Palladium nanoclusters as a label to determine GFAP in human serum from donors with stroke by bimodal detection: inductively coupled plasma-mass spectrometry and linear sweep voltammetry.

Water-soluble, stable, and monodisperse palladium nanoclusters (PdNCs) were synthesized using NaBH4 as a reductant and lipoic acid as a ligand. PdNCs, measured by high-resolution transmission electron microscopy, showed a round shape and a diameter of 2.49 ± 0.02 nm. It was found that each PdNC contains 550 Pd atoms on average. These PdNCs offer high amplification as a label of biochemical reactions when inductively coupled plasma-mass spectrometry (ICP-MS) is used as a detector. In addition, PdNCs have catalytic activity on electrochemical reactions, allowing detection by linear sweep voltammetry (LSV). As a proof of applicability, a competitive immunoassay based on PdNC labels was developed for the determination of glial fibrillary acidic protein (GFAP) in human serum, comparing ICP-MS and LSV detection. GFAP is a biomarker for differentiating between patients with ischemic stroke (IS) and hemorrhagic stroke (HS). The limit of detection (LoD), corresponding to IC10 (4-parameter logistic curve), was 0.03 pM of GFAP, both by ICP-MS and LSV, being lower than the 0.31 pM LoD provided by the ELISA commercial kit. Using the error profile method, 0.03 pM and 0.11 pM LoDs were obtained respectively by ICP-MS and LSV: LoD is lower by ICP-MS due to the better precision of the measurements. The analyses of human serum samples from IS, HS, and control (CT) donors using PdNC labels and detection by ICP-MS and LSV were validated with a commercial ELISA kit (for CT donors only ICP-MS provided enough sensitivity). Results point out toward the future use of PdNCs as a label in other immunoprobes for the determination of specific proteins requiring very low LoDs as well as the development of electrochemical decentralized methodologies.

First-line Double Stentriever Thrombectomy for M1/TICA Occlusions : Initial Experiences.

BACKGROUND: Mechanical thrombectomy is the standard of care for acute ischemic stroke due to large-vessel occlusion; however, mechanical thrombectomy fails to achieve adequate recanalization in nearly one third of these cases. Rescue therapy using two stentrievers simultaneously yields good results in clots refractory to single stentriever treatment. We aimed to determine the safety and efficacy of first-line double stentriever thrombectomy for acute occlusion of the M1 segment of the middle cerebral artery and/or terminal internal carotid artery (TICA). METHODS: This single-center study prospectively enrolled consecutive patients with a single M1/TICA occlusion to undergo double stentriever thrombectomy between May and October 2020. Outcomes included successful recanalization (modified thrombolysis in cerebral infarction, TICI 2b/3), first-pass effect, procedure times, number of device passes, symptomatic intracerebral hemorrhage, National Institutes of Health Stroke Scale Score (NIHSS) at discharge, 90-day functional independence (modified Rankin scale 0-2), and 90-day mortality. RESULTS: We analyzed 39 patients median age 79 years (range 42-96 years); 23 (58.9%) female; 19 (48.7%) with TICA occlusions; 5 (12.8%) with mRS 3-5 at admission; mean NIHSS at admission, 17 ± 4.39). Mean time from symptom onset to final angiogram was 238.0 ± 94.6 min; mean intervention duration was 36.0 ± 24.2 min. The mean number of device passes was 1.5 ± 1.07. All patients had final TICI 2b/3, and 27 (69%) had TICI 2c/3 after the first pass. We observed 3 (7.9%) cases of intracerebral symptomatic hemorrhages. At 90 days, 16 (41%) patients were functionally independent and 9 (23%) had died. The percentage of patients with good clinical outcome at 90 days was 55.5% in the first-pass subgroup. CONCLUSION: Our findings suggest that first-line double stentriever thrombectomy is safe and effective for M1/TICA occlusions.

Initial Experience Performing Mechanical Thrombectomy With the CatchView Mini Device for Distal M2 Segment Middle Cerebral Artery Occlusions.

