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PloS One 2024The risk of major bleeding complications in catheter directed thrombolysis (CDT) for acute limb ischemia (ALI) remains high, with reported major bleeding complication...
INTRODUCTION
The risk of major bleeding complications in catheter directed thrombolysis (CDT) for acute limb ischemia (ALI) remains high, with reported major bleeding complication rates in up to 1 in every 10 treated patients. Fibrinogen was the only predictive marker used for bleeding complications in CDT, despite the lack of high quality evidence to support this. Therefore, recent international guidelines recommend against the use of fibrinogen during CDT. However, no alternative biomarkers exist to effectively predict CDT-related bleeding complications. The aim of the POCHET biobank is to prospectively assess the rate and etiology of bleeding complications during CDT and to provide a biobank of blood samples to investigate potential novel biomarkers to predict bleeding complications during CDT.
METHODS
The POCHET biobank is a multicentre prospective biobank. After informed consent, all consecutive patients with lower extremity ALI eligible for CDT are included. All patients are treated according to a predefined standard operating procedure which is aligned in all participating centres. Baseline and follow-up data are collected. Prior to CDT and subsequently every six hours, venous blood samples are obtained and stored in the biobank for future analyses. The primary outcome is the occurrence of non-access related major bleeding complications, which is assessed by an independent adjudication committee. Secondary outcomes are non-major bleeding complications and other CDT related complications. Proposed biomarkers to be investigated include fibrinogen, to end the debate on its usefulness, anti-plasmin and D-Dimer.
DISCUSSION AND CONCLUSION
The POCHET biobank provides contemporary data and outcomes of patients during CDT for ALI, coupled with their blood samples taken prior and during CDT. Thereby, the POCHET biobank is a real world monitor on biomarkers during CDT, supporting a broad spectrum of future research for the identification of patients at high risk for bleeding complications during CDT and to identify new biomarkers to enhance safety in CDT treatment.
Topics: Humans; Hemorrhage; Thrombolytic Therapy; Prospective Studies; Biomarkers; Male; Female; Fibrinogen; Peripheral Arterial Disease; Aged; Arterial Occlusive Diseases; Middle Aged
PubMed: 38722842
DOI: 10.1371/journal.pone.0302830 -
Acta Neurochirurgica May 2024Stroke, the second leading cause of death globally, often involves ischemia in the vertebrobasilar territory. This condition is underexplored, despite significant...
PURPOSE
Stroke, the second leading cause of death globally, often involves ischemia in the vertebrobasilar territory. This condition is underexplored, despite significant morbidity and mortality risks. The purpose of this study is to present a case of occipital artery to V3 segment vertebral artery bypass, emphasizing the role of quantitative magnetic resonance angiography (qMRA) in assessing flow and guiding surgical intervention.
METHODS
A 66-year-old man with bilateral vertebral artery occlusion presented acute symptoms. qMRA was employed to evaluate flow dynamics and determine the feasibility of a flow augmentation bypass surgery. The occipital artery to left vertebral artery bypass (OA-to-VA) was performed, utilizing an inverted hockey-stick incision and an antegrade inside-out technique. The patency of the bypass was confirmed using both Doppler probe and Indocyanine green.
RESULTS
Postoperative assessments, including computed tomography angiography (CTA) and qMRA, demonstrated the patency of the bypass with improved flow in the basilar artery and left vertebral artery. The patient's condition remained stable postoperatively, with residual peripheral palsy of the left facial nerve.
CONCLUSION
In conclusion, the presented case illustrates the efficacy of the OA-to-VA bypass in addressing symptomatic bilateral vertebral artery occlusion. The study underscores the pivotal role of qMRA in pre- and postoperative assessments, providing noninvasive flow quantification for diagnostic considerations and long-term follow-up in patients with vertebrobasilar insufficiency.
Topics: Humans; Male; Aged; Vertebrobasilar Insufficiency; Vertebral Artery; Cerebral Revascularization; Magnetic Resonance Angiography; Treatment Outcome
PubMed: 38713241
DOI: 10.1007/s00701-024-06099-7 -
Scientific Reports May 2024Acute myocardial infarction (AMI) commonly precedes ventricular remodeling, heart failure. Few dynamic molecular signatures have gained widespread acceptance in...
