Arterial Thrombosis Research Articles

Angiographic findings of pulmonary arterial involvement in Behcet's Disease: Do they correlate with symptoms and acute phase response?

IntroductionBehcet's disease (BD) is a chronic inflammatory disorder with arterial vasculitis. Although, pulmonary artery aneurysm (PAA) is accepted as the prototypic arterial disorder, an increasing presence of pulmonary artery thrombosis (PAT) with or without aneurysms was also reported in recent studies. In this study, we aimed to describe computed tomography pulmonary angiography (CTPA) findings of pulmonary involvement and its correlation with symptoms and acute phase response in BD. MethodIn this retrospective study, 153 CTPA of BD patients were assessed by two radiologists. Clinical and laboratory data were collected from the patient files. Pulmonary artery involvement (PAI) was defined as thrombus or aneurysm in CT angiography. ResultsMost of (85.6 %) our patients were male and median age was 33.7 ± 10 years during angiographic assessments. Sixty-two (40.5 %) angiographies presented a thrombus: 14 subsegmental, 29 segmental, 13 lobar and 6 main branches. Among these, 82.3 % (n = 51) had bilateral involvement. Isolated PAT was present in 58 (93.5 %) angiographies with only 4 (2.6 %) angiographies displaying an aneurysm together with a thrombus. Pulmonary infarction was detected in 9 angiographies. Forty-four (29.3 %) patients, almost all of them under immunosuppressive treatments for other indications, were screened for asymptomatic pulmonary involvement (without any symptoms or increased acute-phase response (APR)), and one fourth of these were diagnosed as having a segmental or subsegmental PAT. ConclusionOur results show that isolated pulmonary thrombosis is the main form of PAI, and isolated pulmonary aneurysm formation is rare in our BD cases. In the presence of pulmonary symptoms with or without increased APRs, involvement of segmental or more proximal parts of pulmonary arteries is most commonly detected. We also observed that PAI may be seen in about one fourth of especially male BD patients without symptoms or increased APR. Our results suggest that BD patients with pulmonary symptoms should be screened by CTPA for PAI, however, further research is needed to clarify the role of routine CTPA screening in asymptomatic BD patients.

Surviving Multiple Cardiac Arrests Secondary to Catastrophic Sero-Negative Antiphospholipid Syndrome: A Case Report

Antiphospholipid syndrome (APS) is an autoimmune disorder which predisposes to venous and arterial thrombosis due to the autoantibodies targeting phospholipids in cell membranes contributing to a pro-thrombotic state. The appropriately named catastrophic anti-phospholipid syndrome (CAPS) is distinguished from classical APS by the rapid involvement of 3+ organs, evidence of areas of small vessel occlusions, and significantly elevated anti-phospholipid titers (Cervera, 2018). To further complicate the matter, there is a growing body of evidence of the existence of sero-negative APS (SNAPS) that are negative for the classical lupus anticoagulant, anticardiolipin antibody (aCL), and anti-beta2 glycoprotein-I but may be positive for non-criteria APS antibodies. Presented below is a patient with SNAPS who responded to the therapy for CAPS despite negative classical autoantibodies. A 34 year old man with a past medical history of chronic alcohol use presented to the ED with a two day history of worsening shortness of breath. The patient was found to have an spO2 of 45-50% on room air and was quickly transitioned to a non-rebreather and subsequently BIPAP. Initial CBC was significant for WBC 22.1, Hg 19.3, Hct 58.5, MCV 100.8, and platelets of 166 consistent with neutrophilic leukocytosis and macrocytic polycythemia. D-dimer >20 was suggestive recent/on-going coagulation and/or fibrinolysis. Due to worsening respiratory failure, he was intubated and admitted to the ICU. While on 3 vasopressors he became bradycardic and a code blue was called for pulseless electrical activity (PEA). After 3 rounds of CPR he achieved return of spontaneous circulation (ROSC) and was taken for urgent CT imaging. After arriving in the radiology department he went into cardiac arrest for two rounds of CPR before achieving ROSC and being scanned and returning to the ICU. Polycythemia tests were drawn which revealed elevated erythropoietin of 52.1 (2.6-18.5) and ultimately negative JAK2. Chest CTA was significant for a PE with a heavy clot burden involving the entire right lung and the left upper and lower lobes. CT C/A/P showed findings of bilateral lower lobe pneumonia, severe gastritis, pancolitis, proctitis, pancreatitis with a 4.6cm pseudocyst, and fatty liver with congestive enhancement. Tissue-type plasminogen activator (tPA) bolus and infusion was initiated based on the imaging findings with the third cardiac arrest occurring 7 minutes later early in the morning. Repeat CBC revealed an Hgb/Hct of 22.2 g/dL and 71.5%, respectively, with a significant drop in platelets down to 103 with occasional large platelets consistent with peripheral destruction of platelets was noted on peripheral blood smear (PBS). Therapeutic phlebotomy of 300mL was subsequently performed with two additional cardiac arrests within 2 hours of each other before vascular surgery was able to perform thrombectomies of the involved pulmonary arteries and initiate catheter-directed thrombolysis. Platelet count dropped while on heparin to 25,000 so a HIT panel was ordered and he was transitioned to argatroban. At this point hematology was consulted who was concerned for CAPS and ordered aPL (anti-phospholipid) tests along with an appropriate panel of labs to rule out alternative causes. Peripheral blood smear did not reveal fragmentation of RBC to suspect TTP. Tests for ACL IgG/IgM and anti-beta2GPI IgG/IgM antibodies, COVID, HIV, ADAMTS deficiency, hereditary thrombophilia, and ANA were negative. High-dose steroids and daily plasma exchanges via vascath was initiated and within 12 hours there was significant improvement. He was extubated and off pressors in 24 hours with improved platelets. Lupus anticoagulant test results were reported after discharge with dVVT mix and PTT LA mix both being prolonged, however, repeat lupus anticoagulant 3 months later was negative. Given the potentially catastrophic effects of a missed CAPS diagnosis, a high level of clinical suspicion is needed as plasma exchange can quickly alleviate an otherwise disastrous condition. Further research into non-criteria APS autoantibodies (IgA)may be able to help guide future SNAPS diagnoses.

