Incidence of acute Deep Vein Thrombosis in pediatric and adolescent orthopedic trauma hospitalized patients and effect of rivaroxaban treatment.

OBJECTIVE: Deep vein thrombosis (DVT) provoked by orthopedic trauma is increasing in pediatric hospitalized patients. The purpose of our study is to identify the prevalence of acute DVT in pediatric and adolescent orthopedic trauma hospitalized patients and focus on evaluating the anticoagulation strategies and the clinical outcomes after a confirmed acute DVT. METHODS: Patients (age ≤18 years) with a confirmed acute DVT admitted for orthopedic trauma between September 2017 and December 2023 were included. Patients were classified into the non-anticoagulation (NA), the in-hospital anticoagulation (IHA), and the in-and-out-of-hospital anticoagulation (IOHA) groups based on their anticoagulation regimen. Efficacy outcomes were the venous thromboembolism (VTE) recurrence within 3 months and change in thrombus burden by repeat imaging at 2 weeks after discharge compared with baseline. Safety outcomes were major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) within 3 months. RESULTS: Of the 11,206 pediatric and adolescent orthopedic trauma inpatients, 94(median age,16 [15, 18] years) were diagnosed with acute DVT, with an incidence of 0.84 %, of which 8(8.5 %) received NA, 41(43.6 %) received IHA, and 45(47.9 %) received IOHA. After the diagnosis of DVT, of patients who received anticoagulation, 97.9 % were treated with rivaroxaban as an oral anticoagulant, and 71.7 % received an LMWH course of ≥5 days before starting rivaroxaban therapy. With a median anticoagulation course of 22(8, 37.3) days, the duration in the IOHA was significantly longer than the IHA (37 days vs. 8 days, p = 0.000). No patients experienced recurrent VTE and MB at 3 months, and 1 received IOHA had a CRNMB event (0 % vs. 0 % vs. 2.2 %, p = 1.000). Thrombus resolution was significantly higher in patients who received anticoagulation therapy (IOHA 91.1 % vs. IHA 80.5 % vs. NA 37.5 %, P = 0.002), and thrombus-no relevant change was significantly lower in patients who received the IOHA strategy compared with the other groups (4.4 % vs. 19.5 % vs. 62.5 %, P = 0.000). CONCLUSIONS: A rivaroxaban-predominant IOHA strategy significantly reduced the thrombotic burden without increasing the risk of bleeding for the treatment of DVT in adolescents with orthopedic trauma. Duration of anticoagulation therapy <6 weeks appears appropriate for adolescent orthopedic trauma-related DVT.

Effectiveness and Safety of Early Versus Routine Switching from Low-Molecular-Weight Heparin to Maintenance Therapy of Rivaroxaban for Acute Iliofemoral Vein Thrombosis: A Retrospective Cohort Study.

BACKGROUND: The anticoagulation strategy of switching to rivaroxaban after 1 week of initial low-molecular-weight heparin (LMWH) therapy is recommended by a guideline for the treatment of acute iliofemoral deep vein thrombosis (DVT). However, the initial rivaroxaban dose in the switching strategy, as well as the effectiveness and safety of the early switching (less than 1 week) to rivaroxaban, remain inadequately substantiated. We aimed to evaluate the effectiveness and safety of early switching from LMWH to maintenance therapy of rivaroxaban (20 mg once daily) for acute iliofemoral DVT. METHODS: A retrospective cohort study was conducted using data from patients with acute iliofemoral DVT who received initial LMWH anticoagulation followed by rivaroxaban maintenance therapy. The clinical outcomes were compared between early (LMWH course ≤7 days) and routine (LMWH course >7 days) switching strategies within 3 months of initiating anticoagulation. RESULTS: 217 patients were included, 59 (27.2%) receiving early switching and 158 (72.8%) receiving routine switching. Compared with routine switching, patients with early switching had a significantly shorter hospital stay (7 days vs. 14 days, P < 0.001). The length of hospital stay was significantly positively correlated with the duration of LMWH (r = 0.762, P < 0.001). The incidences of recurrent venous thromboembolism (5.1% vs. 2.5%, P = 0.606), major bleeding (0% vs. 1.9%, P = 0.564), clinically relevant nonmajor bleeding (1.7% vs. 2.5%, P = 1.000) and all-cause mortality (6.8% vs. 2.5%, P = 0.283) were not statistically different between the 2 groups. CONCLUSIONS: Direct early switching from LMWH to maintenance therapy of rivaroxaban is effective and safe for acute iliofemoral DVT.

