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PLoS Pathogens Jun 2024COVID-associated coagulopathy seemly plays a key role in post-acute sequelae of SARS- CoV-2 infection. However, the underlying pathophysiological mechanisms are poorly...
COVID-associated coagulopathy seemly plays a key role in post-acute sequelae of SARS- CoV-2 infection. However, the underlying pathophysiological mechanisms are poorly understood, largely due to the lack of suitable animal models that recapitulate key clinical and pathological symptoms. Here, we fully characterized AC70 line of human ACE2 transgenic (AC70 hACE2 Tg) mice for SARS-CoV-2 infection. We noted that this model is highly permissive to SARS-CoV-2 with values of 50% lethal dose and infectious dose as ~ 3 and ~ 0.5 TCID50 of SARS-CoV-2, respectively. Mice infected with 105 TCID50 of SARS-CoV-2 rapidly succumbed to infection with 100% mortality within 5 days. Lung and brain were the prime tissues harboring high viral titers, accompanied by histopathology. However, viral RNA and inflammatory mediators could be detectable in other organs, suggesting the nature of a systemic infection. Lethal challenge of AC70 hACE2 Tg mice caused acute onset of leukopenia, lymphopenia, along with an increased neutrophil-to-lymphocyte ratio (NLR). Importantly, infected animals recapitulated key features of COVID-19-associated coagulopathy. SARS-CoV-2 could induce the release of circulating neutrophil extracellular traps (NETs), along with activated platelet/endothelium marker. Immunohistochemical staining with anti-platelet factor-4 (PF4) antibody revealed profound platelet aggregates especially within blocked veins of the lungs. We showed that acute SARS-CoV-2 infection triggered a hypercoagulable state coexisting with ill-regulated fibrinolysis. Finally, we highlighted the potential role of Annexin A2 (ANXA2) in fibrinolytic failure. ANXA2 is a calcium-dependent phospholipid-binding protein that forms a heterotertrameric complexes localized at the extracellular membranes with two S100A10 small molecules acting as a co-receptor for tissue-plasminogen activator (t-PA), tightly involved in cell surface fibrinolysis. Thus, our results revealing elevated IgG type anti-ANXA2 antibody production, downregulated de novo ANXA2/S100A10 synthesis, and reduced ANXA2/S100A10 association in infected mice, this protein might serve as druggable targets for development of antithrombotic and/or anti-fibrinolytic agents to attenuate pathogenesis of COVID-19.
PubMed: 38913740
DOI: 10.1371/journal.ppat.1011777 -
Journal of Cardiothoracic Surgery Jun 2024Esophageal cancer represents a significant public health concern; however, reliable diagnostic and prognostic markers have not been established. This study aimed to...
BACKGROUND
Esophageal 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.
METHODS
Overall, 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.
RESULTS
Preoperative 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.
CONCLUSION
Plasma D-dimer concentrations are clinically valuable in esophageal cancer diagnosis, postoperative recurrence monitoring, and prognosis prediction.
Topics: Humans; Fibrin Fibrinogen Degradation Products; Esophageal Neoplasms; Male; Female; Middle Aged; Aged; Prognosis; Biomarkers, Tumor; Retrospective Studies; Survival Rate; Esophagectomy
PubMed: 38907327
DOI: 10.1186/s13019-024-02895-5 -
PloS One 2024To evaluate the diagnostic accuracy of the aortic dissection detection risk score (ADD-RS) used alone or in combination with D-dimer for detecting acute aortic syndrome... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To evaluate the diagnostic accuracy of the aortic dissection detection risk score (ADD-RS) used alone or in combination with D-dimer for detecting acute aortic syndrome (AAS) in patients presenting with symptoms suggestive of AAS.
METHODS
We searched MEDLINE, EMBASE, and the Cochrane Library from inception to February 2024. Additionally, the reference lists of included studies and other systematic reviews were thoroughly searched. All diagnostic accuracy studies that assessed the use of ADD-RS alone or with D-Dimer for diagnosing AAS compared with a reference standard test (e.g. computer tomographic angiography (CTA), ECG-gated CTA, echocardiography, magnetic resonance angiography, operation, or autopsy) were included. Two reviewers independently selected and extracted data. Risk of bias was appraised using QUADAS-2 tool. Data were synthesised using hierarchical meta-analysis models.
