D-dimer Levels Research Articles

Potential of D-Dimer as a Tool to Rule Out Sac Expansion in Patients With Persistent Type 2 Endoleaks After Endovascular Aneurysm Repair.

In managing type 2 endoleak (T2EL) following endovascular aortic aneurysm repair (EVAR), an indication for reintervention is aneurysm enlargement (AnE). A previous study found that low D-dimer levels (DDLs) at 1 year were associated with reduced AnE risk in patients with persistent T2ELs (pT2ELs). This study analyzed patients with pT2ELs to determine the correlation between DDLs at annual follow-ups and AnE and proposed a follow-up protocol incorporating DDL monitoring. A retrospective review of elective EVAR cases between June 2007 and January 2021 identified "persistent" T2EL as confirmed at both 6- and 12-month contrast-enhanced CT studies. "Isolated" T2EL referred to cases without other endoleak types within 12 months. Inclusion criteria comprised >2 years of follow-up, isolated pT2ELs at 1 year, and DDL data at any annual follow-up over 5 years. The association between DDL and AnE, defined as ≥5 mm expansion within 5 years, was analyzed. A total of 109 patients with DDL data at 288 time points were enrolled. During a median follow-up of 49 months [31-60, IQR], 43 AnE were observed. In patients without AnE and with DDL data at 1 and 2 years (N=77 and 56), lower DDLs were associated with a reduced AnE risk (p=0.03 and 0.01). Optimal cutoff points were 5.4 and 5.3 µg/mL (AUC=0.651 and 0.702) with high negative predictive values (86.9% and 93.8%). Cox regression analyses confirmed that DDLs surpassing the cutoff values correlated significantly with AnE (p=0.042 and p=0.038). Our simulated protocol for omitting imaging studies in patients with stable aneurysms and low DDL might have overlooked one AnE but could have saved 28 imaging studies over 3 years if implemented on our patients. Low DDLs at the 1- and 2-year follow-ups can potentially exclude AnE in pT2EL patients, suggesting DDL monitoring as a resource-saving approach. The management of type 2 endoleaks in post-EVAR patients has been a topic of debate. This retrospective single-center study, featuring strict inclusion criteria, included 109 patients with persistent type 2 endoleaks. The findings indicate that patients with lower D-dimer levels at 1- and 2-year follow-ups are unlikely to experience sac enlargement ≥5 mm within 5 years, even in the presence of type 2 endoleaks. This study suggests that D-dimer monitoring has the potential to reduce reliance on imaging studies for the follow-up of patients with type 2 endoleaks, leading to significant savings in medical resources.

Fungal infection-related conditions and outcomes in severe COVID-19: a nationwide case-control study

BackgroundFungal infections are significant complications of severe coronavirus disease 2019 (COVID-19). Although various risk factors for poor outcomes in patients with COVID-19 have been identified, clinical and treatment factors associated with fungal infections in patients with severe COVID-19 remain unclear. This study aimed to elucidate clinical factors associated with fungal infections during severe COVID-19 treatment.MethodsThis was a post hoc analysis of the J-RECOVER study, a multicenter retrospective observational study involving patients with COVID-19 who required admission at 66 hospitals between January and September 2020. Inclusion criteria were ages ≥ 18 years, COVID-19 diagnosis with reverse-transcription polymerase chain reaction, and treatment with mechanical ventilation (MV). Patients who received antifungal drugs before MV were excluded. Potential predictors were identified through univariate analysis of patient and treatment characteristics between patients with- and those without fungal infection, which was defined as antifungal agent use for ≥ 5 days. To account for facility-specific data clustering, generalized estimating equations (GEE) were employed as adjusted analyses to calculate the relative risks of potentially associated factors. Two sensitivity analyses were performed with modified definitions for the two groups: patients who received antifungal drugs for ≤ 4 days were excluded, and fungal infection was re-defined as antifungal drug use for ≥ 14 days.ResultsAmong 4,915 patients in the J-RECOVER study, 559 adults with COVID-19 who required MV were included. Fungal infections occurred in 57 (10.2%) patients. Univariate analyses identified age, age ≥ 65 years, D-dimer level, remdesivir use, steroid use, and duration of steroid therapy as potential predictors of fungal infections. Multivariate analysis using GEE on these six factors revealed that only the duration of steroid use was significantly associated with an increased risk of fungal infection (odds ratio [OR] for a day increase: 1.01; 95% confidence interval [CI]: 1.00–1.01; p < 0.001). The two sensitivity analyses similarly showed that the duration of steroid use was associated with fungal infection (odds ratio for a day increase: 1.01; 95% CI: 1.00–1.01; p < 0.001 for both).ConclusionsIn patients with severe COVID-19 requiring MV, each additional day of steroid use was associated with prolonged use of antifungal medications for ≥ 5 days.