Background: Mechanical thrombectomy (MT) has become the standard of care for acute ischemic stroke due to large vessel occlusion; however, its safety and efficacy in patients with distal strokes remains unclear. In this study, we investigated the safety and efficacy of MT for distal middle cerebral artery (MCA) occlusions using the CatchView Mini (CVM; Balt, Montmorency, France). Methods: This was a prospective single-center analysis of patients with a single MCA-M2 occlusion treated with the CVM device. Consecutive patients were prospectively enrolled from October 2018 to March 2020. Efficacy outcomes included successful recanalization [modified Thrombolysis in Cerebral Infarction (mTICI) 2b/3], procedure times, and number of device passes. Clinical outcomes included National Institutes of Health Stroke Scale Score (NIHSS) at discharge, 90-day functional independence (modified Rankin Scale 0-2) and safety outcomes included hemorrhagic complications, and 90-day mortality. Results: A total of 45 patients (mean age: 74.0 ± 12.6; 53.3% [24/45] female) were included in the study. Upon admission, 33.3% (15/45) of patients were mRS 3-5; and mean NIHSS was 13.2 ± 4.2 Mean time from symptom onset to final angiography was 250.0 ± 83.4 min with a mean intervention duration of 34.0 ± 12.6 min. The mean number of device passes was 1.8 ± 1.5 final mTICI 2b/3 was achieved in 91.1% (41/45) of patients. Eight hemorrhagic complications (17.8%, 8/34) occurred, none of which were symptomatic. At 90-days, 57.8% (26/45) patients were functionally independent and the rate of mortality was 15.6% (7/45). Conclusions: The present analysis demonstrates a low risk profile and high recanalization success for patients with distal M2 occlusions treated with the CVM device.

GlycA Levels during the Earliest Stages of Rheumatoid Arthritis: Potential Use as a Biomarker of Subclinical Cardiovascular Disease.

This study aimed at evaluating the clinical relevance of glycoprotein profiles during the earliest phases of rheumatoid arthritis (RA) as biomarkers of cardiovascular (CV) risk and treatment response. Then, GlycA and GlycB serum levels were measured using 1H-nuclear magnetic resonance in 82 early RA patients, 14 clinically-suspect arthralgia (CSA), and 28 controls. Serum glycosyltransferase activity was assessed by a colorimetric assay. Subclinical CV disease was assessed by Doppler-ultrasound. We found that GlycA and GlycB serum levels were increased in RA (both p < 0.001), but not in CSA, independently of cardiometabolic risk factors. Increased serum glycosyltransferase activity paralleled GlycA (r = 0.405, p < 0.001) and GlycB levels (r = 0.327, p = 0.005) in RA. GlycA, but not GlycB, was associated with atherosclerosis occurrence (p = 0.012) and severity (p = 0.001). Adding GlycA to the mSCORE improved the identification of patients with atherosclerosis over mSCORE alone, increasing sensitivity (29.7 vs. 68.0%) and accuracy (55.8 vs. 76.6%) and allowing reclassification into more appropriate risk categories. GlycA-reclassification identified patients with impaired lipoprotein metabolism. Finally, baseline GlycA levels predicted poor clinical response upon anti-rheumatic treatment at 6 and 12 months in univariate and multivariate analysis. In sum, increased GlycA levels during the earliest stage of RA can be considered a powerful biomarker for CV risk stratification and treatment response.

Low-density granulocytes and monocytes as biomarkers of cardiovascular risk in systemic lupus erythematosus.