Meta-Analysis of National-Level Genotyping Datasets to Determine the Risk of Thrombosis in Double Heterozygous Carriers of Factor V Leiden and the Prothrombin G20210A Mutation across 876,417 Individuals

Introduction Factor V Leiden (FVL) and the prothrombin G20210A mutation (PTGM) are well-known genetic risk factors for venous thrombosis. However, the clinical significance of double heterozygosity (DH) for FVL and PTGM remains poorly understood. Prior studies of the DH genotype have produced varying risk estimates and were limited by small sample size, heterogenous case and control groups, inclusion restricted to patients presenting for medical attention, and a lack of adjustment for potential confounders. Leveraging deeply-phenotyped, population-scale genomic datasets offers a unique opportunity to surmount these shortcomings and arrive at a more robust estimate of the risk experienced by DH individuals. Methods We utilized two large-scale population-level registries with paired genetic and phenotypic data: the UK Biobank (UKBB) and the FinnGen project. Our analyses focused on 6 genotypes: FVL heterozygous (FVL het), PTGM heterozygous (PTGM het), FVL homozygous (FVL hom), PTGM homozygous (PTGM hom), double heterozygous (DH), and wild-type for both PTGM and FVL (WT). Four thrombotic phenotypes were evaluated, including stroke (CVA), myocardial infarction (MI), peripheral artery disease (PAD), and venous thromboembolism (VTE). Multivariate Firth's logistic regression models adjusting for age, sex, and principal components of ancestry were used to assess risk of thrombotic events between genotypic groups. Sensitivity analyses included 1) restricting the Firth's regression to unrelated participants, and 2) controlling for additional covariates including body mass index (BMI), blood group, smoking status, platelet count, and C-reactive protein (CRP). An additional interaction term for the FVL and PTGM mutations was examined to evaluate whether the two variants functioned in an additive or multiplicative manner. The results were combined using random-effects meta-analysis. Rates of incident VTE were compared between WT and DH individuals using Cox proportional hazards regression and Kaplan Meier analysis. Results In total, we analyzed 485,835 individuals in the UKBB and 390,582 individuals in the FinnGen project. Between the two cohorts, 806,273 individuals were WT, 13,683 were PTGM het, 69 were PTGM hom, 36,600 were FVL het, 402 were FVL hom, and 646 were double heterozygous. As expected, after adjustment for age, sex, and ancestry, an increased risk of VTE was associated with PTGM het (OR = 1.88, 95% CI: 1.56 - 2.26, p = 2.7 x 10 -11) and FVL het (OR = 2.27, 95% CI: 2.03 - 2.54, p = 1.5 x 10 -47) relative to the WT genotype. By contrast, individuals with the DH genotype demonstrated a markedly higher VTE risk relative to WT than either singly heterozygous genotype (OR = 5.24, 95% CI: 3.99 - 6.89, p = 1.4 x 10 -32) ( Figure 1). None of the mutant genotypes was associated with a significantly increased risk of CVA, MI, or PAD, except FVL het carriers experienced a marginally increased risk for PAD, as previously described (OR = 1.17, 95% CI: 1.10 - 1.24, p = 5.2 x 10 -7) ( Figure 2). Estimates for VTE risk associated with the DH genotype were not appreciably different after restricting the analysis to unrelated individuals (OR=5.66, 95% CI: 3.65-8.77, P = 9.7 x 10 -15) or adjusting for additional risk factors (OR=4.40, 95% CI: 3.33-5.72, P = < 1.0 x 10 -16). While VTE risk in individuals with DH genotype appeared additive, we observed a statistically significant interaction term for the two constituent genotypes (OR = 1.3, 95% CI: 1.05 - 1.60, p = 0.017). This finding suggests that although there is a statistically significant multiplicative interaction between the two mutations, they likely behave in an additive manner for the purposes of clinical care. Finally, we found that the rate of incident VTE was significantly higher among PTGM het individuals (P=8.5 x 10 -15), FVL het individuals (P <2 x 10 -16), and DH individuals (P=7.6 x 10 -5) compared to those with the WT genotype. Conclusion and Relevance We have conducted the largest study to date of double heterozygosity for FVL and PTGM. After adjustment for common confounders, DH individuals demonstrate an increased risk of VTE relative to singly heterozygous individuals. By contrast, we found no evidence that DH individuals are at significantly increased risk for arterial thrombosis. Our work may help resolve longstanding uncertainty around the clinical impact of the DH genotype on thrombotic risk.

