Site Of Thrombus Research Articles

Risk and Prognosis of Upper Extremity Deep Vein Thrombosis.

Objectives: We aimed to investigate the clinical features of upper extremity deep vein thrombosis (UEDVT). Methods: We retrospectively reviewed the background, thrombus site, treatment, and outcome of 76 UEDVT patients. Results: Of the 76 UEDVT patients, 44 (57.9%) were men, and 51 (67.1%) were complicated by malignancy, 44 (57.9%) had an indwelling central vein (CV) catheter, 8 (10.5%) had concomitant pulmonary embolization (PE), and 33 (43.3%) were symptomatic. Regarding the thrombus site, the right internal jugular vein was the most common, with 30 cases (35.3%). As regards the treatment method, 53 patients (69.7%) received oral anticoagulants. In 2015, when direct oral anticoagulants (DOACs) was covered by insurance, there were 44 UEDVT cases, of which 34 (77.3%) received DOACs. Outcomes at a mean observation period of 37.5±41.5 months included 40 deaths (52.6%) with a mean survival of 16.3±21.3 months. The most common cause of death was malignancy, with 33 cases (82.5%). Conclusion: In the background of UEDVT, the combination of indwelling CV catheter placement and malignancy was frequently observed. While the risk of recurrence or PE complications is low, the prognosis of UEDVT complicated by malignancy is extremely poor.

P-Selectin mediates targeting of a self-assembling phototherapeutic nanovehicle enclosing dipyridamole for managing thromboses

Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery. We developed self-assembling nanoparticles (NPs) through the optimization of a co-assembly engineering process. These NPs, called DIP-FU-PPy NPs, consist of polypyrrole (PPy), dipyridamole (DIP), and P-selectin-targeted fucoidan (FU) and are designed to be delivered directly to thrombi. DIP-FU-PPy NPs are proposed to offer various potentials, encompassing drug-loading capability, targeted accumulation in thrombus sites, near-infrared (NIR) photothermal-enhanced thrombus management with therapeutic efficacy, and prevention of rethrombosis. As predicted, DIP-FU-PPy NPs prevented thrombus recurrence and emitted visible fluorescence signals during thrombus clot penetration with no adverse effects. Our co-delivery nano-platform is a simple and versatile solution for NIR-phototherapeutic multimodal thrombus control.

Progress on Physical Field-Regulated Micro/Nanomotors for Cardiovascular and Cerebrovascular Disease Treatment.

Cardiovascular and cerebrovascular diseases (CCVDs) are two major vasculature-related diseases that seriously affect public health worldwide, which can cause serious death and disability. Lack of targeting effect of the traditional CCVD treatment drugs may damage other tissues and organs, thus more specific methods are needed to solve this dilemma. Micro/nanomotors are new materials that can convert external energy into driving force for autonomous movement, which can not only enhance the penetration depth and retention rates, but also increase the contact areas with the lesion sites (such as thrombus and inflammation sites of blood vessels). Physical field-regulated micro/nanomotors using the physical energy sources with deep tissue penetration and controllable performance, such as magnetic field, light, and ultrasound, etc. are considered as the emerging patient-friendly and effective therapeutic tools to overcome the limitations of conventional CCVD treatments. Recent efforts have suggested that physical field-regulated micro/nanomotors on CCVD treatments could simultaneously provide efficient therapeutic effect and intelligent control. In this review, various physical field-driven micro/nanomotors are mainly introduced and their latest advances for CCVDs are highlighted. Last, the remaining challenges and future perspectives regarding the physical field-regulated micro/nanomotors for CCVD treatments are discussed and outlined.

Biomimetic Platelet Nanomotors for Site-Specific Thrombolysis and Ischemic Injury Alleviation.