Characteristics of patients with non-severe infections of different SARS-CoV-2 omicron subvariants in China

ObjectiveThe aim of this study was to explore the clinical characteristics of patients infected with different Omicron subvariants presenting non-severe disease, evaluate the safety and efficacy of Azvudine for treatment of COVID-19, in order to broaden understanding of Omicron subvariant infections.MethodA total of 244 individuals with Omicron subvariant (BA.2.76, n = 158; BA.5.1, n = 86) were included in the study. Demographic, clinical, and laboratory data of the study participants were collected and analyzed.ResultPatients infected with BA.5.1 exhibited a higher incidence of clinical symptoms like fatigue (25.58% vs. 2.53%, p &amp;lt; 0.001), headache/dizziness (12.79% vs. 4.43%, p = 0.017), nausea/vomiting (10.47% vs. 1.27%, p = 0.002), viral loads and inflammatory factors, and shorter virus shedding time than those with BA.2.76. There are 28.1% patients reporting mild adverse events following Azvudine administration. After treatment, the levels of anti-SARS-CoV-2 IgG/IgM, white blood cell, and lymphocyte obviously increased, while C-reactive protein, procalcitonin, and D-dimer reduced. Azvudine speeded up the time for virus clearance compared to control treatment (10 vs. 11 days, p = 0.032). Low lymphocyte counts (odd ratio (OR) = 0.607, p = 0.001) and anti-SARS-CoV-2 IgG titer (OR = 0.990, p = 0.028) were the independent risk factors for long nucleic acid negativization duration after infection. Patients with pneumonia were often accompanied by dyspnea, fatigue and high level of D-dimer. Dyspnea (OR = 10.176, p = 0.019) could be used to identify the occurrence of pneumonia in patients infected with Omicron.ConclusionThe study demonstrated the difference in clinical and laboratory parameters between patients infected with Omicron BA.2.76 and BA.5.1, as well as the safety and efficacy of Azvudine therapy. Our study linked patient manifestations to Omicron subvariant, treatment, and clinical outcomes, which is conducive to healthcare providers/policymakers to revise and implement appropriate countermeasures, facilitating appropriately advise for individuals with Omicron subvariant infections.

Increased ferritin, serum lactate dehydrogenase, and aspartate aminotransferase levels predict macrophage activation syndrome complicating systemic lupus erythematosus: a retrospective study

BackgroundThis study aimed to assess the diagnosis of macrophage activation syndrome (MAS) at the onset of active childhood-onset systemic lupus erythematosus (cSLE), which is under-researched, and to compare the characteristics of cSLE with and without MAS, hypothesizing the existence of possible predictors of MAS in active cSLE.MethodsThis study enrolled 157 patients diagnosed with cSLE, with or without MAS, from Nanjing Medical University between January 2018 and May 2023. Data analysis was performed using an independent samples t-test or the Mann–Whitney U-test, the χ2 test, the Youden index to determine the optimal cutoff values for diagnosis, and binary logistic regression analysis to determine the predicted probability.ResultsFifteen patients (9%) had MAS in the active phase, with an SLE disease activity index of 16.6 (range, 6–32). Bone marrow aspirations revealed hemophagocytosis in 8/15 cases (53%). Fever was the most common feature of MAS patients. Lactate dehydrogenase (LDH) and ferritin levels were elevated in the patients. Lower leukocyte, neutrophil, and platelet counts, including serum sodium and fibrinogen, and increased alanine aminotransferase, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), ferritin, triglyceride, and D-dimer levels occurred in MAS patients, unlike those without MAS. Optimal cutoff values for ferritin (≥607.35 ng/ml), LDH (≥424 U/L), and AST (≥61 U/L) were predictors of MAS occurrence in cSLE. No MAS patients experienced recurrence during an 18-month mean follow-up.ConclusionsDespite the narrow scope of the study, elevated levels of ferritin, LDH, and AST may represent indicators of cSLE complicated by MAS. Early diagnosis and treatment may improve outcomes.

Risk factors and a prediction model of severe asparaginase-associated pancreatitis in children.

