Factors associated with high-risk plaque characteristics among patients with medium to severe carotid artery stenosis.

OBJECTIVE: There has been a large discussion in literature regarding the proper management of asymptomatic patients with significant carotid artery stenosis (CAS). This study aims to identify potential risk factors associated with high-risk carotid plaques. METHODS: This is a retrospective study based on a prospective database. Eligible patients had medium to severe symptomatic or asymptomatic carotid stenosis (≥50%, NASCET criteria). This study will analyze patients recruited by our institution as part of the multicenter TAXINOMISIS project (NCT03495830). According to protocol, all patients underwent a colored Duplex ultrasound examination and a magnetic resonance angiography (MRA) at baseline. Carotid plaques were classified according to Gray-Weale ultrasonographic criteria (Types I-V). Main outcomes included the occurrence of symptoms, the high/low echogenicity of the plaque, the existence of intraplaque hemorrhage (IPH) and the existence of lipidic/necrotic core. Secondary, risk factors associated with the aforementioned outcomes were evaluated. RESULTS: A total of 62 patients (mean age: 68.7+/-9.3 years, 66.1% males, 24.2% symptomatic) were recruited by our department. Mean carotid stenosis was 70.81%±13.53%. In multivariate regression analysis, CRP > 2mg/l was strongly associated with symptomatic stenosis (OR=9.92 [1.12-88.178]; P=0.039), and low HDL levels (<1200mmol/l) were associated with lipidic/necrotic plaque core (OR=16.88 [1.10-259.30]; P=0.043). Low HDL levels (OR=7.22 [1.00-51.95], P=0.049) and HbA1c >7% (OR=0.08 [0.01-0.93], P=0.044) were associated with type III/IV plaques whereas HgAbc1 >7% (OR=14.26 [1.21-168.34], P=0.035) was associated with Type V plaques. CONCLUSIONS: This preliminary study has revealed some potential risk factors associated with unstable carotid plaques. This data could help the future development of prognostic models in order to early detect patients that could benefit from further intervention.

Wildfire risk management in the era of climate change.

The August 8, 2023R Lahaina fire refocused attention on wildfires, public alerts, and emergency management. Wildfire risk is on the rise, precipitated through a combination of climate change, increased development in the wildland-urban interface (WUI), decades of unmitigated biomass accumulation in forests, and a long history of emphasis on fire suppression over hazard mitigation. Stemming the tide of wildfire death and destruction will involve bringing together diverse scientific disciplines into policy. Renewed emphasis is needed on emergency alerts and community evacuations. Land management strategies need to account for the impact of climate change and hazard mitigation on forest ecosystems. Here, we propose a long-term strategy consisting of integrating wildfire risk management in wider-scope forest land management policies and strategies, and we discuss new technologies and possible scientific breakthroughs.

The effectiveness of hyperbaric oxygen therapy on the final outcome of patients with sudden sensorineural hearing loss.

PURPOSE: To evaluate the therapeutic effect of the combination of systemic steroids (SS) and hyperbaric oxygen therapy (HBOT) in patients with idiopathic sudden sensorineural hearing loss (SSNHL). MATERIALS AND METHODS: Fifty patients with idiopathic sudden sensorineural hearing loss were allocated into 2 groups: the control group received Dexamethasone IV (SS) and the therapy group received Dexamethasone IV combined with 15 sessions of hyperbaric oxygen therapy (SS + HBOT) as initial treatment. Hearing assessment was performed at the admission to hospital and 3 months after the onset of treatment. Siegel's criteria were used to evaluate the hearing outcomes. Prognostic factors were identified by linear regression analyses. RESULTS: Hearing improvement rate was 64 % in the therapy group and 56 % in the control group, difference which was not statistically significant (p = 0.369). Furthermore, when patients of each group were categorized into 5 subgroups by disease severity (mild, moderate, moderate to severe, severe, profound), differences in treatment outcome between the subgroups of the same severity were not significant. A descending type audiogram curve was proven an unfavorable prognostic factor in both groups, as it led to a significantly lower hearing gain (30 dB) compared to other curve shapes (b = -29.10, 95 % CI = -56.39, -1.82). CONCLUSIONS: The addition of hyperbaric oxygen therapy to systemic steroids caused no significant hearing improvement, despite a mild tendency toward a greater improvement rate within the combination group. More prospective randomized trials with larger series of patients could shed even more light on the effectiveness of combination therapy (SS + HBOT) in patients affected by SSNHL.