Due to the mortality associated with thrombosis and its high recurrence rate, there is a need to investigate antithrombotic approaches. Noninvasive site-specific thrombolysis is a current approach being used; however, its usage is characterized by the following limitations: low targeting efficiency, poor ability to penetrate clots, rapid half-life, lack of vascular restoration mechanisms, and risk of thrombus recurrence that is comparable to that of traditional pharmacological thrombolysis agents. Therefore, it is vital to develop an alternative technique that can overcome the aforementioned limitations. To this end, a cotton-ball-shaped platelet (PLT)-mimetic self-assembly framework engineered with a phototherapeutic poly(3,4-ethylenedioxythiophene) (PEDOT) platform has been developed. This platform is capable of delivering a synthetic peptide derived from hirudin P6 (P6) to thrombus lesions, forming P6@PEDOT@PLT nanomotors for noninvasive site-specific thrombolysis, effective anticoagulation, and vascular restoration. Regulated by P-selectin mediation, the P6@PEDOT@PLT nanomotors target the thrombus site and subsequently rupture under near-infrared (NIR) irradiation, achieving desirable sequential drug delivery. Furthermore, the movement ability of the P6@PEDOT@PLT nanomotors under NIR irradiation enables effective penetration deep into thrombus lesions, enhancing bioavailability. Biodistribution analyses have shown that the administered P6@PEDOT@PLT nanomotors exhibit extended circulation time and metabolic capabilities. In addition, the photothermal therapy/photoelectric therapy combination can significantly augment the effectiveness (ca. 72%) of thrombolysis. Consequently, the precisely delivered drug and the resultant phototherapeutic-driven heat-shock protein, immunomodulatory, anti-inflammatory, and inhibitory plasminogen activator inhibitor-1 (PAI-1) activities can restore vessels and effectively prevent rethrombosis. The described biomimetic P6@PEDOT@PLT nanomotors represent a promising option for improving the efficacy of antithrombotic therapy in thrombus-related illnesses.

Multi-enzyme mimetic iridium nanozymes-based thrombus microenvironment-modulated nanoplatform for enhanced thrombolytic therapy

Intravenous injection of thrombolytic drugs is the most feasible strategy for the clinical treatment of thrombotic diseases, however, its applications are yet limited by narrow therapeutic index, short half-life, and hemorrhagic risk. Inspired by the excessive ROS and inflammatory factors at the thrombus site, we manufactured a thrombus microenvironment-modulated nanosystem, which achieved the targeted delivery of thrombolytic drugs and ROS scavenging agents. Ir monomers (Ir-PVP) with enzyme-mimetic activity were prepared and then wrapped with lumbrokinase (LK) by HA materials of thrombo-inflammatory affinity, forming multifunctional thrombolytic agents Ir-LK@HA. Ir-LK@HA could prolong the biological half-life of LK and target the thrombus site to release LK with reduced bleeding risk. Moreover, Ir-NPs, as both CT imaging contrast agent and ROS scavenger, not only allowed us to observe the progression of thrombolytic treatment through CT imaging in real time, but also played an important role in elimination of excessive ROS at thrombus site. Taken together, the in vitro and in vivo experiments illustrated that Ir-LK@HA with CT function displayed an excellent efficiency in thrombolysis, anti-inflammation and ROS scavenging. Our work may encourage further exploration of thrombus microenvironment-modulated theranostic platforms.

A Biomimicking and Multiarm Self-Indicating Nanoassembly for Site-Specific Photothermal-Potentiated Thrombolysis Assessed in Microfluidic and In Vivo Models.

Thrombolytic and antithrombotic therapies are limited by short circulation time and the risk of off-target hemorrhage. Integrating a thrombus-homing strategy with photothermal therapy are proposed to address these limitations. Using glycol chitosan, polypyrrole, iron oxide and heparin, biomimicking GCPIH nanoparticles are developed for targeted thrombus delivery and thrombolysis. The nanoassembly achieves precise delivery of polypyrrole, exhibiting biocompatibility, selective accumulation at multiple thrombus sites, and enhanced thrombolysis through photothermal activation. To simulate targeted thrombolysis, a microfluidic model predicting thrombolysis dynamics in realistic pathological scenarios is designed. Human blood assessments validate the precise homing of GCPIH nanoparticles to activated thrombus microenvironments. Efficient near-infrared phototherapeutic effects are demonstrated at thrombus lesions under physiological flow conditions ex vivo. The combined investigations provide compelling evidence supporting the potential of GCPIH nanoparticles for effective thrombus therapy. The microfluidic model also offers a platform for advanced thrombolytic nanomedicine development.

GOx-Powered Janus Platelet Nanomotors for Targeted Delivery of Thrombolytic Drugs in Treating Thrombotic Diseases.