We aimed to investigate whether early clinical indicators were associated with eventual disease severity, and to develop a predictive model for severe asparaginase-associated pancreatitis (AAP). Seventy-five acute lymphoblastic leukaemia (ALL) cases with AAP admitted to Shanghai Children's Medical Center from March 2013 to August 2023 were divided into non-severe (n = 44) and severe (n = 31) groups based on Atlanta diagnostic and AAP grading criteria. We compared essential information, asparaginase(ASP) dosage form, cumulative dose, clinical characteristics and laboratory tests between the groups. Statistically significant indicators were analysed with multifactorial logistic regression to identify independent risk factors for severe AAP. Receiver operating characteristic (ROC) curves assessed the early predictive value of age, C-reactive protein (CRP) and fibrinogen (FIB) levels. In the early stages of AAP onset, significant differences in age, CRP, platelet count, red blood cell distribution width, albumin, calcium, FIB, and D-dimer levels were found between the non-severe and severe AAP groups (p < 0.05). Multifactorial logistic regression identified age (odds ratio [OR] = 1.204, p = 0.035), CRP (OR = 1.334, p = 0.003), and FIB (OR = 0.85, p = 0.008) as independent predictors of severe AAP. ROC analysis showed an area under the curves (AUC) for age was 0.681 (95% CI: 0.557-0.805), CRP was 0.766 (95% CI: 0.653-0.880), FIB was 0.735 (95% CI: 0.612-0.857). Optimal cut-off values for age, CRP, and FIB were 9.46 years, 48.5mg/L and 1.265g/L respectively. The combined AUC was 0.916 (95% CI: 0.845-0.986), with 0.903 sensitivity and 0.818 specificity, outperforming individual predictors (p < 0.05). Age, CRP, and FIB levels are good early predictors of severe AAP, and their combination significantly improves predictive accuracy.

COMPARISON OF D-DIMER LEVEL AND PLATELET COUNT IN INDIVIDUALS WITH AND WITHOUT SICKLE CELL ANAEMIA

Aim: This study aimed to assess the D-dimer levels and platelet count in sickle cell anaemia patients and compare with those of the control subjects. Materials and Methods: This study is a cross–sectional comparative study which enrolled 58 sickle cell anaemia patients (25 males and 33 females) in a stable state at the Obafemi Awolowo University Teaching Hospital in Ile-Ife, Osun State, Nigeria, as well as 25 healthy controls (11 males and 24 females). Venous blood (4.5 mL) was collected from both the patient and control into a vial containing 0.5 ml of 3.2% trisodium citrate. D-dimer levels was analysed using ELISA method. Platelet counts were determined (from 5ml venous sample collected with EDTA) using haematology autoanalyzer. Results: There was a significant rise in D-dimer levels in sickle cell patients, with mean values of 1771.86 ng/mL and 1986.00 ng/mL for males and females, respectively, in the steady state compared to the D-dimer levels of controls, with mean values of 199.24 and 322.21 ng/mL for males and females, respectively. Platelet count was significantly higher in SCA patients than in the control subjects. There is perfect correlation between D-dimer and platelet counts in both patients and control (r=1, n=57, P=0.000) and (r=1, n=30, P=0.000) Conclusion: This study showed the hypercoagulable state and thrombotic risk associated with SCA. The strong correlation between D-dimer levels and platelet counts suggests a potential interplay between platelet activation and coagulation activation in SCA, warranting further investigation into therapeutic interventions targeting these pathways.

Effectiveness of the quercetin use in patients with COVID-19 with concomitant type 2 diabetes mellitus

AimTo conduct a comparative analysis of the effectiveness of basic therapy and basic therapy with the inclusion of quercetin in patients with COVID-19 with concomitant type 2 diabetes.Material and methodsThere were examined 60 patients with COVID-19 with concomitant T2DM. Upon admission into the hospital and again after 10 days, serum levels of interleukin-6, C-reactive protein, procalcitonin, ferritin, endothelin-1 were determined, and capillaroscopy of the nail plate was performed. Patients of the group I (30) against the background of protocol therapy received 0.5 g of quercetin intravenously once a day for 10 days. Patients of the group II (30) received to basic therapy.ResultsAfter the treatment in patients of the group I general weakness decreased, body temperature normalized, improved saturation indicators, the level of acute-phase parameters (interleukin-6, CRP and ferritin) significantly decreased, a positive effect of quercetin on the level of D-dimer in blood serum was noted, indices of pericapillary edema and hemosiderin deposition significantly decreased, indices diameter of the arterial part of the capillary and capillary network density significantly increased.ConclusionsThe use of quercetin against the background of basic therapy in patients with COVID-19 and concomitant T2DM reliably reduces the level of acute-phase indices, has an important clinical significance for reducing endothelial dysfunction and for preventing thrombotic complications.

