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Journal of Neuroinflammation Apr 2024The notion that the central nervous system is an immunologically immune-exempt organ has changed over the past two decades, with increasing evidence of strong links and... (Review)
Review
The notion that the central nervous system is an immunologically immune-exempt organ has changed over the past two decades, with increasing evidence of strong links and interactions between the central nervous system and the peripheral immune system, both in the healthy state and after ischemic and hemorrhagic stroke. Although primary injury after stroke is certainly important, the limited therapeutic efficacy, poor neurological prognosis and high mortality have led researchers to realize that secondary injury and damage may also play important roles in influencing long-term neurological prognosis and mortality and that the neuroinflammatory process in secondary injury is one of the most important influences on disease progression. Here, we summarize the interactions of the central nervous system with the peripheral immune system after ischemic and hemorrhagic stroke, in particular, how the central nervous system activates and recruits peripheral immune components, and we review recent advances in corresponding therapeutic approaches and clinical studies, emphasizing the importance of the role of the peripheral immune system in ischemic and hemorrhagic stroke.
Topics: Humans; Hemorrhagic Stroke; Brain Ischemia; Brain; Stroke; Brain Injuries; Brain Neoplasms
PubMed: 38637850
DOI: 10.1186/s12974-024-03101-y -
MedRxiv : the Preprint Server For... May 2024Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed...
INTRODUCTION
Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients like those with SAH have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this approach is safe in this fragile population . Therefore, we assessed the impact of both acute taVNS and repetitive taVNS on cardiovascular function in this study.
METHODS
In this randomized clinical trial, 24 SAH patients were assigned to either a taVNS treatment or a Sham treatment group. During their stay in the intensive care unit, we monitored patient electrocardiogram (ECG) readings and vital signs. We compared long-term changes in heart rate, heart rate variability, QT interval, and blood pressure between the two groups. Additionally, we assessed the effects of acute taVNS by comparing cardiovascular metrics before, during, and after the intervention. We also explored rapidly responsive cardiovascular biomarkers in patients exhibiting clinical improvement.
RESULTS
We found that repetitive taVNS did not significantly alter heart rate, corrected QT interval, blood pressure, or intracranial pressure. However, taVNS increased overall heart rate variability and parasympathetic activity from 5-10 days after initial treatment, as compared to the sham treatment. Acutely, taVNS increased heart rate, blood pressure, and peripheral perfusion index without affecting the corrected QT interval, intracranial pressure, or heart rate variability. The acute post-treatment elevation in heart rate was more pronounced in patients who experienced a decrease of more than 1 point in their Modified Rankin Score at the time of discharge.
CONCLUSIONS
Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a safe immunomodulatory treatment approach for SAH patients. The observed acute increase in heart rate after taVNS treatment may serve as a biomarker for SAH patients who could derive greater benefit from this treatment. NCT04557618.
PubMed: 38633771
DOI: 10.1101/2024.04.03.24304759 -
Annals of Vascular Diseases Mar 2024The Indigo Aspiration System (Penumbra Ltd., Alameda, CA, USA), a catheter-based device intended for the endovascular removal of clots from peripheral arteries and...
The Indigo Aspiration System (Penumbra Ltd., Alameda, CA, USA), a catheter-based device intended for the endovascular removal of clots from peripheral arteries and veins, was launched in Japan to treat acute limb ischemia after the cessation of urokinase sales. The initial application of this system in Japan was on a 96-year-old male patient. He was diagnosed with acute lower limb ischemia, which was caused by an embolism from a left common iliac artery aneurysm. The treatment significantly enhanced the perfusion to his left foot. This case report elaborates on the patient's treatment experience and discusses the indications for using the device.
PubMed: 38628935
DOI: 10.3400/avd.cr.23-00095 -
Annals of Vascular Diseases Mar 2024Since 2013, the Japanese Society for Vascular Surgery has started the project of nationwide registration and tracking database for patients with critical limb ischemia...
Since 2013, the Japanese Society for Vascular Surgery has started the project of nationwide registration and tracking database for patients with critical limb ischemia (CLI) who are treated by vascular surgeons. The purpose of this project is to clarify the current status of the medical practice for the patients with CLI to contribute to the improvement of the quality of medical care. This database, called JAPAN Critical Limb Ischemia Database (JCLIMB), is created on the National Clinical Database and collects data of patients' background, therapeutic measures, early results, and long-term prognosis as long as 5 years after the initial treatment. The limbs managed conservatively are also registered in JCLIMB, together with those treated by surgery and/or endovascular treatment. In 2020, 1299 CLI limbs (male 890 limbs: 69%) were registered by 85 facilities. Arteriosclerosis obliterans has accounted for 99% of the pathogenesis of these limbs. In this manuscript, the background data and the early prognosis of the registered limbs are reported. (This is a translation of Jpn J Vasc Surg 2023; 32: 363-391.).
