Management of carotid atherosclerosis in stroke.

Internal carotid artery atherosclerosis is a major risk factor for stroke, accounting for 15-20% of ischaemic strokes. Revascularisation procedures-either carotid endarterectomy or carotid artery stenting-can reduce the risk of stroke for those with significant (>50%) luminal stenosis but particularly for those with more severe (70-99%) stenosis. However, advances in medical pharmacotherapy have implications for the relative benefit from surgery for symptomatic carotid atherosclerosis, as well as our approach to asymptomatic disease. This review considers the evidence underpinning the current medical and surgical management of symptomatic carotid atherosclerosis, the importance of factors beyond the degree of luminal stenosis, and developments in therapeutic strategies. We also discuss the importance of non-stenotic but high-risk carotid atherosclerotic plaques on the cause of stroke, and their implications for clinical practice.

The Use of CRISPR-Cas9 Genetic Technology in Cardiovascular Disease: A Comprehensive Review of Current Progress and Future Prospective.

Over the last century, there have been major landmark developments in the field of medicine, enabling us to control and cure various diseases on a larger scale. A few of these include the discovery of antibiotics, the development of vaccines, and the origin of organ and tissue transplants. The continued quest for innovation in microbiology and medicine has helped humankind save millions of lives and decrease morbidity at the global level. Genetic medicine has grown significantly in the last two decades and appears to be the next frontier of curative therapies for chronic diseases. One important landmark in genetic medicine is the development of CRISPR (clustered, regularly interspaced short palindromic repeats) technology. In this article, we describe the basic structure and function of the CRISPR-Cas9 system, which, simply put, consists of an RNA part and a protein. It works as a molecular scissor that can perform targeted cuts followed by repairs in and around the genes of interest to attain favorable translational outcomes. We focused on summarizing recent studies using CRISPR-Cas9 technology in diagnosing and treating cardiovascular disease. These studies are primarily experimental and limited to animal models. However, their results are promising enough to anticipate that this technology will undoubtedly be available in clinical medicine in the coming years. CRISPR-Cas9-mediated gene editing has been used to study and potentially treat congenital heart disease, hyperlipidemias, arrhythmogenic cardiomyopathies, and the prevention of ischemia-reperfusion injury. Despite the current progress, we recognize the several challenges this technology faces, including funding for research, improving precision and reproducible results for human subjects, and establishing protocols for ethical compliance so that it is acceptable to the scientific community and the general public.

Comorbidities and their association with COVID-19 mortality in Mexico between January 2020 and August 2021.

By August 17, 2021, 4.3 million people had died globally as a result of SARS-CoV-2 infection. While data collection is ongoing, it is abundantly obvious that this is one of the most significant public health crises in modern history. Consequently, global efforts are being made to attain a greater understanding of this disease and to identify risk factors associated with more severe outcomes. The goal of this study is to identify clinical characteristics and risk factors associated with COVID-19 mortality in Mexico. The dataset used in this study was released by Sistema Nacional de Vigilancia Epidemiologica de Enfermedades Respiratorias (SISVER) de la Secretaría de Salud and contains 2.9 million COVID-19 cases. The effects of risk factors on COVID-19 mortality were estimated using multivariable logistic regression models with generalized estimation equation and Kaplan-Meier curves. Case fatality rates, case hospitalization rates are also reported using the Centers for Disease Control and Prevention (CDC) USA death-to-case ratio method. In general, older males with pre-existing conditions had higher odds of death. Age greater than 40, male sex, hypertension, diabetes, and obesity are associated with higher COVID-19 mortality. End-stage renal disease, chronic obstructive pulmonary disease, and immunosuppression are all linked with COVID-19 patient fatalities. Smoking and Asthma are associated with lower COVID-19 mortality which is consistent with findings from the article published in Nature based on National Health Service (NHS) of UK dataset (17 million cases). Intensive care unit (ICU), patient intubation, and pneumonia diagnosis are shown to substantially increase mortality risk for COVID-19 patients.

Carotid atherosclerotic plaque microcalcification is independently associated with recurrent neurovascular events: A pilot study.

