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Marine Drugs Jun 2024Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated...
Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvβ3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvβ3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvβ3. Activation of the integrin αvβ3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.
Topics: Animals; Sepsis; von Willebrand Factor; Humans; Mice; Human Umbilical Vein Endothelial Cells; Male; Blood Platelets; Disease Models, Animal; Mice, Inbred C57BL; Endothelium, Vascular; Integrin alphaVbeta3; Capillary Permeability
PubMed: 38921594
DOI: 10.3390/md22060283 -
Hospital Pharmacy Aug 2024Andexanet alfa is approved for the reversal of life-threatening or uncontrolled bleeding due to factor-Xa inhibitors. Data are limited on outcomes for patients who...
Andexanet alfa is approved for the reversal of life-threatening or uncontrolled bleeding due to factor-Xa inhibitors. Data are limited on outcomes for patients who receive both andexanet alfa and 4-factor prothrombin complex concentrate (4F-PCC). The aim of this case series is to evaluate the safety and efficacy outcomes in patients receiving the two agents in combination. Electronic medical records of patients who received both 4F-PCC and andexanet alfa for nontraumatic intracranial hemorrhage from January 2019 to March 2022 were retrospectively reviewed. Hemostatic efficacy and complications related to concurrent use of 4F-PCC with andexanet alfa were documented. Nine patients received 4F-PCC and andexanet alfa for reversal of factor Xa inhibitor-associated intracranial bleeding, eight of whom required reversal of apixaban. Of these nine patients, five patients died within 28 days for a 56% incidence of mortality. The average time from 4F-PCC administration to andexanet alfa administration was 3 hours and 9 minutes. Most doses of andexanet alfa were given for concern for bleed expansion after 4F-PCC administration. Hemostatic efficacy based on stability of repeat computed tomography scans post-administration of both agents was found in six patients (66.67%), with a 55.56% n incidence of thromboembolism, including two pulmonary embolisms, two deep vein thromboses, and one renal artery thrombosis. : Risks and benefits should be weighed to determine if there is benefit to adding andexanet alfa to 4F-PCC in patients with incomplete hemostasis and life-threatening hemorrhage. The combination of andexanet alfa and 4F-PCC may increase the risk of thrombotic complications without improving mortality.
PubMed: 38919755
DOI: 10.1177/00185787241229192 -
Clinical Neurology and Neurosurgery Jun 2024Spinal metastases can significantly affect quality of life in patients with cancer and present complex neurosurgical challenges for surgeons. Surgery with...
OBJECTIVE
Spinal metastases can significantly affect quality of life in patients with cancer and present complex neurosurgical challenges for surgeons. Surgery with instrumentation is often indicated to alleviate pain, preserve neurological function, and ensure mechanical stability. However, distortions in the bony anatomy due to oncological disease can decrease the accuracy of pedicle screw placement. Robotic-assisted surgery may offer an opportunity to increase screw accuracy and improve navigation of spinal lesions compared to conventional techniques. Therefore, we presented our institutional experience evaluating robotic-assisted surgical fixation for spinal metastases.
METHODS
Patients undergoing robotic-assisted surgery at a large tertiary care center between January 2019 - January 2023 for the treatment of spinal metastases were identified. Patient characteristics, including demographics, tumor pathology, surgical complications, and post-operative outcomes were extracted. The Gertzbein Robbins classification system (GRS) was used to assess pedicle screw placement accuracy in patients with post-operative computed tomography.
RESULTS
Twenty patients were identified, including 7 females (35 %), with an overall median age of 66 years (range: 39-80 years) and median BMI of 25 kg/m (range: 17-34 kg/m). An average of four spinal levels were instrumented, with metastases located primarily in the thoracic (n=17, 85 %) spine. Common primary tumor types included prostate (n=4), lung (n=2), and plasma cell (n=2) cancers. Most pedicle screws (92 %) were classified as GRS A in patients with postoperative imaging. Post-operative complications were unrelated to the use of the robot, and included pulmonary embolism (n=1), deep vein thrombosis (n=2), and gastric symptoms (n=3). Three patients were readmitted at 30 days, with one reoperation due to tumor recurrence. Four patients were deceased within 6 months of surgery.
CONCLUSIONS
Despite the inherent high-risk nature of these surgeries, this study underscores the safety and efficacy of robotic-assisted surgery in the management of spinal metastases. Robots can be helpful in ensuring accuracy of pedicle screw placement in patients with metastatic disease.
