This study explores the diagnostic value of combining the Padua score with the thrombotic biomarker tissue plasminogen activator inhibitor-1(tPAI-1)for assessing the risk of deep vein thrombosis(DVT)in patients with p...This study explores the diagnostic value of combining the Padua score with the thrombotic biomarker tissue plasminogen activator inhibitor-1(tPAI-1)for assessing the risk of deep vein thrombosis(DVT)in patients with pulmonary heart disease.These patients often exhibit symptoms similar to venous thrombosis,such as dyspnea and bilateral lower limb swelling,complicating differential diagnosis.The Padua Prediction Score assesses the risk of venous thromboembolism(VTE)in hospitalized patients,while tPAI-1,a key fibrinolytic system inhibitor,indicates a hypercoagulable state.Clinical data from hospitalized patients with cor pulmonale were retrospectively analyzed.ROC curves compared the diagnostic value of the Padua score,tPAI-1 levels,and their combined model for predicting DVT risk.Results showed that tPAI-1 levels were significantly higher in DVT patients compared to non-DVT patients.The Padua score demonstrated a sensitivity of 82.61%and a specificity of 55.26%at a cutoff value of 3.The combined model had a significantly higher AUC than the Padua score alone,indicating better discriminatory ability in diagnosing DVT risk.The combination of the Padua score and tPAI-1 detection significantly improves the accuracy of diagnosing DVT risk in patients with pulmonary heart disease,reducing missed and incorrect diagnoses.This study provides a comprehensive assessment tool for clinicians,enhancing the diagnosis and treatment of patients with cor pulmonale complicated by DVT.Future research should validate these findings in larger samples and explore additional thrombotic biomarkers to optimize the predictive model.展开更多
Objective To study and evaluate the treatment of the deep vein thrombosis(DVT) around the renal vein(DVT involving the renal vein and it's surrounding,shortly as DVTAR in our study)by two-positioned filter for cat...Objective To study and evaluate the treatment of the deep vein thrombosis(DVT) around the renal vein(DVT involving the renal vein and it's surrounding,shortly as DVTAR in our study)by two-positioned filter for catheter thrombectomy assisted with a Fogarty balloon.Methods We retrospectivly analysed seven cases of DVTAR and by comparison to elicit the respective effect different methods in DVT treatment.The methods used were:1.direct thrombectomy 2.thrombectomy facillitated by blocking of blood flow with a balloon 3.direct thrombolysis via Peripheral vein and 4.thrombectomy with simultaneous placement of a two-positioned filter with a Fogarty balloon and followed by intubation thrombolysis.Result Segmental pulmonary embolism(PE)or thrombosis in vena cava were still observed by CT angiography(CTA)or venography in those cases treated with the first three methods.As for the 3 cases where two-positioned filter for catheter thrombectomy with Fogarty balloon was used,neither pulmonary embolism during and after the operation nor thrombosis in the inferior vena cava was observed.Conclusion For DVTAR,thrombectomy with simultaneous placement of a two-positioned filter with a Fogarty balloon and followed by intubation thrombolysis can be regarded as safe and effective.展开更多
Objective:Matrix metalloproteinase 13(MMP13)is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens,modifying protein structures and regu...Objective:Matrix metalloproteinase 13(MMP13)is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens,modifying protein structures and regulating inflammatory responses,but its role in deep vein thrombosis(DVT)has not been determined.The purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of DVT.Methods:We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of DVT.After screening genes possibly related to MMP13 in DVT mice,the expression levels of candidate genes in human umbilical vein endothelial cells(HUVECs)and the venous wall were evaluated.The effect of MMP13 on platelet aggregation in HUVECs was investigated in vitro.Results:Among the differentially expressed genes,interleukin 1 beta,podoplanin(Pdpn),and factor VIII von Willebrand factor(F8VWF)were selected for analysis in mice.When MMP13 was inhibited,the expression level of PDPN decreased significantly in vitro.In HUVECs,overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation,while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet aggregation.Conclusions:Inhibiting the expression of MMP13 could reduce the burden of DVT in mice.The mechanism involves downregulating the expression of Pdpn through MMP13,which could provide a novel gene target for DVT diagnosis and treatment.展开更多
BACKGROUND Deep vein thrombosis(DVT)is a significant postoperative concern,particularly in patients undergoing surgery for gastrointestinal(GI)cancers.These patients often present multiple risk factors,including advan...BACKGROUND Deep vein thrombosis(DVT)is a significant postoperative concern,particularly in patients undergoing surgery for gastrointestinal(GI)cancers.These patients often present multiple risk factors,including advanced age and elevated body mass index(BMI),which can increase the likelihood of thromboembolic events.Effec-tive prophylaxis is crucial in this high-risk population to minimize complications such as DVT and pulmonary embolism(PE).This study investigates a compre-hensive DVT prevention protocol,combining mechanical and pharmacological strategies alongside early mobilization,to evaluate its effectiveness and safety in reducing postoperative thrombosis rates among GI cancer surgery patients.AIM To evaluate the effectiveness and safety of postoperative DVT prevention strate-gies in patients with GI cancer.METHODS A prospective cohort study was conducted involving 100 patients who underwent surgery for GI tumors between January and December 2022.All patients received a standardized DVT prevention protocol,which included risk assessment,mecha-nical prophylaxis,pharmacological prophylaxis,and early mobilization.The primary endpoint was the incidence of DVT within 30 days postoperatively.Se-condary outcomes included the occurrence of PE,bleeding complications,and adherence to the protocol.RESULTS The overall incidence of DVT was 7%(7/100 patients).One patient(1%)deve-loped PE.The adherence rate to the prevention protocol was 92%.Bleeding complications were observed in 3%of patients.Significant risk factors for DVT development included advanced age[odds ratio(OR):1.05;95%confidence interval(95%CI):1.01-1.09],higher BMI(OR:1.11;95%CI:1.03-1.19),and longer operative time(OR:1.007;95%CI:1.001-1.013).CONCLUSION Implementing a comprehensive DVT prevention and management protocol for patients undergoing GI tumor surgery resulted in a lower incidence.Strict adherence and individualized risk assessment are crucial for optimizing outcomes.展开更多