Acute myocardial infarction (AMI) commonly precedes ventricular remodeling, heart failure. Few dynamic molecular signatures have gained widespread acceptance in mainstream clinical testing despite the discovery of many potential candidates. These unmet needs with respect to biomarker and drug discovery of AMI necessitate a prioritization. We enrolled patients with AMI aged between 30 and 70. RNA-seq analysis was performed on the peripheral blood mononuclear cells collected from the patients at three time points: 1 day, 7 days, and 3 months after AMI. PLC/LC-MS analysis was conducted on the peripheral blood plasma collected from these patients at the same three time points. Differential genes and metabolites between groups were screened by bio-informatics methods to understand the dynamic changes of AMI in different periods. We obtained 15 transcriptional and 95 metabolite expression profiles at three time points after AMI through high-throughput sequencing. AMI-1d: enrichment analysis revealed the biological features of 1 day after AMI primarily included acute inflammatory response, elevated glycerophospholipid metabolism, and decreased protein synthesis capacity. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) might stand promising biomarkers to differentiate post-AMI stage. Anti-inflammatory therapy during the acute phase is an important direction for preventing related pathology. AMI-7d: the biological features of this stage primarily involved the initiation of cardiac fibrosis response and activation of platelet adhesion pathways. Accompanied by upregulated TGF-beta signaling pathway and ECM receptor interaction, GP5 help assess platelet activation, a potential therapeutic target to improve haemostasis. AMI-3m: the biological features of 3 months after AMI primarily showed a vascular regeneration response with VEGF signaling pathway, NOS3 and SHC2 widely activated, which holds promise for providing new therapeutic approaches for AMI. Our analysis highlights transcriptional and metabolomics signatures at different time points after MI, which deepens our understanding of the dynamic biological responses and associated molecular mechanisms that occur during cardiac repair.
Topics: Humans; Myocardial Infarction; Middle Aged; Male; Female; Metabolomics; Aged; Adult; Transcriptome; Biomarkers; Leukocytes, Mononuclear; Gene Expression Profiling
PubMed: 38702356
DOI: 10.1038/s41598-024-60945-3 -
The American Journal of Cardiology Jul 2024Previous studies have shown an association between acute limb ischemia and higher mortality in patients with acute myocardial infarction. Although peripheral artery...
Previous studies have shown an association between acute limb ischemia and higher mortality in patients with acute myocardial infarction. Although peripheral artery disease (PAD) is a well-known risk factor for development of macrovascular pathology, the effect of its severity is not well investigated in patients hospitalized for acute coronary syndrome (ACS). Using a national cohort of patients with various degrees of PAD, we investigated in-hospital outcomes in patients who were admitted for ACS. Using the 2016 to 2020 Nationwide Readmissions Database, we queried all patients who were hospitalized for ACS (unstable angina, non-ST-elevation myocardial infarction, and ST-elevation myocardial infarction). Patients were further divided into 3 groups, either no PAD (non-PAD), PAD, or critical limb ischemia (CLI). Multivariable models were designed to adjust for patient and hospital factors and examine the association between ACS and PAD severity. Of approximately 3,834,181 hospitalizations for ACS, 6.4% had PAD, 0.2% had CLI, and all others were non-PAD. After risk adjustment, in-hospital mortality was higher by 24% in PAD (adjusted odds ratio 1.24, 95% confidence interval [CI] 1.21 to 1.28) and 86% in CLI (adjusted odds ratio 1.86, 95% CI 1.62 to 2.09) compared with non-PAD. Furthermore, PAD and CLI were linked to 1.23-fold (95% CI 1.20 to 1.26) and 1.67-fold (95% CI 1.45 to 1.86) greater odds of cardiogenic shock compared with non-PAD. Additionally, PAD and CLI were linked with higher odds of mechanical circulatory support usage, cardiac arrest and acute kidney injury compared with non-PAD. Lastly, duration of hospital stay, hospitalization costs and odds of non-home discharge and 30-day readmissions were greater in patients with PAD and CLI compared with non-PAD. PAD severity was associated with worse clinical outcomes in patients with ACS, including in-hospital mortality and resource utilization.