Estimating the Burden of Venous and Arterial Thrombotic Events in Hospitalized Adults with COVID-19; A National Multicenter Cohort Study

Background: Patients infected with Coronavirus Disease 2019 (COVID-19) have clinical and laboratory features consistent with a hypercoaguable state, particularly in more severely ill patients that require hospitalization. However, estimates of thrombotic complications in this high risk population vary widely. A geographic representative cohort to explore the rates of thrombotic events in patients hospitalized with COVID-19 in the United States would be useful to better understand the burden of thrombosis in this population. We aimed to assess the rates of venous and arterial thrombosis events during hospitalization in patients with COVID-19 in a national multicenter cohort study. Methods: We conducted a retrospective cohort study of hospitalized patients diagnosed with COVID-19 from January 1 2020 to January 2023. IRB approval was obtained at each site. Inclusion criteria included adults (> 21 years), hospitalized for >1 day and laboratory confirmation of polymerase chain reaction testing of severe acute respiratory syndrome coronavirus 2. Data were extracted by participating centers in a pre-specified instrument from the electronic medical record at each institution and pooled prior to analysis. Data sources included manual extraction by study investigators in 7 sites and electronic extraction based on billing codes at one site (Cleveland Clinic). Primary outcome was venous thrombotic events, including deep vein thrombosis (DVT), pulmonary embolism (PE). Unusual sites including splanchnic vein thrombosis and cerebral venous thrombosis were included if objectively demonstrated on imaging. Arterial thrombotic events including ischemic stroke, acute coronary syndrome were included as secondary outcomes. Data are presented as proportions, with binomial 95% confidence intervals (CI). Results: We included 33,769 patients from eight medical centers across the United States. Participating hospitals included all four census regions from the North East (Beth Israel Deaconess Medical Center, MA (n=1021) Rochester Regional Hospital, NY (n=99)), South (John Hopkins Medical Institute, ML (n=334); Baycare Health System, FL (n=3734), MidWest (Cleveland Clinic Foundation, OH (n=25467); Henry Ford Health System, MI (973); University of Illinois, IL (1192)) and West (University of California, CA (n=613)). (Figure) Of the total 33,433 hospitalized patients with COVID-19 included, 1684 patients developed a venous thrombotic event during the index hospitalization (5.0%, 95% CI 4.8-5.2) and 261 developed an arterial thrombotic event (0.8%, 95% CI, 95% CI 0.7-0.9). Rates of venous events by individual sites ranged from 2.6-8% and arterial events from 0.3-6.6%. Conclusion: In this national multicenter cohort study that included academic and community hospitals from all four US census regions, we estimated the rates of VTE were over five times more frequent than arterial events in hospitalized patients with COVID-19. Accurate estimates of thrombotic rates and trends can help plan targeted interventions related to strategies around thromboprophylaxis interventions and resource allocation for future surges of COVID-19 cases.

High Risk of Thrombosis in a Prospective Cohort of Adults with Primary Immune Thrombocytopenia

Background: Patients with primary Immune thrombocytopenia (ITP) have an increased risk of bleeding but paradoxically also an increased thromboembolic risk. Aim: The aim of this study was to prospectively assess the occurrence and risk factors of symptomatic venous thrombotic events (VTE) and arterial thrombotic events (ATE) in patients with primary immune thrombocytopenia. Methods: This study included 160 adult patients with primary ITP enrolled in the Vienna ITP Biobank, a dual-center cohort study (Medical University of Vienna; Hanusch Hospital) that prospectively collects data of patients diagnosed with primary ITP (EC 1843/2016). Patients with primary ITP and a history of VTE or ATE, as well as those who experienced new or recurrent thrombotic events (TE) during the observation period, were categorized into two groups: with-thrombosis and without-thrombosis. The patient characteristics were compared using a chi-squared or Fisher's exact test for categorical and for numerical data were performed using the Mann-Whitney-U-test. The association between clinical risk factors and thrombosis were performed by univariable analyses using logistic regression model. Results: Of the 160 ITP patients (Table 1), 22 patients (13.8%) had 25 documented ATE or VTE. These events consisted of 11 ATE (44%), including 7 acute myocardial infarctions, 3 cerebral vascular events (stroke or TIA), and 1 peripheral artery thrombosis, and 14 (65%) venous events (1 superficial vein thrombosis, 7 deep vein thromboses, 2 deep vein thromboses with pulmonary embolism and 4 cases of isolated pulmonary embolism). 8 (36.4%) of 22 patients had a history of thrombosis. 17 (77.3%) patients experienced TE during the median observation period of 2.2 (1-3) years. Of them 14 (82.4%) patients had a new TE and 3 (17.6%) recurrent TE. The cumulative 1- and 5-year incidence of TE accounting for competing mortality were 1.9 % and 5.0%. Four (18.2%) patients with thrombosis died during the follow-up period. The cause of death was unclear for three patients, while one patient died from pulmonary embolism. Patients with thrombosis were significantly older (p=0.001) and had more comorbidities than patients without thrombosis (Table 1). There was no difference in the platelet counts between the groups. Antiphospholipid antibodies were present in 14.4% of the patients, and their prevalence was higher in the thrombosis group (p=0.002). In the univariable regression analysis, factors such as older age ≥75 years (OR 1.06; 95%CI 1.03-1.09, p=0.001) diabetes mellitus (OR 4.02; 95%CI 1.20-13.413, p=0.024), presence of antiphospholipid antibodies (OR 6.04; 95%CI 2.01-25.63, p=0.003), particularly lupus anticoagulant positivity (OR 5.39 95%CI 1.8-13.0, p=0.002), and splenectomy (OR 3.07; 95%CI 1.13-12.63, p=0.031) were significantly associated with a higher risk of arterial and venous thrombotic events among ITP patients. Body-Mas-Index, disease duration, tobacco use, hypertension, and use of corticosteroids or thrombopoietin receptor agonist (TPO-RA) were not associated with increased risk of VTE and ATE. Conclusion: We observed a high rate of ATE and VTE in our patients with primary ITP. Additionally, ITP patients commonly present with typical risk factors for thrombotic events, suggesting a strict management of cardiovascular risk factors. Close monitoring and tailored treatment strategies should minimize the risk of bleeding and thrombotic events.

