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Journal of Pharmaceutical and... Jun 2024TIMP metallopeptidase inhibitor 3 (TIMP-3) may contribute to the pathogenesis of venous thromboembolism (VTE). However, few studies have investigated the effect of...
TIMP metallopeptidase inhibitor 3 (TIMP-3) may contribute to the pathogenesis of venous thromboembolism (VTE). However, few studies have investigated the effect of TIMP-3 on VTE. Therefore, a two-sample Mendelian randomization (MR) analysis was conducted to investigate the association between TIMP-3 levels and VTE. Seven independent single-nucleotide polymorphisms (SNPs) for TIMP-3 levels were obtained from a published genome-wide association study (the KORA Consortium, including 997 Europeans). We obtained outcome datasets for VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) from the FinnGen Consortium. The primary analytical method used in the MR analysis was the inverse variance weighted (IVW) method. To enhance the robustness of the MR results, some other MR methods including weighted median, MR-Egger, and MR-PRESSO were conducted. Moreover, several sensitivity analyses were performed to identify potential horizontal pleiotropy and heterogeneity. In primary IVW MR analyses, per log increase in genetically predicted TIMP-3 levels were positively associated with the incidence of VTE (odds ratio [OR], 1.03; 95 % confidence interval (CI), 1.01, 1.06; P = 0.010), PE (OR, 1.04; 95 % CI, 1.01, 1.08; P = 0.009), and DVT (OR, 1.06; 95 % CI, 1.02, 1.10; P= 0.003). The results of the weighted median, MR-Egger, and MR-PRESSO were similar to the main findings. No unbalanced pleiotropy or heterogeneity was observed. The study suggests that genetically predicted high levels of TIMP-3 may be associated with an increased risk of VTE. These findings indicate that strategies targeting TIMP-3 may provide a basis for the prevention and treatment of VTE. Further investigation is required to clarify this potential mechanism.
PubMed: 38878456
DOI: 10.1016/j.jpba.2024.116290 -
Clinics (Sao Paulo, Brazil) 2024This study aims to elucidate the role of circUSP9X (Circular RNA Ubiquitin Specific Peptidase 9 X-Linked) in the development of venous thrombosis in the lower...
OBJECTIVES
This study aims to elucidate the role of circUSP9X (Circular RNA Ubiquitin Specific Peptidase 9 X-Linked) in the development of venous thrombosis in the lower extremities.
METHODS
An animal model of Deep Vein Thrombosis (DVT) and a hypoxic model of Human Umbilical Vein Endothelial Cells (HUVECs) treated with Cobalt (II) Chloride (CoCl) were developed. The expression levels of circUSP9X, microRNA-148b-3p (miR-148b-3p), and SRC Kinase Signaling Inhibitor 1 (SRCIN1) were quantified using quantitative reverse transcription Polymerase Chain Reaction and Western blot analysis. Cell cytotoxicity, viability, apoptosis, and inflammation in HUVECs were assessed via Lactate Dehydrogenase (LDH) assay, MTT assay, flow cytometry, Enzyme-Linked Immunosorbent Assay, and Western blot, respectively. Hematoxylin and Eosin staining were employed for histopathological examination of the venous tissues in the animal model. The interaction between circUSP9X, miR-148b-3p, and SRCIN1 was further explored through dual-luciferase reporter assays and RNA Immunoprecipitation experiments.
RESULTS
The present findings reveal a significant upregulation of circUSP9X and SRCIN1 and a concurrent downregulation of miR-148b-3p in DVT cases. Knockdown of circUSP9X or overexpression of miR-148b-3p ameliorated CoCl-induced apoptosis in HUVECs, reduced LDH release, enhanced cellular viability, and mitigated inflammation. Conversely, overexpression of circUSP9X intensified CoCl's cytotoxic effects. The effects of manipulating circUSP9X expression were counteracted by the corresponding modulation of miR-148b-3p and SRCIN1 levels. Additionally, circUSP9X knockdown effectively inhibited the formation of DVT in the mouse model. A competitive binding mechanism of circUSP9X for miR-148b-3p, modulating SRCIN1 expression, was identified.
CONCLUSION
circUSP9X promotes the formation of DVT through the regulation of the miR-148b-3p/SRCIN1 axis.
Topics: MicroRNAs; Animals; Venous Thrombosis; Human Umbilical Vein Endothelial Cells; Humans; Up-Regulation; Disease Models, Animal; RNA, Circular; Apoptosis; Male; Mice
PubMed: 38878321
DOI: 10.1016/j.clinsp.2024.100403 -
European Journal of Medical Research Jun 2024Some previous observational studies have linked deep venous thrombosis (DVT) to thyroid diseases; however, the findings were contradictory. This study aimed to...