PubMed: 38628931
DOI: 10.3400/avd.ar.23-00096 -
Journal of Liver Cancer Apr 2024To systematically evaluate inter-reader agreement in the assessment of individual Liver Imaging Reporting and Data System (LI-RADS) category M (LR-M) imaging features in...
BACKGROUNDS/AIMS
To systematically evaluate inter-reader agreement in the assessment of individual Liver Imaging Reporting and Data System (LI-RADS) category M (LR-M) imaging features in computed tomography/magnetic resonance imaging (CT/MRI) LI-RADS v2018, and to explore the causes of poor agreement in LR-M assignment.
METHODS
Original studies reporting inter-reader agreement for LR-M features on multiphasic CT or MRI were identified using the MEDLINE, EMBASE, and Cochrane databases. The pooled kappa coefficient (κ) was calculated using the DerSimonian-Laird random-effects model. Heterogeneity was assessed using Cochran's Q test and I2 statistics. Subgroup meta-regression analyses were conducted to explore the study heterogeneity.
RESULTS
In total, 24 eligible studies with 5,163 hepatic observations were included. The pooled κ values were 0.72 (95% confidence interval, 0.65-0.78) for rim arterial phase hyperenhancement, 0.52 (0.39-0.65) for peripheral washout, 0.60 (0.50-0.70) for delayed central enhancement, 0.68 (0.57-0.78) for targetoid restriction, 0.74 (0.65-0.83) for targetoid transitional phase/hepatobiliary phase appearance, 0.64 (0.49-0.78) for infiltrative appearance, 0.49 (0.30-0.68) for marked diffusion restriction, and 0.61 (0.48-0.73) for necrosis or severe ischemia. Substantial study heterogeneity was observed for all LR-M features (Cochran's Q test: p < 0.01; I2 ≥ 89.2%). Studies with a mean observation size of <3 cm, those performed using 1.5-T MRI, and those with multiple image readers, were significantly associated with poor agreement of LR-M features.
CONCLUSIONS
The agreement for peripheral washout and marked diffusion restriction was limited. The LI-RADS should focus on improving the agreement of LR-M features.
PubMed: 38616543
DOI: 10.17998/jlc.2024.04.05 -
Annals of Vascular Surgery Apr 2024The diagnosis of peripheral arterial disease (PAD) is commonly applied for symptoms related to atherosclerotic obstructions in the lower extremity, though its clinical... (Review)
Review
BACKGROUND
The diagnosis of peripheral arterial disease (PAD) is commonly applied for symptoms related to atherosclerotic obstructions in the lower extremity, though its clinical manifestations range from an abnormal ankle-brachial index to critical limb ischemia. Subsequently, management and prognosis of PAD vary widely with the disease stage. A critical aspect is how this variation is addressed in administrative database-based studies that rely on diagnosis codes for case identification. The objective of this scoping review is to inventory the identification strategies used in studies on PAD that rely on administrative databases, to map the pros and cons of the International Classification of Diseases (ICD) codes applied, and to propose a first outline for a consensus framework for case identification in administrative databases.
METHODS
Registry-based reports published between 2010 and 2021 were identified through a systematic PubMed search. Studies were subcategorized on the basis of the expressed study focus: claudication, critical limb ischemia, or general peripheral arterial disease, and the ICD code(s) applied for case identification mapped.
RESULTS
Ninety studies were identified, of which 36 (40%) did not specify the grade of PAD studied. Forty-nine (54%) articles specified PAD grade studied. Five (6%) articles specified different PAD subgroups in methods and baseline demographics, but not in further analyses. Mapping of the ICD codes applied for case identification for studies that specified the PAD grade studied indicated a remarkable heterogeneity, overlap, and inconsistency.
CONCLUSIONS
A large proportion of registry-based studies on PAD fail to define the study focus. In addition, inconsistent strategies are used for PAD case identification in studies that report a focus. These findings challenge study validity and interfere with inter-study comparison. This scoping review provides a first initiative for a consensus framework for standardized case selection in administrative studies on PAD. It is anticipated that more uniform coding will improve study validity and facilitate inter-study comparisons.