Red cell distribution width to albumin ratio and mortality in acute pulmonary thromboembolism.

The red cell distribution width (RDW)/albumin ratio (RAR) is an inflammation-based prognostic biomarker. To date, its prognostic value in patients with pulmonary thromboembolism (PTE) has been investigated in only one study. This study aimed to assess the effect of RAR on mortality in patients with PTE. Patients admitted for PTE between 2017 and 2023 were retrospectively reviewed. The data collected included demographic information, comorbidities, clinical findings, RDW, albumin, troponin, D-dimer levels, and in-hospital and 30-day mortality outcomes. RAR was calculated by dividing the RDW by albumin. A total of 190 patients were included in the study, of whom 83 (43.7%) were male. The mean age was 63 years (range: 23-89), and the mean RAR was 4.48% ± 1.68% /g/dL. A positive correlation was observed between RAR and both age and troponin level, whereas inverse correlations were noted with systolic blood pressure (sBP), diastolic blood pressure (dBP), and oxygen saturation (SpO2). Using a cutoff value of 5.294 determined by ROC analysis, patients with RAR ≥ 5.294 had a significantly shorter mean survival time than those with RAR value < 5.294 (16.310 months vs35.163 months; log-rank test, P < 0.001). Multivariate Cox regression analysis identified malignancy (hazard ratio [HR], 4.213; 95% confidence interval [CI], 1.103-16.090; P = 0.035) and RAR (HR: 1.295, 95% CI: 1.035-1.621, P = 0.024) as independent predictors of survival. In conclusion, an RAR value ≥ 5.294 was associated with significantly shorter survival, underscoring its potential utility as a prognostic marker in clinical practice for non-massive PTE.

Pulmonary embolism diagnosis with D-dimer levels and computed tomography

Pulmonary embolism diagnosis with D-dimer levels and computed tomography

The endothelial NO synthase content in the blood serum of patients with coronavirus disease (COVID-19) with pneumonia in association with hemostatic parameters depending on the clinical course and its prognostic significance

Aim: to investigate the content of eNOS in the blood serum of patients with coronavirus disease (COVID-19) with pneumonia in association with hemostatic parameters and to determine its prognostic value in assessing the risk of oxygen dependence and death. Material and methods. There were 123 patients with COVID-19 with pneumonia under observation. All patients were examined and treated in accordance with the Order of the Ministry of Health of Ukraine No. 722 dated 28.03.2020. The eNOS content in the patients’ serum was determined by enzyme-linked immunosorbent assay. Results. It was found that the content of eNOS in the blood serum of patients with COVID-19 with pneumonia at the time of hospitalization was 9.0 [7.0; 12.0] days lower (p &lt; 0.001) than in healthy subjects. The development of oxygen dependence in patients with COVID-19 with pneumonia was accompanied by worsening of endothelial dysfunction and procoagulant changes, which was confirmed by a decrease in the content of eNOS in the blood serum (p &lt; 0.001), an increase in the level of fibrinogen (p &lt; 0.05) and D-dimer (p &lt; 0.05). The threshold level of eNOS in the blood serum ≤327.09 pg/ml (AUC = 0.861, p &lt; 0.001) was predictive of the onset of oxygen dependence. In patients with COVID-19 with pneumonia who subsequently died, at the time of hospitalization, eNOS levels were lower (p &lt; 0.001) than in patients who recovered, which was combined with a higher level of D-dimer (p &lt; 0.05) and its more frequent increase (p = 0.04) compared with patients who recovered. The eNOS content in the blood serum of patients with COVID-19 with pneumonia was correlated (p &lt; 0.05) not only with the lethal outcome of the disease, but also with the formation of thrombotic complications, which occurred more often in patients with COVID-19 with pneumonia in the event of an adverse outcome (p = 0.0001). The threshold level of eNOS in the blood serum ≤201.75 pg/ml (AUC = 0.892, p &lt; 0.001) was indicative of a high probability of death. Conclusion. The eNOS content in the blood serum of patients with COVID-19 pneumonia at the time of hospitalization is lower (p &lt; 0.001) than in healthy individuals, and the degree of its decrease depends on the severity of the disease, the development of oxygen dependence and the subsequent outcome of this disease. Limiting levels of eNOS in the blood serum of patients with COVID-19 pneumonia, which are important for predicting the risk of developing oxygen dependence and fatal outcome of the disease, have been established.

