hospitalized patients. The dosing guideline allowed for dose escalation from standard prophylactic levels to escalated prophylactic or therapeutic levels, depending on the patient's risk profile for VTE. The primary endpoints included in-hospital survival comparing between fix and dynamic adjustment treatment groups. Secondary endpoints encompassed major and clinically relevant non-major bleeding (CRNMB) events, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration. Findings Among the 260 COVID-19-infected patients hospitalized between March 15th and June 15th, 2020. The patients received fixed anticoagulant dosage in 188, 72.3%) patients, while 72 (27.7%) were up-titrated according to the protocol. In-hospital survival at 30 days demonstrated superiority among patients whose anticoagulation was up-titrated to either escalated prophylactic or therapeutic (80.2%) compared to receiving fixed anticoagulant dosage (51.3%) (p=0.01). Bleeding events were significantly higher in up-titrate group (12.5%) compared to fixed anticoagulant dosage group (2.13%). Most of them are CRNMB. Conclusion A dynamic, D-dimer-based dose escalation of anticoagulation for hospitalized patients with COVID-19 holds promise in improving in-hospital mortality rates without a significant increase in fatal bleeding events.

Predictive Value of D-dimer in Children with Acute Pyelonephritis

Background: The diagnosis of acute febrile urinary tract infection (UTI) relies on various clinical and laboratory findings, which have shown conflicting results. Objectives: This study aimed to evaluate the utility of serum D-dimer in distinguishing acute pyelonephritis (APN) from other acute bacterial febrile infections. Methods: This cross-sectional study included 47 children with a confirmed UTI (verified by positive urine culture) and 47 children with other bacterial febrile infections. Serum D-dimer levels were measured in all patients before starting antibacterial treatment. Results: A total of 94 febrile children were evaluated, with females outnumbering males. Significant differences between the two groups were observed for microscopic hematuria (P = 0.044), bacteriuria (P ˂ 0.001), white blood cell (WBC) count (P = 0.047), and hemoglobin (Hgb) (P = 0.035), but not for serum D-dimer (P = 0.327). Binary logistic regression analysis revealed that Hgb (P = 0.019) had a significant predictive value in APN, whereas serum D-dimer did not. Serum D-dimer was found to be an unreliable biomarker for distinguishing febrile UTI from other bacterial febrile infections. Conclusions: Based on our findings, while D-dimer levels increase in various acute bacterial febrile infections, they are not effective in differentiating febrile UTI from other bacterial infections.

Metformin use and its association with various outcomes in COVID-19 patients with diabetes mellitus: a retrospective cohort study in a tertiary care facility

Background Evidence shows that diabetes raises the probability of contracting COVID-19 and associated complications. We hypothesize that metformin, being pleiotropic, may improve COVID-19 in diabetics. Methods A retrospective cohort study was conducted with 421 COVID-19 patients with diabetes, hospitalized between 1st April 2020 and 31st March 2022 in a tertiary-care hospital. Patients with metformin or its combination constituted the study cohort (SC; n = 221), while other antidiabetics constituted the reference cohort (RC; n = 200). Results SC and RC were matched for mean age ± SD (SC: 53.3 ± 5.7 vs. RC: 54.3 ± 8.2 years). The mean length of hospitalization (days) was significantly shorter in SC (9.0 ± 5.7) than in RC (12.7 ± 6) (p < 0.02). Metformin use was associated with reduction in mortality risk (OR: 0.106, 95% CI = 0.039–0.287; p < 0.001). Moreover, SC also improved levels of LDH (OR: 0.243, 95% CI = 0.104–0.566; p < 0.001), CRP (OR: 0.281, 95% CI = 0.120–0.659; p < 0.004), and D-dimer (OR: 0.220, 95% CI = 0.089–0.539; p < 0.001) than RC. The calculated number needed to treat for metformin was 3.1. Conclusion Metformin users have a decrease in hospital stay and mortality rates and improvement in LDH, CRP, and D-dimer levels. Therefore, metformin might protect against mortality in COVID-19 with diabetes.