Antiplatelet Agents Inhibit Platelet Adhesion and Aggregation on Glass Surface Under Physiological Flow Conditions: Toward a Microfluidic Platelet Functional Assay Without Additional Adhesion Protein Modification.

As the pathogenesis of arterial thrombosis often includes platelet adhesion and aggregation, antiplatelet agents are commonly used to prevent thromboembolic events. Here, a new microfluidic method without additional adhesion protein modification was developed to quantify the inhibitory effect of antiplatelet drugs on the adhesion and aggregation behavior of platelets on glass surfaces under physiological flow conditions. Polydimethylsiloxane-glass microfluidic chips were fabricated by soft photolithography. Blood samples from healthy volunteers or patients before and after taking antiplatelet drugs flowed through the microchannels at wall shear rates of 300 and 1500 second -1 , respectively. The time to reach 2.5% platelet aggregation surface coverage (Ti), surface coverage (A 150s ), and mean fluorescence intensity (F 150s ) were used as quantitative indicators. Aspirin (80 μM) prolonged Ti and reduced F 150s . Alprostadil, ticagrelor, eptifibatide, and tirofiban prolonged Ti and reduced A 150s and F 150s in a concentration-dependent manner, whereas high concentrations of alprostadil did not completely inhibit platelet aggregation. Aspirin combined with ticagrelor synergistically inhibited platelet adhesion and aggregation; GPIb-IX-von Willebrand factor inhibitors partially inhibited platelet aggregation, and the inhibition was more pronounced at 1500 than at 300 second -1 . Patient administration of aspirin or (and) clopidogrel inhibited platelet adhesion and aggregation on the glass surface under flow conditions. This technology is capable of distinguishing the pharmacological effects of various antiplatelet drugs on inhibition of platelet adhesion aggregation on glass surface under physiological flow conditions, which providing a new way to develop microfluidic platelet function detection method without additional adhesive protein modification for determining the inhibitory effects of antiplatelet drugs in the clinical setting.

Antiphospholipid Antibodies and Vascular Thrombosis in Patients with Severe Forms of COVID-19.

Antiphospholipid antibodies (aPLA) are a laboratory criterion for the classification of antiphospholipid syndrome (APS) and are known to cause clinical symptoms such as vascular thrombosis or obstetric complications. It is suggested that aPLA may be associated with thromboembolism in severe COVID-19 cases. Therefore, we aimed to combine clinical data with laboratory findings of aPLA at four time points (admission, worsening, discharge, and 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. In 111 patients with COVID-19 pneumonia, current and past history of thrombosis and pregnancy complications were recorded. Nine types of aPLA were determined at four time points: anticardiolipin (aCL), anti-β2-glycoprotein I (anti- β2GPI), and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG, or IgA isotypes. During hospitalization, seven patients died, three of them due to pulmonary artery thromboembolism (none were aPLA positive). Only one of the five who developed pulmonary artery thrombosis was aPLA positive. Out of 9/101 patients with a history of thrombosis, five had arterial thrombosis and none were aPLA positive at admission and follow-up; four had venous thrombosis, and one was aPLA positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPLA positive at discharge only, compared to 26.1% without a history of thrombosis (p = 0.041). Patients with severe forms of COVID-19 and positive aPLA should receive the same dose and anticoagulant medication regimen as those with negative aPLA because those antibodies are mostly transiently positive and not linked to thrombosis and fatal outcomes.

Prevalence of Thromboembolic Events, Including Venous Thromboembolism and Arterial Thrombosis, in Patients with COVID-19: A Systematic Review with Meta-Analysis.

