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Age and Ageing Jun 2024Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent... (Review)
Review
Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent claudication, whilst chronic limb-threatening ischaemia (CLTI), the end stage of PAD, presents with rest pain and/or tissue loss. PAD is an age-related condition present in over 10% of those aged ≥65 in high-income countries. Guidelines regarding definition, diagnosis and staging of PAD and CLTI have been updated to reflect the changing patterns and presentations of disease given the increasing prevalence of diabetes. Recent research has changed guidelines on optimal medical therapy, with low-dose anticoagulant plus aspirin recommended in some patients. Recently published randomised trials highlight where bypass-first or endovascular-first approaches may be optimal in infra-inguinal disease. New techniques in endovascular surgery have increased minimally invasive options for ever more complex disease. Increasing recognition has been given to the complexity of patients with CLTI where a high prevalence of both frailty and cognitive impairment are present and a significant burden of multi-morbidity and polypharmacy. Despite advances in minimally invasive revascularisation techniques and reduction in amputation incidence, survival remains poor for many with CLTI. Shared decision-making is essential, and conservative management is often appropriate for older patients. There is emerging evidence of the benefit of specialist geriatric team input in the perioperative management of older patients undergoing surgery for CLTI. Recent UK guidelines now recommend screening for frailty, cognitive impairment and delirium in older vascular surgery patients as well as recommending all vascular surgery services have support and input from specialist geriatrics teams.
Topics: Humans; Peripheral Arterial Disease; Aged; Endovascular Procedures; Risk Factors; Chronic Limb-Threatening Ischemia; Vascular Surgical Procedures; Age Factors; Practice Guidelines as Topic
PubMed: 38877714
DOI: 10.1093/ageing/afae114 -
Journal of the Korean Society of... May 2024To examine the technical considerations of endovascular treatment for aortoiliac occlusive disease (AIOD) based on a 10-year experience in Songklanagarind Hospital.
PURPOSE
To examine the technical considerations of endovascular treatment for aortoiliac occlusive disease (AIOD) based on a 10-year experience in Songklanagarind Hospital.
MATERIALS AND METHODS
This retrospective cohort study included 210 patients who underwent endovascular treatment for symptomatic AIOD between January 2010 and December 2020. The patients' clinical and lesion characteristics, including technical considerations of the procedure, were collected, analyzed, and stratified using the Transatlantic Inter-Society Consensus (TASC).
RESULTS
Most patients (80%) in this study had chronic limb-threatening ischemia lesions, with an occlusion rate of 37%. The technical success rate of TASC C & D was lower than that of TASC A & B, 84.4% vs. 99.2% ≤ 0.001. A technical success rate of 93.3% (14/15) was found for the femoral and brachial approach, compared with a success rate of 89.0% (57/64) for the unibifemoral approach in TASC C & D, without a statistically significant difference ( = 0.076). However, the puncture site complications in this route were up to 17.6%, which is the highest rate compared with other techniques. These complications could be treated either conservatively or minimally invasively.
CONCLUSION
In cases of failed femoral access, simultaneous femoral and brachial approaches improved the technical success rate of endovascular recanalization of TASC C & D aortoiliac occlusions.
PubMed: 38873374
DOI: 10.3348/jksr.2023.0116 -
World Neurosurgery Jun 2024Continuous bedside monitoring of brain tissue oxygen levels is a crucial component in the management of comatose patients suffering from acute brain injury on...
BACKGROUND
Continuous bedside monitoring of brain tissue oxygen levels is a crucial component in the management of comatose patients suffering from acute brain injury on neurointensive care units. Ensuring sufficient brain oxygenation is recognized as an essential objective within neurocritical care, aimed at safeguarding patients from secondary ischemia. Hypoperfusion in occipital and the posterior watershed regions often remains undetected, as the placement of probes in these areas is challenging. A major concern is that patients would have to lie on the traditionally used implanted bolts due to the occipital entry point of the probes. Therefore, we present a novel technique compatible with magnetic resonance imaging that enables bedside placement of brain tissue oxygen probes without the use of a bolt in these areas.