Association Between Left Ventricular Diastolic Dysfunction, Systemic Inflammation, and Gastrointestinal Symptoms in HIV-Positive Patients on Antiretroviral Therapy

Background/Objectives: Despite advancements in antiretroviral therapy (ART), HIV-positive individuals face heightened risks of cardiovascular and gastrointestinal (GI) complications, often linked to persistent systemic inflammation. Left ventricular diastolic dysfunction (LVDD), prevalent in HIV patients, exacerbates this inflammatory state and may contribute to worsened GI symptoms. This study aims to explore the association between LVDD, systemic inflammation, and gastrointestinal symptoms in HIV-positive patients undergoing ART. The primary objective is to analyze how LVDD contributes to the inflammatory burden and its impact on gastrointestinal health in this population. Methods: This cross-sectional study included 320 participants divided into three groups: HIV-positive with LVDD (n = 80), HIV-positive without LVDD (n = 120), and HIV-negative controls (n = 120). Levels of inflammatory biomarkers—CRP, IL-6, TNF-α, fibrinogen, IL-1β, IFN-γ, and D-dimer—were measured, and GI symptoms were assessed. Echocardiographic evaluations were performed to determine LVDD presence and severity, while multivariate logistic regression identified predictors of GI complications. Results: Patients in the HIV + LVDD group exhibited significantly elevated levels of TNF-α, CRP, and D-dimer compared to other groups, correlating with higher incidences of nausea, diarrhea, and abdominal pain. TNF-α emerged as the strongest predictor of GI symptoms, underscoring its role in the pathophysiology linking cardiovascular and GI distress in this population. Persistent inflammation and coagulation abnormalities in the ART + LVDD group suggest that ART alone may not fully mitigate these complications. Conclusions: Our findings emphasize the compounded inflammatory burden in HIV patients with LVDD, highlighting the need for integrated approaches that address both cardiovascular and GI symptoms. Anti-inflammatory therapies targeting specific biomarkers like TNF-α could improve clinical outcomes, supporting a more comprehensive strategy to managing HIV-related comorbidities beyond viral suppression.

The association between mortality due to COVID-19 and coagulative parameters: a systematic review and meta-analysis study

Aims and objectivesThis systematic review and meta-analysis study evaluated the association between mortality due to COVID-19 and coagulative factors.MethodsA systematic search was conducted on electronic databases including PubMed, Scopus, and the Web of Science from the beginning of the pandemic until October 2024 to identify relevant studies on COVID-19 patients and their laboratory findings related to coagulation markers and mortality outcome. Eligibility criteria were defined based on the PICO framework, and data extraction was performed by two authors independently using a standardized sheet. Statistical analysis was accomplished using the random effects model, and heterogeneity among studies was assessed using the I2 test. R and RStudio were used for statistical analysis and visualization.ResultsOur systematic literature search yielded 6969 studies, with 48 studies meeting the inclusion criteria for our meta-analysis. The mean platelet count was significantly lower in deceased COVID-19 patients compared to survivors (20.58), while activated partial thromboplastin time (aPTT) and fibrinogen levels did not show significant differences. The pooled mean difference of D-Dimer, International Normalized Ratio (INR), and prothrombin time (PT) were significantly lower in survived patients (-2.45, -0.10, and -0.84, respectively). These findings suggest that platelet count, D-Dimer, INR, and PT may serve as potential indicators of mortality in COVID-19 patients.ConclusionThe results of our systematic review and meta-analysis revealed a significant reduction in the pooled platelet count among deceased individuals when compared to survivors. However, no significant distinctions were observed in the pooled mean activated aPTT and fibrinogen levels between the deceased and survivor groups. On the other hand, there were noticeable variations in the pooled estimated mean of INR, PT, and D-Dimer levels, with significantly higher values in the deceased group compared to those who survived.