PubMed: 38917745
DOI: 10.1016/j.clineuro.2024.108393 -
Europace : European Pacing,... Jun 2024Atrial fibrillation (AF) ablation and left atrial appendage occlusion (LAAO) are increasingly performed as individual procedures. Pulsed field ablation (PFA) has...
BACKGROUND AND AIMS
Atrial fibrillation (AF) ablation and left atrial appendage occlusion (LAAO) are increasingly performed as individual procedures. Pulsed field ablation (PFA) has significantly reduced procedure duration and may be advantageous for the combined approach.
METHODS
We have launched a program for simultaneous AF ablation using PFA and LAAO for patients qualifying for both treatments and excluding those with complex anatomy. We compare procedure duration and fluoroscopy time against individual procedures (either AF ablation or LAAO alone), all performed by the same operators and using consistent technologies.
RESULTS
We performed the combined procedure in 10 patients (50% male; median age 70 years) and excluded two patients (17%) because of complex LAA anatomy. No death, stroke or major bleeding, including pericardial effusion, occurred. For single procedure comparison, 207 AF ablation procedures and 61 LAAO procedures were available. Total median procedure duration was 79 minutes (range 60; 125) for the combined procedure, 71 minutes (25; 241) for individual AF ablation (51 minutes without and 78 minutes with 3D electroanatomic mapping) and 47 minutes (15; 162) for individual LAAO. Respective fluoroscopy times were 21 (15; 26), 15 (5; 44) and 10 (3; 50) minutes. For the combined procedure, femoral vein access to last PFA application lasted 49 minutes (34; 93) and LAAO added 20 minutes (15; 37).
CONCLUSION
Simultaneous PFA-based AF ablation and LAAO in carefully selected patients is feasible, safe, and can be executed within a short overall procedure duration.
PubMed: 38917059
DOI: 10.1093/europace/euae176 -
Europace : European Pacing,... Jun 2024Technological advancements have contributed to the enhanced precision and lesion flexibility in pulsed-field ablation (PFA) by integrating a three-dimensional mapping...
AIMS
Technological advancements have contributed to the enhanced precision and lesion flexibility in pulsed-field ablation (PFA) by integrating a three-dimensional mapping system combined with a point-by-point ablation strategy. Data regarding the feasibility of this technology remain limited to some clinical trials. This study aims to elucidate initial real-world data on catheter ablation utilizing a lattice-tip focal PFA/radiofrequency ablation (RFA) catheter in patients with persistent atrial fibrillation (AF).
METHODS AND RESULTS
Consecutive patients who underwent catheter ablation for persistent AF via the lattice-tip PFA/RFA catheter were enrolled. We evaluated acute procedural data including periprocedural data as well as the clinical follow-up within a 90-day blanking period. In total, 28 patients with persistent AF underwent AF ablation either under general anaesthesia (n = 6) or deep sedation (n = 22). In all patients, pulmonary vein isolation was successfully achieved. Additional linear ablations were conducted in 21 patients (78%) with a combination of successful anterior line (n = 13, 46%) and roof line (n = 19, 68%). The median procedural and fluoroscopic times were 97 (interquartile range, IQR: 80-114) min and 8.5 (IQR: 7.2-9.5) min, respectively. A total of 27 patients (96%) were interviewed during the follow-up within the blanking period, and early recurrent AF was documented in four patients (15%) including one case of recurrent AF during the hospital stay. Neither major nor minor procedural complication occurred.
CONCLUSION
In terms of real-world data, our data confirmed AF ablation feasibility utilizing the lattice-tip focal PFA/RFA catheter in patients with persistent AF.
Topics: Humans; Atrial Fibrillation; Male; Catheter Ablation; Female; Middle Aged; Treatment Outcome; Aged; Pulmonary Veins; Equipment Design; Cardiac Catheters; Recurrence; Time Factors
PubMed: 38916275
DOI: 10.1093/europace/euae129 -
Cureus Jun 2024Cardiac computed tomography (CT) images sometimes show a donut-like oval structure on the antero-superior wall of the left atrium (LA). What is a donut? Left atrium...
Cardiac computed tomography (CT) images sometimes show a donut-like oval structure on the antero-superior wall of the left atrium (LA). What is a donut? Left atrium diverticula (LADs) are common, but there are many unknown features of LADs. The direct effects of pulmonary vein thrombi (PVTs) on the heart are poorly understood. Herein, we report a case report in which we describe the different effects of edoxaban on LA thrombi, the LAD, coronary artery collaterals, early repolarizations, and end-QRS notches using cardiac CT and transesophageal echocardiography (TEE). First, we showed that there was a LAD on the anterior wall of the LA where the LA thrombi from the right lower pulmonary vein (RLPV) thrombi were connected. To our knowledge, this is the first report to reveal LAD's annular transformation and the beneficial effect of edoxaban on the end-QRS notch.