RESULTS
We selected 13 studies from the 2017 citations identified, including six studies evaluating combinations of ADD-RS alongside D-dimer>500ng/L. Summary sensitivities and specificities (95% credible interval) were: ADD-RS>0 94.6% (90%, 97.5%) and 34.7% (20.7%, 51.2%), ADD-RS>1 43.4% (31.2%, 57.1%) and 89.3% (80.4%, 94.8%); ADD RS>0 or D-Dimer>500ng/L 99.8% (98.7%, 100%) and 21.8% (12.1%, 32.6%); ADD RS>1 or D-Dimer>500ng/L 98.3% (94.9%, 99.5%) and 51.4% (38.7%, 64.1%); ADD RS>1 or ADD RS = 1 with D-dimer>500ng/L 93.1% (87.1%, 96.3%) and 67.1% (54.4%, 77.7%).
CONCLUSIONS
Combinations of ADD-RS and D-dimer can be used to select patients with suspected AAS for imaging with a range of trade-offs between sensitivity (93.1% to 99.8%) and specificity (21.8% to 67.1%).
Topics: Humans; Fibrin Fibrinogen Degradation Products; Aortic Dissection; Syndrome; Sensitivity and Specificity; Acute Disease; Computed Tomography Angiography; Acute Aortic Syndrome
PubMed: 38905181
DOI: 10.1371/journal.pone.0304401 -
Cells Jun 2024Authors have demonstrated that apoptosis activation is a pathway related to cartilage degradation characteristics of the OA process. Autophagy is an adaptive response to...
Authors have demonstrated that apoptosis activation is a pathway related to cartilage degradation characteristics of the OA process. Autophagy is an adaptive response to protect cells from various environmental changes, and defects in autophagy are linked to cell death. In this sense, decreased autophagy of chondrocytes has been observed in OA articular cartilage. The aim of this work was to study the role of OA mitochondria in apoptosis, autophagy, and senescence, using OA and Normal (N) transmitochondrial cybrids. Results: OA cybrids incubated with menadione showed a higher percentage of late apoptosis and necrosis than N cybrids. Stimulation of cybrids with staurosporine and IL-1β showed that OA cybrids were more susceptible to undergoing apoptosis than N cybrids. An analysis of the antioxidant response using menadione on gene expression revealed a lower expression of nuclear factor erythroid 2-like 2 and superoxide dismutase 2 in OA than N cybrids. Activation of microtubule-associated protein 1A/1B-light chain 3 was reduced in OA compared to N cybrids. However, the percentage of senescent cells was higher in OA than N cybrids. Conclusion: This work suggests that mitochondria from OA patients could be involved in the apoptosis, autophagy, and senescence of chondrocytes described in OA cartilage.
Topics: Autophagy; Humans; Osteoarthritis; Apoptosis; Cellular Senescence; Mitochondria; Chondrocytes; Microtubule-Associated Proteins; NF-E2-Related Factor 2; Superoxide Dismutase; Aged; Interleukin-1beta; Male; Middle Aged; Vitamin K 3; Female
PubMed: 38891108
DOI: 10.3390/cells13110976 -
BMC Musculoskeletal Disorders Jun 2024Suction drainages are commonly used after total knee arthroplasty (TKA) procedures; however, their use is somewhat controversial. Recently, some reports have claimed...
BACKGROUND
Suction drainages are commonly used after total knee arthroplasty (TKA) procedures; however, their use is somewhat controversial. Recently, some reports have claimed that the administration of tranexamic acid (TXA) may prevent postoperative bleeding following TKAs. Although numerous studies have reported regarding different dosages, timings of administration, or drain clamping times for intravenous and intra-articular TXA injections (IA-TXAs), few have examined whether suction drainage is necessary when TXA is administered. In this study, we compared using suction drainage without TXA administration and IA-TXA without suction drainage and aimed to examine the need for suction drainage during IA-TXA.