Analysis of prognosis of neurological sequelae in children with carbon monoxide poisoning

This study retrospectively analyzed children admitted to the Fourth Affiliated Hospital of Guangxi Medical University for CO (carbon monoxide) poisoning from January 2018 to December 2022 and followed up on their neurological sequelae for a long time. The study was approved by the Ethics Committees of the Fourth Affiliated Hospital of Guangxi Medical University (the identification code was KY2023131) and informed consent was obtained from all participants and/or their legal guardians. The study complied with the Declaration of Helsinki. Through Global Deterioration Scale [GDS], we further compared the differences between children with and without cognitive impairment, and identified some risk factors for long-term cognitive impairment in children after CO poisoning. The GDS score of the patient was based on the follow-up score, and we only conducted one follow-up and recorded the GDS score throughout the entire study period. The follow-up time interval is defined as the time from the first discharge of the patient to our follow-up. A total of 113 children were encompassed in the study, with an average follow-up of 3.6 years (3.6 ± 1.5 years). Among them, 13 children (11.5%, 13/113) had cognitive abnormalities. The utilization of gas water heaters in enclosed bathrooms (101 cases, 89.4%) constituted the most frequent cause of CO poisoning among children in this study, followed by heating with fire (11 cases, 9.7%). Furthermore, one child was left by his father in a running car, thereby resulting in poisoning. The clinical manifestations of CO poisoning in children were mainly consciousness disorders (67 cases, 59.3%), dizziness or headache (37 cases, 32.7%), and other manifestations including irritability, crying, vomiting, limb weakness, and limb twitching, a total of 9 cases. The duration of consciousness disorders in children with cognitive abnormalities was mostly more than one day, with a median of 5 days, and the hospitalization time was longer. Children with cognitive abnormalities had higher C-reactive protein (CRP) levels, higher D-dimer levels, and higher liver enzyme levels. The most common imaging change after CO poisoning in children was cerebral edema, with two cases of subarachnoid hemorrhage observed and one case of demyelinating changes observed. For children with coma time less than one hour, there were few abnormal changes in cranial imaging. Children with cognitive abnormalities were more likely to develop epilepsy (38.5%, 5/13) and other system damage (53.8%, 7/13) during hospitalization, including pulmonary infection (3 cases), stressful gastrointestinal bleeding (2 cases), electrolyte imbalance (2 cases), dysfunction of liver, kidney or myocardial (3 cases), and some children had multiple system damage at the same time. There were statistical differences in the admission CO hemoglobin level, fibrinogen, D-dimer, high-sensitivity CRP, neuron enolase, alanine aminotransferase or aspartate aminotransferase (ALT or AST), lactate dehydrogenase, length of hospital stay, discharge and admission Glasgow Coma Scale (GCS), seizure frequency, duration of consciousness disorders more than one day, cranial imaging changes, use of ventilators, presence of other system damage, the number of hyperbaric oxygen (HBO) treatments, and whether the patients were transferred to another hospital between the two groups of children. Multivariate logistic regression analysis showed that head imaging changes and consciousness disorders lasting for more than a day were statistical differences. For children with unconsciousness lasting for more than one hour, it is advisable to contemplate conducting a head imaging examination as soon as possible within 3 days after CO exposure to guide the treatment during the acute phase.Characteristic alterations in cranial imaging and a longer duration of consciousness disorders (exceeding one day) might be correlated with subsequent neurological sequelae. For children with CO poisoning presenting these characteristics, active treatment can be implemented, encompassing but not restricted to HBO treatments, to minimize subsequent damage to the greater extent possible. So, for children who were unconscious for more than one day or presented characteristic changes in cranial imaging, long-term follow-up should be carried out to determine whether delayed encephalopathy or subsequent cognitive impairment occurs.

Predictive Value of Plasma D-Dimer for Cerebral Herniation Post-Thrombectomy in Acute Ischemic Stroke Patients.

Cerebral hernia is a serious complication after thrombectomy in patients with acute ischemic stroke (AIS). This study aims to explore the predictive value of emergency preoperative plasma D-dimer levels in cerebral herniation after successful thrombectomy. Between January 2019 and December 2023, patients with AIS who received a successful thrombectomy in our single comprehensive stroke center were retrospectively enrolled. We conducted a statistical analysis on the data using SPSS 26.0. Receiver operating characteristic curve (ROC) was used to evaluate the predictive value of D-dimer level for cerebral herniation. Among 278 enrolled patients, 20 cases (7.19%) experienced cerebral herniation. In patients with cerebral hernia, the score of the National Institutes of Health Stroke Scale was higher (16.5 vs 12.0, P < 0.001), the Alberta Stroke Plan early CT score was lower (6.5 vs 8.0, P < 0.001), the score of collateral circulation was lower (2.0 vs 3.0, P < 0.001), the proportion of eTICI blood flow grading of 3 of the occluded vessel was less (35% vs 75.19%), the proportion of pathogenesis of large atherosclerosis was less (5.00% vs 46.51%, P < 0.001), and the level of plasma D-dimer was higher (2.61 vs 0.82). After adjusting for potential confounders, the level of D-dimer (adjusted OR = 1.131, 95% CI 1.022-1.250, P = 0.017) was significantly correlated with cerebral hernia. Based on the ROC curve, the sensitivity and specificity of D-dimer in predicting cerebral herniation were 75.0% and 73.3%, respectively, and the area under the curve was 0.766. Although our study had certain limitations, we found that elevated emergency preoperative plasma D-dimer level is an independent predictive factor for the cerebral herniation after successful thrombectomy in patients with AIS, which is of great clinical significance.