Effect of reduced saturation and elevated D-dimer and interleukin 6 levels on vessel density and foveal avascular zone in patients with COVID-19 bilateral pneumonia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can affect multiple organs, including the eyes. This study aimed to identify associations between vascular density (VD) and the foveal avascular zone (FAZ), assessed using optical coherence tomography angiography (OCTA), and baseline levels of D-dimers and interleukin 6 (IL-6) in patients with bilateral COVID-19 pneumonia, depending on oxygen saturation (SpO2) on admission. The study included patients with COVID-19 bilateral pneumonia due to SARS-CoV-2 infection who were hospitalized between March and May 2021. Ophthalmological examination was performed 2 months after hospitalization. Optical coherence tomography angiography was used for the automatic assessment of the central retinal VD and the manual assessment of FAZ. A significant monotonic negative relationship was observed between SpO2 . 90% and VD in some areas of the superficial capillary plexus (SCP) (p = 0.048) and choriocapillaris (p = 0.021), and the mean VD in the deep capillary plexus (DCP) (p = 0.048). No significant monotonic negative relationship was noted between SpO2 . 90% and the FAZ in the SCP (p = 0.075). However, there was a significant monotonic positive relationship between VD in the nasal choriocapillaris and D-dimer levels in patients with SpO2 . 90% (p = 0.003, respectively). Finally, a monotonic negative relationship was identified between foveal VD in the DCP and IL-6 levels in patients with SpO2 . 90% (p = 0.027). An OCTA study conducted 2 months after hospitalization for COVID-19 bilateral pneumonia showed reduced VD in those with SpO2 . 90% and elevated levels of D-dimers and IL-6 during hospitalization. Optical coherence tomography angiography testing can provide monitoring of ocular status in patients following SARS-CoV-2 infection, especially those who report visual disturbances.

Analysis of ultrasound and magnetic resonance imaging characteristics of kaposiform hemangioen dothelioma

ObjectiveThe present study aims to investigate the ultrasound and magnetic resonance imaging (MRI) characteristics of kaposiform hemangioen dothelioma (KHE).MethodsA retrospective analysis was conducted on the clinical data of children diagnosed with KHE through postoperative pathology. Patients were divided into two groups: the KHE group and the KHE with Kasabach-Merritt Phenomenon (KMP) group (KMP group). Laboratory indicators, ultrasound, and MRI data were collected and analyzed statistically to summarize the imaging characteristics of the disease.ResultsThe levels of platelets and fibrinogen in the KHE group were significantly higher than those in the KMP group, while D-dimer levels, prothrombin time, and activated partial thromboplastin time were lower (P < 0.05). Ultrasound characteristics comparison revealed that lesions extending to the fat layer (42.47% vs. 54.24%) and invading the muscle layer (38.36% vs. 69.49%) were less common in the KHE group compared to the KMP group, with the lesion diameter being smaller in the KHE group (P < 0.05). The Adler grading predominantly showed Grade II (45.21%) in the KHE group, whereas Grade III (93.22%) was more prevalent in the KMP group (P < 0.05). MRI analysis indicated that the incidence of lesions invading the muscle layer and the presence of flow voids were lower in the KHE group compared to the KMP group (P < 0.05).ConclusionKHE patients with KMP exhibit lesions that are more prone to extending into the fat layer and invading the muscle layer, with larger diameters and abundant blood flow. Additionally, the MRI images of the lesions may exhibit flow voids.

Association of clonal haematopoiesis with recurrent venous thromboembolism: A case-control study.

Venous thromboembolism (VTE) is the third most common cardiovascular disease. Clonal haematopoiesis (CH) is linked to cardiovascular disease risk, but its potential association with VTE remains poorly understood. We assessed the prevalence of CH in patients with recurrent VTE (n = 107; median age [IQR] 57 [48-63] years, 44.9% female) and matched healthy controls (n = 127; median age [IQR] 53 [45-60] years, 51.2% female) to investigate a putative association of CH with VTE risk. We detected 12 CH-associated mutations in 11 (10.3%) VTE cases and six mutations in 5 (3.9%) controls. Thus, patients with recurrent VTE tended to have higher odds of presenting with CH compared to controls (OR: 2.74, 95% CI: 0.95-9.16). Moreover, the odds of detecting CH were significantly higher in VTE cases in the subgroup of individuals without thrombophilia (OR: 4.58, 95% CI: 1.48-15.99). VTE cases with CH showed elevated platelet counts compared to cases and controls without CH (median [IQR]: 292 [254-298], 223 [198-260] and 220 [185-259] × 109/L; both p < 0.01). Fibrinogen, sP-selectin, D-dimer and hsCRP levels did not differ according to CH status. Overall, we identified a trend for an association between CH and recurrent VTE, particularly in individuals without underlying thrombophilia, warranting further research in this patient group.