PubMed: 38615752
DOI: 10.1016/j.avsg.2024.02.008 -
International Journal of Molecular... Apr 2024Peripheral arterial disease (PAD) strikes more than 200 million people worldwide and has a severe prognosis by potentially leading to limb amputation and/or death,...
Peripheral arterial disease (PAD) strikes more than 200 million people worldwide and has a severe prognosis by potentially leading to limb amputation and/or death, particularly in older patients. Skeletal muscle mitochondrial dysfunctions and oxidative stress play major roles in this disease in relation with ischemia-reperfusion (IR) cycles. Mitochondrial dynamics through impairment of fission-fusion balance may contribute to skeletal muscle pathophysiology, but no data were reported in the setting of lower-limb IR despite the need for new therapeutic options. We, therefore, investigated the potential protective effect of mitochondrial division inhibitor-1 (mDivi-1; 50 mg/kg) in young (23 weeks) and old (83 weeks) mice submitted to two-hour ischemia followed by two-hour reperfusion on systemic lactate, muscle mitochondrial respiration and calcium retention capacity, and on transcripts specific for oxidative stress and mitochondrial dynamics. At the systemic levels, an IR-related increase in circulating lactate was still major despite mDivi-1 use (+305.9% < 0.0001, and +269.4% < 0.0001 in young and old mice, respectively). Further, IR-induced skeletal muscle mitochondrial dysfunctions (more severely impaired mitochondrial respiration in old mice (OXPHOS CI state, -68.2% < 0.0001 and -84.9% < 0.0001 in 23- and 83-week mice) and reduced calcium retention capacity (-46.1% < 0.001 and -48.2% = 0.09, respectively) were not corrected by mDivi-1 preconditioning, whatever the age. Further, mDivi-1 treatment did not oppose superoxide anion production (+71.4% < 0.0001 and +37.5% < 0.05, respectively). At the transcript level, markers of antioxidant enzymes (SOD 1, SOD 2, catalase, and GPx) and fission markers (Drp1, Fis) remained unchanged or tended to be decreased in the ischemic leg. Fusion markers such as mitofusin 1 or 2 decreased significantly after IR in both groups. In conclusion, aging enhanced the deleterious effects or IR on muscle mitochondrial respiration, and in this setting of lower-limb IR, mDivi-1 failed to protect the skeletal muscle both in young and old mice.
Topics: Humans; Animals; Mice; Aged; Mitochondrial Dynamics; Calcium; Ischemia; Peripheral Arterial Disease; Muscle, Skeletal; Lactic Acid; Mitochondrial Diseases; Superoxide Dismutase; Quinazolinones
PubMed: 38612835
DOI: 10.3390/ijms25074025 -
Journal of Clinical Medicine Apr 2024: In vascular medicine, peripheral arterial disease (PAD) and diabetic foot syndrome (DFS) are often considered synonymous with respect to the need for... (Review)
Review
: In vascular medicine, peripheral arterial disease (PAD) and diabetic foot syndrome (DFS) are often considered synonymous with respect to the need for revascularization. In PAD patients, clinical symptoms reflect the degree of atherosclerotic disease, since peripheral innervation, including pain sensation, is not usually compromised. In DFS patients, however, symptoms of relevant foot ischemia are often absent and progression of ischemia goes unnoticed owing to diabetic polyneuropathy, the loss of nociception being the main trigger for foot ulcers. This review analyzes the fundamental differences between PAD and DFS against the background of polyneuropathy. : The literature research for the 2014 revision of the German evidence-based S3-PAD-guidelines was extended to 2023. : Vascular examination is imperative for both, PAD and DFS. Stage-dependent revascularization is of utmost importance in PAD patients, especially those suffering from critical limb-threatening ischemia (CLTI). Successful therapy of DFS goes further, including infection and metabolic control, wound management, offloading the foot and lifelong prophylaxis in the course of a multidisciplinary treatment concept. Revascularization is not needed in all cases of DFS. : There are fundamental differences between PAD and DFS with respect to pathophysiology, the anatomical distribution of arterial occlusive processes, the clinical symptoms, the value of diagnostic tools such as the ankle-brachial index, and classification. Also, therapeutic concepts differ substantially between the two patient populations.
PubMed: 38610906
DOI: 10.3390/jcm13072141 -
Scientific Reports Apr 2024Smoking may increase the risk of diabetic foot disease and ulceration. It does so by impairing glycaemic control and promoting the formation of advanced glycated...