Many studies have evaluated thromboembolic events in COVID-19 patients, and most of them have reported a high estimation of the prevalence of such events. The present study sought to evaluate the prevalence of thromboembolic events in patients with COVID-19. This study is a systematic review with meta-analysis that investigated thromboembolic events in patients with COVID-19 from the start of the pandemic to August 31, 2021. The 4 main databases for collecting articles were Medline, Scopus, Google Scholar, and Web of Science. Deep vein thrombosis, pulmonary embolism, arterial thrombosis, and the overall rate of thromboembolic events were considered primary outcomes. In a total of 63 studies (104 920 patients with COVID-19), the overall thrombosis rate was 21% (95% CI, 18% to 25%), the rate of deep vein thrombosis was 20% (95% Cl, 16% to 25%), the rate of pulmonary embolism was 8% (95% Cl, 6% to 10%), and the rate of arterial thrombosis was 5% (95% Cl, 3% to 7%). The prevalence of all primary outcomes in critically ill patients admitted to the intensive care unit (ICU) was significantly higher (P<0.05). In older patients, the prevalence of overall thrombosis, pulmonary embolism, or deep vein thrombosis was significantly higher (P<0.05). This study showed that COVID-19 increases the risk of thromboembolic events, especially in elderly and critically ill patients admitted to the ICU. Therefore, more strategies are needed to prevent thromboembolic events in patients with COVID-19, especially in ICU-admitted and elderly patients.

Differential vascular endothelial cell toxicity of established and novel BCR-ABL tyrosine kinase inhibitors.

BCR-ABL tyrosine kinase inhibitors (TKIs) have dramatically improved survival in Philadelphia chromosome-positive leukemias. Newer BCR-ABL TKIs provide superior cancer outcomes but with increased risk of acute arterial thrombosis, which further increases in patients with cardiovascular comorbidities and mitigates survival benefits compared to imatinib. Recent studies implicate endothelial cell (EC) damage in this toxicity by unknown mechanisms with few side-by-side comparisons of multiple TKIs and with no available data on endothelial impact of recently approved TKIs or novels TKIs being tested in clinical trials. To characterize BCR-ABL TKI induced EC dysfunction we exposed primary human umbilical vein ECs in 2D and 3D culture to clinically relevant concentrations of seven BCR-ABL TKIs and quantified their impact on EC scratch-wound healing, viability, inflammation, and permeability mechanisms. Dasatinib, ponatinib, and nilotinib, the TKIs associated with thrombosis in patients, all significantly impaired EC wound healing, survival, and proliferation compared to imatinib, but only dasatinib and ponatinib impaired cell migration and only nilotinib enhanced EC necrosis. Dasatinib and ponatinib increased leukocyte adhesion to ECs with upregulation of adhesion molecule expression in ECs (ICAM1, VCAM1, and P-selectin) and leukocytes (PSGL1). Dasatinib increased permeability and impaired cell junctional integrity in human engineered microvessels, consistent with its unique association with pleural effusions. Of the new agents, bafetinib decreased EC viability and increased microvessel permeability while asciminib and radotinib did not impact any EC function tested. In summary, the vasculotoxic TKIs (dasatinib, ponatinib, nilotinib) cause EC toxicity but with mechanistic differences, supporting the potential need for drug-specific vasculoprotective strategies. Asciminib and radotinib do not induce EC toxicity at clinically relevant concentrations suggesting a better safety profile.

NDUFB11 and NDUFS3 regulate arterial atherosclerosis and venous thrombosis: Potential markers of atherosclerosis and venous thrombosis.

Atherosclerosis is a chronic disease that thickens the blood vessel walls and narrows the lumen. Venous thrombosis is a blood clot that forms in the body's deep veins or pulmonary arteries. However, the relationship between NDUFB11 and NDUFS3 and atherosclerosis and venous thrombosis is unclear. We employed data files that combined atherosclerosis and chronic stress groups. Subsequently, we conducted differential gene expression analysis (DEGs) and performed weighted gene co-expression network analysis (WGCNA). We constructed and analyzed a protein-protein interaction (PPI) network. Further analyses included functional enrichment analysis, gene set enrichment analysis (GSEA), gene expression heatmaps, immune infiltration analysis, and mRNA analysis. By comparing our findings with the Comparative Toxicogenomics Database (CTD), we identified the most relevant diseases associated with the core genes. Additionally, we utilized TargetScan to screen for miRNAs regulating the central DEGs. To validate our results, we conducted Western Blot experiments at the cellular level. A total of 1747 DEGs were co-identified. According to the Gene Ontology (GO) analysis of differentially expressed genes, they were primarily enriched in mitochondrial gene expression, mitochondrial envelope, organelle membrane, and mitochondrial inner membrane categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target cells were mainly enriched in metabolic pathways, ribosomes, and histidine metabolism. The intersection of enriched terms from both GO and KEGG analyses showed significant enrichment in mitochondrial gene expression, mitochondrial envelope, organelle inner membrane, ribosomal structural constituents, histidine metabolism, and oxidative phosphorylation. Eight core genes were identified, including NDUFS5, UQCRQ, COX6C, COX7B, ATP5ME, NDUFS3, NDUFA3, and NDUFB11. The gene expression heatmap demonstrated that core genes (NDUFB11 and NDUFS3) were downregulated in atherosclerosis with venous thrombosis samples and upregulated in normal samples. CTD analysis revealed that the core genes NDUFB11 and NDUFS3 were associated with pain, arterial diseases, atherosclerosis, arteritis, venous thrombosis formation, and venous thromboembolism. We added Western Blot basic cell experiment for verification. NDUFB11 and NDUFS3 are downregulated in atherosclerosis and venous thrombosis, associated with poorer prognosis, and may serve as potential biomarkers for both diseases.