PubMed: 38915833
DOI: 10.7759/cureus.62962 -
Cureus Jun 2024The interaction between the right upper pulmonary vein (RUPV) and the right lower pulmonary vein (RLPV) is poorly understood. In this paper, using transesophageal...
The interaction between the right upper pulmonary vein (RUPV) and the right lower pulmonary vein (RLPV) is poorly understood. In this paper, using transesophageal echocardiography (TEE) and 80-slice multidetector computed tomography (80-MDCT), we report that the RUPV thrombi and the RLPV thrombi invade the left atrium (LA) and reach the anterior wall of the LA. To our knowledge, this is the first study to directly show the connection between the RUPV thrombi and the RLPV thrombi on the anterior wall of the LA using TEE and 80-MDCT.
PubMed: 38915832
DOI: 10.7759/cureus.62959 -
Self-sealing atrio-oesophageal fistula as a complication of pulmonary vein isolation: a case report.European Heart Journal. Case Reports Jun 2024Atrio-oesophageal fistulas (AEFs) are an uncommon complication of pulmonary vein ablation, and its diagnosis is challenging. Multidisciplinary interventions and...
BACKGROUND
Atrio-oesophageal fistulas (AEFs) are an uncommon complication of pulmonary vein ablation, and its diagnosis is challenging. Multidisciplinary interventions and diagnostic imaging are usually required and may play a role in the initial assessment.
CASE SUMMARY
A 69-year-old female with atrial fibrillation who had undergone recent pulmonary vein ablation consulted with unspecific symptoms and sudden hemiparesis. Brain imaging showed pneumocephalus and acute infarcts. Chest computed tomography (CT) was highly suspicious for AEF. Surgical exploration revealed a swollen mediastinum attached to the right inferior pulmonary vein.
DISCUSSION
Non-specific symptoms after pulmonary vein ablation should prompt the suspicion of complications. In the presence of fever or neurological deficit, AEF must be suspected and assessed with a contrast-enhanced chest CT, which has become the gold standard. In brain imaging, pneumocephalus and multiple punctate acute infarcts might also indicate the presence of this complication.
PubMed: 38915738
DOI: 10.1093/ehjcr/ytae283 -
Chinese Medical Journal Jun 2024
PubMed: 38915226
DOI: 10.1097/CM9.0000000000003194 -
Acta Pharmacologica Sinica Jun 2024Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have obvious advantages over MSC therapy. But the strong procoagulant properties of MSC-EVs pose a...
Lethal pulmonary thromboembolism in mice induced by intravenous human umbilical cord mesenchymal stem cell-derived large extracellular vesicles in a dose- and tissue factor-dependent manner.
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have obvious advantages over MSC therapy. But the strong procoagulant properties of MSC-EVs pose a potential risk of thromboembolism, an issue that remains insufficiently explored. In this study, we systematically investigated the procoagulant activity of large EVs derived from human umbilical cord MSCs (UC-EVs) both in vitro and in vivo. UC-EVs were isolated from cell culture supernatants. Mice were injected with UC-EVs (0.125, 0.25, 0.5, 1, 2, 4 μg/g body weight) in 100 μL PBS via the tail vein. Behavior and mortality were monitored for 30 min after injection. We showed that these UC-EVs activated coagulation in a dose- and tissue factor-dependent manner. UC-EVs-induced coagulation in vitro could be inhibited by addition of tissue factor pathway inhibitor. Notably, intravenous administration of high doses of the UC-EVs (1 μg/g body weight or higher) led to rapid mortality due to multiple thrombus formations in lung tissue, platelets, and fibrinogen depletion, and prolonged prothrombin and activated partial thromboplastin times. Importantly, we demonstrated that pulmonary thromboembolism induced by the UC-EVs could be prevented by either reducing the infusion rate or by pre-injection of heparin, a known anticoagulant. In conclusion, this study elucidates the procoagulant characteristics and mechanisms of large UC-EVs, details the associated coagulation risk during intravenous delivery, sets a safe upper limit for intravenous dose, and offers effective strategies to prevent such mortal risks when high doses of large UC-EVs are needed for optimal therapeutic effects, with implications for the development and application of large UC-EV-based as well as other MSC-EV-based therapies.
PubMed: 38914677
DOI: 10.1038/s41401-024-01327-3