Association of thrombophilic genes (MTHFR, MTR and MTRR) polymorphisms and homocysteine level in relation to the increased risk of thrombosis among COVID-19 patients

BackgroundPatients with COVID-19 have an increased risk of thrombosis and coagulopathy. Homocysteine, an amino acid essential to coagulation, is thought to be involved in such conditions, as its level is mediated by the presence of some single nucleotide polymorphisms (SNPs) in certain genes including MTHFR, MTR and MTRR. AimThe current study aimed to assess the significant role of MTHFR (C677T and A1298C), MTR A2756G and MTRR A66G SNPs as risk factors for thrombosis among Egyptian COVID-19 patients and their effect on homocysteine level. Subjects and methodsThis case-control study was carried out on 90 Egyptian COVID-19 cases, divided into 45 non-complicated cases and 45 complicated cases with thrombosis, in addition to 80 healthy control individuals. DNA was isolated from blood samples of all the participants. The genotyping was performed using real-time PCR; in addition, serum homocysteine level was estimated. ResultsThe MTHFR (C677T and A1298C), MTR A2756G and MTRR A66G variants revealed a significant higher risk of thrombosis under different genetic models including the homozygous comparison of the co-dominant (20 % vs. 2.3 %, OR = 15.88, p = 0.007), the dominant (62.2 % vs. 33.3 % OR = 3.29, p = 0.006) and the allelic models (41.1 % vs. 17.8 %, OR = 3.2, p < 0.001) for MTHFR C677T and also the dominant (77.8 % vs. 51.1 %, OR = 3.3, p = 0.008) and the allelic models (52.2 % vs. 31.1 %, OR = 2.4, p = 0.004) for MTHFR A1298C. In addition, the heterozygous comparison of the co-dominant (60 vs. 11.1, OR = 12.7, p < 0.001), the dominant (62.2 % vs. 11.1 %, OR = 13.1, p < 0.001) and the allelic models (32.2 % vs. 5.6 %, OR = 8.08, p < 0.001) for MTR A2756G and the heterozygous and homozygous comparisons of the co-dominant model [(53.3 % vs. 31.1 %, OR = 3.4, p = 0.03) and (13.4 % vs. 2.2 %, OR = 12.0, p = 0.049), respectively], the dominant (66.4 % vs. 33.3 %, OR = 4.0, p = 0.001) and the allelic models (40 % vs. 17.8 %, OR = 3, p = 0.001) for MTRR A66G. Moreover, MTHFR (C677T and A1298C), MTR A2756G, and MTRR A66G variants were also associated with high levels of serum homocysteine (p = 0.045, 0.001, 0.005 and 0.039, respectively). The homocysteine level was related to the disease severity by its correlation with higher LDH (rs = 0.49, p < 0.001), CRP (rs = 0.44, p < 0.001), IL-6 (rs = 0.46, p < 0.001) and D-dimer (rs = 0.66, p < 0.001) levels. The multivariate regression analysis showed that homocysteine and the dominant models of MTHFR (C677T and A1298C), MTR A2756G and MTRR A66G were independent predictors of susceptibility to thrombosis among COVID-19 patients [(OR = 1.02, p = 0.007), (OR = 1.15, p = 0.043), (OR = 1.2, p = 0.024), (OR = 1.42, p < 0.001), (OR = 1.19, p = 0.021), respectively]. ConclusionMTHFR (C677T and A1298C), MTR A2756G, and MTRR A66G gene variants were associated with high homocysteine and D-dimer levels that carried a risk for thrombosis among COVID-19 patients and associated with the disease progression.

Hyper fibrinolysis state in COVID 19 and its correlation to lipid parameters

BackgroundCoronavirus disease 2019 (COVID 19) is associated with systemic effects involving especially the respiratory and cardiovascular system. The unique features of this condition are disseminated intravascular coagulation, excess fibrin degradation products due to abnormality in the coagulation system that could independently predict mortality. Abberations in lipid parameters that normally predict cardiovascular disease (CVD) were compared with D-dimer levels as risk markers in patients with COVID 19. MethodsA hospital based cross sectional study was conducted over a period of five months in patients aged 30 to 70 years diagnosed with COVID-19. The patients were categorised based on the D-dimer levels as: Group I <0.5μg/ml (Normal), Group II 0.5-2.0μg/ml (Intermediate high), Group III >2.0μg/ml (Very high). The lipid parameters, atherogenic indices were compared between the three groups. ResultsThe mean age of the selected COVID-19 patients was 49.3± 19.1 years of which 63 were males and 37 females (2:1). Significantly high D-dimer levels were detected which had a weak positive correlation with TG, Atherogenic Index Plasma (AIP). Significant rise in TC, LDL and Non-HDL was seen in Group II. Increasing trend of AIP was seen across the groups. D-dimer showed a weak positive correlation with TG, AIP and statistically non-significant negative correlation with rest of the lipid parameters. ConclusionThough an overall increase in D-dimer, TG and AIP was observed in COVID-19 patients, categorization based on D-dimer status detected lowering LDL and increasing AIP on deterioration of disease state.