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.

ANAKINRA EFFICACY IN COVID-19 PNEUMONIA GUIDED BY SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR: ASSOCIATION WITH THE INFLAMMATORY BURDEN OF THE HOST.

Anakinra was approved by the European Medicines Agency and received Emergency Use Authorization by the Food and Drug Administration of the United States for patients with COVID-19 pneumonia at risk for severe respiratory failure (SRF) with blood levels of suPAR (soluble urokinase plasminogen activator receptor) ≥ 6 ng/ml. We report the final results of the phase II open-label single-arm SAVE trial in a large population. Patients with COVID-19 pneumonia and suPAR levels ≥6 ng/ml received subcutaneously anakinra 100mg once daily for 10 days. The primary outcome was the incidence of SRF by day 14. Secondary outcomes were 30-day mortality, incidence of SRF according to time delay for start of treatment, safety and associations with the inflammatory burden of the host. From March 2020 to March 2022, 992 patients were enrolled. The incidence of SRF was 18.8% similar to the results of the phase III pivotal trial. The overall 30-day mortality was 9.5%. Participants were divided into four subgroups of time delay between symptoms onset and start of anakinra. The incidence of SRF was similar for all subgroups. Serious adverse events were reported in 15.4%; only 3 were possibly related to anakinra. The most common adverse event was increased liver function tests. A post-hoc comparison with the pivotal phase III trial showed similar anakinra outcomes among patients' subgroups by levels of inflammatory mediators and D-dimers. Results support similar efficacy of anakinra with the pivotal registrational trial for COVID-19 pneumonia. The lack of a comparator group is a limitation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04357366.

Obesity is associated with higher levels of circulating cytokines involved in the development of cardiovascular disease in people living with HIV.

Obesity is increasingly described in people living with HIV (PLWH), but its impact on immune activation and inflammation in HIV is still poorly characterised. We aimed to analyse the difference in circulating cytokines involved in pathways associated with co-morbidities in PLWH according to the presence or absence of obesity. Age and sex matched PLWH with and without obesity (BMI ≥30 kg/m2) from a multicentre, prospective cohort were recruited with a 1:2 ratio. Twenty-three biomarkers covering pathways associated with systemic inflammation (hsCRP, IL-2, IL-6, TNFR1, TNFR2, TNF-α, IFN-γ, IL-18), coagulation (vWF, D-dimer, sCD40L), endothelial function (E-selectin, P-selectin, sICAM-1, sVCAM-1), atherosclerosis (MPO, Lp-PLA2), immune regulation (IL-1RA), innate immune activation (MIP-1, MCP-1, sCD163, sCD14) and microbial translocation (LBP) were measured in the two groups. Between-group difference in biomarkers were assessed using Mann-Whitney test. Associations between obesity and biomarkers were assessed using logistic regression adjusted for age, gender, ethnicity, smoking status, and antiretroviral therapy (ART). Ninety-nine ART-treated PLWH were included in the analysis (33 with obesity, 66 without obesity). PLWH with obesity had higher levels of hsCRP, IL-6, vWF, D-dimer, E-selectin, MPO, IL-1RA, and LBP. Six markers (hsCRP, IL-6, vWF, E-selectin, MPO, IL-1RA), reflecting systemic inflammation, coagulation and atherosclerosis pathways were associated with increased odds of obesity in the adjusted logistic regression model: hsCRP (aOR 2.7, 95% CI [1.7, 4.29]), IL-6 (3.77 [1.43, 9.93]), vWF (5.33 [1.51, 18.75]), E-selectin (6.28 [1.36, 29.04]), MPO (6.85 [1.87, 25.04]), IL-1RA (6.45 [2.28, 18.2]). No association was observed between obesity and markers of innate immune activation and gut microbial translocation. Obesity in PLWH was associated with activation of systemic inflammatory, endothelial, atherosclerosis and coagulation pathways, rather than those associated with innate immune activation and gut microbial translocation. These pathways point towards an unfavourable cardiovascular profile in PLWH with obesity, which will have to be further explored in future studies on long-term outcomes.