Smoking may increase the risk of diabetic foot disease and ulceration. It does so by impairing glycaemic control and promoting the formation of advanced glycated end-products. Additionally, smoking is known to delay surgical wound healing and accelerate peripheral arterial disease. We aimed to determine whether toe pressures differed in smokers with a foot ulcer, when compared to non-smokers and ex-smokers, as well as ulcer outcomes at 12 months, among patients attending Blacktown Hospital High Risk Foot Service (HRFS). This study is a retrospective analysis of our prospectively collected clinic database. Eligible participants were adults attending the HRFS between June 2020 and April 2022. Participants were included if they had an ulcer, at least one systolic toe pressure reading completed at their initial visit and attended at least one follow-up visit. Participants were followed until healing, loss to follow-up or a minimum of 12 months. A total of 195 participants were included; 36 smokers, 82 ex-smokers, and 77 controls who had never smoked. Smoking status was by self-report. Current smokers were significantly younger at initial presentation (p = .002) and tended towards lower socioeconomic status (p = .067). Current smokers were significantly more likely to have ischaemic grade 3 toe pressures (< 30 mmHg) of their left foot (p = .027), suggestive of reduced perfusion. At the end of follow up period, smokers had the numerically highest rates of minor amputations. In conclusion, smokers ulcerate younger and are more likely to have grade 3 ischaemia. Collecting information about the brachial artery pressures and the time since the last cigarette may clarify any relationship between smoking and toe pressures.Trial registration: WSLHD HREC ethics approval 2111-02 and ANZCTR registration 382470. Registered on 15/09/2021.
Topics: Adult; Humans; Ulcer; Retrospective Studies; Tobacco Smoking; Smokers; Foot Diseases; Toes
PubMed: 38609449
DOI: 10.1038/s41598-024-59158-5 -
RMD Open Apr 2024Compare the risk of extended major adverse cardiovascular (CV) event (MACE) composite outcomes and component events in patients with rheumatoid arthritis (RA) treated... (Randomized Controlled Trial)
Randomized Controlled Trial
Risk of extended major adverse cardiovascular event endpoints with tofacitinib versus TNF inhibitors in patients with rheumatoid arthritis: a post hoc analysis of a phase 3b/4 randomised safety study.
OBJECTIVES
Compare the risk of extended major adverse cardiovascular (CV) event (MACE) composite outcomes and component events in patients with rheumatoid arthritis (RA) treated with tofacitinib versus tumour necrosis factor inhibitors (TNFi) in Oral Rheumatoid Arthritis Trial (ORAL) Surveillance.
METHODS
Patients with RA aged ≥50 years and with ≥1 additional CV risk factor received tofacitinib 5 mg or 10 mg two times per day or TNFi. MACE (non-fatal myocardial infarction (MI), non-fatal stroke or CV death (MACE-3)) was extended by sequential addition of CV events (hospitalisation for unstable angina (MACE-4), coronary revascularisation (MACE-5), transient ischaemic attack (MACE-6), peripheral vascular disease (MACE-7)), heart failure (HF) hospitalisation (MACE-8) and venous thromboembolism (VTE; (MACE-8 plus VTE)). HRs (tofacitinib vs TNFi) were evaluated for MACE and individual components.
RESULTS
HRs for MACE-4 to MACE-8 with combined and individual tofacitinib doses versus TNFi were similar. Risk of MACE-8 plus VTE appeared similar with tofacitinib 5 mg two times per day versus TNFi (HR 1.12 (0.82 to 1.52)), but higher with tofacitinib 10 mg two times per day versus TNFi (HR 1.38 (1.02 to 1.85)). Risk of MI was higher with tofacitinib versus TNFi, but difference in risk of other individual CV events was not suggested. Across extended MACE definitions, risk appeared higher with tofacitinib versus TNFi in those with atherosclerotic CV disease or age ≥65 years.
CONCLUSION
In ORAL Surveillance, risk of composite CV endpoints combining all ischaemic CV events and HF did not appear different with tofacitinib versus TNFi. The totality of CV risk was higher with tofacitinib 10 mg two times per day versus TNFi, driven by an increase in VTE.
TRIAL REGISTRATION NUMBER
NCT02092467.
Topics: Humans; Arthritis, Rheumatoid; Heart Failure; Myocardial Infarction; Piperidines; Pyrimidines; Tumor Necrosis Factor Inhibitors; Venous Thromboembolism
PubMed: 38609322
DOI: 10.1136/rmdopen-2023-003912