Computational modeling of atherosclerotic plaque progression in carotid lesions with moderate degree of stenosis.

Carotid atherosclerotic plaque growth leads to the progressive luminal stenosis of the vessel, which may erode or rupture causing thromboembolism and cerebral infarction, manifested as stroke. Carotid atherosclerosis is considered the major cause of ischemic stroke in Europe and thus new imaging-based computational tools that can improve risk stratification and management of carotid artery disease patients are needed. In this work, we present a new computational approach for modeling atherosclerotic plaque progression in real patient-carotid lesions, with moderate to severe degree of stenosis (>50%). The model incorporates for the first time, the baseline 3D geometry of the plaque tissue components (e.g. Lipid Core) identified by MR imaging, in which the major biological processes of atherosclerosis are simulated in time. The simulated plaque tissue production results in the inward remodeling of the vessel wall promoting luminal stenosis which in turn predicts the region of the actual stenosis progression observed at the follow-up visit. The model aims to support clinical decision making, by identifying regions prone to plaque formation, predict carotid stenosis and plaque burden progression, and provide advice on the optimal time for patient follow-up screening.

Omentin Is Independently Associated with Stroke Severity and Ipsilateral Carotid Artery Stenosis in Patients with Acute Cerebral Ischemia.

Mounting evidence indicates an association between adipokines and inflammation-related atherosclerosis. Here, we sought to investigate the association of vaspin and omentin with clinical characteristics and outcomes of patients with acute cerebral ischemia (ACI). Consecutive ACI patients were evaluated within 24 h from symptom-onset. Stroke aetiology was classified using TOAST criteria. Adipokines were assayed using quantikine enzyme immunoassay commercially available kits. Stroke severity was assessed by NIHSS-score, and ipsilateral carotid stenosis (≥50% by NASCET criteria) by ultrasound and CT/MR angiography. Major cerebrovascular events were assessed at three months. We included 135 ACI patients (05 (78%) and 30 (22%) with acute ischemic stroke and transient ischemic attack, respectively; mean age ± SD: 59 ± 10 years; 68% men; median NIHSS-score: 3 (IQR:1-7)). Omentin was strongly correlated to admission stroke severity (Spearman rho coefficient: +0.303; p < 0.001). Patients with ipsilateral carotid stenosis had higher omentin levels compared to patients without stenosis (13.3 ± 8.9 ng/mL vs. 9.5 ± 5.5 ng/mL, p = 0.014). Increasing omentin levels were independently associated with higher stroke severity (linear regression coefficient = 0.290; 95%CI: 0.063-0.516; p = 0.002) and ipsilateral carotid stenosis (linear regression coefficient = 3.411; 95%CI: 0.194-6.628; p = 0.038). No association of vaspin with clinical characteristics and outcomes was found. Circulating omentin may represent a biomarker for the presence of atherosclerotic plaque, associated with higher stroke severity in ACI patients.

Calibrations and validations of biological models with an application on the renal fibrosis.

We calibrate a mathematical model of renal tubulointerstitial fibrosis by Hao et al which is used to explore potential drugs for Lupus Nephritis, against a real data set of 84 patients. For this purpose, we present a general calibration procedure which can be used for the calibration analysis of other biological systems as well. Central to the procedure is the idea of designing a Bayesian Gaussian process (GP) emulator that can be used as a surrogate of the fibrosis mathematical model which is computationally expensive to run massively at every input value. The procedure relies on detecting influential model parameters by a GP-based sensitivity analysis, and calibrating them by specifying a maximum likelihood criterion, tailored to the application, which is optimized via Bayesian global optimization.

Left ventricular geometry as a major determinant of left ventricular ejection fraction: physiological considerations and clinical implications.

The limited myocardial fibre thickening and shortening alone cannot explain the marked left ventricular (LV) volume reduction during LV ejection. This can only be achieved with LV helical (spiral) orientation of myocardial fibres, which is determined by the non-contractile LV myocardial components (intrasarcomeric and extrasarcomeric cytoskeleton, extracellular matrix). Preservation of LV ejection fraction (LVEF) in heart failure (HF) is due to the presence of normal ellipsoid LV configuration and spiral myocardial fibre orientation. Conversely, reduction of LVEF in HF results from spherical LV configuration associated with impaired myocardial fibre orientation. These mechanisms are supported by the fact that biomarkers of inflammation and fibrosis are strong predictors of LV reverse remodelling in HF with reduced LVEF (HFrEF) and therapeutic interventions in HFrEF that retard or inhibit extracellular matrix remodelling are effective, whereas those that increase myocardial contractility are ineffective. Thus, current classification of HF, based on LVEF, should be revised, and future therapy in HF should focus on interventions affecting the non-contractile LV myocardial components rather than on LV myocardial contractility.