BACKGROUND
Some previous observational studies have linked deep venous thrombosis (DVT) to thyroid diseases; however, the findings were contradictory. This study aimed to investigate whether some common thyroid diseases can cause DVT using a two-sample Mendelian randomization (MR) approach.
METHODS
This two-sample MR study used single nucleotide polymorphisms (SNPs) identified by the FinnGen genome-wide association studies (GWAS) to be highly associated with some common thyroid diseases, including autoimmune hyperthyroidism (962 cases and 172,976 controls), subacute thyroiditis (418 cases and 187,684 controls), hypothyroidism (26,342 cases and 59,827 controls), and malignant neoplasm of the thyroid gland (989 cases and 217,803 controls. These SNPs were used as instruments. Outcome datasets for the GWAS on DVT (6,767 cases and 330,392 controls) were selected from the UK Biobank data, which was obtained from the Integrative Epidemiology Unit (IEU) open GWAS project. The inverse variance weighted (IVW), MR-Egger and weighted median methods were used to estimate the causal association between DVT and thyroid diseases. The Cochran's Q test was used to quantify the heterogeneity of the instrumental variables (IVs). MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO) was used to detect horizontal pleiotropy. When the causal relationship was significant, bidirectional MR analysis was performed to determine any reverse causal relationships between exposures and outcomes.
RESULTS
This MR study illustrated that autoimmune hyperthyroidism slightly increased the risk of DVT according to the IVW [odds ratio (OR) = 1.0009; p = 0.024] and weighted median methods [OR = 1.001; p = 0.028]. According to Cochran's Q test, there was no evidence of heterogeneity in IVs. Additionally, MR-PRESSO did not detect horizontal pleiotropy (p = 0.972). However, no association was observed between other thyroid diseases and DVT using the IVW, weighted median, and MR-Egger regression methods.
CONCLUSIONS
This study revealed that autoimmune hyperthyroidism may cause DVT; however, more evidence and larger sample sizes are required to draw more precise conclusions.
Topics: Humans; Venous Thrombosis; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Thyroid Diseases; Genetic Predisposition to Disease; Hyperthyroidism
PubMed: 38877527
DOI: 10.1186/s40001-024-01933-1 -
BMC Neurology Jun 2024We present a rare case of NeuroBehcet's-related intracranial hypertension without cerebral venous thrombosis (NBrIHwCVT), occurring as the first presentation of... (Review)
Review
BACKGROUND
We present a rare case of NeuroBehcet's-related intracranial hypertension without cerebral venous thrombosis (NBrIHwCVT), occurring as the first presentation of NeuroBehcet's. In addition, we describe the novel use of subcutaneous tocilizumab for this indication. This is followed by a review of the literature on this topic.
CASE
The patient was a 28-year-old lady of Southern Chinese origin with a known history of Behcet's disease with oral ulcers and ocular findings for which she was on mycophenolate mofetil and adalimumab. She presented with a headache and bilateral disc swelling associated with an intracranial pressure (ICP) of > 40cmH20. There were no structural lesions or cerebral venous thrombosis (CVT) on imaging. Initial lumbar puncture had raised leucocytes and protein. We discuss diagnostic challenges given persistently elevated ICP despite subsequent non-inflammatory cerebrospinal fluid (CSF) profiles and non-response to acetazolamide. She eventually showed a response to immunosuppressant therapy in the form of pulsed methylprednisolone, cyclophosphamide and subsequently subcutaneous tocilizumab, supporting the diagnosis of NBrIHwCVT. Complete normalization of ICP remains challenging. Her disease course was severe, unusual for her ethnicity.
LITERATURE REVIEW
We identified 34 patients (including ours) from 14 publications. We found that the majority of NBrIHwCVT patients were young (average age of 34 years), with a slight female preponderance. Of the 17 cases in the literature with available data on CSF profile, none had raised leucocytes whilst one patient had elevated protein. Patients were generally treated with steroids and occasionally azathioprine, in line with the suspected autoimmune pathophysiology. Of 22 patients with data on outcome, six (27%) were noted to have recurrence of symptoms generally occurring a few months later.
CONCLUSION
As demonstrated by this case, NBrIHwCVT can present with BD with raised ICP even if there is no prior history of NB, central Asian ethnicity, cerebral venous thrombosis or features of inflammation on the CSF. We demonstrated how novel use of Tocilizumab may have a role in the management of NBrIHwCVT. Based on our literature review, patients were more likely to be young, female, display a non-inflammatory CSF picture, be treated with steroids and harbour a possibility of recurrence.