Risk factors for inferior vena cava filter thrombosis in traumatic fracture patients with deep venous thrombosis of lower extremity: A single-center experience.

OBJECTIVE: To explore the risk factors for inferior vena cava filter (IVCF) thrombus in orthopedic trauma patients who underwent filter placement with ongoing anticoagulation in clinical settings. METHODS: We retrospectively analyzed clinical data from fracture patients with lower extremity acute deep vein thrombosis (DVT) implanted with an IVCF admitted to Tianjin Hospital from January 2017 to December 2019. Potential risk factors, such as gender, age, diabetes, hypertension, fracture sites, thrombus location, free-floating thrombus, filter type, Injury Severity Score (ISS), and postoperative D-dimer values, were analyzed by the Chi-square test, t-test, logistic regression, and receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 662 patients were included in our study, and filter-related thrombosis was present in 67 (10.1%) patients. No significant differences were observed in age, gender, hypertension, diabetes, fracture site, free-floating thrombus, filter type, indwelling time, and postoperative D-dimer level. Thrombus location and ISS were significantly different (p < 0.05). Popliteal DVT (P-DVT) (odds ratio [OR]: 2.130, p = 0.018) and ISS (OR: 1.135, p = 0.000) were associated with filter thrombus. Patients with P-DVT were prone to a small filter thrombus (OR: 3.231, p = 0.037). From the ROC curve analysis, the diagnostic value of ISS was 24.5 and 26.5 for patients with filter and massive filter thrombus, respectively. CONCLUSION: Thrombus location and ISS were independent risk factors for filter thrombus in patients with traumatic fractures. P-DVT had a higher potential to result in a small filter thrombus and an ISS value >26.5, which was considered a significant massive filter thrombus predictor.

Retrievable inferior vena cava filter to prevent pulmonary embolism in patients with fractures and deep venous thrombosis of lower extremities: a single-center experience.

OBJECTIVE: To evaluate the effectiveness of inserting a retrievable inferior vena cava filter (IVCF) to prevent pulmonary embolism (PE) in patients with bone fractures and acute deep venous thrombosis (DVT) before major orthopedic surgery. METHODS: Clinical data of patients with fractures and acute DVT who underwent IVCF insertion were analyzed. The patients were divided into above-knee DVT (AKDVT), popliteal vein thrombosis (PVT), and below-knee DVT (BKDVT) groups. RESULTS: An IVCF was successfully implanted in 964 patients, among whom 929 were followed up (335, 470, and 124 in AKDVT, PVT, and BKDVT groups, respectively). There was no significant difference in the incidence of filter thrombosis among the groups (11.04%, 11.70%, and 8.06%, respectively). No symptomatic PE occurred during follow-up. The mean filter indwelling time was 18.4 ± 4.3 days, and the total filter removal rate was 76.87%. There was no significant difference in the rate of filter implantation, retrieval, complications, or mortality among the groups. CONCLUSIONS: Retrievable filters can effectively prevent PE before orthopedic surgery in patients with fractures and acute DVT of the lower limbs. AKDVT more readily forms a ≥1-cm thrombus in the IVCF than does BKDVT, and PVT more readily forms a <1-cm thrombus than does AKDVT.

MicroRNA-494 inhibition protects nucleus pulposus cells from TNF-α-induced apoptosis by targeting JunD.