Purpose: Few studies have evaluated the association between malnutrition and the risk of preoperative deep vein thrombosis (DVT) in patients undergoing primary total joint arthroplasty. This study aimed to investigate...Purpose: Few studies have evaluated the association between malnutrition and the risk of preoperative deep vein thrombosis (DVT) in patients undergoing primary total joint arthroplasty. This study aimed to investigate the prevalence of preoperative DVT in Japanese patients undergoing total knee arthroplasty (TKA) and the importance of malnutrition in the risk of preoperative DVT. Methods: We retrospectively analyzed 394 patients admitted for primary TKA at our institution between January 2019 and December 2023. All patients scheduled for TKA at our institution had serum D-dimer levels measured preoperatively. Lower-limb ultrasonography was examined to confirm the presence of DVT in patients with D-dimer levels ≥ 1.0 µg/mL or who were considered to be at high risk of DVT by the treating physician. Based on the results of lower-limb ultrasonography, all patients were divided into the non-DVT and DVT groups. The incidence of and risk factors for preoperative DVT were investigated, as well as the correlation of DVT with the patient’s nutritional parameters. We used two representative tools for nutritional assessment: the Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status Score. Results: The mean age was 77.8 ± 6.9 years. Preoperative DVT was diagnosed in 57 of the 394 (14.5%) patients. Multivariate logistic regression analysis showed that advanced age and malnutrition status, assessed using the GNRI, were independent risk factors for preoperative DVT. Conclusion: A high incidence of preoperative DVT was observed in patients who underwent TKA. Malnutrition status, as assessed using the GNRI, increased the risk of preoperative DVT. Our findings suggest that clinicians should consider these factors when tailoring preventive strategies to mitigate DVT risk in patients undergoing TKA.展开更多
Upper extremity deep vein thrombosis(UEDVT)is less common than lower extremity DVT but is a cause of significant morbidity and mortality in intensive care unit patients.Increasing cancer incidence,prolonged life expec...Upper extremity deep vein thrombosis(UEDVT)is less common than lower extremity DVT but is a cause of significant morbidity and mortality in intensive care unit patients.Increasing cancer incidence,prolonged life expectancy and increasing use of intravascular catheters and devices has led to an increased incidence of UEDVT.It is also associated with high rates of complications like pulmonary embolism,post-thrombotic syndrome and recurrent thrombosis.Clinical prediction scores and D-dimer may not be as useful in identifying UEDVT;hence,a high suspicion index is required for diagnosis.Doppler ultrasound is commonly employed for diagnosis,but other tests like computed tomography and magnetic resonance imaging venography may also be required in some patients.Contrast venography is rarely used in patients with clinical and ultrasound findings discrepancies.Anticoagulant therapy alone is sufficient in most patients,and thrombolysis and surgical decompression is seldom indicated.The outcome depends on the cause and underlying comorbidities.展开更多
BACKGROUND Deep vein thrombosis(DVT)of the lower extremity is one of the most common postoperative complications,especially after craniocerebral surgery.DVT may lead to pulmonary embolism,which has a devastating impac...BACKGROUND Deep vein thrombosis(DVT)of the lower extremity is one of the most common postoperative complications,especially after craniocerebral surgery.DVT may lead to pulmonary embolism,which has a devastating impact on patient prognosis.This study aimed to investigate the incidence and risk factors of DVT in the lower limbs following craniocerebral surgery.AIM To identify independent risk factors for the development of postoperative DVT and to develop an effective risk prediction model.METHODS The demographic and clinical data of 283 patients who underwent craniocerebral surgery between December 2021 and December 2022 were retrospectively analyzed.The independent risk factors for lower extremity DVT were identified by univariate and multivariate analyses.A nomogram was created to predict the likelihood of lower extremity DVT in patients who had undergone craniocerebral surgery.The efficacy of the prediction model was determined by receiver operating characteristic curve using the probability of lower extremity DVT for each sample.RESULTS Among all patients included in the analysis,47.7%developed lower extremity DVT following craniocerebral surgery.The risk of postoperative DVT was higher in those with a longer operative time,and patients with intraoperative intermittent pneumatic compression were less likely to develop postoperative DVT.CONCLUSION The incidence of lower extremity DVT following craniocerebral surgery is significant,highlighting the importance of identifying independent risk factors.Interventions such as the use of intermittent pneumatic compression during surgery may prevent the formation of postoperative DVT.展开更多
The aim of this study was to describe the characteristics of patients with deep vein thrombosis (DVT) of the pelvic limbs at the time of diagnosis, and their course after hospitalization, in order to improve the manag...The aim of this study was to describe the characteristics of patients with deep vein thrombosis (DVT) of the pelvic limbs at the time of diagnosis, and their course after hospitalization, in order to improve the management of DVT in our context. This was a descriptive longitudinal study, based on cases of deep vein thrombosis recorded between 1 January 2015 and 30 September 2018, in the cardiology and internal medicine department of the Brazzaville University Hospital Centre. During the study period, 4678 patients were hospitalized, including 52 with DVT. Thirty-three were reassessed. The frequency of DVT was 1.1% and the average hospitalization rate was 13.9 cases/year. The 33 patients were divided into 20 women and 13 men (sex ratio: 0.65). The mean age of the patients was 51.4 ± 17.8 years (extremes: 16 and 85 years). The main aetiological factors were cancer (19.1%), sickle cell disease (3%) and HIV immunosuppression (3%). The predominant risk factors were: prolonged immobilization (42.9%), pregnancy, long travel and obesity in the same number of cases (n = 3, i.e. 14.2%). The DVT involved the left pelvic limb in 75.8% of cases. Anticoagulants were administered in all patients, and compression stockings were worn in 97% of cases. The mean time to re-evaluation was 10.9 ± 9.4 months (extremes: three and 35 months). The mean measurements of the limb where the thrombosis had occurred at diagnosis and reassessment showed a significant difference. Venous Doppler showed compressible veins (60.6%), varicosities (36.3%), incompressible veins (30.3%) and thrombus (21.2%). Complications were: post-phlebitic disease (42.4%), death (21.2%), pulmonary embolism (18.2%), recurrence (18.2%). The DVT remains relatively rare, and its conventional therapeutic management is satisfactory. Systematic venous Doppler ultrasound reassessment should enable patients at risk of recurrence to be identified.展开更多