Topics: Humans; Female; Adult; Intracranial Hypertension; Behcet Syndrome; Antibodies, Monoclonal, Humanized; Immunosuppressive Agents
PubMed: 38877431
DOI: 10.1186/s12883-024-03708-x -
Heart, Lung & Circulation Jun 2024Occurrence of chronic thromboembolic disease (CTED) after 3 or 6 months of standard and effective anticoagulation is not uncommon in patients with acute pulmonary...
BACKGROUND
Occurrence of chronic thromboembolic disease (CTED) after 3 or 6 months of standard and effective anticoagulation is not uncommon in patients with acute pulmonary embolism (PE). To date, there has been no scoring model for the prediction of CTED occurrence.
METHODS
A Prediction Rule for CTED (PRC) was established in the establishment cohort (n=1,124) and then validated in the validation cohort (n=211). Both original and simplified versions of the PRC score were provided by using different scoring and cut-offs.
RESULTS
The PRC score included 10 items: active cancer (3.641; 2.338-4.944; p<0.001), autoimmune diseases (2.218; 1.545-2.891; p=0.001), body mass index >30 kg/m (2.186; 1.573-2.799; p=0.001), chronic immobility (2.135; 1.741-2.529; p=0.001), D-dimer >2,000 ng/mL (1.618; 1.274-1.962; p=0.005), PE with deep vein thrombosis (3.199; 2.356-4.042; p<0.001), previous venous thromboembolism (VTE) history (5.268; 3.472-7.064; p<0.001), thromboembolism besides VTE (4.954; 3.150-6.758; p<0.001), thrombophilia (3.438; 2.573-4.303; p<0.001), and unprovoked VTE (2.227; 1.471-2.983; p=0.001). In the establishment cohort, the sensitivity, specificity, Youden index (YI), and C-index were 85.5%, 79.7%, 0.652, and 0.821 (0.732-0.909) when using the original PRC score, whereas they were 87.9%, 74.6%, 0.625, and 0.807 (0.718-0.897) when using the simplified one, respectively (Kappa coefficient 0.819, p-value of McNemar's test 0.786). In the validation cohort, the sensitivity, specificity, YI, and C-index were 86.3%, 76.3%, 0.626, and 0.815 (0.707-0.923) when using the original PRC score, whereas they were 85.0%, 78.6%, 0.636, and 0.818 (0.725-0.911) when using the simplified one, respectively (Kappa coefficient 0.912, p-value of McNemar's test 0.937); both were better than that of the DASH score (72.5%, 69.5%, 0.420, and 0.621 [0.532-0.710]).
CONCLUSIONS
A prediction score for CTED occurrence, termed PRC, predicted the likelihood of CTED occurrence after 3 or 6 months of standard anticoagulation in hospitalised patients with a diagnosis of acute PE.
PubMed: 38876846
DOI: 10.1016/j.hlc.2024.03.011 -
International Journal of Surgery Case... Jul 2024The most frequent location of thrombosis development in acute mesenteric venous thrombosis is the superior mesenteric vein. It is an uncommon but potentially fatal...
INTRODUCTION
The most frequent location of thrombosis development in acute mesenteric venous thrombosis is the superior mesenteric vein. It is an uncommon but potentially fatal condition. Patients with underlying medical conditions that interfere with the Virchow Triad hypercoagulability, stasis, and endothelial injury are more likely to experience it.
PRESENTATION
A 37-year-old female reported to our emergency department with a 5-day history of severe abdominal discomfort, vomiting, and constipation, as well as two episodes of bleeding per rectum. The patient had a clean medical history, no HTN, no diabetes, no chronic medication, no history of contraceptive pill use or non-steroid anti-inflammatory drug use, no history of chronic disease or operation. Patient was directly transferred to the intensive care unit for additional evaluation and preoperative stabilization.
DISCUSSION
A patient with acute mesenteric venous thrombosis and possible intestinal damage is the case we've presented. Upon presentation patient was unstable, we assessed her condition and transferred to the intensive care unit for stabilization and pre-operative preparation. She didn't respond to conservative management and we had to operate, we highly emphasize how crucial it is for early intervention in these type of conditions. Acute mesenteric venous thrombosis is a complicated case due to its nonspecific symptoms, it requires a multidisciplinary team approach between internal medicine and surgical team to plan for the most appropriate treatment strategy suitable for each patient as all options are associated with significant risks. Multiple options are available for the management of mesenteric venous thrombosis. In patients with peritoneal signs to suggestive bowel infarction or perforation or those who failed to progress with conservative management, operative intervention may be necessary. Other options include anticoagulation therapy, local or systemic thrombolysis, interventional or surgical thrombectomy.