Topics: Humans; Peripheral Arterial Disease; Male; Female; Acute Coronary Syndrome; Aged; Hospital Mortality; Middle Aged; Hospitalization; United States; Health Resources; Length of Stay; Severity of Illness Index; Aged, 80 and over; Retrospective Studies; Shock, Cardiogenic; Risk Factors; Patient Readmission
PubMed: 38701873
DOI: 10.1016/j.amjcard.2024.04.049 -
JTCVS Open Apr 2024Minimally invasive segmental artery coil embolization was introduced to prevent spinal cord ischemia after endovascular repair of thoracoabdominal aortic aneurysms....
OBJECTIVE
Minimally invasive segmental artery coil embolization was introduced to prevent spinal cord ischemia after endovascular repair of thoracoabdominal aortic aneurysms. There is no consensus on whether the endovascular occlusion of segmental arteries feeding directly the anterior radiculomedullary artery and anterior spinal artery can be safely performed without causing spinal cord ischemia. Our aim was to investigate the feasibility and clinical impact of endovascular occlusion of segmental arteries supplying the anterior spinal artery during minimally invasive segmental artery coil embolization in patients with thoracoabdominal aortic aneurysms.
METHODS
Between January 2018 and July 2020, 54 patients (36 male; mean age, 71.1 ± 9.3 years) underwent direct embolization of segmental arteries feeding the anterior radiculomedullary artery before endovascular repair of thoracoabdominal aortic aneurysms. End points included technical success of minimally invasive segmental artery coil embolization of segmental arteries, anterior radiculomedullary artery, neurological complications, and in-hospital mortality after minimally invasive segmental artery coil embolization and endovascular repair of thoracoabdominal aortic aneurysms.
RESULTS
The thoracoabdominal aortic aneurysm classification was type I (n = 8), type II (n = 24), type III (n = 11), and type IV (n = 11). During minimally invasive segmental artery coil embolization, 388 segmental arteries were occluded, each patient having 7.2 ± 3.1 coiled segmental arteries occluding 64.5% (25-100%) of open segmental arteries within the treated aortic segment. Altogether, 66 anterior radiculomedullary arteries were seen originating between Th8 and L3 levels from 85 (21.9%) segmental arteries. In 10 patients (18.5%), 2 large anterior radiculomedullary arteries were identified, and 1 patient (1.9%) showed 3 anterior radiculomedullary arteries on the spinal arteriography. No spinal cord ischemia or procedure-related complications occurred after minimally invasive segmental artery coil embolization. After 47.9 ± 39.4 days, all patients received endovascular repair of their thoracoabdominal aortic aneurysms. There was no in-hospital mortality. One male patient developed incomplete temporary spinal cord ischemia after endovascular repair.
CONCLUSIONS
Minimally invasive segmental artery coil embolization of segmental arteries feeding the anterior spinal artery in patients with thoracoabdominal aortic aneurysms to prevent spinal cord ischemia after endovascular repair is feasible and clinically safe.
PubMed: 38690411
DOI: 10.1016/j.xjon.2024.02.016 -
Seminars in Thrombosis and Hemostasis Jul 2024Ischemic limb injury can be broadly classified into arterial (absent pulses) and venous/microvascular (detectable pulses); the latter can be divided into two overlapping... (Review)
Review
Ischemic limb injury can be broadly classified into arterial (absent pulses) and venous/microvascular (detectable pulses); the latter can be divided into two overlapping disorders-venous limb gangrene (VLG) and symmetrical peripheral gangrene (SPG). Both VLG and SPG feature predominant acral (distal) extremity ischemic necrosis, although in some instances, concomitant nonacral ischemia/skin necrosis occurs. Historically, for coagulopathic disorders with prominent nonacral ischemic necrosis, clinician-scientists implicated depletion of natural anticoagulants, especially involving the protein C (PC) system. This historical review traces the recognition of natural anticoagulant depletion as a key feature of nonacral ischemic syndromes, such as classic warfarin-induced skin necrosis, neonatal purpura fulminans (PF), and meningococcemia-associated PF. However, only after several decades was it recognized that natural anticoagulant depletion is also a key feature of predominantly acral ischemic microthrombosis syndromes-VLG and SPG-even when accompanying nonacral thrombosis is not present. These acquired acral limb ischemic syndromes typically involve the triad of (a) disseminated intravascular coagulation, (b) natural anticoagulant depletion, and (c) a localizing explanation for microthrombosis occurring in one or more limbs, either deep vein thrombosis (helping to explain VLG) or circulatory shock (helping to explain SPG). In most cases of VLG or SPG there are one or more events that exacerbate natural anticoagulant depletion, such as warfarin therapy (e.g., warfarin-associated VLG complicating heparin-induced thrombocytopenia or cancer hypercoagulability) or acute ischemic hepatitis ("shock liver") as a proximate factor predisposing to severe depletion of hepatically synthesized natural anticoagulants (PC, antithrombin) in the setting of circulatory shock.