METHODS
We conducted bedside implantations of Licox brain tissue oxygenation probes through Frazier's point utilizing peripheral venous cannulas on burr holes eliminating the need for bolts.
RESULTS
A novel approach was successfully established for the bedside implantation of a Licox brain tissue oxygenation probe for occipital regions.
CONCLUSION
This technical note describes the feasibility of a novel, simple and straightforward bedside technique for boltless implantation of Licox brain tissue oxygen probes leading to rigid fixation and compatibility with magnetic resonance imaging.
PubMed: 38871288
DOI: 10.1016/j.wneu.2024.06.008 -
Translational Stroke Research Jun 2024N-Methyladenosine (mA) is a neuronal-enriched, reversible post-transcriptional modification that regulates RNA metabolism. The mA-modified RNAs recruit various...
N-Methyladenosine (mA) is a neuronal-enriched, reversible post-transcriptional modification that regulates RNA metabolism. The mA-modified RNAs recruit various mA-binding proteins that act as readers. Differential mA methylation patterns are implicated in ischemic brain damage, yet the precise role of mA readers in propagating post-stroke mA signaling remains unclear. We presently evaluated the functional significance of the brain-enriched mA reader YTHDF1, in post-stroke pathophysiology. Focal cerebral ischemia significantly increased YTHDF1 mRNA and protein expression in adult mice of both sexes. YTHDF1 male, but not female, mice subjected to transient middle cerebral artery occlusion (MCAO) showed worsened motor function recovery and increased infarction compared to sex-matched YTHDF1 mice. YTHDF1 male, but not female, mice subjected to transient MCAO also showed significantly perturbed expression of genes related to inflammation, and increased infiltration of peripheral immune cells into the peri-infarct cortex, compared with sex-matched YTHDF1 mice. Thus, this study demonstrates a sexual dimorphism of YTHDF1 in regulating post-ischemic inflammation and pathophysiology. Hence, post-stroke epitranscriptomic regulation might be sex-dependent.
PubMed: 38869772
DOI: 10.1007/s12975-024-01267-4 -
Annals of Surgical Treatment and... Jun 2024The anatomical distribution, characteristics of lesions, and treatment modalities for peripheral artery disease (PAD) are diverse. Endovascular intervention is popular...
PURPOSE
The anatomical distribution, characteristics of lesions, and treatment modalities for peripheral artery disease (PAD) are diverse. Endovascular intervention is popular for symptomatic PAD, for both intermittent claudication (IC) and chronic limb-threatening ischemia (CLTI). We aimed to investigate the endovascular devices used by comparing patients with PAD referred for endovascular revascularization with IC and CLTI.
METHODS
We identified 736 patients with PAD enrolled in the multicenter PAD registry in South Korea from 2019 to 2022. Of these patients, 636 received endovascular treatment at the time of this study. After excluding missing data, we analyzed 506 patients with IC or CLTI. Patients' characteristics, target lesions, and endovascular device data such as type, length, balloon diameter, and stent, were examined. Procedure outcomes of the aortoiliac, femoropopliteal, and below-the-knee lesions were analyzed.
RESULTS
Patients with CLTI were more likely to have diabetes mellitus, below-the-knee interventions, and multilevel PAD than the IC group. Patients with IC had more aortoiliac artery lesions and underwent atherectomies than the CLTI group (63.3% and 61.1% 39.7% and 40.6%, respectively; P < 0.001). In patients with femoropopliteal lesions, those with CLTI were more revascularized with stents than the patients with IC, without significant differences (35.3% 29.1%, P = 0.161). Compared to the IC group, the CLTI patients showed significantly worse rates of primary patency, amputation, and mortality (P = 0.029, P < 0.001, and P < 0.001, respectively).