BACKGROUND: Microcalcification and macrocalcification are critical processes in atherosclerotic plaque progression, though how these processes relate to the risk of stroke recurrence in symptomatic carotid atherosclerosis is poorly understood. METHODS: We performed a post hoc analysis of data from the ICARUSS (Imaging Carotid Atherosclerosis in the Recovery and Understanding of Stroke Severity) study, where individuals with acute ischemic stroke originating from ipsilateral carotid stenosis of ⩾ 50% underwent 18F-sodium fluoride positron emission tomography (NaF-PET) to measure microcalcification. Tracer uptake was quantified using maximum tissue-to-background ratio (TBRmax). Macrocalcification was measured on computed tomography (CT) using Agatston scoring. Patients were followed up for 6 months for recurrent ipsilateral neurovascular events. RESULTS: Five (27.8%) of 18 individuals had a recurrent ischemic stroke or transient ischemic attack. Ipsilateral carotid plaque NaF uptake at baseline was higher in those with recurrent events compared to those without, and this association remained after adjustment for other vascular risk factors (adjusted odds ratio (aOR) = 1.24, 1.03-1.50). Macrocalcification score in the symptomatic artery was also significantly independently associated with ipsilateral recurrence, but the effect size was relatively smaller (aOR = 1.12, 1.06-1.17 for each 100 unit increase). CONCLUSIONS: Our findings indicate that microcalcification in symptomatic carotid plaques is independently associated with ipsilateral ischemic stroke recurrence. Furthermore, differences in the extent of active microcalcification in macrocalcified plaques may help explain variation in the relationship between calcified carotid plaques and stroke recurrence reported in the literature. Our pilot study indicates that evaluation of carotid artery microcalcification using NaF-PET may be a useful method for risk-stratification of carotid atherosclerosis, though our findings require confirmation in larger cohorts.

Exploring the antioxidant and antimicrobial potential of three common seaweeds of Saint Martin's Island of Bangladesh.

Antioxidants, which have long been deemed an indispensable guardian of human health, play a pivotal role in bolstering the body's defense against a plethora of diseases. Three well-recognized seaweeds in Bangladesh, including Caulerpa racemosa, Padina tetrastromatica, and Hypnea musciformis, were subjected to meticulous analysis to reveal their phytochemical composition, antioxidant activity, and antimicrobial efficacy using advanced spectroscopic and disc diffusion methods. Intriguingly, we observed that C. racemosa emerges as frontrunners, possessing a substantial arsenal of phenol (143.08 ± 18.51 mg gallic acid equivalent g─1) and flavonoid (63.79 ± 2.16 mg rutin equivalent g─1). More fundamentally, C. racemosa exhibits a notable enrichment in the content of tannin (73.58 mg RE g─1) and chlorophyll (13.50 mg g─1), as well as, antioxidant capacity (4457.67 µg g─1). P. tetrastromatica, on the other hand, displayed commendable effectiveness in scavenging the DPPH radical, with percentages ranging from 53.98 to 62.17%. In terms of hydroxyl radical (OH•) scavenging activity, C. racemosa exhibited the highest efficacy at 400 g mL─1. Fascinatingly, C. racemosa exhibited an impressive antioxidant potential, as evidenced by its exceptionally low IC50 value of 5.58 µg mL-1 for OH• scavenging, whereas P. tetrastromatica showed impressively low value of 0.96 µg mL-1 for DPPH scavenging. Although the three seaweeds demonstrated limited efficacy against a spectrum of five human pathogenic bacteria, their potential as abundant sources of antioxidants remains unscathed. Notably, heatmap and PCA analysis revealed that C. racemosa and P. tetrastromatica emerge as the leading contender for studied antioxidant compounds, demonstrating their proclivity for antioxidant extraction, a trait that could be exploited for large-scale production of these valuable compounds.

Molecular magnetic resonance imaging of myeloperoxidase activity identifies culprit lesions and predicts future atherothrombosis.

Aims: Unstable atherosclerotic plaques have increased activity of myeloperoxidase (MPO). We examined whether molecular magnetic resonance imaging (MRI) of intraplaque MPO activity predicts future atherothrombosis in rabbits and correlates with ruptured human atheroma. Methods and results: Plaque MPO activity was assessed in vivo in rabbits (n = 12) using the MPO-gadolinium (Gd) probe at 8 and 12 weeks after induction of atherosclerosis and before pharmacological triggering of atherothrombosis. Excised plaques were used to confirm MPO activity by liquid chromatography-tandem mass spectrometry (LC-MSMS) and to determine MPO distribution by histology. MPO activity was higher in plaques that caused post-trigger atherothrombosis than plaques that did not. Among the in vivo MRI metrics, the plaques' R1 relaxation rate after administration of MPO-Gd was the best predictor of atherothrombosis. MPO activity measured in human carotid endarterectomy specimens (n = 30) by MPO-Gd-enhanced MRI was correlated with in vivo patient MRI and histological plaque phenotyping, as well as LC-MSMS. MPO-Gd retention measured as the change in R1 relaxation from baseline was significantly greater in histologic and MRI-graded American Heart Association (AHA) type VI than type III-V plaques. This association was confirmed by comparing AHA grade to MPO activity determined by LC-MSMS. Conclusion: We show that elevated intraplaque MPO activity detected by molecular MRI employing MPO-Gd predicts future atherothrombosis in a rabbit model and detects ruptured human atheroma, strengthening the translational potential of this approach to prospectively detect high-risk atherosclerosis.

Understanding patient and family experiences of critical care in Bangladesh and India: What are the priority actions to promote person-centred care?

