Efficacy of recanalization therapy for ischemic stroke: multicenter hospital network experience.

PURPOSE: Stroke is a leading cause of long-term disability with high mortality rate in the first year after the event. In Campania, mechanical thrombectomy treatment significantly increases in the last 3 years, as well as hospitals delivering acute stroke treatments. The aim of this study is to demonstrate how a full opening of our stroke network improves stroke management and stroked patients' survival in Campania. MATERIAL AND METHODS: In Federico II University Hospital of Naples acting as a HUB center of 7 peripheral SPOKE hospitals in regional territory, 68 patients with acute ischemic stroke were evaluated with NIHSS and m-RS clinical scores and neuroradiological ASPECT scores, from January 1 to December 31, 2021. At hospital discharge, NIHSS score and three months after m-RS score were re-assessed to evaluate the therapeutic effects. RESULTS: Forty-two of 68 patients (63%) admitted to our hub center had ischemic acute stroke at CT evaluation; 29 patients had ASPECT score > 7 (69%), and 6 a score < 7 (14%). At admission, NIHSS score mean value was 10.75, and m-RS score mean value was 0.74. At discharge, NIHSS score mean value was 7.09. After three months, m-RS score mean value was 0.74. DISCUSSION: The inter-company agreement between Federico II University and several peripheral hospitals allows an absolute and relative increase in endovascular mechanical thrombectomy and intravenous thrombolysis procedures, with a relative prevalence of mechanical thrombectomy. A regional implementation of the stroke multi-disciplinary care system is hardly needed to ensure the optimum treatment for the largest number of patients, improving patient's outcome.

Dyslipidemia in Transplant Patients: Which Therapy?

Cardiovascular disease is the most important cause of death worldwide in recent years; an increasing trend is also shown in organ transplant patients subjected to immunosuppressive therapies, in which cardiovascular diseases represent one of the most frequent causes of long-term mortality. This is also linked to immunosuppressant-induced dyslipidemia, which occurs in 27 to 71% of organ transplant recipients. The aim of this review is to clarify the pathophysiological mechanisms underlying dyslipidemia in patients treated with immunosuppressants to identify immunosuppressive therapies which do not cause dyslipidemia or therapeutic pathways effective in reducing hypercholesterolemia, hypertriglyceridemia, or both, without further adverse events.

Case Report: Genetic Analysis of PEG-Asparaginase Induced Severe Hypertriglyceridemia in an Adult With Acute Lymphoblastic Leukaemia.

PEG-Asparaginase (also known as Pegaspargase), along with glucocorticoids (predominantly prednisolone or dexamethasone) and other chemotherapeutic agents (such as cyclophosphamide, idarubicin, vincristine, cytarabine, methotrexate and 6-mercaptopurine) is the current standard treatment for acute lymphoblastic leukaemia in both children and adults. High doses of PEG-asparaginase are associated with side effects such as hepatotoxicity, pancreatitis, venous thrombosis, hypersensitivity reactions against the drug and severe hypertriglyceridemia. We report a case of a 28-year-old male who was normolipidemic at baseline and developed severe hypertriglyceridemia (triglycerides of 1793 mg/dl) following treatment with PEG-asparaginase for acute lymphoblastic leukaemia. Thorough genetic analysis was conducted to assess whether genetic variants could suggest a predisposition to this drug-induced metabolic condition. This genetic analysis showed the presence of a rare heterozygous missense variant c.11G > A-p.(Arg4Gln) in the APOC3 gene, classified as a variant of uncertain significance, as well as its association with four common single nucleotide polymorphisms (SNPs; c.*40C > G in APOC3 and c.*158T > C; c.162-43G > A; c.-3A > G in APOA5) related to increased plasma triglyceride levels. To our knowledge this is the first case that a rare genetic variant associated to SNPs has been related to the onset of severe drug-induced hypertriglyceridemia.

Carotid Atherosclerosis, Ultrasound and Lipoproteins.

Carotid artery plaques are considered a measure of atherosclerosis and are associated with an increased risk of atherosclerotic cardiovascular disease, particularly ischemic strokes. Monitoring of patients with an elevated risk of stroke is critical in developing better prevention strategies. Non-invasive imaging allows us to directly see atherosclerosis in vessels and many features that are related to plaque vulnerability. A large body of evidence has demonstrated a strong correlation between some lipid parameters and carotid atherosclerosis. In this article, we review the relationship between lipids and atherosclerosis with a focus on carotid ultrasound, the most common method to estimate atherosclerotic load.

Inhibitors of Protein Convertase Subtilisin/Kexin 9 (PCSK9) and Acute Coronary Syndrome (ACS): The State-of-the-Art.