Goal: The purpose of this research is to analyze the clinical characteristics, diagnosis, treatment, and prognosis of critical care patients with phlegmasia cerulea dolens (PCD) caused by deep vein thrombosis. Our goa...Goal: The purpose of this research is to analyze the clinical characteristics, diagnosis, treatment, and prognosis of critical care patients with phlegmasia cerulea dolens (PCD) caused by deep vein thrombosis. Our goal is to improve both awareness and early diagnosis and treatment of rare clinical diseases. Furthermore, we aim to examine advancements in the diagnosis and treatment of deep vein thrombosis. Method: The clinical information of patients with PCD received in 2022 was subject to retrospective analysis. The author conducted a search of 191 publications with a focus on PCD, from January 2010 to July 2022, from databases such as the China National Knowledge Infrastructure (CNKI), Wanfang Data, PubMed, etc. The results were used to summarize the examinations, diagnostic criteria, and treatment progress of PCD patients. Additionally, the author conducted another search using keywords such as “Venous thromboembolism” and “Anticoagulant drugs” to summarize research progress in anticoagulant drugs and the treatment of VTE. The search was limited to relevant. Outcome: Six months prior to admission, the patient, a 68-year-old female, developed sunken edema and cyanosis in both her lower extremities and was diagnosed with lower extremity deep vein thrombosis complicated by PCD, lower extremity ischemic necrosis, and septicemia. This diagnosis was made using a combination of CT and lower extremity vascular ultrasound-related examinations, as well as a significantly elevated D-dimer value. Despite active treatment and aggressive measures, such as anti-infection, organ function maintenance, anticoagulation, and improvement of microcirculatory disorders, the patient’s family declined corresponding surgical treatment and interventional surgery for the lower extremity due to objective factors, and the patient ultimately succumbed to her illness. The clinical characteristics of this patient were similar to those of the 14 cases of PCD reported by Xie Fei et al. in 2022. Conclusion: For patients with malignancy, it is crucial to start anticoagulation and physical prevention of DVT early on. Patients with DVT complicated by PCD have a variety of surgical options available to them, including surgical embolization or PMT (percutaneous mechanical thrombus ablation), CDT (catheter contact thrombolysis), and fascial ventriculotomy decompression [1]. Additionally, it may be necessary to place an inferior venous filter. Although the incidence of this disease is low accounting for approximately 5% of all patients with iliofemoral deep vein thrombosis [2], the prognosis is poor, as the mortality rate can reach up to 40% - 60% due to venous gangrene, with an overall mortality rate of 20% - 40% [3]. To increase the survival rate, it is important to diagnose and treat this disease as early as possible.展开更多
The etiology of deep vein thrombosis(DVT) is still not elucidated nowadays.Based on the accordance between DVT incidence and the anemophilous pollen concentration in the air,we proposed the hypothesis that allergic ...The etiology of deep vein thrombosis(DVT) is still not elucidated nowadays.Based on the accordance between DVT incidence and the anemophilous pollen concentration in the air,we proposed the hypothesis that allergic reaction induced by anemophilous pollen may cause "idiopathic" DVT,and proinflammatory factors may play an important role in the thrombosis process.展开更多
BACKGROUND:To investigate the clinical effectiveness of a pneumatic compression device(PCD)combined with low-molecular-weight heparin(LMWH)for the prevention and treatment of deep vein thrombosis(DVT)in trauma patient...BACKGROUND:To investigate the clinical effectiveness of a pneumatic compression device(PCD)combined with low-molecular-weight heparin(LMWH)for the prevention and treatment of deep vein thrombosis(DVT)in trauma patients.METHODS:This study retrospectively analyzed 286 patients with mild craniocerebral injury and clavicular fractures admitted to our department from January 2016 to February 2020.Patients treated with only LMWH served as the control group,and patients treated with a PCD combined with LMWH as the observation group.The incidence of DVT,postoperative changes in the visual analogue scale(VAS)score,and coagulation function were observed and compared between the two groups.Excluding the influence of other single factors,binary logistic regression analysis was used to evaluate the use of a PCD in the patient’s postoperative coagulation function.RESULTS:After excluding 34 patients who did not meet the inclusion criteria,252 patients were were included.The incidence of DVT in the observation group was significantly lower than that in the control group(5.6%vs.15.1%,χ^(2)=4.605,P<0.05).The postoperative VAS scores of the two groups were lower than those before surgery(P<0.05).The coagulation function of the observation group was significantly higher than that of the control group,with a better combined anticoagulant effect(P<0.05).There were no significant differences between the two groups in preoperative or postoperative Glasgow Coma Scale scores,intraoperative blood loss,postoperative infection rate,or length of hospital stay(P>0.05).According to logistic regression analysis,the postoperative risk of DVT in patients who received LMWH alone was 1.764 times that of patients who received LMWH+PCD(P<0.05).The area under the receiver operating characteristic(AUROC)curve of partial thromboplastin time(APTT)and platelet(PLT)were greater than 0.5,indicating that they were the influence indicators of adding PCD to prevent DVT.Excluding the influence of other variables,LMWH+PCD effectively improved the coagulation function of patients.CONCLUSIONS:Compared with LMWH alone,LMWH+PCD could improve blood rheology and coagulation function in patients with traumatic brain injury and clavicular fracture,reduce the incidence of DVT,shorten the length of hospital stay,and improve the clinical effectiveness of treatment.展开更多
QRAL contraceptives are widely used to prevent pregnancy. A number of studies have dem- onstrated the increased risk of venous throm- boembolism in women taking oral contracep-tives.1, 2 Pulmonary embolism (PE) and ...QRAL contraceptives are widely used to prevent pregnancy. A number of studies have dem- onstrated the increased risk of venous throm- boembolism in women taking oral contracep-tives.1, 2 Pulmonary embolism (PE) and deep vein throm- bosis (DVT) are two clinical presentations of venous thromboembolism which share the same predisposing factors.3 This article described a female patient who taked oral contraceptives and had an unhealthy life habit de- veloped PE and DVT. CASE DESCRIPTION展开更多