Failure rate of D-dimer testing in patients with high clinical probability of pulmonary embolism: Ancillary analysis of three European studies.

In patients with a high clinical probability of pulmonary embolism (PE), the high prevalence can lower the D-dimer negative predictive value and increase the risk of diagnostic failure. It is therefore recommended that these high-risk patients should undergo chest imaging without D-dimer testing although no evidence supports this recommendation. The objective was to evaluate the safety of ruling out PE based on D-dimer testing among patients with a high clinical probability of PE. This was a post hoc analysis of three European studies (PROPER, MODIGLIANI, and TRYSPEED). Patients were included if they presented a high clinical probability of PE (according to either the Wells or the revised Geneva score) and underwent D-dimer testing. The D-dimer-based strategy ruled out PE if the D-dimer level was below the age-adjusted threshold (i.e., <500 ng/mL in patients aged less than 50 and age × 10 ng/mL in patients older than 50). The primary endpoint was a thromboembolic event in patients with negative D-dimer either at index visit or at 3-month follow-up. A Bayesian approach estimated the probability that the failure rate of the D-dimer-based strategy was below 2% given observed data. Among the 12,300 patients included in the PROPER, MODIGLIANI, and TRYSPEED studies, 651 patients (median age 68 years, 60% female) had D-dimer testing and a high clinical probability of PE and were included in the study. PE prevalence was 31.3%. Seventy patients had D-dimer levels under the age-adjusted threshold, and none of them had a PE after follow-up (failure rate 0.0% [95% CI 0.0%-6.5%]). Bayesian analysis reported a credible interval of 0.0%-4.1%, with a 76.2% posterior probability of a failure rate below 2%. In this study, ruling out PE in high-risk patients based on D-dimer below the age-adjusted threshold was safe, with no missed PE. However, the large CI of the primary endpoint precludes a definitive conclusion.

Angiopoietin-2 and D-dimer add prognostic information to clinical risk in pulmonary arterial hypertension

Thrombosis and endothelial injury are pathologic hallmarks of pulmonary arterial hypertension (PAH). We aimed to evaluate whether markers of endothelial dysfunction and coagulation in the blood would provide insight into disease activity, treatment response, and outcomes in PAH. MethodsWe prospectively collected baseline and 3-month follow-up blood samples from treatment-naïve PAH patients (n=22) and those who had a clinical indication to intensify therapy (n=19). In addition, we recruited 12 healthy people and clinically stable PAH patients (n=45) as controls who had two blood samples collected twice within 14 days. We generated platelet-free plasma and measured D-dimer, angiopoietin-2, thrombin time, soluble P-selectin, von Willebrand factor, and vascular endothelial growth factor. We assessed treatment response with Reveal Lite 2 scores (all patients had NT-pro-BNP, 6-minute-walk, and functional class assessment at both visits) and followed clinical outcomes for 3 years. ResultsAngiopoietin-2 levels were elevated and fell with response to effective therapy (drop in Reveal Lite 2 score). At follow-up, persistently elevated angiopoietin-2 levels predicted clinical events and even identified low-risk participants who subsequently had events. D-dimer levels were also elevated in PAH patients but didn’t change in response to therapy. Several other abnormalities in endothelial and platelet activation were identified (including elevated soluble P-selectin, elevated von Willebrand factor, and elevated vascular endothelial growth factor) but these did not change with treatment or predict outcome. ConclusionsAngiopoietin-2 and D-dimer are elevated in PAH patients and may add prognostic information to routine clinical assessment.

Relation Between Monocyte-to-lymphocyte Ratio and Depressive Symptoms in Patients with Non-severe COVID-19 Infection