METHODS
This retrospective study was conducted on 217 patients who had received TKA for osteoarthritis; 104 were placed on suction drainage after TKA without TXA (Group A), whereas the remaining 113 received IA-TXA immediately after surgery without suction drainage (Group B). Our clinical evaluation included assessments of the need for transfusion, presence of postoperative complications, incidence of deep vein thrombosis (DVT), and changes in hemoglobin (Hb), hematocrit (Hct), and D-dimer levels.
RESULTS
No significant differences were observed in terms of postoperative complications and preoperative Hb, Hct, or D-dimer levels between the two groups. Although the prevalence of DVT was significantly higher in Group B (p < 0.05), all cases were asymptomatic. Hb and Hct levels were significantly lower in Group A than in Group B at 1, 3, 7, and 14 days postoperatively (p < 0.05), although none of the cases required blood transfusions. D-dimer levels were significantly higher in Group A than in Group B at 1 and 3 days postoperatively (p < 0.05).
CONCLUSION
Suction drainage might not be necessary when IA-TXA is administered after TKA procedures.
Topics: Humans; Tranexamic Acid; Retrospective Studies; Arthroplasty, Replacement, Knee; Female; Male; Aged; Suction; Injections, Intra-Articular; Antifibrinolytic Agents; Middle Aged; Postoperative Hemorrhage; Aged, 80 and over; Osteoarthritis, Knee; Venous Thrombosis; Treatment Outcome
PubMed: 38890633
DOI: 10.1186/s12891-024-07604-w -
Immunity, Inflammation and Disease Jun 2024Acute pancreatitis (AP) is an inflammatory disease of the pancreas, and the prognosis of severe AP (SAP) is poor. The study aimed to identify promising biomarkers for...
OBJECTIVES
Acute pancreatitis (AP) is an inflammatory disease of the pancreas, and the prognosis of severe AP (SAP) is poor. The study aimed to identify promising biomarkers for predicting the occurrence and survival outcome of SAP patients.
MATERIALS AND METHODS
Two hundred and forty AP patients were retrospectively recruited, in which 72 cases with SAP. Blood test was done for collection of laboratory indicators. After treatment, the mortality of patients was recorded.
RESULTS
Patients in the SAP group had higher intensive care unit admissions and longer hospital stays (p < .001). Among laboratory parameters, significantly high values of C-reactive protein (CRP), triglycerides and glucose (TyG) index, Von willebrand factor antigen (vWF:Ag) and D-dimer were found in SAP groups relative to non-SAP ones. Receiver operating characteristic curve indicated the good performance of CRP, TyG index, vWF:Ag and D-dimer in SAP diagnosis. Among all SAP cases, 51 survived while 21 died. TyG index (odds ratio [OR] = 6.914, 95% confidence interval [CI] = 1.193-40.068, p = .028), vWF:Ag (OR = 7.441, 95% CI = 1.236-244.815, p = .028), and D-dimer (OR = 7.987, 95% CI = 1.251-50.997, p = .028) were significantly related to survival outcome of SAP patients by multiple logistic regression analysis. Both TyG index and vWF showed favorable efficiency in predicting overall prognosis. The area under the curve for the multivariate model (PRE = -35.908 + 2.764 × TyG + 0.021 × vWF:Ag) was 0.909 which was greater than 0.9, indicating its excellent performance in prognosis prediction.
CONCLUSION
CRP, TyG index, vWF:Ag, and D-dimer values on admission may be potential clinical predictors of the development of SAP. Moreover, TyG index and vWF:Ag may be helpful to predict survival outcome.