BACKGROUND Deep vein thrombosis(DVT)may cause pulmonary embolus,leading to late deaths.The systemic inflammatory and hypercoagulable state of moderate and severe acute pancreatitis(non-mild acute pancreatitis,NMAP)pat...BACKGROUND Deep vein thrombosis(DVT)may cause pulmonary embolus,leading to late deaths.The systemic inflammatory and hypercoagulable state of moderate and severe acute pancreatitis(non-mild acute pancreatitis,NMAP)patients may contribute to the development of venous thromboembolism.Accurate prediction of DVT is conducive to clinical decisions.AIM To develop and validate a potential new prediction nomogram model for the occurrence of DVT in NMAP.METHODS NMAP patient admission between 2013.1.1 and 2018.12.31 at the West China Hospital of Sichuan University was collected.A total of 220 patients formed the training set for nomogram development,and a validation set was constructed using bootstrapping with 100 resamplings.Univariate and multivariate logistic regression analyses were used to estimate independent risk factors associated with DVT.The independent risk factors were included in the nomogram.The accuracy and utility of the nomogram were evaluated by calibration curve and decision curve analysis,respectively.RESULTS A total of 220 NMAP patients over 60 years old were enrolled for this analysis.DVT was detected in 80(36.4%)patients.The final nomogram included age,sex,surgery times,D-dimer,neutrophils,any organ failure,blood culture,and classification.This model achieved good concordance indexes of 0.827(95%CI:0.769-0.885)and 0.803(95%CI:0.743-0.860)in the training and validation sets,respectively.CONCLUSION We developed and validated a prediction nomogram model for DVT in older patients with NMAP.This may help guide doctors in making sound decisions regarding the administration of DVT prophylaxis.展开更多
BACKGROUND The artificial liver support system(ALSS)is an effective treatment method for liver failure,but it requires deep venous intubation and long-term indwelling catheterization.However,the coagulation mechanism ...BACKGROUND The artificial liver support system(ALSS)is an effective treatment method for liver failure,but it requires deep venous intubation and long-term indwelling catheterization.However,the coagulation mechanism disorder of basic liver failure diseases,and deep venous thrombosis(DVT)often occur.AIM To evaluate the risk factors for DVT following use of an ALSS and establish a risk assessment score.METHODS This study was divided into three stages.In the first stage,the risk factors for DVT were screened and the patient data were collected,including ALSS treatment information;biochemical indices;coagulation and hematology indices;complications;procoagulant use therapy status;and a total of 24 indicators.In the second stage,a risk assessment score for DVT after ALSS treatment was developed.In the third stage,the DVT risk assessment score was validated.RESULTS A total of 232 patients with liver failure treated with ALSS were enrolled in the first stage,including 12 with lower limb DVT.Logistic regression analysis showed that age[odds ratio(OR),1.734;P=0.01],successful catheterization time(OR,1.667;P=0.005),activity status(strict bed rest)(OR,3.049;P=0.005),and D-dimer level(≥500 ng/mL)(OR,5.532;P<0.001)were independent risk factors for DVT.We then established a scoring system for risk factors.In the validation group,a total of 213 patients with liver failure were treated with ALSS,including 14 with lower limb DVT.When the cutoff value of risk assessment was 3,the specificity and sensitivity of the risk assessment score were 88.9%and 85.7%,respectively.CONCLUSION A simple risk assessment scoring system was established for DVT patients with liver failure treated with ALSS and was verified to have good sensitivity and specificity.展开更多
BACKGROUND Abnormalities of the inferior vena cava(IVC)are uncommon,and in many cases they are asymptomatic.Even so,it is vital that clinicians be aware of such anomalies prior to surgery in affected individuals.In th...BACKGROUND Abnormalities of the inferior vena cava(IVC)are uncommon,and in many cases they are asymptomatic.Even so,it is vital that clinicians be aware of such anomalies prior to surgery in affected individuals.In the present report,we describe a rare anatomical variation of the IVC.CASE SUMMARY A 66-year-old male was admitted to the hospital due to deep vein thrombosis of the right lower extremity.Upon contrast-enhanced computed tomography imaging,we found that this patient presented with a case of left-sided IVC draining into the hemiazygos vein,while his hepatic vein was directly draining into the atrium.CONCLUSION Cases of left-sided IVC can increase patient susceptibility to thromboembolism owing to the resultant changes in blood flow and/or associated vascular compression.展开更多
Objective:To investigate and analyze the long-term clinical effects of acupoint application combined with pneumatic compression therapy in the prevention of deep venous thrombosis after hip fracture surgery among the ...Objective:To investigate and analyze the long-term clinical effects of acupoint application combined with pneumatic compression therapy in the prevention of deep venous thrombosis after hip fracture surgery among the elderly.Methods:Sixty elderly patients who had undergone hip fracture surgery from February 2021 to February 2022 were selected as the research subjects.The patients were divided into two groups via drawing lots.Both the groups received nursing care,but the patients in the observation group were treated with TCM acupoint application combined with pneumatic compression therapy,whereas the control group received pneumatic compression therapy.The evaluation indicators included the patients’quality of life and complications.Results:The incidence of lower extremity deep vein thrombosis in the observation group was more than twice(0.3%),whereas the incidence of lower extremity complications in the control group was more than 6 times(20%).There was a significant difference between the two groups(p<0.05).Conclusion:Traditional Chinese medicine acupoint application combined with pneumatic compression therapy is beneficial for the prevention of postoperative lower extremity deep vein thrombosis among elderly patients.In addition,the patients’overall quality-of-life scores in both physiological and psychological aspects improved significantly,which carries significant clinical reference value.展开更多
BACKGROUND The contradictory process of coagulation and anticoagulation maintains normal physiological function,and platelets(PLTs)play a key role in hemostasis and bleeding.When severe thrombocytopenia and deep vein ...BACKGROUND The contradictory process of coagulation and anticoagulation maintains normal physiological function,and platelets(PLTs)play a key role in hemostasis and bleeding.When severe thrombocytopenia and deep vein thrombosis(DVT)occur simultaneously,the physician will be confronted with a great challenge,especially when interventional thrombectomy fails.CASE SUMMARY We describe a 52-year-old woman who suffered from myelodysplastic syndrome with severe thrombocytopenia and protein S deficiency with right lower extremity DVT.In this patient,the treatment of DVT was associated with numerous contradictions due to severe thrombocytopenia,especially when interventional thrombectomy was not successful.Fortunately,fondaparinux sodium effectively alleviated the thrombus status of the patient and gradually decreased the D-dimer level.In addition,no increase in bleeding was noted.The application of eltrombopag stimulated the maturation and differentiation of megakaryocytes and increased the peripheral blood PLT count.The clinical symptoms of DVT in the right lower extremities in this patient significantly improved.The patient resumed daily life activities,and the treatment effects were independent of PLT transfusion.CONCLUSION This is a contradictory and complex case,and fondaparinux sodium and eltrombopag may represent a good choice for the treatment of DVT in patients with severe thrombocytopenia.展开更多