Low efficiency of targeting and delivery toward the thrombus site poses challenges to using thrombolytic drugs. Inspired by the biomimetic system of platelet membranes (PMs) and glucose oxidase (GOx) modification technologies, we develop a novel GOx-powered Janus nanomotor by asymmetrically attaching the GOx to polymeric nanomotors coated with the PMs. Then the PM-coated nanomotors were conjugated with urokinase plasminogen activators (uPAs) on their surfaces. The PM-camouflaged design conferred excellent biocompatibility to the nanomotors and improved their targeting ability to thrombus. The Janus distribution of GOx also allows the uneven decomposition of glucose in biofluids to produce a chemophoretic motion, increasing the drug delivery efficiency of nanomotors. In addition, these nanomotors are located at the lesion site due to the mutual adhesion and aggregation of platelet membranes. Furthermore, thrombolysis effects of nanomotors are enhanced in static and dynamic thrombus as well as in mouse models. It is believed that the novel PM-coated enzyme-powered nanomotors represent a great value for thrombolysis treatment.

Role of 18 F-FDG PET/CT in the diagnosis of benign vs. malignant tumor thrombus.

Hypercoagulable state is a complication of various infections, and inflammatory processes and is a common scenario in cancer patients also. Timely diagnosis and treatment are essential to reduce further complications in such patients. The present study aimed to assess the role of FDG PET/CT in the diagnosis of benign vs. malignant tumor thrombus and to determine cut-off SUVmax to differentiate them. We retrospectively reviewed all FDG PET/CT scans of patients done in our department from January 2017 to March 2022. All scans were reviewed by two experienced nuclear medicine physicians. A total of 135 patients who had venous or arterial thrombus in FDG PET/CT scans were included. All the FDG PET/CT scans of 135 patients were analyzed for primary tumor site and/or site of thrombus. Additional clinical data were collected for patients with benign conditions in the form of ESR and CRP if available and doubtful cases were followed up by HPE reports and/or CEMRI. The SUV max of the primary tumor(in cancer patients), thrombus, and background (aorta) were calculated. A total of 135 patients (108 cancer patients and 27 with benign thrombus) were included with an age range of 3 to 86 years (median 50 years). There were 91 males and 44 females. Of 108 cancer patients, the most common cancers were hepatocellular cancer - 38 (35.18%), renal cell cancer - 28(25.92%), and carcinoma of the thyroid - 6 (5.55%). Of 108 cancer patients, 36 (33.33%) had tumor thrombosis in inferior vena cava, 31 (28.70%) in the portal vein, and 41 (37.96%) in other vessels (renal vein, jugular vein, etc.). Of 27 patients with benign conditions,13 had venous thrombi, 11 had arterial thrombus and three had atrial thrombus and the most common thrombus sites were thoraco-abdominal aorta in seven (25.92%) and right atrium in three (11.11%) patients. In the subgroup of 108 oncological patients, the mean SUV max of the primary tumors was 17.67 (range 2.1-91.0; median 10.82), thrombi were 17.61 (range 2.14-90.11; median 14.56) and background was 5.29 (range 0.29-25.00; median 3.12). Of 27 patients with benign conditions, the mean SUV max of the thrombi was 11.09 (range 1.98-31; median 8.10) and the background was 9.80 (range 1.46-24.50; median 10.20) The ESR was raised in 13 of 26 patients (mean 35.84, range 10.98-62.00, median 35.00) and CRP was raised 22 of 26 patients (mean11.46, range 3.45-24.50, median 20.40). Upon plotting the receiver operating curve, a cutoff SUV max of 12.7 with a sensitivity of 62.96% and specificity of 77.77% was produced to demarcate tumor thrombus from benign thrombus. FDG PET/CT plays a significant role in the detection of thrombo-embolic disease and can differentiate benign thrombus from tumor thrombus.

Cryo-Shocked Platelet Coupled with ROS-Responsive Nanomedicine for Targeted Treatment of Thromboembolic Disease.