OBJECTIVE: The aim was to evaluate the most relevant cell populations involved in vascular homeostasis as potential biomarkers of SLE-related cardiovascular disease (CVD). METHODS: Low-density granulocytes (LDGs), monocyte subsets, endothelial progenitor cells, angiogenic T (Tang) cells, CD4+CD28null and Th1/Th17 lymphocytes and serum cytokine levels were quantified in 109 SLE patients and 33 controls in relationship to the presence of subclinical carotid atheromatosis or cardiovascular disease. A second cohort including 31 recent-onset SLE patients was also included. RESULTS: Raised monocyte and LDG counts, particularly those LDGs negative for CD16/CD14 expression (nLDGs), in addition to the ratios of monocytes and nLDGs to high-density lipoprotein-cholesterol (HDLc) molecules (MHR and nLHR, respectively), were present in SLE patients with traditional risk factors or subclinical atheromatosis but not in those who were CV-free, thus revealing their value in the identification of patients at risk of CVD, even at the onset of disease. Accordingly, nLDGs were correlated positively with carotid intima-media thickness (cIMT) and with inflammatory markers (CRP and IL-6). A bias towards more differentiated monocyte subsets, related to increased IFN-α and IL-17 serum levels, was also observed in patients. Intermediate monocytes were especially expanded, but independently of their involvement in CVD. Finally, CD4+CD28null, Th17 and Th1 lymphocytes were increased, with CD4+CD28null and Th17 cells being associated with cIMT, whereas endothelial progenitor and Tang cell levels were reduced in all SLE patients. CONCLUSION: The present study highlights the potential use of MHR and nLHR as valuable biomarkers of CVD risk in SLE patients, even at diagnosis. The increased amounts of nLDGs, monocytes, Th17 and senescent-CD28null subsets, coupled with reduced pro-angiogenic endothelial progenitor cells and Tang cells, could underlie the development of atheromatosis in SLE.

Dual energy CT in the management of antiplatelet therapy in patients with acute ischemic stroke for carotid obstruction.

BACKGROUND AND PURPOSE: Acute tandem occlusions often require carotid stenting. Combination of mechanical and pharmacologic therapies in addition to antiplatelet drugs administered to prevent acute stent thrombosis might increase the risk of intracerebral hemorrhage. We present a protocol of antiplatelet regimen based on early post-procedural dual-energy CT (DE-CT). MATERIAL AND METHODS: Fifty consecutive stroke patients with tandem occlusions treated with acute carotid stenting after intracranial thrombectomy and TICI 2b/3 were reviewed. All patients received intravenous lysine acetylsalicylate during the procedure. Dual (aspirin+clopidogrel with or without clopidogrel load, groups A and B, respectively) or mono (aspirin) antiplatelet regimen (group C) was administered 12-24 h later according to brain DE-CT findings. Carotid ultrasonography was performed at 24 h and before discharge. We evaluated the rate of subsequent symptomatic intracranial hemorrhage (SICH) and acute stent thrombosis in each group. RESULTS: Between June 2014 and December 2016, 50 patients were included (mean age 66 years, 76% men, baseline NIHSS 16, median time from symptom onset to recanalization 266 min). According to DE-CT, 24 patients were assigned to group A, 19 to group B and 7 to group C (4 of them had SICH at that time). One patient suffered a subsequent SICH (belonging to group B). There was only one stent thrombosis without clinical repercussions in group B. CONCLUSIONS: DE-CT may contribute to select antiplatelet regimen after acute carotid stenting in tandem occlusions.

IgM anti-phosphorylcholine antibodies associate with senescent and IL-17+ T cells in SLE patients with a pro-inflammatory lipid profile.