BACKGROUND: Human nucleus pulposus cell (HNPC) apoptosis plays an important role in the development of intervertebral disc degeneration (IVDD). Our previous research revealed that among all of the dysregulated microRNAs in the degenerated nucleus pulposus tissues of patient with IVDD, miRNA-494 (miR-494) is the most significantly increased. However, the influence of miR-494 HNPC apoptosis has not been confirmed. OBJECTIVE: This study was designed to evaluate the effect of miR-494 on the HNPC apoptosis induced by TNF-α and to explore the possible mechanism of this process. METHODS: First, HNPCs were stimulated with TNF-α at different concentrations (0 ng/ml, 10 ng/ml, 50 ng/ml, or 100 ng/ml) for 0 h, 8 h, 16 h, or 24 h. Annexin V-PE/7-AAD assays and real-time quantitative PCR were used to detect the cell apoptosis rates and miR-494 expression. Second, we successfully knocked down endogenous miR-494 in HNPCs via lentiviral antigomiR-494 vector infection and then stimulated with TNF-α (100 ng/ml, 16 h). The rates of apoptosis and miR-494 expression were then detected again. Additionally, a dual-luciferase reporter assay and western blotting were used to determine whether JunD is a target of miR-494. Finally, western blotting was used to analyze the expression of cytochrome C. RESULTS: We found that the rate of apoptosis increased with concentration, time (p < 0.05) and miR-494 expression (p < 0.05). The rate of apoptosis in the 100 ng/ml, 16 h group appeared to be suitable. After transfection, the apoptosis rate and miR-494 expression were significantly decreased in the antigomiR-494+TNF-α group compared to the controls (p < 0.05). We also revealed that JunD is a target of miR-494. Western blotting analysis demonstrated that treatment with the lentiviral antigomiR-494 vector resulted in increased expression of JunD (p < 0.05) and decreased expression of cytochrome C (p < 0.05). CONCLUSION: These results indicated that miR-494 is a novel regulator of HNPC apoptosis induced by TNF-α. The knock-out of miR-494 expression protected the HNPCs from apoptosis via the up-regulation of JunD, which was possibly mediated via cytochrome C apoptotic signaling. These findings suggest that the miR-494/JunD signaling pathway might represent a novel therapeutic target for the prevention of IVDD.

Low magnitude of tensile stress represses the inflammatory response at intervertebral disc in rats.

OBJECTIVE: This study aims to determine if the involvement of tensile stress affects the expressions of inflammatory cytokines interleukin-17(IL-17), interleukin-1ß (IL-1ß), and inducible nitric oxide synthase (iNOS) at intervertebral discs in vivo. MATERIAL AND METHOD: Sixty-four female Sprague-Dawley rats were randomly divided into four groups: sham, tail-suspended (TS), tail-suspended with needle puncture (TSNP), and single-needle puncture (SNP) groups. A tail-suspension device provides low magnitude of tensile stress (2.45 Newton (N)), and aseptic needle puncture on the tail disc induces inflammatory response. After 4 weeks, the treated discs were harvested for histologic analysis, quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). RESULT: Pathological examination demonstrated that compared to the sham group, the morphologies of nucleus pulposus (NP) and anulus fibrosus (AF) in TS, SNP, and TSNP groups displayed degenerative changes in varying degrees. Results from RT-qPCR showed that IL-17 and iNOS mRNA expression levels were significantly higher in both TSNP and SNP groups than those in the sham groups. Expression of IL-17 and iNOS are not significantly different between the sham and TS groups (P > 0.05). Compared with the SNP group, the mRNA expression of IL-17 and iNOS in the TSNP groups were markedly decreased (P < 0.05). The regulation of IL-1ß and IL-17 detected by ELISA was coincident with the qRT-PCR results. CONCLUSION: The results from this study suggested that relatively low magnitude tensile stress might play an essential role in the anti-inflammatory process and the relief of low-back pain (LBP).

Ischemic postconditioning decreases matrix metalloproteinase-2 expression during ischemia-reperfusion of myocardium in a rabbit model: A preliminary report.

OBJECTIVE: To investigate the effect of ischemic postconditioning on the expression of matrix metalloproteinase (MMP)-2 during ischemia-reperfusion of myocardium in a rabbit model. METHODS: Thirty-six male New Zealand white rabbits were randomly divided into sham, ischemia-reperfusion and ischemic postconditioning groups. Myocardial ischemia-reperfusion was created by ligating the left anterior descending coronary artery for 30 min followed by 3 h of reperfusion. Myocardial infarction sizes were determined by dual staining with triphenyltetrazolium chloride and trypan blue. Plasma levels of MMP-2 were measured using ELISA. Myocardial MMP-2 messenger RNA was analyzed by reverse transcription polymerase chain reaction. RESULTS: The mean (± SD) infarct size in the ischemic postconditioning group was significantly smaller compared with the ischemia-reperfusion group (37.1±3.8% versus 57.5±1.9%; P=0.02). The incidence of ventricular tachycardia in the ischemic postconditioning group was also lower than in the ischemia-reperfusion group (8.5% versus 75%; P=0.003). MMP-2 messenger RNA expression in the ischemic postconditioning group was significantly lower compared with the ischemia-reperfusion group (0.4944±0.0476 versus 0.6989±0.0694; P=0.02). CONCLUSION: Ischemic postconditioning reduces myocardial ischemia-reperfusion injury, possibly by inhibiting the expression of MMP-2.