TPostoperative deep venous thrombosis is a more common clinical problem,and its preventive significance is greater than treatment.Compared with drug therapy,stress therapy has a definite effect and a wider range of ap...TPostoperative deep venous thrombosis is a more common clinical problem,and its preventive significance is greater than treatment.Compared with drug therapy,stress therapy has a definite effect and a wider range of applications,which is of great significance in clinical application.This article summarizes the relevant guidelines and recommendations for the prevention of deep vein thrombosis after surgery,the classification of specific treatment methods,the application situation and precautions in various types of surgery.展开更多
基金Sichuan Province Medical Research Project Plan(Project No.S21113)。
文摘This study explores the diagnostic value of combining the Padua score with the thrombotic biomarker tissue plasminogen activator inhibitor-1(tPAI-1)for assessing the risk of deep vein thrombosis(DVT)in patients with pulmonary heart disease.These patients often exhibit symptoms similar to venous thrombosis,such as dyspnea and bilateral lower limb swelling,complicating differential diagnosis.The Padua Prediction Score assesses the risk of venous thromboembolism(VTE)in hospitalized patients,while tPAI-1,a key fibrinolytic system inhibitor,indicates a hypercoagulable state.Clinical data from hospitalized patients with cor pulmonale were retrospectively analyzed.ROC curves compared the diagnostic value of the Padua score,tPAI-1 levels,and their combined model for predicting DVT risk.Results showed that tPAI-1 levels were significantly higher in DVT patients compared to non-DVT patients.The Padua score demonstrated a sensitivity of 82.61%and a specificity of 55.26%at a cutoff value of 3.The combined model had a significantly higher AUC than the Padua score alone,indicating better discriminatory ability in diagnosing DVT risk.The combination of the Padua score and tPAI-1 detection significantly improves the accuracy of diagnosing DVT risk in patients with pulmonary heart disease,reducing missed and incorrect diagnoses.This study provides a comprehensive assessment tool for clinicians,enhancing the diagnosis and treatment of patients with cor pulmonale complicated by DVT.Future research should validate these findings in larger samples and explore additional thrombotic biomarkers to optimize the predictive model.
文摘Objective To study and evaluate the treatment of the deep vein thrombosis(DVT) around the renal vein(DVT involving the renal vein and it's surrounding,shortly as DVTAR in our study)by two-positioned filter for catheter thrombectomy assisted with a Fogarty balloon.Methods We retrospectivly analysed seven cases of DVTAR and by comparison to elicit the respective effect different methods in DVT treatment.The methods used were:1.direct thrombectomy 2.thrombectomy facillitated by blocking of blood flow with a balloon 3.direct thrombolysis via Peripheral vein and 4.thrombectomy with simultaneous placement of a two-positioned filter with a Fogarty balloon and followed by intubation thrombolysis.Result Segmental pulmonary embolism(PE)or thrombosis in vena cava were still observed by CT angiography(CTA)or venography in those cases treated with the first three methods.As for the 3 cases where two-positioned filter for catheter thrombectomy with Fogarty balloon was used,neither pulmonary embolism during and after the operation nor thrombosis in the inferior vena cava was observed.Conclusion For DVTAR,thrombectomy with simultaneous placement of a two-positioned filter with a Fogarty balloon and followed by intubation thrombolysis can be regarded as safe and effective.
基金supported by grants from General Project of Yunnan Basic Research Program(No.202301AT070104)the Joint Project of Kunming Medical University and Science and Technology Department of Yunnan Province(No.202001AY070001-185)+1 种基金the Joint Project of Kunming Medical University and Science and Technology Department of Yunnan Province(No.202101AY070001-119)Yunnan Provincial Orthopedic and Sports Rehabilitation Clinical Medicine Research Center(No.202102AA310068).
文摘Objective:Matrix metalloproteinase 13(MMP13)is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens,modifying protein structures and regulating inflammatory responses,but its role in deep vein thrombosis(DVT)has not been determined.The purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of DVT.Methods:We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of DVT.After screening genes possibly related to MMP13 in DVT mice,the expression levels of candidate genes in human umbilical vein endothelial cells(HUVECs)and the venous wall were evaluated.The effect of MMP13 on platelet aggregation in HUVECs was investigated in vitro.Results:Among the differentially expressed genes,interleukin 1 beta,podoplanin(Pdpn),and factor VIII von Willebrand factor(F8VWF)were selected for analysis in mice.When MMP13 was inhibited,the expression level of PDPN decreased significantly in vitro.In HUVECs,overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation,while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet aggregation.Conclusions:Inhibiting the expression of MMP13 could reduce the burden of DVT in mice.The mechanism involves downregulating the expression of Pdpn through MMP13,which could provide a novel gene target for DVT diagnosis and treatment.
文摘BACKGROUND Deep vein thrombosis(DVT)is a significant postoperative concern,particularly in patients undergoing surgery for gastrointestinal(GI)cancers.These patients often present multiple risk factors,including advanced age and elevated body mass index(BMI),which can increase the likelihood of thromboembolic events.Effec-tive prophylaxis is crucial in this high-risk population to minimize complications such as DVT and pulmonary embolism(PE).This study investigates a compre-hensive DVT prevention protocol,combining mechanical and pharmacological strategies alongside early mobilization,to evaluate its effectiveness and safety in reducing postoperative thrombosis rates among GI cancer surgery patients.AIM To evaluate the effectiveness and safety of postoperative DVT prevention strate-gies in patients with GI cancer.METHODS A prospective cohort study was conducted involving 100 patients who underwent surgery for GI tumors between January and December 2022.All patients received a standardized DVT prevention protocol,which included risk assessment,mecha-nical prophylaxis,pharmacological prophylaxis,and early mobilization.The primary endpoint was the incidence of DVT within 30 days postoperatively.Se-condary outcomes included the occurrence of PE,bleeding complications,and adherence to the protocol.RESULTS The overall incidence of DVT was 7%(7/100 patients).One patient(1%)deve-loped PE.The adherence rate to the prevention protocol was 92%.Bleeding complications were observed in 3%of patients.Significant risk factors for DVT development included advanced age[odds ratio(OR):1.05;95%confidence interval(95%CI):1.01-1.09],higher BMI(OR:1.11;95%CI:1.03-1.19),and longer operative time(OR:1.007;95%CI:1.001-1.013).CONCLUSION Implementing a comprehensive DVT prevention and management protocol for patients undergoing GI tumor surgery resulted in a lower incidence.Strict adherence and individualized risk assessment are crucial for optimizing outcomes.