OBJECTIVE: The aim was to evaluate whether T cell subsets and the lipid profile could be linked to the cardioprotective effect of IgM anti-phosphorylcholine (PC) antibodies in SLE. METHODS: Anti-PC antibodies were quantified by ELISA in 197 patients and 99 controls and analysed in relationship to clinical features, treatments and serum lipids. Carotid atheromatosis was evaluated by ultrasonography; Th1, Th17, Treg and CD4+CD28null cells by flow cytometry; and cytokine serum levels by immunoassays, in a subgroup of 120 SLE patients and 33 controls. RESULTS: IgM anti-PC serum levels were reduced in SLE patients compared with controls (P < 0.001) and were associated with age (ß= -0.252; P = 0.002), high-density lipoprotein (HDL; ß = 0.271; P = 0.001), low-density lipoprotein (LDL; ß= -0.192; P = 0.017) and glucocorticoid treatment (ß= -0.201; P = 0.012), whereas the IgG-to-IgM anti-PC ratio was increased (P = 0.007) and associated with age (ß = 0.194; P = 0.028) and SLEDAI (ß = 0.250; P = 0.005). Also, patients with clinical or subclinical cardiovascular disease exhibited reduced IgM anti-PC levels compared with their cardiovascular disease-free counterparts, regardless of glucocorticoid usage (P = 0.001). CD4+CD28null and Th17 cells were increased in SLE patients compared with controls (P < 0.01) and correlated inversely with IgM anti-PC levels. These associations were observed in patients displaying high triglyceride or low HDL levels, even after adjusting for clinical parameters and treatments (CD4+CD28null: ß = -0.455, P = 0.001; Th17: ß= -0.280, P = 0.035), but not in those with a normal lipid profile. High triglyceride and low HDL profiles were related to low IgM anti-PC and Treg levels, respectively, whereas both lipid profiles were associated with inflammatory markers and cytokines. CONCLUSION: The present study provides evidence for an association of IgM anti-PC antibodies with pro-atherogenic T cell subsets in SLE, with a high triglyceride/low HDL lipid profile playing a facilitating major role.

Serum Levels of Anti-PON1 and Anti-HDL Antibodies as Potential Biomarkers of Premature Atherosclerosis in Systemic Lupus Erythematosus.

The present study aimed to evaluate the possible role of immunoglobulin G (IgG) antibodies against high-density lipoproteins (HDL) and paraoxonase 1 (PON1) as possible biomarkers of cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). To this end, levels of these autoantibodies, PON1 activity and total antioxidant capacity were quantified in serum samples from 198 SLE patients, 100 healthy controls (HC) and 42 non-autoimmune individuals with traditional cardiovascular risk factors. PON1 rs662 polymorphism was analysed in a subgroup of patients and controls. Subclinical CVD were determined by Doppler ultrasound in 118 SLE patients and 30 HC, analysing carotid intima-media thickness (IMT) and blood flow parameters in internal carotid, middle cerebral and basilar arteries. Serum levels of both anti-HDL and anti-PON1 antibodies were increased in SLE patients compared with HC (p < 0.001); however, only anti-PON1 antibodies, in addition to disease activity, were significant predictors of the impaired PON1 function in SLE (ß = -0.143, p = 0.045). Conversely, anti-HDL antibodies were associated with higher risk of CVD (odds ratio: 3.69; p = 0.012) and lower HDL levels at disease onset (ρ = -0.324, p = 0.044). Finally, anti-PON1 antibodies were associated with carotid IMT in SLE (ß = 0.201, p = 0.008) and inversely related to cranial arteries blood flow velocities in patients with clinical and subclinical CVD (all p < 0.001). In sum, these findings allowed us to propose serum levels of anti-PON1 and anti-HDL antibodies as potential early biomarkers of endothelial damage and premature atherosclerosis in SLE, thus constituting useful therapeutic targets for the prevention of future CVD in these patients.

Safety and Efficacy of Mechanical Thrombectomy in Acute Ischemic Stroke of Anticoagulated Patients-A Prospective Observational Study.

BACKGROUND: Anticoagulated patients (APs) are excluded from the acute stroke management with alteplase in Europe, not in the United States. They could benefit from mechanical thrombectomy (MT), which was not undoubtedly proven. There are scarce data about its results in such patients. The authors' aim is to analyze the efficacy and safety of MT in APs presenting with an acute stroke in our institution. METHODS: Prospective observational study comparing 30 APs and 109 non-anticoagulated patients (N-APs) underwent direct MT without alteplase. Demographic data, clinical severity (National Institutes of Health Stroke Scale [NIHSS]), efficacy (recanalization thrombolysis in cerebral infarction [TICI] ≥ 2b and modified Rankin Scale score ≤ 2 at 3 months), and security (symptomatic intracranial hemorrhage [SICH], mortality at 3 months) were compared between both groups. RESULTS: In both groups men were more frequent (63.3% of APs were men and 61.5% of N-APs were men). Mean age was 73 in APs and 67.2 in N-APs. Median NIHSS was similar (17 APs; 16 N-APs), also TICI greater than or equal to 2b (93.3% APs; 89.9% N-APs). The 3-month modified Rankin Scale score less than or equal to 2 was 46.7% in APs and 55.2% in N-APs (P = .40). SICH was present in 16.7% of APs and 8.3% of N-APs (P = .15). Mortality at 3 months was 6.7% in APs and 19% in N-APs (P = .08). CONCLUSIONS: MT is a valid treatment option in APs. It achieves an efficacy as in N-APs with a tendency to suffer more from SICH, but lower mortality. We hypothesize that cardioembolic clots may be easier to be removed than atherotrombotics, and that embolic stroke in APs might be less severe than that in N-APs or might suffer less of other complications than atherotrombotics.