[Research progress of Wnt/beta-catenin and nuclear factor-kappa B pathways and their relevance to intervertebral disc degeneration].

OBJECTIVE: To review the progress of the mechanisms of Wnt/beta-catenin and nuclear factor-kappa B (NF-kappaB) pathways in the process of the intervertebral disc degeneration. METHODS: The related literature about the mechanisms of Wnt/beta-catenin and NF-kappaB pathways in the process of the intervertebral disc degeneration was reviewed, analyzed, and summarized. RESULTS: Wnt/beta-catenin and NF-kappaB pathways are both activated in the process of the intervertebral disc degeneration, and exist interaction. However, the specific mechanisms and interactive mediums of Wnt/beta-catenin and NF-kappaB pathways in the process of the intervertebral disc degeneration are still unclear. CONCLUSION: The mechanisms of Wnt/beta-catenin and NF-kappaB pathways in the process of the intervertebral disc degeneration have to be studied deeply.

Impact of acute pulmonary embolism on plasma and tissue hepatocyte growth factor: an experimental study.

This study was designed to investigate the impact of acute pulmonary embolism (PE) on plasma and tissue hepatocyte growth factor (HGF). PE was established in 16 New Zealand white rabbits by intravenous injection of autologous blood clots. Another 16 sham-operated rabbits were used as control. Plasma HGF levels and tissue HGF expression was measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The plasma HGF levels in the PE group were elevated 1 hour after PE (P < .01). In the lung tissue samples, the positive HGF expression ratio was 91.7% and 20.8%, respectively, in the PE and the control group (P < .01). The positive HGF expression ratio in the right ventricular tissue samples in the PE group was higher than in the control group (75.0% versus 20.9%; P < .01). The positive HGF expression ratio in the liver samples in the PE and the control groups was 33.3% and 16.7%, respectively (P < .05). In conclusion, acute PE was associated with a significant increase in plasma HGF. Acute PE was also associated with an enhanced HGF expression in the lungs, the right ventricle, and the liver.

Effect of primary percutaneous coronary intervention on serum collagen biomarkers following acute myocardial infarction.

OBJECTIVE: The aim of this study was to investigate the effect of primary percutaneous coronary intervention (PCI) on serum collagen biomarkers following acute myocardial infarction (AMI). METHODS AND RESULTS: Thirty-eight patients were enrolled into a primary PCI (n = 16) and a control (n = 22) group. The PCI group received successful PCI within 6 h of MI, whereas the control group received no PCI or thrombolytic therapy. Serum type I procollagen (PICP) and type III procollagen (PIIINP) were measured by enzyme-linked immunosorbent assay (ELISA). The baseline characteristics were similar between the PCI and control groups. There was no significant difference in left ventricular end-systolic, end-diastolic volume or ejection fraction between the two groups 30 min after MI (P > 0.05). A significant increase in PICP and PIIINP was noted in both groups 3 days after MI (P < 0.01). PICP and PIIINP in the PCI group declined overtime to the pre-PCI level, whereas they remained high in the control group. In the PCI group, the mean serum PICP and PIIINP on day 7, 14 and 30 was lower than in the control group (P < 0.01). CONCLUSIONS: AMI is associated with an increase in serum biomarkers of collagen synthesis. Early and successful PCI is associated with a reduction in serum collagen biomarkers.

Effects of xuezhikang on proliferation and adhesion capacity of cultured endothelial progenitor cells: An in vitro study.