Thrombolysis with tissue plasminogen activator (tPA) provides the most common therapy for ischemic stroke onset within the past 4.5 h. However, enhanced neutrophil infiltration and secondary blood-brain barrier injury caused by tPA administration have limited its therapeutic application, and tPA treatment is often accompanied by hemorrhagic transformation. To overcome the limitations of thrombolysis by tPA, maximize the therapeutic efficacy, and improve the safety, herein, we report a cryo-shocked platelet-based cell-hitchhiking drug delivery system, which consists of cryo-shocked platelet (CsPLT) and reactive oxygen species (ROS)-responsive liposomes loaded with thrombolytic tPA and anti-inflammation drug aspirin (ASA). CsPLT and liposomes were facilely conjugated via host-guest interactions. Under the guidance of CsPLT, it selectively accumulated in the thrombus site and quickly released the therapeutic payloads in response to the high ROS. tPA subsequently exhibited localized thrombolytic activity to suppress the expansion of thrombus, while ASA assisted in the inactivation of reactive astrogliosis, microglial/macrophage, and obstruction of neutrophil infiltration. This cryo-shocked platelet-hitchhiking tPA/ASA delivery system not only improves the thrombus-targeting efficiency of the two drugs for highly localized thrombolytic effects and anti-inflammation actions and platelets inactivation but also provides insights to the development of targeted drug delivery systems for thromboembolic disease treatment.

Magnetic Response Combined with Bioactive Ion Therapy: A RONS-Scavenging Theranostic Nanoplatform for Thrombolysis and Renal Ischemia-Reperfusion Injury.

Currently, the limited efficacy of antithrombotic treatments is attributed to the inadequacy of pure drugs and the low ability of drugs to target the thrombus site. More importantly, timely thrombolysis is essential to reduce the sequelae of cardiovascular disease, but ischemia-reperfusion injury (IRI) remains a major challenge that must be solved after blood flow recovery. Herein, a multifunctional therapeutic nanoparticle (NP) based on Fe3O4 and strontium ions encapsulated in mesoporous polydopamine was successfully constructed and then loaded with TNK-tPA (FeM@Sr-TNK NPs). The NPs (59.9 min) significantly prolonged the half-life of thrombolytic drugs, which was 3.04 times that of TNK (19.7 min), and they had good biological safety. The NPs were shown to pass through vascular models with different inner diameters, curvatures, and stenosis under magnetic targeting and to enable accurate diagnosis of thrombi by photoacoustic imaging. NPs combined with the magnetic hyperthermia technique were used to accelerate thrombolysis and quickly open blocked blood vessels. Then, renal IRI-induced functional metabolic disorder and tissue damage were evidently attenuated by scavenging toxic reactive oxygen and nitrogen species and through the protective effects of bioactive ion therapy, including reduced apoptosis, increased angiogenesis, and inhibited fibrosis. In brief, we constructed a multifunctional nanoplatform for integrating a "diagnosis-therapy-protection" approach to achieve comprehensive management from thrombus to renal IRI, promoting the advancement of related technologies.

Seizures, deep vein thrombosis, and pulmonary emboli in a severe case of May–Thurner syndrome: a case report

BackgroundMay–Thurner syndrome is a vascular disorder caused by the right common iliac artery compressing the left common iliac vein against the lumbar spine, causing distal venous stasis and potentially leading to fibrous change in the venous wall structure. Although May–Thurner syndrome is most commonly discovered in females upon investigation of new-onset deep vein thrombosis, we present the case of an otherwise healthy 29-year-old male with severe May–Thurner syndrome who presented with seizures, bilateral deep vein thrombosis, and diffuse pulmonary emboli. Seizures constituted the earliest presenting symptoms for the patient. Although it is difficult to prove that the patient’s seizures were related to the May–Thurner syndrome, this possible association renders this case extraordinary.Case presentationThis report describes the case of a 29-year-old previously healthy white male with a severe case of left-sided May–Thurner syndrome that required extensive medical and interventional treatment. The patient experienced two seizures, one month apart, both of which occurred while residing at high altitude. The patient had no prior history of seizures, and epilepsy was ruled out. Three weeks after the second seizure, he presented to the emergency room with hemoptysis, dyspnea, and severe leg pain. Sites of thrombus were confirmed in both legs and diffusely in the lungs. Etiological work-up after treatment with intravenous tissue plasminogen activator revealed May–Thurner syndrome. Hematology workup including genetic testing showed no evidence of coagulopathy. Bilateral common iliac venous stents were placed to attempt definitive treatment. Despite stenting, the patient had another thrombotic event with associated sequelae after discontinuation of anticoagulation. The patient has not had another seizure since the stents were placed. Despite the negative testing, the patient remains on lifelong chemoprophylaxis in the event of an undiscovered hypercoagulopathy.ConclusionsThe care team theorizes that the seizures resulted from hypoxia due to May–Thurner syndrome-induced hemostasis and associated thrombotic events, the high-altitude location of his residence at the time he experienced the seizures, and shallow breathing during sleep. For patients with lower limb venous thrombosis, May–Thurner syndrome should be considered in the differential diagnosis. Endovascular treatment followed by extended prophylactic anticoagulation therapy until the patient is determined to be no longer at risk for thrombosis is recommended. Post-venoplasty thrombosis is a common complication of endovascular treatment of May–Thurner syndrome and should be carefully monitored.