CONCLUSION
Among Korean patients with PAD, there is a significant difference in baseline and lesion characteristics, endovascular strategies, and short-term follow-up outcomes among those with IC and CLTI.
PubMed: 38868587
DOI: 10.4174/astr.2024.106.6.344 -
Perfusion Jun 2024For veno-arterial extracorporeal membrane oxygenation (ECMO), the femoral artery is the preferred cannulation site (femoro-femoral: Vf-Af). This results in retrograde...
RATIONALE
For veno-arterial extracorporeal membrane oxygenation (ECMO), the femoral artery is the preferred cannulation site (femoro-femoral: Vf-Af). This results in retrograde aortic flow, which increases the left ventricular afterload and can lead to severe pulmonary edema and thrombosis of the cardiac chambers. Right axillary artery cannulation (femoral-axillary: Vf-Aa) provides partial anterograde aortic flow, which may prevent some complications. This study aimed to compare the 90-day mortality and complication rates between VF-AA and VF-AF.
METHODS
Consecutive adult patients with cardiogenic shock who received peripheral VA-ECMO between 2013 and 2019 at our institution were retrospectively included. The exclusion criteria were refractory cardiac arrest, multiple VA-ECMO implantations due to vascular access changes, weaning failure, or ICU readmission. A statistical approach using inverse probability of treatment weighting was used to estimate the effect of the cannulation site on the outcomes. The primary endpoint was the 90-day mortality. The secondary endpoints were vascular access complications, stroke, and other complications related to retrograde blood flow. Outcomes were estimated using logistic regression analysis.
RESULTS
VA-ECMO was performed on 534 patients. Patients with refractory cardiac arrest ( = 77 (14%)) and those supported by multiple VA-ECMO ( = 92, (17%)) were excluded. Out of the 333 patients studied ( = 209 Vf-Aa; = 124 VF-AF), the main indications for VA-ECMO implantation were post-cardiotomy (33%, = 109), dilated cardiomyopathy (20%, = 66), post-cardiac transplantation (15%, = 50), acute myocardial infarction (14%, = 46) and other etiologies (18%, = 62). The median SOFA score was 9 [7-11], and the crude 90-day mortality rate was 53% ( = 175). After IPTW, the 90-day mortality was similar in the Vf-Aa and VF-AF groups (54% vs 58%, IPTW-OR = 0.84 [0.54-1.29]). Axillary artery cannulation was associated with significantly fewer local infections (OR = 0.21, 95% CI:0.09-0.51), limb ischemia (OR = 0.37, 95% CI:0.17-0.84), bowel ischemia (OR = 0.16, 95% CI:0.05-0.51) and pulmonary edema (OR = 0.52, 95% CI:0.29-0.92) episodes, but with a higher rate of stroke (OR = 2.87, 95% CI:1.08-7.62) than femoral artery cannulation.
CONCLUSION
Compared to VF-AF, axillary cannulation was associated with similar 90-day mortality rates. The high rate of stroke associated with axillary artery cannulation requires further investigation.
PubMed: 38867368
DOI: 10.1177/02676591241261330 -
Frontiers in Cardiovascular Medicine 2024Diabetes worsens the outcomes of a number of vascular disorders including peripheral arterial disease (PAD) at least in part through induction of chronic inflammation....