Topics: Humans; Necrosis; Thrombosis; Ischemia; Extremities; History, 20th Century
PubMed: 38688305
DOI: 10.1055/s-0044-1786356 -
Journal of Endovascular Therapy : An... Apr 2024The purpose of this review and meta-analysis is to determine the clinical outcome differences between patients with chronic limb-threatening ischemia who underwent... (Review)
Review
PURPOSE
The purpose of this review and meta-analysis is to determine the clinical outcome differences between patients with chronic limb-threatening ischemia who underwent direct versus indirect angiosome revascularization using either the surgical or endovascular approach.
MATERIALS AND METHODS
The data sources used for article selection included PubMed, Embase/Medline, Cochrane reviews, and Web of Science (All studies were in English and included up to September 2023). All articles included were comparative in design, including retrospective, prospective, and randomized controlled trials that compared the clinical outcomes between direct and indirect angiosome-guided revascularization in chronic limb-threatening ischemia. A random-effects model was used to determine the measure of association between direct revascularization and amputation-free survival, wound healing, and overall survival. Publication bias was assessed with both Begg's and Egger's test, and heterogeneity was calculated using an I.
RESULTS
Data from 9 articles were analyzed and reported in this review. Direct revascularization was associated with improved amputation-free survival (odds ratio [OR]=2.632, confidence interval [CI]: 1.625, 4.265), binary wound healing (OR=2.262, CI: 1.518, 3.372), and overall survival (OR=1.757, CI: 1.176, 2.625). Time until wound healed was not associated with either direct or indirect revascularization (Standard Mean Difference [SMD]=-2.15, p=0.11). There was a low risk of bias across all studies according to the RoB 2.0 tool.
CONCLUSION
Direct revascularization is associated with improved amputation-free survival, overall survival, and wound healing in chronic limb-threatening ischemic patients compared to the indirect approach.
CLINICAL IMPACT
Preservation of the lower extremity is critical for preventing mortality and maintaining independence. The benefit of angiosome-guided revascularization for chronic limb-threatening ischemia remains controversial. The authors of this article aim to review the current literature and compare direct and indirect angiosome-guided intervention for preserving the lower extremity. Current findings suggest direct angiosome-guided intervention reduces amputation rates and improves survival; however, many trials neglect to address the multifactorial approach needed in wound care management.
PubMed: 38687701
DOI: 10.1177/15266028241248524 -
Heliyon Apr 2024Aneurysmal subarachnoid hemorrhage (aSAH) is a serious type of hemorrhagic stroke. It is very important to predict the prognosis at early phase. In this work, we intend...
BACKGROUND
Aneurysmal subarachnoid hemorrhage (aSAH) is a serious type of hemorrhagic stroke. It is very important to predict the prognosis at early phase. In this work, we intend to characterize early changes in peripheral blood cells after aSAH and explore the association between peripheral blood cells and clinical outcomes after aSAH.
METHODS
aSAH patients admitted between December 2019 and September 2022 were enrolled. A retrospective observational study was performed. Total leukocytes, monocytes, neutrophils, erythrocytes, lymphocytes and platelets counts were recorded on the day of admission (day 1), day 3, day 5 and day 7. Statistical tests included Chi-square test, analysis of variance and multivariate logistic regression (MLR) models. 197 patients were analyzed.
RESULTS
Leukocytes and neutrophils were higher in poor outcome groups from day 1 to day 7 and in delayed cerebral ischemia (DCI) groups from day 3 to day 7. Lymphocytes were higher at day 5 and day 7 in good outcome groups and no DCI groups. Neutrophil-to-lymphocyte ratio (NLR) was lower from day 3 to day 7 in good outcome groups and no DCI groups. Erythrocytes were higher from day 3 to day 7 in good outcome groups and no DCI groups. Lymphocytes were negatively related to poor outcomes on day 1 (OR = 0.457), indicating higher lymphocytes predicted good outcomes, Neutrophils were positively related to poor outcomes on day 3 (OR = 3.003) indicating higher neutrophils predicted poor outcomes. Lymphocytes were negatively related to DCI on day 5 (OR = 0.388) indicating higher lymphocytes predicted no DCI, Erythrocytes were negatively related to DCI on day 5 (OR = 0.335) and day 7 (OR = 0.204) indicating higher erythrocytes predicted no DCI. The improved ability of neutrophils, lymphocytes and erythrocytes to predict DCI or poor functional outcomes were revealed by ROC curve analysis.