Convexity subarachnoid haemorrhage secondary to internal carotid stenosis: an indication for revascularisation.

With increasing prevalence due to an ageing population, carotid artery stenosis is a significant cause of stroke morbidity and mortality. The indication for revascularisation treatment in symptomatic carotid stenosis is widely documented and accepted in the scientific community. However, treatment of asymptomatic carotid stenosis remains controversial. We report a case of a 78-year-old woman who was admitted with a convexity subarachnoid haemorrhage (cSAH) secondary to an asymptomatic high-grade carotid artery stenosis. Two months later, she suffered an atherothrombotic ischaemic stroke and was referred to surgery. Transcranial Doppler studies showed impaired cerebral vasoreactivity and, after endarterectomy, the patient developed a reperfusion syndrome; both findings consisting of exhausted collaterals as the underlying mechanism. We propose that cSAH secondary to a high-grade internal carotid artery stenosis is a high risk marker for stroke, and revascularisation therapy should be considered.

Chronic migraine does not increase posterior circulation territory (PCT) infarct-like lesions.

UNLABELLED: Two population-based studies have found an increased prevalence of posterior circulation territory (PCT) infarct-like lesions in migraine, which seemed to increase with attack frequency. OBJECTIVE: To determine whether chronic migraine (CM) patients are at increased risk of PCT infarct-like lesions. METHODS: We prospectively obtained brain MRIs from adult women fulfilling CM criteria. To keep radiologists blinded we also obtained brain MRIs in 15 episodic migraine (EM) patients. MRIs were acquired on a 1.5 T unit. Protocol included whole brain weighted images in sagittal T1 (5 mm slices), axial FLAIR T2 (3 mm) and combined proton density and T2 fast spin echo (3 mm). Two independent neuroradiologists carefully analyzed all the images. RESULTS: One hundred women with CM participated. Their ages ranged from 18 to 68 years (mean 43.7) and the length of CM ranged from 0.5 to 38 years (mean 9.8). Sixty-three patients (63%) had at least one vascular risk factor. Thirty-three met analgesic overuse criteria. Fifty-one had a history of migraine with aura attacks, though aura frequency was below one per month in all patients except one. Eleven were not on preventatives. We found PCT infarct-like lesions in only 6 CM patients aged 42-64 years (mean age 54 years) who had at least two vascular risk factors. CONCLUSIONS: As frequency of PCT infarct-like lesions in our CM patients was in the low range than that found for EM in general population studies, we conclude that frequency of migraine attacks itself is not a factor increasing PCT infarct-like lesion risk.

Headache as a crucial symptom in the etiology of convexal subarachnoid hemorrhage.