BACKGROUND: Endothelial progenitor cells (EPCs) might be useful in the management of coronary artery disease (CAD). OBJECTIVE: The aim of this study was to investigate the effects of xuezhikang, an extract of Chinese red yeast rice, on the proliferation and adhesion capacity of EPCs from the peripheral blood of patients with stable CAD. METHODS: Mononuclear cells from 20 Chinese patients (14 men, 6 women; mean [SD] age, 64.5 [2.8] years [range, 60-69 years]) were isolated using densitygradient centrifugation. After 4 days in culture, the attached cells were treated with different concentrations of xuezhikang (50, 125, 250, and 500 ng/mL; 20 samples/group), atorvastatin (10 ng/mL; n = 20), or phosphate-buffered saline (control, n = 20) for 3 days. Cells that were positive for 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled acetylated low-density lipoprotein and lectin were defined as EPCs. They were counted by 2 independent investigators in ≥4 randomly selected highpower fields per well. EPCs were then treated and adherent cells were counted by the independent investigators who were blinded to study drug administration. RESULTS: The mean (SD) number of cultured EPCs in the xuezhikang 50-, 125-, 250-, and 500-ng/mL groups (205 [28], 244 [31], 283 [42], and 334 [43] cells, respectively; all, P < 0.001) was significantly increased in a dose-dependent manner compared with the control group (167 [36] cells). The adhesion capacity of the EPCs was significantly greater in the 4 xuezhikang groups (51 [9], 62 [10], 71 [11], and 83 [12] cells; all, P < 0.001) when compared with that of the control group (41 [7] cells). Both the number of EPCs (327 [49] cells) and the number of adhesive EPCs (84 [15] cells) in the atorvastatin group were also significantly increased compared with the control group (both, P < 0.001); however, these increases were not significantly different from those in the xuezhikang 500-ng/mL group. CONCLUSIONS: Xuezhikang was associated with significantly enhanced proliferation and adhesion capacity of EPCs derived from the peripheral blood of these patients with stable CAD. These effects were not significantly different between xuezhikang and atorvastatin.

Relationship between accessory pathway location and occurrence of atrial fibrillation in patients with atrioventricular re-entrant tachycardia.

OBJECTIVE: To study the relationship between the location of atrioventricular accessory pathways and occurrence of atrial fibrillation (AF) in patients with atrioventricular re-entrant tachycardia (AVRT). METHODS: The clinical features and location of accessory pathways in patients with a history of AF were compared with those of patients with no history of AF. RESULTS: Patients with AF (n=44) were older, more likely to be male and more likely to have multiple or manifest accessory pathways than patients without AF (n=373). There was no significant difference in the location of accessory pathways between the two groups. Multivariate regression analysis showed older age, male sex, and multiple and manifest pathways were independent predictors of AF in patients with AVRT (P<0.01). CONCLUSIONS: The location of accessory pathways does not appear to play a critical role in the pathogenesis of AF in patients with AVRT. Older patients with multiple or manifest accessory pathways are at an increased risk of clinical AF.

A new approach for transseptal catheterization in patients undergoing percutaneous balloon mitral valvuloplasty.

AIMS: To evaluate the safety and efficacy of a new approach for transseptal catheterization in patients undergoing percutaneous balloon mitral valvuloplasty (PBMV). METHODS: One hundred and two patients with rheumatic mitral stenosis were randomized into two groups. In the study group (RA approach), an imaginary horizontal line was drawn from the top end of the tricuspid valve under anteroposterior fluoroscopic view. The intersection of the horizontal line and the right edge of the corresponding thoracic vertebra was defined as the upper border of the Fossa ovalis. The atrial septum was punctured from a point 0.5 cm below the upper border of the Fossa ovalis. In the control group (LA approach), an imaginary horizontal line was drawn between the upper and middle third of the left atrium, and the intersection of this horizontal line and the right edge of the corresponding thoracic vertebra was used as an atrial septum puncture point. RESULTS: Atrial septum puncture succeeded in all patients in the study group and in 72.6% of the patients in the control group (p < 0.01). The average fluoroscopy times for transseptal catheterization in the study and the control groups were 2.0 +/- 0.5 and 3.0 +/- 1.0 min, respectively (p < 0.01). Transseptal catheterization was subsequently achieved using the RA approach in the 14 patients from the control group in whom the LA approach failed. CONCLUSIONS: The RA approach is a safe and effective means for transseptal catheterization in patients undergoing PBMV.