Acute Coronary Syndrome (ACS) remains one of the most frequent causes of morbidity and mortality in the world. Although the age- and gender-adjusted incidence of ACS is decreasing, the mortality associated with this condition remains high, especially 1-year after the acute event. Several studies demonstrated that PCSK9 inhibitors therapy determine a significant reduction of major adverse cardiovascular events (MACE) in post-ACS patients, through a process of plaque modification, by intervening in lipid metabolism and platelet aggregation and finally determining an improvement in endothelial function. In the EVACS (Evolocumab in Acute Coronary Syndrome) study, evolocumab allows >90% of patients to achieve LDL-C < 55 mg/dL according to ESC/EAS guidelines compared to 11% of patients who only receive statins. In the EVOPACS (EVOlocumab for Early Reduction of low-density lipoprotein (LDL)-cholesterol Levels in Patients With Acute Coronary Syndromes) study, evolocumab determined LDL levels reduction of 40.7% (95% CI: 45.2 to 36.2; p < 0.001) and allowed 95.7% of patients to achieve LDL levels <55 mg/dL. In ODYSSEY Outcome trial, alirocumab reduced the overall risk of MACE by 15% (HR = 0.85; CI: 0.78-0.93; p = 0.0003), with a reduced risk of all-cause mortality (HR = 0.85; CI: 0.73-0.98: nominal p = 0026), and fewer deaths for coronary heart disease (CHD) compared to the control group (HR = 0.92; CI: 0.76-1.11; p = 0.38). The present review aimed at describing the beneficial effect of PCSK9 inhibitors therapy early after ACS in reducing LDL circulating levels (LDL-C) and the risk of major adverse cardiovascular events, which was very high in the first year and persists higher later after the acute event.

Association between Non-HDL-C/HDL-C Ratio and Carotid Intima-Media Thickness in Post-Menopausal Women.

Atherogenic lipoproteins (particularly, very low-density lipoproteins, VLDL) are associated with subclinical atherosclerosis. The present study aims at evaluating whether routinely analysed lipid parameters are associated with carotid intima-media thickness, a proxy for subclinical atherosclerosis. Lipid parameters from 220 post-menopausal women undergoing ultrasound investigation of the carotid arteries were analysed. Forty-five percent of women showed subclinical atherosclerosis on carotid ultrasound. The mean carotid intima-media thickness was 1.26 ± 0.38 mm. The mean value of the non-HDL-C/HDL-C ratio was 3.1 ± 1.2. Univariate analysis showed a significant association between non-HDL-C/HDL-C ratio and intima-media thickness (r = 0.21, p = 0.001). After adjusting for cardiovascular risk factors (age, systolic blood pressure, smoking, body mass index Homeostasis model assessment: insulin resistance and high-sensitivity C-Reactive-Protein), multivariate analysis showed a significant association between non-HDL-C/HDL-C ratio and intima-media thickness (ß = 0.039, p = 0.04). Logistic regression analysis showed that the highest tertile of the non-HDL-C/HDL-C ratio was associated with the presence of carotid plaques (OR = 3.47, p = 0.003). Finally, a strong correlation between non-HDL-C/HDL-C ratio and cholesterol bound to VLDL (r = 0.77, p < 0.001) has been found. Non-HDL-C/HDL-C ratio is associated with the presence of carotid atherosclerosis in post-menopausal women and is strongly correlated to VLDL-C levels.

Carotid artery diameter and wall stiffness in proteinuric renal disease without severely reduced kidney function.

PURPOSE: To evaluate the carotid artery diameter, and wall thickness and stiffness in patients with glomerulopathy and proteinuria without severely reduced kidney function. METHODS: We compared 30 control subjects to 30 patients with glomerular disease, proteinuria, and glomerular filtration rate > 30 ml/min/1.73 m(2) : membranous glomerulonephritis (n = 13), minimal change disease (n = 2), focal and segmental glomerulosclerosis (n = 3), IgA nephropathy (n = 5), lupus nephritis (n = 5), antiphospholipid antibody nephropathy (n = 1), cryoglobulinemic glomerulonephritis (n = 1). The laboratory evaluations included carotid artery diameter, intima-media thickness, and stiffness measurements. RESULTS: Carotid cross-sectional area of intima-media complex was thicker in patients (18.6 ± 1.4 [x ± SEM]) than in controls (14.8 ± 0.6 mm(2) , p = 0.014), as was carotid artery wall stiffness (8.96 ± 0.86 versus 5.65 ± 0.38, [x ± SEM], p < 0.01). This difference remained significant after adjustment for age, sex, and metabolic cardiovascular risk factors: carotid stiffness was 9.19 ± 0.67 (99% confidence interval [CI] 7.40-10.98)] in patients and 4.80 ± 0.75 (99% CI 2.79-7.11) in controls; adjusted mean difference 4.40 (99% CI 1.46-7.34); p <0.001. CONCLUSIONS: This study showed, for the first time, signs of altered structural and elastic properties of the arterial wall in patients with proteinuria and glomerular disease without severely reduced kidney function.