Topics: Humans; Male; Female; Middle Aged; Pancreatitis; Retrospective Studies; Prognosis; Adult; Fibrin Fibrinogen Degradation Products; C-Reactive Protein; Biomarkers; Aged; von Willebrand Factor; ROC Curve; Acute Disease; Triglycerides; Blood Glucose; Severity of Illness Index
PubMed: 38888384
DOI: 10.1002/iid3.1267 -
Medicine Jun 2024The aim was to investigate the independent risk factors for lower extremity deep vein thrombosis (DVT) after total knee arthroplasty, and to establish a nomogram... (Observational Study)
Observational Study
The aim was to investigate the independent risk factors for lower extremity deep vein thrombosis (DVT) after total knee arthroplasty, and to establish a nomogram prediction model accordingly. Data were collected from total knee replacement patients from January 2022 to December 2023 in our hospital. Unifactorial and multifactorial logistic regression analyses were used to determine the independent risk factors for lower extremity DVT after total knee arthroplasty and to establish the corresponding nomogram. The receiver operating characteristic curves were plotted and the area under the curve was calculated, and the calibration curves and decision curves were plotted to evaluate the model performance. A total of 652 patients with total knee arthroplasty were included in the study, and 142 patients after total knee arthroplasty developed deep veins in the lower extremities, with an incidence rate of 21.78%. After univariate and multivariate logistic regression analyses, a total of 5 variables were identified as independent risk factors for lower extremity DVT after total knee arthroplasty: age > 60 years (OR: 1.70; 95% CI: 1.23-3.91), obesity (OR: 1.51; 95% CI: 1.10-1.96), diabetes mellitus (OR: 1.80; 95% CI: 1.23-2.46), D-dimer > 0.5 mg/L (OR: 1.47; 95% CI: 1.07-1.78), and prolonged postoperative bed rest (OR: 1.64; 95% CI: 1.15-3.44). the nomogram constructed in this study for lower extremity DVT after total knee arthroplasty has good predictive accuracy, which helps physicians to intervene in advance in patients at high risk of lower extremity DVT after total knee arthroplasty.
Topics: Humans; Arthroplasty, Replacement, Knee; Female; Male; Venous Thrombosis; Middle Aged; Nomograms; Risk Factors; Aged; Lower Extremity; Postoperative Complications; Fibrin Fibrinogen Degradation Products; ROC Curve; Retrospective Studies; Logistic Models; Age Factors; Incidence
PubMed: 38875414
DOI: 10.1097/MD.0000000000038517 -
Medical Science Monitor : International... Jun 2024BACKGROUND This prospective study from a single center aimed to compare the perioperative blood loss (PBL) in 79 patients with intertrochanteric fractures (IF) treated... (Randomized Controlled Trial)
Randomized Controlled Trial
Perioperative Administration of Tranexamic Acid and Low Molecular Weight Heparin for Enhanced Blood Management in Intertrochanteric Fractures: A Randomized Controlled Study.
BACKGROUND This prospective study from a single center aimed to compare the perioperative blood loss (PBL) in 79 patients with intertrochanteric fractures (IF) treated with intramedullary nailing (IMN) using 3 regimens of combined tranexamic acid (TXA) and low molecular weight heparin (LMWH), proposing a novel therapy of 4-dose TXA. MATERIAL AND METHODS We recruited 79 patients and randomly divided them into 3 groups. The 4-dose TXA group (22 patients) received 1.0 g intravenous TXA 30 min before surgery and 1.0 g at intervals of 3, 6, and 9 h before surgery. The 1-dose TXA group (25 patients) received 1.0 g intravenous TXA 30 min before surgery, while the control group (32 patients) did not receive TXA. LMWH was applied 12 h after surgery in each group. The primary metrics evaluated included hidden blood loss (HBL), total blood loss (TBL), and the number and incidence rate of deep vein thrombosis (DVT). RESULTS Analysis of the HBL revealed that the 4-dose TXA group had the lowest average (583.13±318.08 ml), followed by the 1-dose TXA group (902.94±509.99 ml), and the control group showed the highest (1154.39±452.06 ml) (P<0.05). A similar result was observed for TBL (4-dose group: 640.86±337.22 ml, 1-dose group: 971.74±511.14 ml, control group: 1226.27±458.22 ml, P<0.05). Regarding DVT, the 4-dose TXA group had 5 cases (incidence rate 22.73%), the 1-dose TXA group had 6 cases (incidence rate 24.00%), and the control group had 8 cases (incidence rate 25.00%), with no significant difference among groups (P>0.05). CONCLUSIONS Treatment using 4-dose TXA and LMWH can effectively reduce PBL without increasing the DVT risk in IF patients with IMN.