文摘Purpose: Few studies have evaluated the association between malnutrition and the risk of preoperative deep vein thrombosis (DVT) in patients undergoing primary total joint arthroplasty. This study aimed to investigate the prevalence of preoperative DVT in Japanese patients undergoing total knee arthroplasty (TKA) and the importance of malnutrition in the risk of preoperative DVT. Methods: We retrospectively analyzed 394 patients admitted for primary TKA at our institution between January 2019 and December 2023. All patients scheduled for TKA at our institution had serum D-dimer levels measured preoperatively. Lower-limb ultrasonography was examined to confirm the presence of DVT in patients with D-dimer levels ≥ 1.0 µg/mL or who were considered to be at high risk of DVT by the treating physician. Based on the results of lower-limb ultrasonography, all patients were divided into the non-DVT and DVT groups. The incidence of and risk factors for preoperative DVT were investigated, as well as the correlation of DVT with the patient’s nutritional parameters. We used two representative tools for nutritional assessment: the Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status Score. Results: The mean age was 77.8 ± 6.9 years. Preoperative DVT was diagnosed in 57 of the 394 (14.5%) patients. Multivariate logistic regression analysis showed that advanced age and malnutrition status, assessed using the GNRI, were independent risk factors for preoperative DVT. Conclusion: A high incidence of preoperative DVT was observed in patients who underwent TKA. Malnutrition status, as assessed using the GNRI, increased the risk of preoperative DVT. Our findings suggest that clinicians should consider these factors when tailoring preventive strategies to mitigate DVT risk in patients undergoing TKA.
文摘Upper extremity deep vein thrombosis(UEDVT)is less common than lower extremity DVT but is a cause of significant morbidity and mortality in intensive care unit patients.Increasing cancer incidence,prolonged life expectancy and increasing use of intravascular catheters and devices has led to an increased incidence of UEDVT.It is also associated with high rates of complications like pulmonary embolism,post-thrombotic syndrome and recurrent thrombosis.Clinical prediction scores and D-dimer may not be as useful in identifying UEDVT;hence,a high suspicion index is required for diagnosis.Doppler ultrasound is commonly employed for diagnosis,but other tests like computed tomography and magnetic resonance imaging venography may also be required in some patients.Contrast venography is rarely used in patients with clinical and ultrasound findings discrepancies.Anticoagulant therapy alone is sufficient in most patients,and thrombolysis and surgical decompression is seldom indicated.The outcome depends on the cause and underlying comorbidities.
文摘BACKGROUND Deep vein thrombosis(DVT)of the lower extremity is one of the most common postoperative complications,especially after craniocerebral surgery.DVT may lead to pulmonary embolism,which has a devastating impact on patient prognosis.This study aimed to investigate the incidence and risk factors of DVT in the lower limbs following craniocerebral surgery.AIM To identify independent risk factors for the development of postoperative DVT and to develop an effective risk prediction model.METHODS The demographic and clinical data of 283 patients who underwent craniocerebral surgery between December 2021 and December 2022 were retrospectively analyzed.The independent risk factors for lower extremity DVT were identified by univariate and multivariate analyses.A nomogram was created to predict the likelihood of lower extremity DVT in patients who had undergone craniocerebral surgery.The efficacy of the prediction model was determined by receiver operating characteristic curve using the probability of lower extremity DVT for each sample.RESULTS Among all patients included in the analysis,47.7%developed lower extremity DVT following craniocerebral surgery.The risk of postoperative DVT was higher in those with a longer operative time,and patients with intraoperative intermittent pneumatic compression were less likely to develop postoperative DVT.CONCLUSION The incidence of lower extremity DVT following craniocerebral surgery is significant,highlighting the importance of identifying independent risk factors.Interventions such as the use of intermittent pneumatic compression during surgery may prevent the formation of postoperative DVT.
文摘The aim of this study was to describe the characteristics of patients with deep vein thrombosis (DVT) of the pelvic limbs at the time of diagnosis, and their course after hospitalization, in order to improve the management of DVT in our context. This was a descriptive longitudinal study, based on cases of deep vein thrombosis recorded between 1 January 2015 and 30 September 2018, in the cardiology and internal medicine department of the Brazzaville University Hospital Centre. During the study period, 4678 patients were hospitalized, including 52 with DVT. Thirty-three were reassessed. The frequency of DVT was 1.1% and the average hospitalization rate was 13.9 cases/year. The 33 patients were divided into 20 women and 13 men (sex ratio: 0.65). The mean age of the patients was 51.4 ± 17.8 years (extremes: 16 and 85 years). The main aetiological factors were cancer (19.1%), sickle cell disease (3%) and HIV immunosuppression (3%). The predominant risk factors were: prolonged immobilization (42.9%), pregnancy, long travel and obesity in the same number of cases (n = 3, i.e. 14.2%). The DVT involved the left pelvic limb in 75.8% of cases. Anticoagulants were administered in all patients, and compression stockings were worn in 97% of cases. The mean time to re-evaluation was 10.9 ± 9.4 months (extremes: three and 35 months). The mean measurements of the limb where the thrombosis had occurred at diagnosis and reassessment showed a significant difference. Venous Doppler showed compressible veins (60.6%), varicosities (36.3%), incompressible veins (30.3%) and thrombus (21.2%). Complications were: post-phlebitic disease (42.4%), death (21.2%), pulmonary embolism (18.2%), recurrence (18.2%). The DVT remains relatively rare, and its conventional therapeutic management is satisfactory. Systematic venous Doppler ultrasound reassessment should enable patients at risk of recurrence to be identified.