Background and Aim: Mental health of non-hospitalized patients and those with non-severe infections has attracted lower attention in comparison to other patients. Circulating monocytes are deeply involved in all stages of COVID-19 infection. The present study aimed to investigate the relationship between monocyte-to-lymphocyte ratio (MLR) and depressive symptoms in patients with non-severe COVID-19 infection. Methods: The study included 312 patients with non-severe COVID-19 infection diagnosed on the basis of a positive reverse-transcriptase polymerase chain reaction (RT-PCR) test of nasopharyngeal swabs. Depressive symptoms were assessed using the validated Arabic version of the 7-item Hamilton Depression Rating Scale (HAMD). According to the obtained scores, patients were classified to have mild (10-13), moderate (14-17), or severe depression (&gt;17). Results: The present study included 312 patients with non-severe COVID-19. According to HAMDS, clinically significant depression was diagnosed in 144 patients (46.2 %). They comprised 38 patients (12.2 %) with mild depression, 30 patients (9.6 %) with mild-tomoderate depression and 76 patients (24.4 %) with moderate-to-severe depression. Multivariate logistic regression analysis identified male sex [OR (95% CI): 2.07 (1.27-3.36), p = 0.003], presence of dyspnea [(OR (95 % CI): 1.99 (1.21-3.27), p = 0.007], D dimer levels [OR (95% CI): 2.32 (1.19-4.52), p = 0.013], MLR [OR (95% CI): 0.52 (0.28-0.99), p = 0.046] and abnormal CT findings [OR (95% CI): 1.79 (1.08-2.95), p = 0.023] as significant predictors of depression in the studied patients. Conclusion: Low MLR is related to depressive symptoms in patients with non-severe covid-19 infection. Other predictors include male sex, dyspnea, abnormal CT findings and elevated D-dimer levels.

Analysis of immunological and biochemical parameters after booster dose vaccination using protein-based and inactivated virus vaccine for safety

IntroductionHeterologous vaccines enhance the immune response to new variants and allow flexibility in booster administration when the original vaccine is unavailable. Studies show that heterologous boosters can generate comparable or superior antibody responses compared to homologous boosters. Considering rare side effects is essential in evaluating COVID-19 vaccines, especially those associated with ChAdOx1-S (AstraZeneca) and Ad26.COV2.S (Janssen), including blood clotting and idiopathic thrombocytopenia. Severe side effects, such as myocarditis and pericarditis, may occur after Pfizer or Moderna boosters but are rare. MethodsThis study administered two vaccines: the Sinopharm inactivated virus vaccine and the Razi-CoV-Pars (RCP) booster. Various evaluations included biochemical markers, coagulation factors, autoimmune antibodies, and antibodies against concerning variants. ResultsAll 90 participants exhibited a notable rise in antibody levels against the variant of concern (VOC). Participants receiving the Razi-CoV-Pars booster after Sinopharm/BBIBP-CorV showed significantly higher antibody levels (Wuhan ∼ 3.25 times, Delta ∼4 times, Omicron ∼ 14 times) compared to those receiving Sinopharm's homologous vaccine. No significant changes (P: <0.05) were found in LDH, CPK, CK-MB, ANA, and Anti-CCP levels. However, individuals receiving Sinopharm's booster after two doses showed a significant increase (4 cases) in D-Dimer levels. ConclusionThe Razi-CoV-Pars vaccine demonstrates a favorable safety profile and promising potential as an effective booster against current variants, particularly due to its significant protective titer against Omicron.

Pathogenesis and Biomarkers of Cancer-Related Ischemic Stroke.

To investigate the pathogenesis of cancer-related ischemic stroke (CRIS) and to search for reliable biomarkers of CRIS. Patients with CRIS, only-cancer and only-ischemic stroke who were hospitalized in the First Affiliated Hospital of Guangxi Medical University from May 2022 to January 2024 were recruited, and laboratory and clinical data of the three groups were collected. Peripheral venous blood was collected and enzyme-linked immunosorbent assay (ELISA) was used to detect markers of coagulation (D-dimer) and endothelial integrity (intercellular adhesion molecule-1 (ICAM-1)). The study included 16 patients with CRIS, as well as 16 patients with only-cancer and 16 patients with only-ischemic stroke. Among patients with CRIS, the most common cancer was lung cancer, and the most common pathological type was adenocarcinoma. It was found that compared with patients with only-cancer and only-ischemic stroke, the hemoglobin and lymphocyte percentage in patients with CRIS were decreased (P<0.05), while the neutrophil percentage and neutrophil to lymphocyte ratio (NLR) were increased (P<0.05). Compared with only-ischemic stroke group, the lymphocyte absolute value in patients with CRIS was decreased (P<0.05), and platelet to lymphocyte ratio (PLR), globulin, prothrombin time (PT), international normalized ratio (INR) and ICAM-1 were increased (P<0.05). D-dimer level was higher in patients with CRIS than in only-cancer group (P<0.05). In the present study, the increased NLR, PLR, ICAM-1 and D-dimer were expected to be biomarkers of CRIS, indicating that hypercoagulability mediated by cancer inflammation and endothelial damage may be the pathogenesis of CRIS. The novel findings in the present study will facilitate clinicians to identify the patients at high risk of CRIS. Because of the small sample size, the findings need to be validated by prospective large-sample studies in the future.