Characterization of the plasminogen activator inhibitor type 1 gene (PAI-1) and its role in the development of arterial thrombosis

Characterization of the plasminogen activator inhibitor type 1 gene (PAI-1) and its role in the development of arterial thrombosis

Enhanced recovery after surgery (ERAS) in sacral tumour surgery and comprehensive description of a multidisciplinary program: a prospective study in a specialized hospital in China.

There were fewer data to guide the application of enhanced recovery after surgery (ERAS) theory into sacral tumour surgery. In the present study, we were aiming to describe a multidisciplinary program of ERAS and evaluate the availability in sacral tumour surgery. This was a prospective study of patients with sacral tumour between March 2021 and September 2021 at a single centre. We proposed a multidisciplinary program of ERAS for pre-admission, preoperative, intraoperative, postoperative, and post-discharge clinical care which positively influenced outcomes of patients with sacral tumour. All patients were prospectively assigned into two groups, ERAS group in which patients received ERAS protocols (n = 63), No-ERAS group in which patients had conventional clinical pathways (n = 62). Patient data were collected which included demographics, preoperative preparation, detailed information of surgical procedure, 60-day reoperation rate, 60-day readmission, postoperative length of stay (PLOS), time to first ambulation and flatus after surgery, time to removal of last drainage tube, and visual analogue scale (VAS) score at first ambulation and discharge. Complications referred to ones that occurred within 60 days after surgery. The above parameters were compared between ERAS group and No-ERAS group. Time to first ambulation after surgery in ERAS group (mean 20.9 h) was significantly shorter than that in No-ERAS group (mean 104.3 ho). Meanwhile, time to first flatus after surgery in ERAS group (mean 26.7 h) was also significantly shorter than that in No-ERAS group (mean 37.3 h). Patients in ERAS group had statistically shorter PLOS (10.7 days) as compared to that in No-ERAS group (13.8 days). In ERAS group, 19 of 63 patients (30.2%) were discharged within seven days after surgery as compared to seven of 62 patients (11.3%) in No-ERAS group. VAS score at first ambulation in ERAS group was not obviously higher than that in No-ERAS group though the time of first ambulation in ERAS group was statistically earlier than one in No-ERAS group. Furthermore, VAS score at discharge in ERAS group was significantly lower than that in No-ERAS group. The rate of postoperative incision necrosis was 6.3% (4/63) in ERAS group and 8.1% (5/62) in No-ERAS group and all of these nine patients underwent reoperation before discharge. The difference was not statistically significant in the wound complication of incision necrosis and 60-day reoperation rate. Only one readmission occurred in No-ERAS group due to the surgical site infection and also there was no significant difference of 60-day readmission rate between these two groups. Furthermore, there was no statistical difference of complications of femoral artery thrombosis and rectal rupture between ERAS group and No-ERAS group. Our proposed ERAS pathway for sacral tumour surgery and early walking facilitate safe and prompt discharge. ERAS protocols of sacral tumour surgery could decrease PLOS without significantly increasing postoperative complications, 60-day readmission rate and 60-day reoperation rate. The application of ERAS pathway in the field of sacral tumour surgery should have personalized feature with regard to resection type.

Normothermic Regional Perfusion in Controlled Donation After Circulatory Determination of Death Simultaneous Pancreas – Kidney Transplantation

Simultaneous pancreas-kidney transplantation is the optimal treatment for patients with type 1 diabetes and renal failure. The use of pancreas grafts from donation after circulatory death (DCD), using normothermic regional perfusion (NRP), is still marginal worldwide, mainly due to possible additional risks of graft dysfunction and complications compared with grafts from donors after brain death. Case series of patients who underwent simultaneous pancreas-kidney transplantation after DCD-NRP between January 2018 and September 2022. This study evaluated early postoperative grafts and survival outcomes. Four patients were included. One patient lost the pancreatic graft due to arterial thrombosis requiring transplantectomy. Another patient required a laparotomy due to hemoperitoneum. Overall, 1-year pancreas and kidney graft survival was 75% and 100%, respectively. One patient developed a lymphoma during the follow-up. The use of pancreas grafts from DCD after NRP preservation is safe and feasible. Comparative studies with donors after brain death grafts and larger series are required to confirm the feasibility of DCD-NRP pancreas transplantation.