文摘Goal: The purpose of this research is to analyze the clinical characteristics, diagnosis, treatment, and prognosis of critical care patients with phlegmasia cerulea dolens (PCD) caused by deep vein thrombosis. Our goal is to improve both awareness and early diagnosis and treatment of rare clinical diseases. Furthermore, we aim to examine advancements in the diagnosis and treatment of deep vein thrombosis. Method: The clinical information of patients with PCD received in 2022 was subject to retrospective analysis. The author conducted a search of 191 publications with a focus on PCD, from January 2010 to July 2022, from databases such as the China National Knowledge Infrastructure (CNKI), Wanfang Data, PubMed, etc. The results were used to summarize the examinations, diagnostic criteria, and treatment progress of PCD patients. Additionally, the author conducted another search using keywords such as “Venous thromboembolism” and “Anticoagulant drugs” to summarize research progress in anticoagulant drugs and the treatment of VTE. The search was limited to relevant. Outcome: Six months prior to admission, the patient, a 68-year-old female, developed sunken edema and cyanosis in both her lower extremities and was diagnosed with lower extremity deep vein thrombosis complicated by PCD, lower extremity ischemic necrosis, and septicemia. This diagnosis was made using a combination of CT and lower extremity vascular ultrasound-related examinations, as well as a significantly elevated D-dimer value. Despite active treatment and aggressive measures, such as anti-infection, organ function maintenance, anticoagulation, and improvement of microcirculatory disorders, the patient’s family declined corresponding surgical treatment and interventional surgery for the lower extremity due to objective factors, and the patient ultimately succumbed to her illness. The clinical characteristics of this patient were similar to those of the 14 cases of PCD reported by Xie Fei et al. in 2022. Conclusion: For patients with malignancy, it is crucial to start anticoagulation and physical prevention of DVT early on. Patients with DVT complicated by PCD have a variety of surgical options available to them, including surgical embolization or PMT (percutaneous mechanical thrombus ablation), CDT (catheter contact thrombolysis), and fascial ventriculotomy decompression [1]. Additionally, it may be necessary to place an inferior venous filter. Although the incidence of this disease is low accounting for approximately 5% of all patients with iliofemoral deep vein thrombosis [2], the prognosis is poor, as the mortality rate can reach up to 40% - 60% due to venous gangrene, with an overall mortality rate of 20% - 40% [3]. To increase the survival rate, it is important to diagnose and treat this disease as early as possible.
文摘The etiology of deep vein thrombosis(DVT) is still not elucidated nowadays.Based on the accordance between DVT incidence and the anemophilous pollen concentration in the air,we proposed the hypothesis that allergic reaction induced by anemophilous pollen may cause "idiopathic" DVT,and proinflammatory factors may play an important role in the thrombosis process.
文摘BACKGROUND:To investigate the clinical effectiveness of a pneumatic compression device(PCD)combined with low-molecular-weight heparin(LMWH)for the prevention and treatment of deep vein thrombosis(DVT)in trauma patients.METHODS:This study retrospectively analyzed 286 patients with mild craniocerebral injury and clavicular fractures admitted to our department from January 2016 to February 2020.Patients treated with only LMWH served as the control group,and patients treated with a PCD combined with LMWH as the observation group.The incidence of DVT,postoperative changes in the visual analogue scale(VAS)score,and coagulation function were observed and compared between the two groups.Excluding the influence of other single factors,binary logistic regression analysis was used to evaluate the use of a PCD in the patient’s postoperative coagulation function.RESULTS:After excluding 34 patients who did not meet the inclusion criteria,252 patients were were included.The incidence of DVT in the observation group was significantly lower than that in the control group(5.6%vs.15.1%,χ^(2)=4.605,P<0.05).The postoperative VAS scores of the two groups were lower than those before surgery(P<0.05).The coagulation function of the observation group was significantly higher than that of the control group,with a better combined anticoagulant effect(P<0.05).There were no significant differences between the two groups in preoperative or postoperative Glasgow Coma Scale scores,intraoperative blood loss,postoperative infection rate,or length of hospital stay(P>0.05).According to logistic regression analysis,the postoperative risk of DVT in patients who received LMWH alone was 1.764 times that of patients who received LMWH+PCD(P<0.05).The area under the receiver operating characteristic(AUROC)curve of partial thromboplastin time(APTT)and platelet(PLT)were greater than 0.5,indicating that they were the influence indicators of adding PCD to prevent DVT.Excluding the influence of other variables,LMWH+PCD effectively improved the coagulation function of patients.CONCLUSIONS:Compared with LMWH alone,LMWH+PCD could improve blood rheology and coagulation function in patients with traumatic brain injury and clavicular fracture,reduce the incidence of DVT,shorten the length of hospital stay,and improve the clinical effectiveness of treatment.
文摘QRAL contraceptives are widely used to prevent pregnancy. A number of studies have dem- onstrated the increased risk of venous throm- boembolism in women taking oral contracep-tives.1, 2 Pulmonary embolism (PE) and deep vein throm- bosis (DVT) are two clinical presentations of venous thromboembolism which share the same predisposing factors.3 This article described a female patient who taked oral contraceptives and had an unhealthy life habit de- veloped PE and DVT. CASE DESCRIPTION
基金Supported by The Sichuan Provincial Department of Science and Technology Supporting Project,No.2018SZ03811.3.5 project for disciplines of excellence,West China Hospital,Sichuan University,No.ZYJC18027.
