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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 -
Journal of Clinical Medicine Apr 2024The presence of a primary cardiac tumor in a pediatric patient is a rare echocardiographic finding.
BACKGROUND
The presence of a primary cardiac tumor in a pediatric patient is a rare echocardiographic finding.
CASE REPORT
We report the case of an 11-year-old female patient with multiple peripheral embolisms, due to a gigantic left ventricular tumor, with a unique echocardiographic appearance. The patient was referred to the emergency department due to acute pain and loss of sensitivity in both of her legs. Past medical history was significant for acute lymphoblastic leukemia. Upon physical examination, suspicion of bilateral lower leg ischemia was raised. Doppler arterial ultrasound of both legs confirmed the suspicion mentioned above, as the right lower extremity suffered from partial arterial occlusion of the external iliac artery and total occlusion of the femoral arteries. Meanwhile, in the left lower extremity, the occlusion was localized in the proximal tibio-peroneal artery. Cardiac sonography revealed a massive, mobile, left ventricular intracavitary mass. Aside from its large dimensions (6.3 cm by 3 cm), its aspect was striking as well as it had very mobile and friable edges. Emergency bilateral endarterectomy and excision of the left ventricular tumor were performed alongside systemic anticoagulant therapy, with excellent results, as no tumoral residual masses could be seen in the left ventricle, and the arterial blood flow was restored completely in both lower extremities. The histopathological aspect of the excised masses was that of a myxoma. The patient recovered well after surgery and was discharged on postoperative day 14.
CONCLUSION
Despite only a handful of cases of cardiac myxomas being reported due to their rarity in the pediatric population, clinical presentation with peripheric embolism triggered a high index of suspicion of embolic mechanism in our patient and prompted a rapid assessment and successful management.
PubMed: 38673460
DOI: 10.3390/jcm13082189 -
Biomedicines Apr 2024Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or... (Review)
Review
BACKGROUND
Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or gangrene. Several studies have demonstrated that inflammation and endothelial dysfunction are some of the main substrates of CLTI.
METHODS
A narrative review was conducted and reported according to PRISMA guidelines. Three databases were searched-Web of Science, Medline, and EMBASE-for the studies assessing CLTI and the biological markers related to it.
RESULTS
We included 22 studies, and all the markers identified (C-reactive protein, D-dimers, fibrinogen, cytokines, IL-6, TNF-α, ICAM-1 (Intracellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1), neutrophile-to-lymphocytes ratio (NLR), IL-8, Pentraxin-3, neutrophil gelatinase-associated lipocalin (NGAL), calprotectin, E-selectin, P-selectin, neopterin, High-Mobility Group Box-1 protein (HGMB-1), Osteoprotegerin (OPG) and Sortilin) were positively associated with advanced CLTI, with major limb or major cardiovascular events in these patients.
CONCLUSIONS
All the studied markers had increased values in patients with CLTI, especially when associated with diabetes mellitus, proving a very important association between diabetes and major limb or cardiovascular events in these patients. There is a need for more studies to validate these markers in terms of diagnosis or prognosis in CLTI patients and in trying to find new medical strategies that target inflammation or endothelial dysfunction in these patients.
PubMed: 38672153
DOI: 10.3390/biomedicines12040798 -
Frontiers in Immunology 2024Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting illness that can progress to systemic lupus erythematosus (SLE) in approximately 30% of cases. Neurological...
Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting illness that can progress to systemic lupus erythematosus (SLE) in approximately 30% of cases. Neurological injuries can occur in both diseases, albeit with distinct presentations. Venous sinus thrombosis is a serious cerebrovascular complication in patients with neuropsychiatric SLE but is rarely observed in patients with KFD. The involvement of various antibodies, particularly antiphospholipid antibodies, can cause vascular endothelial cell injury, resulting in focal cerebral ischemia and intracranial vascular embolism in SLE. However, there are cases in which thrombotic pathology occurs without antiphospholipid antibody positivity, attributed to vascular lesions. In this report, we present a case of KFD and lupus encephalopathy featuring cerebral venous sinus thrombosis, despite the patient being negative for antiphospholipid antibody. We also conducted a comparative analysis of C3 and C4 levels in cerebrospinal fluid (CSF) and peripheral blood, along with the protein ratio in CSF and serum, to elucidate the pathological changes and characteristics of lupus encephalopathy.
Topics: Humans; Histiocytic Necrotizing Lymphadenitis; Sinus Thrombosis, Intracranial; Lupus Erythematosus, Systemic; Female; Adult
PubMed: 38665917
DOI: 10.3389/fimmu.2024.1389993 -
Internal Medicine (Tokyo, Japan) Jul 2024A 29-year-old Japanese woman was admitted to our hospital with a fever, cardiogenic shock, and cardiac arrest. Laboratory data indicated multiple organ failure in...
A 29-year-old Japanese woman was admitted to our hospital with a fever, cardiogenic shock, and cardiac arrest. Laboratory data indicated multiple organ failure in addition to hemoconcentration, hypoalbuminemia, and myocardial damage. The coronary angiography findings were normal, and fulminant myocarditis was suspected. Venoarterial peripheral extracorporeal membrane oxygenation and an Impella CP left ventricular assist device were initiated, along with the administration of positive inotropic agents. However, hypovolemic shock and hypoalbuminemia progressed along with severe anemia, and the patient died 18 hours after admission. The patient was diagnosed with systemic capillary leak syndrome associated with coronavirus disease 2019.
Topics: Humans; Capillary Leak Syndrome; Female; COVID-19; Adult; Fatal Outcome; SARS-CoV-2; Extracorporeal Membrane Oxygenation; Shock, Cardiogenic
PubMed: 38658337
DOI: 10.2169/internalmedicine.3637-24 -
Journal of Cardiology Cases Apr 2024Aortic mural thrombus (AMT) in the absence of aneurysm or atherosclerosis is a rare clinical finding and an uncommon cause of peripheral arterial embolization. AMT in a...
UNLABELLED
Aortic mural thrombus (AMT) in the absence of aneurysm or atherosclerosis is a rare clinical finding and an uncommon cause of peripheral arterial embolization. AMT in a normal artery is usually attributed to systemic hypercoagulability. We describe a case of subacute lower limb ischemia due to AMT associated with active ulcerative colitis (UC). A 46-year-old man with active UC was referred to our hospital for the evaluation and treatment of left leg pain. Ultrasound and contrast computed tomography showed occlusion of the left popliteal artery, and an AMT in the abdominal aorta between the inferior mesenteric artery and the aortic bifurcation. We started anticoagulant therapy, intravenous infliximab, and cytapheresis. Four weeks after initiating anticoagulation therapy, we were able to successfully treat the AMT with anticoagulation therapy without surgical thrombectomy. The inflammatory status of ulcerative colitis was also under control, and AMT had not recurred at 1 year after treatment. Invasive therapies are often selected to treat AMT. However, if a patient's hypercoagulable state is controlled, AMT can safely be treated with anticoagulation therapy alone without recurrence.
LEARNING OBJECTIVE
Aortic mural thrombus (AMT) in the absence of aneurysm or atherosclerosis is a rare clinical finding and an uncommon cause of peripheral arterial embolization. AMT in a normal artery is usually attributed to systemic hypercoagulability. We describe a case of subacute lower limb ischemia due to AMT associated with active ulcerative colitis. We controlled the ulcerative colitis condition and successfully treated the AMT with anticoagulation therapy alone.
PubMed: 38646077
DOI: 10.1016/j.jccase.2023.12.006