Favorable Pulse Wave Augmentation Indices and Left Ventricular Diastolic Profile in ß-Thalassemia Minor.

ß-Thalassemia minor (ß-Τm) is associated with rheological and biochemical alterations that can affect cardiovascular function. We aimed to evaluate the elastic arterial properties and the pulse wave augmentation indices in a population of patients with ß-Τm. Seventy-five individuals with ß-Τm (age 55.5 [42.75-65.25], women 48%) and 127 controls (age 57 years [48-63], women 55.1%) underwent comprehensive echocardiographic evaluation and applanation tonometry of the radial and femoral artery. Pulse wave analysis revealed that augmentation pressure, augmentation index (AIx), and heart rate-corrected AIx were significantly lower (median [interquartile range]: 8.75 [4.625-13] vs 11 [6.5-14.5], P = .017; 26.5 [17.5-33.375] vs 30.5 [20.75-37.5], P = .014; and 22.25 [15.125-29.5] vs 27 [20.5-33], P = .008, respectively) in the ß-Τm group compared to controls. The left atrial active emptying volume was significantly lower and the isovolumic relaxation time was shorter in the ß-Τm group compared to the control group (10.2 [7.4-14.4] vs 12.0 [8.6-15.8], P = .040 and 78 [70-90] vs 90 [70-104], P = .034, respectively). ß-Thalassemia minor is associated with favorable pulse wave augmentation indices and left ventricular diastolic function profile in asymptomatic individuals with cardiovascular risk factors.

SPECT and PET in ischemic heart failure.

Heart failure is a common clinical syndrome associated with significant morbidity and mortality worldwide. Ischemic heart disease is the leading cause of heart failure, at least in the industrialized countries. Proper diagnosis of the syndrome and management of patients with heart failure require anatomical and functional information obtained through various imaging modalities. Nuclear cardiology techniques play a main role in the evaluation of heart failure. Myocardial single photon emission computed tomography (SPECT) with thallium-201 or technetium-99 m labelled tracers offer valuable data regarding ventricular function, myocardial perfusion, viability, and intraventricular synchronism. Moreover, positron emission tomography (PET) permits accurate evaluation of myocardial perfusion, metabolism, and viability, providing high-quality images and the ability of quantitative analysis. As these imaging techniques assess different parameters of cardiac structure and function, variations of sensitivity and specificity have been reported among them. In addition, the role of SPECT and PET guided therapy remains controversial. In this comprehensive review, we address these controversies and report the advances in patient's investigation with SPECT and PET in ischemic heart failure. Furthermore, we present the innovations in technology that are expected to strengthen the role of nuclear cardiology modalities in the investigation of heart failure.

Digital clubbing: forms, associations and pathophysiology.

Among proposed mechanisms to explain digital clubbing, the release of cytokines, specifically vascular endothelial growth factor and platelet-derived growth factor, from aggregated platelets and megakaryocytes has emerged as the most likely explanation. This review describes these and other contributory processes.

Usefulness of Rabbit Anti-thymocyte Globulin in Patients With Giant Cell Myocarditis.

Giant cell myocarditis (GCM) is an aggressive inflammatory myocardial disease. Immunosuppression is an effective treatment for some cases. However, the duration of action of agents such as muromonab CD3 is short and others such as the calcineurin inhibitors may lead to renal failure. Here we describe the outcome of a novel approach to treatment using rabbit anti-thymocyte globulin (RATG). A retrospective analysis of 6 patients treated with RATG for GCM was performed. Diagnosis was confirmed by endomyocardial biopsy, and RATG was administered with a high dose of corticosteroids. None of the patients had cytokine release syndrome or leukopenia, and 5 had thrombocytopenia (2 of them severe). Only 1 had a serious bleeding event that occurred after implantation of mechanical circulatory support. None developed impaired renal function after the treatment. Five were successfully discharged home with an increase in global left ventricular ejection fraction of 29%. Four are currently alive without recurrent disease, 1 of them after heart transplantation, with a mean follow-up of 970 days (423 to 1,875 days), left ventricular ejection fraction of 53%, and all in current New York Heart Association Classification class ≤II. Only 1 case had GCM recurrence. There were 2 deaths: one because of intracranial bleeding after mechanical circulatory support implantation and the other caused by primary graft dysfunction. In conclusion, patients with GCM can be successfully immunosuppressed with RATG and corticosteroids, thereby avoiding renal impairment. Early thrombocytopenia is the main adverse event. Larger cohorts of patients are necessary to compare the different immunosuppressant strategies available for GCM in a randomized fashion.