Peri-procedural tight glycemic control during early percutaneous coronary intervention is associated with a lower rate of in-stent restenosis in patients with acute ST-elevation myocardial infarction.

OBJECTIVE: We examined the effects of peri-procedural intensive glycemic control (IGC) during early percutaneous coronary intervention (PCI) on restenosis rate in hyperglycemic patients with ST-segment elevation myocardial infarction (STEMI). RESEARCH DESIGN AND METHODS: A total of 165 hyperglycemic patients (glucose ≥ 140 mg/dl) with first STEMI undergoing PCI were studied. Patients were randomized to IGC for almost 24 h after PCI (n = 82; glucose, 80-140 mg/dl) followed by multidose sc insulin during the hospital stay or conventional glycemic control (CGC; n = 83; glucose, 180-200 mg/dl) followed by conventional therapy. Coronary angiography was performed at study entry and at 6-month follow-up. Blood samples for glycemia, hemoglobin A1c, inflammatory markers (C-reactive protein and TNF-α), monocyte chemoattractant-protein-1, and oxidative stress (nitrotyrosine) were collected immediately before and 24 h, 30 and 180 d after PCI. RESULTS: After insulin infusion, mean plasma glucose during the peri-procedural period was greater in the CGC group than in the IGC group (CGC, 191 ± 15 mg/dl; IGC, 145 ± 35 mg/dl; P < 0.001). After the insulin infusion period, the levels of markers of oxidative stress (nitrotyrosine), inflammation (C-reactive protein, TNF-α), and monocyte chemoattractant-protein-1 were significantly higher in CGC patients compared with IGC patients. Moreover, ICG during PCI reduces restenosis by half (48 and 24%) at 6 months. During follow-up, there was no difference in mortality rates, glucose, inflammatory and oxidative stress markers among the groups. In-stent restenosis was positively associated with mean plasma glucose levels as well as oxidative stress and inflammatory markers during the insulin infusion period. CONCLUSIONS: In hyperglycemic patients with STEMI, optimal peri-procedural glycemic control by reducing oxidative stress and inflammation may improve the outcome after PCI.

Comparison of two diets of varying glycemic index on carotid subclinical atherosclerosis in obese children.

Childhood obesity is associated with an increased carotid intima-media thickness (IMT) and stiffness. Increased carotid wall thickening and rigidity are considered markers of subclinical atherosclerosis. The aim of the present study was to test the effect of two hypocaloric diets of varying glycemic index on weight loss and markers of subclinical atherosclerosis in obese children. Seventy consecutive obese children attending the Outpatient Weight Clinic of the Department of Pediatrics were invited to participate in an intensive dietary protocol. Twenty-six accepted and were randomly assigned to two different groups: the first group followed a hypocaloric low-glycemic index diet and the second a hypocaloric high-glycemic index diet. Anthropometric measures and biochemical tests were performed in all children. Quantitative B-mode ultrasound scans were used to measure intima-media thickness (IMT) and diameters of the common carotid artery. Considering both groups together, at 6 months, body mass index decreased from 28.3 +/- 3.1 to 25.8 +/- 3.3 kg/m(2), systolic blood pressure from 119 +/- 12 to 110 +/- 11 mmHg (P< 0.001), diastolic blood pressure from 78 +/- 8 to 74 +/- 7 mmHg (P< 0.001), IMT from 0.48 +/- 0.05 to 0.43 +/- 0.07 mm (P< 0.001), stiffness from 3.57 +/- 1.04 to 2.98 +/- 0.94 mm (P = 0.002), and high-sensitivity C-reactive protein from 1.5 +/- 0.9 (values log transformed) to 0.4 +/- 1.1 (P < 0.001). No differences were detectable in fasting serum triglycerides, total cholesterol, and high-density lipoprotein cholesterol. Insulin resistance (calculated by the HOmeostatic Model Assessment index [HOMA] score) significantly reduced only in the low-glycemic-index diet group (P < 0.04). In conclusion, this study confirms a benefit of hypocaloric diets on carotid IMT and stiffness in obese children and demonstrates, for the first time, an amelioration of insulin sensitivity in obese children after a low-glycemic index diet. These results justify the advice to obese children to follow a low-glycemic index diet in order to improve their cardiometabolic profile.