文摘BACKGROUND Deep vein thrombosis(DVT)may cause pulmonary embolus,leading to late deaths.The systemic inflammatory and hypercoagulable state of moderate and severe acute pancreatitis(non-mild acute pancreatitis,NMAP)patients may contribute to the development of venous thromboembolism.Accurate prediction of DVT is conducive to clinical decisions.AIM To develop and validate a potential new prediction nomogram model for the occurrence of DVT in NMAP.METHODS NMAP patient admission between 2013.1.1 and 2018.12.31 at the West China Hospital of Sichuan University was collected.A total of 220 patients formed the training set for nomogram development,and a validation set was constructed using bootstrapping with 100 resamplings.Univariate and multivariate logistic regression analyses were used to estimate independent risk factors associated with DVT.The independent risk factors were included in the nomogram.The accuracy and utility of the nomogram were evaluated by calibration curve and decision curve analysis,respectively.RESULTS A total of 220 NMAP patients over 60 years old were enrolled for this analysis.DVT was detected in 80(36.4%)patients.The final nomogram included age,sex,surgery times,D-dimer,neutrophils,any organ failure,blood culture,and classification.This model achieved good concordance indexes of 0.827(95%CI:0.769-0.885)and 0.803(95%CI:0.743-0.860)in the training and validation sets,respectively.CONCLUSION We developed and validated a prediction nomogram model for DVT in older patients with NMAP.This may help guide doctors in making sound decisions regarding the administration of DVT prophylaxis.
基金Supported by China Public Health Alliance,No.GWLM202031.
文摘BACKGROUND The artificial liver support system(ALSS)is an effective treatment method for liver failure,but it requires deep venous intubation and long-term indwelling catheterization.However,the coagulation mechanism disorder of basic liver failure diseases,and deep venous thrombosis(DVT)often occur.AIM To evaluate the risk factors for DVT following use of an ALSS and establish a risk assessment score.METHODS This study was divided into three stages.In the first stage,the risk factors for DVT were screened and the patient data were collected,including ALSS treatment information;biochemical indices;coagulation and hematology indices;complications;procoagulant use therapy status;and a total of 24 indicators.In the second stage,a risk assessment score for DVT after ALSS treatment was developed.In the third stage,the DVT risk assessment score was validated.RESULTS A total of 232 patients with liver failure treated with ALSS were enrolled in the first stage,including 12 with lower limb DVT.Logistic regression analysis showed that age[odds ratio(OR),1.734;P=0.01],successful catheterization time(OR,1.667;P=0.005),activity status(strict bed rest)(OR,3.049;P=0.005),and D-dimer level(≥500 ng/mL)(OR,5.532;P<0.001)were independent risk factors for DVT.We then established a scoring system for risk factors.In the validation group,a total of 213 patients with liver failure were treated with ALSS,including 14 with lower limb DVT.When the cutoff value of risk assessment was 3,the specificity and sensitivity of the risk assessment score were 88.9%and 85.7%,respectively.CONCLUSION A simple risk assessment scoring system was established for DVT patients with liver failure treated with ALSS and was verified to have good sensitivity and specificity.
文摘BACKGROUND Abnormalities of the inferior vena cava(IVC)are uncommon,and in many cases they are asymptomatic.Even so,it is vital that clinicians be aware of such anomalies prior to surgery in affected individuals.In the present report,we describe a rare anatomical variation of the IVC.CASE SUMMARY A 66-year-old male was admitted to the hospital due to deep vein thrombosis of the right lower extremity.Upon contrast-enhanced computed tomography imaging,we found that this patient presented with a case of left-sided IVC draining into the hemiazygos vein,while his hepatic vein was directly draining into the atrium.CONCLUSION Cases of left-sided IVC can increase patient susceptibility to thromboembolism owing to the resultant changes in blood flow and/or associated vascular compression.
文摘Objective:To investigate and analyze the long-term clinical effects of acupoint application combined with pneumatic compression therapy in the prevention of deep venous thrombosis after hip fracture surgery among the elderly.Methods:Sixty elderly patients who had undergone hip fracture surgery from February 2021 to February 2022 were selected as the research subjects.The patients were divided into two groups via drawing lots.Both the groups received nursing care,but the patients in the observation group were treated with TCM acupoint application combined with pneumatic compression therapy,whereas the control group received pneumatic compression therapy.The evaluation indicators included the patients’quality of life and complications.Results:The incidence of lower extremity deep vein thrombosis in the observation group was more than twice(0.3%),whereas the incidence of lower extremity complications in the control group was more than 6 times(20%).There was a significant difference between the two groups(p<0.05).Conclusion:Traditional Chinese medicine acupoint application combined with pneumatic compression therapy is beneficial for the prevention of postoperative lower extremity deep vein thrombosis among elderly patients.In addition,the patients’overall quality-of-life scores in both physiological and psychological aspects improved significantly,which carries significant clinical reference value.
基金Supported by the Zhejiang Province Administration of Traditional Chinese Medicine,No.2017ZB034 and No.2020ZB096the Zhejiang University of Traditional Chinese Medicine School-Level Fund,No.2019ZG06the National Nonprofit Institute Research Grant for Institute of Basic Theory for Chinese Medicine,CACMS,No.YZ-202142.
文摘BACKGROUND The contradictory process of coagulation and anticoagulation maintains normal physiological function,and platelets(PLTs)play a key role in hemostasis and bleeding.When severe thrombocytopenia and deep vein thrombosis(DVT)occur simultaneously,the physician will be confronted with a great challenge,especially when interventional thrombectomy fails.CASE SUMMARY We describe a 52-year-old woman who suffered from myelodysplastic syndrome with severe thrombocytopenia and protein S deficiency with right lower extremity DVT.In this patient,the treatment of DVT was associated with numerous contradictions due to severe thrombocytopenia,especially when interventional thrombectomy was not successful.Fortunately,fondaparinux sodium effectively alleviated the thrombus status of the patient and gradually decreased the D-dimer level.In addition,no increase in bleeding was noted.The application of eltrombopag stimulated the maturation and differentiation of megakaryocytes and increased the peripheral blood PLT count.The clinical symptoms of DVT in the right lower extremities in this patient significantly improved.The patient resumed daily life activities,and the treatment effects were independent of PLT transfusion.CONCLUSION This is a contradictory and complex case,and fondaparinux sodium and eltrombopag may represent a good choice for the treatment of DVT in patients with severe thrombocytopenia.
基金General Project of the National Science and Nature Foundation of China(No.81774310)
文摘TPostoperative deep venous thrombosis is a more common clinical problem,and its preventive significance is greater than treatment.Compared with drug therapy,stress therapy has a definite effect and a wider range of applications,which is of great significance in clinical application.This article summarizes the relevant guidelines and recommendations for the prevention of deep vein thrombosis after surgery,the classification of specific treatment methods,the application situation and precautions in various types of surgery.