Patients' experiences in the intensive care unit (ICU) can enhance or impair their subsequent recovery. Improving patient and family experiences on the ICU is an important part of providing high quality care. There is little evidence to guide how to do this in a South Asian critical care context. This study addresses this gap by exploring the experiences of critically ill patients and their families in ICUs in Bangladesh and India. We elicit suggestions for improvements from patients, families and staff and highlight examples of practices that support person-centred care. This multi-site hospital ethnography was carried out in five ICUs in government hospitals in Bangladesh and India, selected using purposive sampling. Qualitative data were collected using non-participant observation and semi-structured interviews and analysed using reflexive thematic analysis. A total of 108 interviews were conducted with patients, families, and ICU staff. Over 1000 hours of observation were carried out across the five study sites. We identified important mediators of patient and family experience that span many different aspects of care. Factors that promote person-centred care include access to ICU for families, support for family involvement in care delivery, clear communication with patients and families, good symptom management for patients, support for rehabilitation, and measures to address the physical, environmental and financial needs of the family. This study has generated a list of recommendations that can be used by policy makers and practitioners who wish to implement person-centred principles in the ICU.

Stem cell therapy for heart failure in the clinics: new perspectives in the era of precision medicine and artificial intelligence.

Stem/progenitor cells have been widely evaluated as a promising therapeutic option for heart failure (HF). Numerous clinical trials with stem/progenitor cell-based therapy (SCT) for HF have demonstrated encouraging results, but not without limitations or discrepancies. Recent technological advancements in multiomics, bioinformatics, precision medicine, artificial intelligence (AI), and machine learning (ML) provide new approaches and insights for stem cell research and therapeutic development. Integration of these new technologies into stem/progenitor cell therapy for HF may help address: 1) the technical challenges to obtain reliable and high-quality therapeutic precursor cells, 2) the discrepancies between preclinical and clinical studies, and 3) the personalized selection of optimal therapeutic cell types/populations for individual patients in the context of precision medicine. This review summarizes the current status of SCT for HF in clinics and provides new perspectives on the development of computation-aided SCT in the era of precision medicine and AI/ML.

Adherence to vascular care guidelines for emergency revascularization of chronic limb-threatening ischemia.

Objective: In 2022, the National Health Service Commissioning for Quality and Innovation (CQUIN) indicator for vascular surgery, with its pay-for-performance incentive for timely (5-day) revascularization of chronic limb-threatening ischemia (CLTI), was introduced. We sought to assess its effects in terms of (1) changes in the care pathway process measures relating to timing and patient outcomes; and (2) adherence to the Peripheral Arterial Disease Quality Improvement Framework (PAD-QIF) guidelines for patients admitted with CLTI. Methods: A retrospective before-and-after cohort study was performed from January to June 2022 of nonelective admissions for CLTI who underwent revascularization (open, endovascular, or hybrid) at Cambridge University Hospitals National Health Service Foundation Trust, a regional vascular "hub." The diagnostic and treatment pathway timing-related process measures recommended in the PAD-QIF were compared between two 3-month cohorts-before vs after introduction of the CQUIN. Results: For the two cohorts (before vs after CQUIN), 17 of 223 and 17 of 219 total admissions met the inclusion criteria, respectively. After introduction of financial incentives, the percentage of patients meeting the 5-day targets for revascularization increased from 41.2% to 58.8% (P = .049). Improvements were also realized in the attainment of PAD-QIF targets for a referral-to-admission time of ≤2 days (from 82.4% to 88.8%; P = .525) and admission-to-specialist-review time of ≤14 hours (from 58.8% to 76.5%; P = .139). An increase also occurred in the percentage of patients receiving imaging studies within 2 days of referral (from 58.8% to 70.6%; P = .324). The reasons for delay included operating list pressures and unsuitability for intervention (eg, active COVID-19 [coronavirus disease 2019] infection). No statistically significant changes to patient outcomes were observed between the two cohorts in terms of complications (pre-CQUIN, 23.5%; post-CQUIN, 41.2%; P = .086), length of stay (pre-QUIN, 12.0 ± 12.0 days; post-QUIN, 15.0 ± 21.0 days; P = .178), and in-hospital mortality (pre-QUIN, 0%; post-QUIN, 5.9%). Other PAD-QIF targets relating to delivery of care were poorly documented for both cohorts. These included documented staging of limb threat severity with the WIfI (wound, ischemia, foot infection) score (2.9% of patients; target >80%), documented shared decision-making (47.1%; target >80%), documented issuance of written information to patient (5.9%; target 100%), and geriatric assessment (6.3%; target >80%). Conclusions: The pay-for-performance incentive CQUIN indicators appear to have raised the profile for the need for early revascularization to treat CLTI, engaging senior hospital management, and reducing the time to revascularization in our cohort. Further data collection is required to detect any resultant changes in patient outcomes. Documentation of guideline targets for delivery of care was often poor and should be improved.