CONCLUSION
Acute mesenteric venous thrombosis is a complex situation that calls for a multidisciplinary team approach between the surgical and internal medicine departments to determine the best course of action for each patient, as there are major risks involved with each alternative. If peritonism is present, it is preferable to assess and resuscitate as soon as possible and to proceed with surgery.
PubMed: 38875832
DOI: 10.1016/j.ijscr.2024.109872 -
Medicine Jun 2024The aim of this study is to describe the general information, disease and treatment of venous thromboembolism (VTE) in critically ill patients, to explore the... (Observational Study)
Observational Study
The aim of this study is to describe the general information, disease and treatment of venous thromboembolism (VTE) in critically ill patients, to explore the characteristics of severe patients with deep venous VTE and provide clinical reference data for the prevention and treatment of VTE in critically ill patients. This study carried out a retrospective study on the medical records of patients who were treated in the intensive care unit of Affiliated Hospital of Jining Medical College from 2020 to 2022. The general data, general conditions, drug use, past history, VTE prevention measures, post-VTE conditions, and Padua risk score of 297 patients with VTE during the period of hospitalization in intensive care unit (ICU) were classified and statistically analyzed. A total of 297 including 171 male and 126 male patient medical records were included in the analysis, we compared multiple clinical indicators between male and female patients. Compared to women, male patients have a higher acute physiology and chronic health evaluation II score(APACHE-II score) (P = .027), a higher state of consciousness (P = .003), a higher rate of smoking and drinking history (P < .001), a lower rate of heart failure (P = .003) and chronic depression (P = .013), and a higher rate of recommended operations for male patients after VTE (P = .031). The prothrombin time (PT) (P = .041) and activated partial thromboplastin time (APTT) (P = .040) of male patients were significantly higher than those of female patients, while triglyceride (P = .009) and total cholesterol (TC) (P = .001) were significantly lower than those of female patients. The difference in D-dimer (P = .739) was not significant. This study shows that male and female patients with VTE in the ICU have significant differences in general characteristics, general clinical conditions, history of past illness, thrombosis character, and examination items, this may be the reason for the different rates of VTE between male and female patients in the ICU.
Topics: Humans; Male; Female; Retrospective Studies; Venous Thromboembolism; Middle Aged; Critical Illness; Sex Factors; Aged; Adult; Risk Factors; Intensive Care Units; APACHE
PubMed: 38875425
DOI: 10.1097/MD.0000000000038423 -
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 -
Acta Neurochirurgica Jun 2024The management of perioperative venous thrombembolism (VTE) prophylaxis is highly variable between neurosurgical departments and general guidelines are missing. The main...
BACKGROUND
The management of perioperative venous thrombembolism (VTE) prophylaxis is highly variable between neurosurgical departments and general guidelines are missing. The main issue in debate are the dose and initiation time of pharmacologic VTE prevention to balance the risk of VTE-based morbidity and potentially life-threatening bleeding. Mechanical VTE prophylaxis with intermittend pneumatic compression (IPC), however, is established in only a few neurosurgical hospitals, and its efficacy has not yet been demonstrated. The objective of the present study was to analyze the risk of VTE before and after the implementation of IPC devices during elective neurosurgical procedures.
METHODS
All elective surgeries performed at our neurosurgical department between 01/2018-08/2022 were investigated regarding the occurrence of VTE. The VTE risk and associated mortality were compared between groups: (1) only chemoprophylaxis (CHEMO; surgeries 01/2018-04/2020) and (2) IPC and chemoprophylaxis (IPC; surgeries 04/2020-08/2022). Furthermore, general patient and disease characteristics as well as duration of hospitalization were evaluated and compared to the VTE risk.
RESULTS
VTE occurred after 38 elective procedures among > 12.000 surgeries. The number of VTEs significantly differed between groups with an incidence of 31/6663 (0.47%) in the CHEMO group and 7/6688 (0.1%) events in the IPC group. In both groups, patients with malignant brain tumors represented the largest proportion of patients, while VTEs in benign tumors occurred only in the CHEMO group.
CONCLUSION
The use of combined mechanical and pharmacologic VTE prophylaxis can significantly reduce the risk of postoperative thromboembolism after neurosurgical procedures and, therefore, reduce mortality and morbidity.
Topics: Humans; Neurosurgical Procedures; Venous Thromboembolism; Female; Male; Middle Aged; Intermittent Pneumatic Compression Devices; Aged; Adult; Postoperative Complications; Retrospective Studies; Elective Surgical Procedures; Anticoagulants; Risk Factors
PubMed: 38874608
DOI: 10.1007/s00701-024-06129-4