Topics: Humans; Tranexamic Acid; Female; Male; Hip Fractures; Heparin, Low-Molecular-Weight; Aged; Blood Loss, Surgical; Venous Thrombosis; Prospective Studies; Middle Aged; Perioperative Care; Antifibrinolytic Agents; Aged, 80 and over; Fracture Fixation, Intramedullary
PubMed: 38875178
DOI: 10.12659/MSM.944063 -
Journal of Orthopaedic Surgery and... Jun 2024The role of red blood cell (RBC) counts as potential independent risk factors for deep vein thrombosis (DVT) in patients with spinal cord injury (SCI) remains uncertain.... (Observational Study)
Observational Study
BACKGROUND
The role of red blood cell (RBC) counts as potential independent risk factors for deep vein thrombosis (DVT) in patients with spinal cord injury (SCI) remains uncertain. This study aims to clarify the associations between RBC counts and DVT incidence among this population.
METHODS
A retrospective analysis was performed on 576 patients with SCI admitted to the rehabilitation medicine department from January 1, 2017 to December 31, 2021. After exclusions, 319 patients were analyzed, among which 94 cases of DVT were identified.
RESULTS
Mode of injury, D-dimer and anticoagulant therapy were significant covariates (P < 0.05). Age, fibrinogen, D-dimer, anticoagulant therapy and American Spinal Cord Injury Association impairment scale (AIS) grades were associated with RBC counts and DVT incidence (P < 0.05). Adjusting for these factors, a 1.00 × 10^12/L increase in RBC counts correlated with a 45% decrease in DVT incidence (P = 0.042), revealing a "U" shaped relationship with a pivot at 4.56 × 10^12/L (P < 0.05).
CONCLUSION
RBC counts below 4.56 × 10^12/L serve as a protective factor against DVT, while counts above this threshold pose a risk. These findings could inform the development of DVT prevention strategies for patients with SCI, emphasizing the need for targeted monitoring and management of RBC counts.
Topics: Humans; Spinal Cord Injuries; Retrospective Studies; Venous Thrombosis; Male; Female; Incidence; Middle Aged; Adult; Risk Factors; Erythrocyte Count; Aged; Fibrin Fibrinogen Degradation Products; Anticoagulants; Time Factors
PubMed: 38867298
DOI: 10.1186/s13018-024-04838-1 -
Scientific Reports Jun 2024There remains no optimal anticoagulation protocol for continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in pediatric patients with...
There remains no optimal anticoagulation protocol for continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in pediatric patients with elevated D-dimer levels. We aimed to assess the effects of different anticoagulation strategies on the risk of CRRT filter clotting in these patients. Pediatric patients undergoing CRRT were retrospectively grouped based on pre-CRRT D-dimer levels and anticoagulant: D-RCA group (normal D-dimer, RCA only, n = 22), D+ RCA group (elevated D-dimer, RCA only, n = 50), and D+ RCA+ systemic heparin anticoagulation (SHA) group (elevated D-dimer, RCA combined with SHA, n = 55). The risk of filter clotting and incidence of bleeding were compared among the groups. Among the groups, the D+ RCA+ SHA group had the longest filter lifespan; further, the incidence of bleeding was not increased by concurrent use of low-dose heparin for anticoagulation. Moreover, concurrent heparin anticoagulation was associated with a decreased risk of filter clotting. Contrastingly, high pre-CRRT hemoglobin and D-dimer levels and post-filter ionized calcium level > 0.4 mmol/L were associated with an increased risk of filter clotting. RCA combined with low-dose heparin anticoagulation could reduce the risk of filter clotting and prolong filter lifespan without increasing the risk of bleeding in patients with elevated D-dimer levels undergoing CRRT.
Topics: Humans; Anticoagulants; Heparin; Continuous Renal Replacement Therapy; Male; Female; Citric Acid; Child; Fibrin Fibrinogen Degradation Products; Child, Preschool; Retrospective Studies; Infant; Hemorrhage; Blood Coagulation; Adolescent; Renal Replacement Therapy
PubMed: 38866989
DOI: 10.1038/s41598-024-64433-6