Incidence and risk factors of silent deep venous thromboembolism before interval debulking surgery in ovarian cancer patients, a tertiary centre experience

ObjectiveTo determine the prevalence and risk factors for the development of asymptomatic venous thromboembolism (VTE) in ovarian cancer patients who underwent interval cytoreductive surgery after finishing neoadjuvant chemotherapy. MethodsThis is a prospective observational trial. Female patients with pathologically proven ovarian cancer who received neoadjuvant chemotherapy without clinical evidence of VTE were included. ResultsA total of 107 patients were enrolled in this study. The mean age was 53.37 years, and the mean body mass index (BMI) was 34.11 kg/m2. Seven (6.5 %) patients suffered from silent VTE, as documented by bilateral Doppler ultrasound in the pre- and postoperative settings. The mean age of the patients in the VTE group was 56.17 years, and their mean body mass index was 31.71 Kg/m2. Their median serum CA125 concentration was elevated (325.6 units/ml). On the other hand, the median D-dimer level was elevated by 678 ng/ml fibrinogen equivalent units (FEUs) in the same group of patients. In the present study, comorbidities did not influence the incidence of VTE, as the 7 patients who were diagnosed with VTE did not have any comorbidities. Most of the patients who were diagnosed with serous adenocarcinoma (71.4 %) or stage IIIc disease (57.1 %) were most likely to develop VTE. ConclusionSilent VTE is more prevalent in patients with advanced-stage ovarian cancer and serous carcinomas

PERSISTENT COAGULATION ABNORMALITIES IN RECOVERED COVID-19 PATIENTS FOLLOWING VACCINATION: A RETROSPECTIVE ANALYSIS

This retrospective observational study assessed persistent coagulation abnormalities in individuals who recovered from COVID-19 and subsequently received two doses of COVID-19 vaccination. The study enrolled 250 individuals, aged 20–50 years, and evaluated four primary coagulation markers: prothrombin time, activated partial thromboplastin time, D-dimer, and fibrinogen. Blood samples were analyzed using the STA-R coagulation analyzer. Results indicated that 10% of participants exhibited elevated D-dimer levels, 34% had elevated prothrombin times, and 85% displayed prolonged activated partial thromboplastin times, while 7.2% showed increased fibrinogen levels. Statistical analysis revealed significant deviations in D-dimer, activated partial thromboplastin time, and fibrinogen from standard reference ranges. These abnormalities suggest a possible hypercoagulable state post-vaccination, potentially due to vaccine-induced mechanisms that activate coagulation pathways. Findings align with reports of vaccine-induced thrombotic complications, especially in adenovirus-vectored vaccines. This study underscores the importance of monitoring coagulation parameters in vaccinated individuals with prior COVID-19 infection to ensure vaccine safety and efficacy. Future studies should investigate the underlying mechanisms of these coagulation changes and their clinical implications.

Prognostic significance of serum interleukin-6 in severe/critical COVID-19 patients treated with tocilizumab: a detailed observational study analysis

Baseline IL-6 levels have been found to be non-predictive of subsequent outcomes following tocilizumab treatment, highlighting the need for more reliable predictive markers. To address this, a retrospective analysis was conducted on the clinical profiles, diagnostic tests, and follow-up prognoses of 60 patients with severe or critical COVID-19, all of whom were identified as experiencing a cytokine storm and subsequently received tocilizumab treatment. Among the patients, the overall survival rate during follow-up was 80%, with further analysis revealing that advanced age was an independent risk factor for adverse outcomes. Following tocilizumab administration, a statistically significant increase in IL-6 and D-dimer levels was observed, while markers such as C-reactive protein (CRP), procalcitonin (PCT), and fibrinogen demonstrated reductions compared to pre-treatment values. Specifically, IL-6 levels initially surged briefly after tocilizumab intervention before gradually diminishing. To assess the prognostic utility of IL-6, the Receiver Operating Characteristic (ROC) curve was employed, which yielded an area under the curve (AUC) of 0.812, indicating strong predictive capability, with a sensitivity of 100% and a specificity of 53.49%. The optimal cut-off value for IL-6 was identified at 147.79 pg/mL. In conclusion, IL-6 levels tend to rise transiently following tocilizumab therapy, before gradually declining. These post-treatment IL-6 measurements may serve as a valuable biomarker for assessing prognosis in patients undergoing this treatment.