Emergency Liver Retransplantation With Marginal Donors

The goal of the present study is to determine if using marginal donors negatively impacts the outcomes of emergency liver retransplantation. A retrospective case-control study was performed, including all emergency liver retransplantations done in our center between 1990 and 2021. Recipients from the control group received the second grafts from "ideal donors", and patients from the case group received them from marginal donors. Analyzed variables included demographics of recipients and donors, complications, and survival rates. 38 emergency retransplantations were performed. 23 recipients were included in the control group, and the remaining 15 were in the case group. The second donors from the case group were significantly older (mean age 58 vs 71 years old, P < 0.0001). On the contrary, there were no differences between groups regarding the mean age of recipients, comorbidities, Model for End-Stage Liver Disease scores, or causes of retransplantation (the most common was hepatic artery thrombosis). No differences were found in early perioperative death rates (control group 26.1% vs case group 20%, P =1) and, although the case group seemed to have slightly poorer outcomes in long-term survival (control group 70%, 61%, and 55% vs case group 73%, 59%, and 39%, respectively, at 1, 5, and 10 years), the differences were not statistically significant (log-rank=0.808). The use of marginal donors for emergency liver retransplantation was proved safe in our study, as there were no differences in complications or in short- or mid-term survival rates.

Clinical analysis of twenty-one cases of acute ischemic stroke related to Trousseau syndrome.

Trousseau syndrome (TS) is relatively rare and easily overlooked by clinicians, causing misdiagnosis and affecting subsequent treatment. In this study, clinical features, laboratory examination, imaging features, treatment, and prognosis of patients with TS were discussed. From February 2018 to April 2022, cases of 21 patients with malignant tumors complicated by acute ischemic stroke (AIS) were admitted to the Neurology Department of the hospital, and were retrospectively analyzed and discussed based on the literature. Twenty-one cases were included in the study. Of these, 95.23% (20/21) developed AIS 6-21months after the onset of malignant tumors, 9.52% (2/21) had ischemic stroke as the first symptom, 4.76% (1/21) had recurrent ischemic stroke, and 14.29% (3/21) subsequently experienced venous and arterial thrombosis events; 80.95% (17/21) were pathologically confirmed to have adenocarcinoma; and 90.47% (19/21) of infarction cases involved multiple blood vessel feeding sites. MRI showed multiregional, multifocal patchy infarcts. D-dimer concentration was higher than normal in all patients. In addition, 61.90% (13/21) of the patients had poor outcomes according to mRS. TS is a rare clinical type. It is often associated with adenocarcinoma, and the treatment is different from that of conventional cerebral infarction and the prognosis is very poor. In clinical practice, for AIS of unknown cause, if MRI shows multiple small lesions accompanied by a significant increase in D-dimer, routine screening for latent malignant tumors is recommended.

Angiotensin-II for vasoplegia following cardiac surgery.

The objective of this study was to describe the implementation and outcomes of a protocol outlining angiotensin-II utilization for vasoplegia following cardiac surgery. This was a retrospective chart review at a single-center university hospital. Included patients received angiotensin-II for vasoplegia refractory to standard interventions, including norepinephrine 20mcg/min and vasopressin 0.04 units/min, following cardiac surgery between April 2021 and April 2022. 30 patients received angiotensin-II for refractory vasoplegia. Adjunctive agents at angiotensin-II initiation included corticosteroids (26 patients; 87%), epinephrine (26 patients; 87%), dobutamine (17 patients; 57%), dopamine (9 patients; 30%), milrinone (2 patients; 7%), and hydroxocobalamin (4 patients; 13%). At 3hours, the median mean arterial pressure increased from baseline (70 vs 61.5mmHg, p = .0006). Median norepinephrine doses at angiotensin-II initiation, 1hour, 3hours, and angiotensin-II discontinuation were 0.22, 0.16 (p = .0023), 0.10 (p < .0001), and 0.07 (p < .0001) mcg/kg/min. Median dobutamine doses decreased throughout angiotensin-II infusion from eight to six mcg/kg/min (p = .0313). Other vasoactive medication doses were unchanged. Three patients (10%) subsequently received hydroxocobalamin. Thirteen (43.3%) and five (16.7%) patients experienced mortality by day 28 and venous or arterial thrombosis events, respectively. The administration of angiotensin-II to vasoplegic patients following cardiac surgery was associated with increased mean arterial pressure, reduced norepinephrine dosages, and reduced dobutamine dosages.