Platelet-Covered Nanocarriers for Targeted Delivery of Hirudin to Eliminate Thrombotic Complication in Tumor Therapy.

Most patients are at high risk of thrombosis during cancer treatment. However, the major discrepancy in the therapeutic mechanisms and microenvironment between tumors and thrombosis makes it challenging for a panacea to treat cancer while being able to eliminate the risk of thrombosis. Herein, we developed a biomimetic MnOx/Ag2S nanoflower platform with platelet membrane modification (MnOx@Ag2S@hirudin@platelet membrane: MAHP) for the long-term release of anticoagulant drugs to treat thrombosis together with tumor therapy. This MAHP platform could achieve the targeted delivery of hirudin to the thrombus site and perform the controlled release under the irradiation of near-infrared light, demonstrating effective removal of the thrombus. Moreover, MAHP could inhibit tumor progression and prolong the survival time of mice with thromboembolic complications.

Biomimetic Nanoplatelets to Target Delivery Hirudin for Site-Specific Photothermal/Photodynamic Thrombolysis and Preventing Venous Thrombus Formation.

Due to the high recurrence rate and mortality of venous thrombosis, there is an urgent need for research on antithrombotic strategies. Because of the short half-life, poor targeting capabilities, bleeding complications, and neurotoxic effects of conventional pharmacological thrombolysis methods, it is essential to develop an alternative strategy to noninvasive thrombolysis and decrease the recurrence rate of venous thrombosis. A platelet-mimetic porphyrin-based covalent organic framework-engineered melanin nanoplatform, to target delivery of hirudin to the vein thrombus site for noninvasive thrombolysis and effective anticoagulation, is first proposed. Owing to the thrombus-hosting properties of platelet membranes, the nanoplatform can target the thrombus site and then activate hyperthermia and reactive oxygen species for thrombolysis under near-infrared light irradiation. The photothermal therapy/photodynamic therapy combo can substantially improve the effectiveness (85.7%) of thrombolysis and prevent secondary embolism of larger fragments. Afterward, the highly loaded (97%) and slow-release hirudin (14 days) are effective in preventing the recurrence of blood clots without the danger of thrombocytopenia. The described biomimetic nanostructures offer a promising option for improving the efficacy of thrombolytic therapy and reducing the risk of bleeding complications in thrombus associated diseases.

A Synergistic and Efficient Thrombolytic Nanoplatform: A Mechanical Method of Blasting Combined with Thrombolytic Drugs.

Thrombosis is a common disease that poses a great threat to life and health. Most thrombolytic effects of traditional treatments or nanomedicine are not efficient or safe enough. Therefore, we designed a nanoparticle (NP) with a combination of a phase transition material and thrombolytic drugs for efficient and safe thrombolysis. A thrombus fibrin-targeted and phase transition NP was designed and contained perfluorohexane (PFH) and the thrombolytic drug rtPA core, with CREKA polypeptides attached to the shell of the PLGA NPs. Characterization of the phase transition and ultrasound imaging of the NPs was carried out under low-intensity focused ultrasound (LIFU). LIFU-responsive drug release in vitro was also explored. Under the synergistic effect of PFH and rtPA, the efficient thrombolysis ability of the NPs was studied in vitro and in vivo. In vivo monitoring of thrombosis and biosafety were also verified. The PPrC NPs had good ultrasound imaging ability under LIFU irradiation and were related to the phase transition characteristics of the NPs. CREKA polypeptides can effectively increase the aggregation of the NPs on thrombi. Under static and dynamic conditions in vitro, the "liquid to gas" transformation effect of PFH can perform the destruction function of the excavator at the thrombus site and promote the specific release of rtPA, and the subsequent rtPA drug thrombolysis can further fully dissolve the thrombus. In vivo experiments showed that the NPs can monitor the formation of thrombi and have good thrombolytic effects, with significantly reduced bleeding side effects. The biochemical indexes of the rats were within normal limits after treatment. PPrC NPs loaded with PFH and rtPA combining a mechanical way of blasting with thrombolytic drugs may be a promising new and reliable approach for thrombus monitoring and treatment.