CONCLUSIONS
The dynamic changes of peripheral blood cell counts were related to poor functional outcomes and DCI after aSAH. Elevated neutrophils, leukocytes, NLR, and decreased lymphocytes, erythrocytes were accompanied by DCI and poor outcome. Neutrophils, lymphocytes and erythrocytes counts could be beneficial to predict DCI and outcomes after aSAH.
PubMed: 38681624
DOI: 10.1016/j.heliyon.2024.e29763 -
Pharmaceutics Apr 2024To better understand ischaemia-related molecular alterations, temporal changes in angiogenic Aminopeptidase N (APN/CD13) expression and glucose metabolism were assessed...
BACKGROUND
To better understand ischaemia-related molecular alterations, temporal changes in angiogenic Aminopeptidase N (APN/CD13) expression and glucose metabolism were assessed with PET using a rat model of peripheral arterial disease (PAD).
METHODS
The mechanical occlusion of the base of the left hindlimb triggered using a tourniquet was applied to establish the ischaemia/reperfusion injury model in Fischer-344 rats. 2-[F]FDG and [Ga]Ga-NOTA-c(NGR) PET imaging performed 1, 3, 5, 7, and 10 days post-ischaemia induction was followed by Western blotting and immunohistochemical staining for APN/CD13 in ischaemic and control muscle tissue extracts.
RESULTS
Due to a cellular adaptation to hypoxia, a gradual increase in [Ga]Ga-NOTA-c(NGR) and 2-[F]FDG uptake was observed from post-intervention day 1 to 7 in the ischaemic hindlimbs, which was followed by a drop on day 10. Conforming pronounced angiogenic recovery, the NGR accretion of the ischaemic extremities differed significantly from the controls 5, 7, and 10 days after ischaemia induction ( ≤ 0.05), which correlated with the Western blot and immunohistochemical results. No remarkable radioactivity was depicted between the normally perfused hindlimbs of either the ischaemic or the control groups.
CONCLUSIONS
The PET-based longitudinal assessment of angiogenesis-associated APN/CD13 expression and glucose metabolism during ischaemia may continue to broaden our knowledge on the pathophysiology of PAD.
PubMed: 38675203
DOI: 10.3390/pharmaceutics16040542 -
International Journal of Molecular... Apr 2024The circadian rhythms generated by the master biological clock located in the brain's hypothalamus influence central physiological processes. At the molecular level, a... (Review)
Review
The circadian rhythms generated by the master biological clock located in the brain's hypothalamus influence central physiological processes. At the molecular level, a core set of clock genes interact to form transcription-translation feedback loops that provide the molecular basis of the circadian rhythm. In animal models of disease, a desynchronization of clock genes in peripheral tissues with the central master clock has been detected. Interestingly, patients with vascular dementia have sleep disorders and irregular sleep patterns. These alterations in circadian rhythms impact hormonal levels, cardiovascular health (including blood pressure regulation and blood vessel function), and the pattern of expression and activity of antioxidant enzymes. Additionally, oxidative stress in vascular dementia can arise from ischemia-reperfusion injury, amyloid-beta production, the abnormal phosphorylation of tau protein, and alterations in neurotransmitters, among others. Several signaling pathways are involved in the pathogenesis of vascular dementia. While the precise mechanisms linking circadian rhythms and vascular dementia are still being studied, there is evidence to suggest that maintaining healthy sleep patterns and supporting proper circadian rhythm function may be important for reducing the risk of vascular dementia. Here, we reviewed the main mechanisms of action of molecular targets related to the circadian cycle and oxidative stress in vascular dementia.
Topics: Animals; Humans; Circadian Clocks; Circadian Rhythm; Dementia, Vascular; Oxidative Stress; Signal Transduction; Molecular Targeted Therapy
PubMed: 38673986
DOI: 10.3390/ijms25084401