Diabetes worsens the outcomes of a number of vascular disorders including peripheral arterial disease (PAD) at least in part through induction of chronic inflammation. However, in experimental PAD, recovery requires the nuclear factor-kappa B (NF-κB) activation. Previously we showed that individually, both ischemia and high glucose activate the canonical and non-canonical arms of the NF-κB pathway, but prolonged high glucose exposure specifically impairs ischemia-induced activation of the canonical NF-κB pathway through activation of protein kinase C beta (PKCβ). Although a cascade of phosphorylation events propels the NF-κB signaling, little is known about the impact of hyperglycemia on the canonical and non-canonical NF-κB pathway signaling. Moreover, signal upstream of PKCβ that lead to its activation in endothelial cells during hyperglycemia exposure have not been well defined. In this study, we used endothelial cells exposed to hyperglycemia and ischemia (HGI) and an array of approximately 250 antibodies to approximately 100 proteins and their phosphorylated forms to identify the NF-κB signaling pathway that is altered in ischemic EC that has been exposed to high glucose condition. Comparison of signals from hyperglycemic and ischemic cell lysates yielded a number of proteins whose phosphorylation was either increased or decreased under HGI conditions. Pathway analyses using bioinformatics tools implicated BLNK/BTK known for B cell antigen receptor (BCR)-coupled signaling. Inhibition of BLNK/BTK in endothelial cells by a specific pharmacological inhibitor terreic acid attenuated PKC activation and restored the IκBα degradation suggesting that these molecules play a critical role in hyperglycemic attenuation of the canonical NF-κB pathway. Thus, we have identified a potentially new component of the NF-κB pathway upstream of PKC in endothelial cells that contributes to the poor post ischemic adaptation during hyperglycemia.
PubMed: 38854657
DOI: 10.3389/fcvm.2024.1345421 -
Brain Research Bulletin Aug 2024Limb remote ischemic postconditioning (LRIP) and paeoniflorin (PF) both can ameliorate cerebral ischemia reperfusion (I/R) injury. At present, whether LRIP combined with...
BACKGROUND
Limb remote ischemic postconditioning (LRIP) and paeoniflorin (PF) both can ameliorate cerebral ischemia reperfusion (I/R) injury. At present, whether LRIP combined with PF can achieve better therapeutic effect is unknown.
PURPOSE
This study explored the alleviating effect and mechanism of LRIP in combination with PF on cerebral I/R injury in rats.
METHODS
Middle cerebral artery occlusion (MCAO) surgery was performed on rats except Sham group. Then PF (2.5 mg/kg, 5 mg/kg, 10 mg/kg) was administrated by intraperitoneal injection 10 min before the start of reperfusion. LRIP was operated on the left femoral artery at 0 h of reperfusion. Behavioral testing was used to assess neurological impairment, while TTC staining was used to examine infarct volume. Protein expression of MyD88, TRAF6, p38-MAPK and phosphorylation of p47 in neutrophils from rat peripheral blood were tested by Western blot. Rat bone marrow neutrophils were extracted and incubated for 24 h with serum from rats after LRIP combined with PF. p38 MAPK inhibitor group was administrated SB203580 while the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor group was administrated Apocynin. Neutrophils were stimulated by fMLP (10 μM). Reactive oxygen species (ROS) production and protein expression of MyD88, TRAF6, p38 MAPK, and p47 (ser 304 and ser 345) were detected.
RESULTS
LRIP combined with PF (5 mg/kg) reduced cerebral infarct volume, ameliorated neurological deficit score (NDS), decreased fMLP-stimulated ROS release and downregulated the protein expression of MyD88, TRAF6, p38-MAPK and phosphorylation of p47 (ser 304 and ser 345) in neutrophils.
CONCLUSION
The protective effect of LRIP combined with PF on cerebral I/R injury was better than either alone. Taken together, we provided solid evidence to demonstrate that the combination of LRIP and PF had potential to alleviate cerebral I/R injury, which was regulated by MyD88-TRAF6-p38 MAPK pathway and neutrophil NADPH oxidase pathway.
Topics: Animals; Neutrophils; Male; Ischemic Postconditioning; Reperfusion Injury; Glucosides; Rats, Sprague-Dawley; Rats; Monoterpenes; Brain Ischemia; NADPH Oxidases; Infarction, Middle Cerebral Artery; p38 Mitogen-Activated Protein Kinases; NADP; Signal Transduction
PubMed: 38852654
DOI: 10.1016/j.brainresbull.2024.111006 -
Annals of Vascular Surgery Jun 2024The Vascular Outcomes Study of aspirin (ASA) Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for peripheral artery disease (PAD) trial...