Risk factors for the development of persistent type II endoleaks after endovascular repair of infrarenal abdominal aortic aneurysms.

PURPOSE: To determine, based on preoperative imaging findings, which patients treated with endovascular abdominal aneurysm repair are at high risk for the development of persistent type II endoleaks. MATERIALS AND METHODS: Preoperative computed tomography (CT) angiographies of 136 patients, treated endovascularly, were retrospectively examined for possible anatomic predictors of type II endoleak development. Specifically, the number of patent aortic branches and thrombus load parameters (i.e., thickness, perimeter, area, and localization) were recorded. Thrombus load parameters were evaluated at the level of maximum aneurysm diameter, at the level of sac lumbar arteries' ostia, and at the level of inferior mesenteric artery ostium. Follow-up CT angiographies were also studied for the presence of persistent type II endoleaks (present at six-month follow-up examination). The association of these anatomic features with the development of persistent type II endoleaks was assessed using logistic regression analysis. RESULTS: Aortic branch patency increased the risk for persistent type II endoleak development, while thrombus load parameters decreased this risk. In multiple logistic regression analysis, the total number of patent aortic branches (odds ratio = 4.23, 95% confidence interval = 1.72-10.42, P = 0.002 for each additional branch), and the percentage of aortic perimeter covered by a thrombus at the level of the sac lumbar arteries' ostia (odds ratio = 0.16, 95% confidence interval = 0.06-0.44, P < 0.001 for a 15% increase) were independent predictors. CONCLUSION: Anatomic characteristics of a preoperative aorta can be used to predict patients with higher risk for persistent type II endoleak development.

Palliative treatment of rectal carcinoma recurrence using radiofrequency ablation.

PURPOSE: To evaluate the safety and efficacy of CT-guided radiofrequency (RF) ablation for the palliative treatment of recurrent unresectable rectal tumors. MATERIALS AND METHODS: Twenty-seven patients with locally recurrent rectal cancer were treated with computed tomography (CT)-guided RF ablation. Therapy was performed with the patient under conscious sedation with a seven- or a nine-array expandable RF electrode for 8-10 min at 80-110°C and a power of 90-110 W. All patients went home under instructions the next day of the procedure. Brief Pain Inventory score was calculated before and after (1 day, 1 week, 1 month, 3 months, and 6 months) treatment. RESULTS: Complete tumor necrosis rate was 77.8% (21 of a total 27 procedures) despite lesion location. BPI score was dramatically decreased after the procedure. The mean preprocedure BPI score was 6.59, which decreased to 3.15, 1.15, and 0.11 at postprocedure day 1, week 1, and month 1, respectively, after the procedure. This decrease was significant (p < 0.01 for the first day and p < 0.001 for the rest of the follow-up intervals (paired Student t test; n - 1 = 26) for all periods during follow-up. Six patients had partial tumor necrosis, and we were attempted to them with a second procedure. Although the necrosis area showed a radiographic increase, no complete necrosis was achieved (secondary success rate 65.6%). No immediate or delayed complications were observed. CONCLUSION: CT-guided RF ablation is a minimally invasive, safe, and highly effective technique for treatment of malignant rectal recurrence. The method is well tolerated by patients, and pain relief is quickly achieved.

Industrial emergency planning modeling: a first step toward a robustness analysis tool.

The purpose of this paper is to present a model-based approach to the analysis of the robustness of industrial emergency plans, established by the European Union SEVESO II Directive. Robustness is defined in terms of the capacity of the mechanism to respond to deteriorated conditions. Analysis of emergency plans has been so far based mainly upon lessons learned from past major accidents or exercises, which do not allow for an integral analysis of the response mechanism. The proposed methodology is based upon a systemic, hierarchical and generic model of an internal or external industrial emergency plan, using the FIS modeling approach. The process generally found within an industrial emergency plan is identified through the model. Potential failures are estimated through an a priori analysis of the plan model and an a posteriori analysis of lessons learned from exercises and past accidents. Assessment of the plan's functions is carried out via assessment checklists, structured via the systemic model for each of the plan's process. This approach can hence be used as a toolbox both for the assessment of existing plans and the development of industrial emergency plans.