Successful treatment of aortic arch mural thrombosis with low-dose, ultra-slow-flow thrombolysis: a case report and literature review

Aortic arch thrombosis represents a severe condition which usually requires surgical treatment in specialized centers. Treatments described in literature are mostly surgery or sodium heparin infusion. Here we describe an off-label use of alteplase in aortic arch thrombosis in a patient in whom sodium heparin treatment failed and surgery was not possible due to the site of thrombus. We report the case of a 34-year-old postpartum patient who was admitted to our hospital for aortic arch thrombosis. She had no genetic disorders for hypercoagulability, only a family history for ischemic cerebrovascular accident. As treatment with sodium heparin failed and surgery was not possible due to the site of thrombus, she received a low-dose, ultra-slow-flow treatment with alteplase for 75 hours with successful removal of the thrombus. No side effects from alteplase were observed. Considering the safety and efficacy in this patient, as well as the easiness by which it can be reproduced in the majority of clinical settings, this treatment may be a viable option in cases of aortic arch thrombosis when conventional treatments are not applicable or available.

Prognosis of Patients with Venous Thromboembolism and Cancer in India

Introduction: Venous thromboembolism (VTE) is common in cancer patients and is considered one of the leading causes of death. Although activation of coagulation system is linked to tumor biology and considered as poor prognostic feature, there are several temporary/provoking factors such as perioperative period, immobilization, and debility that may cause VTE in these patients. It is not clear whether patients with such provoked VTE have different prognoses compared to patients without provoked VTE. Aim: To understand the overall prognosis of patients with cancer-associated thrombosis deep vein thrombosis (DVT) and whether there is a difference in survival between patients who underwent surgery (with or without chemotherapy) and patients who did not undergo surgery. Materials and Methods: This is a combined retrospective and prospective study. Electronic medical records of all patients who underwent VTE treatment between September 2014 and September 2019 were reviewed. Only patients who had DVT in the lower limb associated with malignancy were included in the study. Demographics, clinical, type, stage and type of cancer, and prophylactic treatment received and mortality data were collected. Results: Of 1364 patients treated for VTE, 86 patients (6.3%) had cancer-associated DVT. The mean age was 57 years (range 26–80 years) and 52 patients (60.46%) were female. The most common malignancies were cervix (15.11%), breast (12.79%), and colorectal (12.79%). Majority (68.60%) of the cancer patients were in the stages III and IV, other than having malignancy the most common risk factors were age, obesity, and postsurgery. Forty-three patients had surgery (with or without chemotherapy/radiotherapy). The left leg was commonly involved (53.48%) and the site of thrombus was in iliac (51.68%), femoral (16.85%), or popliteal veins (2.24%). All patients were initially started on low-molecular-weight heparin (LMWH) and then switched to Non-Vitamin K antagonist oral anticoagulants (NOAC) in 29 patients (33.72%) and VKA in 43 patients (50%). In seven patients, LMWH was continued (8.13%). Fifty-seven out of 86 patients (66.27%) were available for follow-up. Eighteen out of 57 patients (31.57%) were alive with an overall mortality of 59.64% and 1 year mortality of 37.5%. In patients who underwent surgery (with or without chemotherapy/radiotherapy), the overall mortality was 58.13% compared to 85.71% in patients who did not undergo surgery. Conclusion: VTE in cancer patients is not uncommon in India and is associated with high mortality. Patients with provoked DVT due to surgery (perioperative period) might have better survival compared to patients who did not undergo surgery.

Development of a sigmoid sinus dural arteriovenous fistula secondary to sigmoid sinus thrombosis after resection of a foramen magnum meningioma: illustrative case.

The precise etiology of dural arteriovenous fistula (DAVF) is still unknown. The authors reported a case of delayed postoperative sigmoid sinus (SS) DAVF secondary to SS thrombosis after resection of a foramen magnum meningioma through a suboccipital craniotomy. The authors visualized the clear architecture of the DAVF using fusion three-dimensional computer graphics (3DCG) images reconstructed from multimodal imaging studies. These fusion 3DCG images revealed that the feeders of the DAVF had connected through neovascularization to the SS at the previous thrombus site. The authors also reviewed previously reported cases of DAVFs that developed after craniotomy. This study indicated that SS stenosis and occlusion with sinus thrombosis are possible risk factors for delayed postoperative DAVF that demand special consideration.