Hematological disorders as a complication of COVID-19

Background. Coronavirus disease (COVID-19) can affect the blood and hemostasis systems and lead to complications that require intensive care. The aim is to detect such common complications by studying literary sources and clinical experience. Materials and methods. The search for relevant literature was conducted in PubMed, and in the other databases such as Science Direct, Google Scholar, Scopus and Web of Science. The literature search was done using the keywords “COVID-19”, “SARS-CoV-2” in combination with “coagulation dysfunction”, “coagulopathy”, “hematological manifestations”, “hematological parameters”, “deep vein thrombosis”, “pulmonary embolism”, “arterial thrombosis”, “D-dimer”, “fibrinogen”, “lymphopenia”, “thrombocytopenia”. Results. COVID-19-associated coagulopathy is characterized by high levels of D-dimer and fibrin degradation products in blood plasma, changes in prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count. Endothelial dysfunction caused by coronavirus leads to an increased risk of thrombotic complications, both in venous and arterial systems, additionally to the existing higher risk of thrombosis in the intensive care unit. The venous thromboembolism frequency among unvaccinated hospitalized patients and during ultrasound screening is significantly higher. Coronavirus disease can lead to arterial thrombosis in areas such as the aorta, kidneys, cerebral and peripheral arteries. COVID-19 can cause enhanced-fibrinolytic-type disseminated intravascular coagulation or limited thrombotic microangiopathy. According to research, patients with severe COVID-19 usually had leukocytosis, lymphopenia, and an elevated neutrophil-to-lymphocyte ratio. Thrombocytopenia is observed not only during the acute coronavirus disease, but also in the post-COVID-19 period. Both thrombosis and bleeding can occur in patients undergoing extracorporeal membrane oxygenation. Conclusions. A high level of D-dimer, a prolongation of prothrombin time, an increase or a quick decrease in fibrinogen level, lymphopenia, neutrophilia, and an increase in the neutrophil-to-lymphocyte ratio are considered prognostic factors for the severity of coronavirus disease. Deep vein thrombosis and pulmonary embolism are the most common thrombotic events in patients with COVID-19. Arterial thrombosis occurs more often in the cerebral arteries and arteries of the extremities.

Cardiovascular Effects of Anabolic-Androgenic Steroids in Dietary Supplements

Dietary supplements are regularly consumed by more than 70 % of the US population, as well as by competitive and non-competitive athletes. Anabolic-androgenic steroids (AAS) are frequently found in dietary supplements, and have the potential for multi-organ toxicity, including significant effects on the cardiovascular system. Cardiovascular toxicities of AAS include coronary artery effects, e.g. spasm, thrombosis and plaque rupture, leading to acute coronary syndromes and myocardial infarctions, as well as direct myocardial toxicity, causing left ventricular hypertrophy, fibrosis and dysfunction. Coronary and myocardial effects converge towards a common final pathway, causing heart failure, life-threatening arrhythmias and sudden cardiac death. The unregulated nature of AAS in dietary supplements has many ramifications. Both coaches and athletes should be aware that testing positive for a prohibited substance (including AAS) constitutes a potential doping violation. We advocate for improved education of the public at large regarding the potential for AAS to be included in dietary supplements, as well as its regulation by the appropriate authorities.

Reconstruction of the ulnar artery in Guyon’s canal with an arterial graft: Anatomical study

Ulnar artery thrombosis in Guyon’s canal can lead to vascular insufficiency in the fingers. The recommended treatment is resection and reconstruction of the pathological area. A bypass may be necessary, which may be venous or arterial. Arterial bypasses have better long-term patency; however, they are a source of donor-site complications.We carried out an anatomical study on 11 upper limbs and 7 lower limbs from cadavers to identify a technically accessible arterial graft, of a diameter suitable for bypassing the ulnar artery in Guyon’s canal and with acceptable scar sequelae (few predicted postoperative complications, discreet size and/or location of scar).Three grafts were considered: anterior interosseous artery, radial recurrent artery and descending genicular artery. The various grafts were dissected and harvested from cadaver specimens, then their lengths and diameters were measured. The diameter of the candidate grafts was compared to the diameter of the distal ulnar artery.The diameter of the descending genicular artery matched the ulnar artery better than the radial recurrent artery or the anterior interosseous artery (103% vs 44% and 67%, respectively). Mean graft length was 6.6 cm. The anatomical configuration of the descending genicular artery allowed Y-shaped bypasses to be performed. Harvesting this artery appears to cause little damage and allows bypasses up to 6 cm to be performed.Despite its smaller diameter making it necessary to perform a microvascular size adjustment, the anterior interosseous artery is a candidate graft because it is long enough (119 mm) and located near the surgical site. Level of evidenceV.

Liver transplantation for pediatric patients with congenital heart disease: A single-center study in mainland China.

Liver transplantation (LT) is a serious cardiovascular stressor for patients with end-stage liver disease (ESLD). Data on the effects of cardiovascular diseases on pediatric LT is limited. No study on LT for pediatric patients with ESLD combined with congenital heart disease (CHD) has been reported from mainland China. A total of 1005 patients were included in this study. The Kaplan-Meier method with log-rank testing was used to evaluate survival outcomes between groups. Univariable and multivariable Cox regression models were used to determine the risk factors for patient and graft survival. The most common indication for LT was biliary atresia (BA 90.3%). The prevalence of CHD was 3.8% (38). 42 CHD were found in 38 patients. The incidence of death and graft loss was more common in the CHD group than in the no-CHD group (13.2% vs. 5.0%, p = .045 and 15.8% vs. 6.2%, p = .019, respectively). The 5-year patient survival and graft survival in the CHD group versus the no-CHD group was 86.8% versus 94.7% (log-rank p = .022) and 84.2% versus 93.5% (log-rank p = .015), respectively. No significant differences were observed in re-transplantation, hepatic artery thrombosis (HAT), and portal vein thrombosis (PVT). After adjusting for age, BMI, etiology of LT, and other confounding factors, we can still find that the presence of CHD was associated with patient and graft survival after LT. The presence of CHD was associated with higher mortality and lower graft survival after LT. If possible, the cardiac defects should be addressed prior to LT.