BACKGROUND: Convexal subarachnoid hemorrhage has been associated with different diseases, reversible cerebral vasoconstriction syndrome and cerebral amyloid angiopathy being the 2 main causes. OBJECTIVE: To investigate whether headache at onset is determinant in identifying the underlying etiology for convexal subarachnoid hemorrhage. METHODS: After searching in the database of our hospital, 24 patients were found with convexal subarachnoid hemorrhage in the last 10 years. The mean age of the sample was 69.5 years. We recorded data referring to demographics, symptoms and neuroimaging. RESULTS: Cerebral amyloid angiopathy patients accounted for 46% of the sample, 13% were diagnosed with reversible cerebral vasoconstriction syndrome, 16% with several other etiologies, and in 25%, the cause remained unknown. Mild headache was present only in 1 (9%) of the 11 cerebral amyloid angiopathy patients, while severe headache was the dominant feature in 86% of cases of the remaining etiologies. CONCLUSION: Headache is a key symptom allowing a presumptive etiological diagnosis of convexal subarachnoid hemorrhage. While the absence of headache suggests cerebral amyloid angiopathy as the more probable cause, severe headache obliges us to rule out other etiologies, such as reversible cerebral vasoconstriction syndrome.

Long term evolution of patients treated in a TIA unit.

BACKGROUND: Transient ischemic attacks (TIA) entail a high risk of stroke recurrence, which depends on the etiology. New organizational models have been created, but there is not much information about the long-term evolution of patients managed according to these premises. Our aim is to refer the follow-up of patients attended according to our model of TIA Unit. METHODS: TIA Unit is located in the Emergency Department and staffed by vascular neurologists. Patients admitted during the Neurology night shift stayed in such Unit <48h with complete etiological study. Preventive treatment is instituted in patients discharged to a high resolution Neurology consult, in order to review in <2 weeks and subsequent follow-up. RESULTS: During a year 161 patients were attended, being admitted to the hospital 8.6%. A total of 1470 hospital days were avoided. Recurrence at 90 days was of 0.6%. Mean follow-up was 18.14 ± 8.02 months (0-34), total recurrence 6.2% (70% cardioembolic strokes). There were no complications derived from treatment. Cardiological events were recorded in 10.6%, neoplastic in 5%, cognitive impairment in 11%. There were 3 deaths unrelated nor to the stroke or its treatment. CONCLUSIONS: This model allows an early diagnosis and treatment of TIA, preventing recurrences of stroke in a long term. It detects atherothrombotic strokes, most of them admitted to the hospital, and it shows a greater difficulty for detecting all cardioembolic strokes. TIA Unit appeared to be safe in using anticoagulation therapy, as the follow-up shows. It shows the same quality of management than hospital admission, with a significant saving in hospital stays.

Oral anticoagulation in elderly patients as secondary prevention of cardioembolic strokes.

BACKGROUND: Stroke incidence increases with age. Atrial fibrillation (AF) is an important risk factor for ischemic stroke and its incidence also increases with age. However oral anticoagulant therapy (OAT) tends to be underused in the elderly population. METHODS: Elderly patients (> = 80 years) with an ischemic stroke admitted in our department between 1/7/2003 and 31/6/2005 were prospectively evaluated. Baseline characteristics, risk factors, treatment and etiology according to TOAST criteria were recorded. Patients treated with OAT were followed up in order to assess any side effect and stroke recurrence. Mean follow-up was of 19.5 months (7-45) from discharge. RESULTS: Sixty four out of a hundred and fifty nine elderly patients (40.25%) were classified as cardioembolic; mean age was 84.5 years (80-97) and 64.6% were women. AF had been previously identified in 60% of them (16.9% were on OAT and 40.6% on antiplatelet therapy). At discharge, 32 patients (49.2%) were on OAT. In the follow-up 4 patients (12.5%) suffered systemic haemorrhages (3 urinary, 1 gastrointestinal bleeding), with no change in their functional status. Mean INR in this group was 5.9 34567891011 and, in 3 of them, OAT was cancelled. No brain haemorrhages were recorded. Ischemic stroke recurred in 4 patients (INR < 1.8 in 3 of them; the other, INR 2.35). Three patients had died at the end of the follow-up, one of them as a consequence of ischemic stroke recurrence. DISCUSSION: Twenty eight point eight of stroke patients admitted in the period of study were >80 years. The high proportion of cardioembolic strokes in this age segment contrasts with the general underuse of OAT as antithrombotic prophylaxis. Our study suggests that OAT is a safe strategy when carefully prescribed, even for elderly patients.