A Fibrinogen-Mimicking, Activated-Platelet-Sensitive Nanocoacervate Enhances Thrombus Targeting and Penetration of Tissue Plasminogen Activator for Effective Thrombolytic Therapy.

The development of a fibrinolytic system with long circulation time, high thrombus targeting, efficient thrombus penetration, effective thrombolysis, and minimal hemorrhagic risk remains a major challenge. Herein, inspired by fibrinogen binding to activated platelets in thrombosis, this article reports a fibrinogen-mimicking, activated-platelet-sensitive nanocoacervate to enhance thrombus penetration of tissue plasminogen activator (tPA) for targeted thrombolytic therapy. This biomimetic nanothrombolytic system, denoted as RGD-Chi@tPA, is constructed by "one-pot" coacervation through electrostatic interactions between positively charged arginine-glycine-aspartic acid (RGD)-grafted chitosan (RGD-Chi) and negatively charged tPA. Flow cytometry and confocal laser scanning microscopy measurements show targeting of RGD-Chi@tPA to activated platelets. Controlled tPA release triggered by activated platelets at a thrombus site is demonstrated. Its targeted fibrinolytic and thrombolytic activities are measured in in vitro models. The pharmacokinetic profiles show that RGD-Chi@tPA can significantly prolong circulation time compared to free tPA. In a mouse tail thrombus model, RGD-Chi@tPA displays efficient thrombus targeting and penetration, enabling a complete vascular recanalization as confirmed by the fluorescence imaging, histochemical assay, and laser speckle contrast imager. Consequently, RGD-Chi@tPA induces a substantial enhancement in thrombolysis with minimal hemorrhagic risk compared to free tPA. This simple, effective, and safe platform holds great promise for the development of thrombolytic nanomedicines.

Thrombus Distribution in Vaccine-induced Immune Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination.

This case series reports 40 patients (median age, 41 years [interquartile range (IQR) 32- 52, 22 men) with confirmed vaccine-induced immune thrombotic thrombocytopaenia after administration of their first ChAdOx1 nCov-19 (AstraZeneca) vaccine: 80% (n=32) developed symptoms within the first 14 days and 20% (n=8) within 14-28 days. The location and extent of thrombi were evaluated using CT, MRI and ultrasound. Of the 40, 73% (n=29) presented with neurological symptoms and had confirmed cerebral venous sinus thrombosis, 30% (n=12) had extension of their primary thrombus, and 20% (n=8) died. 83% of those who underwent additional imaging (25 of 30) had occult thrombosis.

Comparative evaluation of enema alone and in combination with oral polyethylene glycol for bowel preparation before transvaginal pelvic floor reconstruction in elderly patients: a retrospective cohort study

The aim of this retrospective study was to assess the value of using an enema alone for mechanical bowel preparation (MBP) before transvaginal pelvic floor reconstruction (TPFR) in patients ≥65 years old. In total, 190 patients were included [81 in the enema group vs. 109 in the enema + polyethylene glycol (PEG) group]. The levels of serum potassium (p = .004) and calcium (p = .005) were higher in the enema group after surgery. The decrease in serum calcium was more significant in the enema + PEG group (p = .027). More patients in the enema + PEG group developed hypokalaemia (p = .035) or hypocalcaemia (p = .008) after surgery. The incidence of thrombus and surgical site infection was similar and earlier bowel movement was evident in the enema group (p = .000). Overall, the enema group used more laxatives (p = .026). Using enema alone before TPFR reduces the incidence of electrolyte disturbances with no increase in surgical complications in elderly patients. IMPACT STATEMENT What is already known on this subject? TPFR is an effective treatment for pelvic organ prolapse (POP) in elderly women. Bowel preparation performed before gynecological surgery can reduce surgical site infection, but increase discomfort and electrolyte disturbance. What do the results of this study add? The levels of serum potassium and calcium were lower in the enema + PEG group than in the enema group after surgery and more patients developed hypokalaemia or hypocalcaemia in the enema + PEG group. The incidence of thrombus and surgical site infection was similar between the two groups. Bowel movement was earlier in the enema group. What are the implications of these findings for clinical practice and/or future research? Using enema alone before TPFR reduces the incidence of electrolyte disturbance and does not increase surgical complications. This conclusion needs to be confirmed by random controlled trial studies in the future.