BACKGROUND
The Vascular Outcomes Study of aspirin (ASA) Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for peripheral artery disease (PAD) trial demonstrated the superiority of ASA and low-dose rivaroxaban (Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial dosing) compared with ASA alone in reducing major adverse cardiovascular events and major adverse limb events. We studied the COMPASS discharge prescription patterns in patients with symptomatic PAD who have undergone revascularization in our institution, since the time of publication of the Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD trial.
METHODS
All patients included in this study had documented lower-extremity atherosclerotic PAD and were eligible for COMPASS dosing. Revascularization strategies included endovascular (n = 299), suprainguinal bypass (n = 18), and infrainguinal bypass (n = 36).
RESULTS
COMPASS prescription patterns for the composite of endovascular and surgical strategies demonstrated a consistently low rate over time, without a trend toward increasing use. COMPASS dosing was prescribed as often as antiplatelet monotherapy (33.4% COMPASS vs. 34.6% antiplatelet monotherapy). This low COMPASS prescription rate was driven by significantly lower COMPASS prescriptions following endovascular therapy compared to surgical bypass (28.8% endovascular vs. 59.3% surgical bypass). COMPASS prescriptions following surgical bypass showed better trends; half of suprainguinal bypass patients (50.0%) and two-thirds of infrainguinal bypass patients (63.9%) were discharged on COMPASS. Despite patients with chronic limb-threatening ischemia (CLTI) representing a high-risk limb presentation, COMPASS prescriptions were low (29.8%), as opposed to patients without CLTI, and did not show a trend toward increasing use. In patients who underwent reinterventions throughout the observation period, there was a low conversion rate from ASA alone to COMPASS (3/26, 11.5%).
CONCLUSIONS
In this observational study, one-third of patients were undertreated by prescription of antiplatelet monotherapy, indicating that there is significant room for medical optimization. This is especially true of patients undergoing endovascular treatment, including the high-risk subgroup of patients with CLTI. We highlight the importance of dual pathway antithrombotic therapy in patients eligible for COMPASS dosing to optimize best current evidence medical therapy.
PubMed: 38851315
DOI: 10.1016/j.avsg.2024.04.005 -
ACS Applied Bio Materials Jun 2024Critical limb ischemia (CLI) refers to a severe condition resulting from gradual obstruction in the supply of blood, oxygen, and nutrients to the limbs. The most...
Critical limb ischemia (CLI) refers to a severe condition resulting from gradual obstruction in the supply of blood, oxygen, and nutrients to the limbs. The most promising clinical solution to CLI is therapeutic angiogenesis. This study explored the potency of pro-angiogenic terbium hydroxide nanorods (THNR) for treatment of CLI, with a major focus on their impact on ischemia-induced maladaptive alterations in endothelial cells as well as on vascularization in ischemic limbs. This study demonstrated that, in hypoxia-exposed endothelial cells, THNR improve survival and promote proliferation, migration, restoration of nitric oxide production, and regulation of vascular permeability. Based on molecular studies, these attributes of THNR can be traced to the stimulation of PI3K/AKT/eNOS signaling pathways. Besides, Wnt/GSK-3β/β-catenin signaling pathways may also play a role in the therapeutic actions of THNR. Furthermore, in the murine model of CLI, THNR administration can integrally re-establish blood perfusion with concomitant reduction of muscle damage and inflammation. Additionally, improvement of locomotor activities and motor coordination in ischemic limbs in THNR treated mice is also evident. Overall, the study demonstrates that THNR have the potential to be developed as an efficacious and cost-effective alternative clinical therapy for CLI, using a nanomedicine approach.
PubMed: 38848346
DOI: 10.1021/acsabm.4c00252