Are ABO Gene Alleles Responsible for Cardiovascular Diseases and Venous Thromboembolism and Do They Play a Role in COVID?

Cardiovascular diseases (CVD) including coronary heart disease and stroke are leading causes of death and disability globally. Studies of the association between ABO blood groups and CVD have consistently demonstrated an increased risk of coronary heart disease, myocardial infarction, cerebral ischaemic stroke, peripheral arterial disease and venous thromboembolism (VTE) including deep vein thrombosis and pulmonary thromboembolism in patients who possess a non-O blood group type. The most likely mechanism is thought to be the increase in von Willebrand Factor (vWF) and factor VIII levels seen in patients with a non-O blood group. Other postulated mechanisms include elevations in circulating inflammatory markers such as endothelial cell and platelet adhesion molecules in subjects with a non-O blood group. More recently, it has also been recognised that individuals with a non-O blood group type carry a higher risk of SARS-C0V-2 infection and COVID-19 related complications. The increased levels in vWF and factor VIII amongst individuals with a non-O blood group who have contracted SARS-CoV-2 infection may result in an additive thrombophilic effect to that caused by the SARS-CoV-2 virus. Another postulated mechanism is that individuals with an O-blood group are protected by anti-A and B antibodies which possibly inhibit the binding of the SARS-CoV-2 spike protein to lung epithelium angiotensin converting enzyme-2 receptors. There are over 35 minor blood groups on red blood cells, some of which such as Kidd, Lewis and Duffy have been associated with CVD either alone or in combination with a non-O blood group allele(s). However, their role in SARS-CoV-2 infection and mechanism of action for an association with CVD remain unknown. This review explores the relationship between ABO and minor blood groups with CVD and VTE, with a focus on potential mechanisms underlying this relationship and the potential role of ABO blood group types in COVID

Functional Outcomes at 90 Days in Octogenarians Undergoing Thrombectomy for Acute Ischemic Stroke: A Prospective Cohort Study and Meta-Analysis

Background: Elderly patients account for 30% of acute ischemic stroke (AIS) but are under-represented in randomized controlled trials of endovascular thrombectomy (EVT). Meta-analysis of “real world” studies evaluating 90-day outcomes in elderly patients ≥80 years have been limited to small numbers undergoing EVT with older generation devices.Methods: A retrospective analysis of 181 prospectively collected patients who received EVT for anterior circulation AIS at an Australian center over 2.5-years. The study aims to determine (i) 90-day functional outcomes (modified Rankin Scale mRS 0–2) in patients ≥80 vs. <80 years, (ii) the interaction of prognostic factors and age and (iii) compare our data to those previously reported using a meta-analysis of outcomes in observational studies using second generation thrombectomy devices.Results: We analyzed 2,387 patients (≥80 years, n = 649; <80 years, n = 1,738) from 14 studies including our study (≥80 years, n = 71; <80 years, n = 110). Twenty-eight percent of our and 30% of the meta-analysis elderly cohort achieved good 90-day mRS compared to 55 and 52%, respectively of younger patients (p < 0.001). Twenty-seven percent of our and 26% of the meta-analysis elderly cohort died compared to 16% (p = 0.07) and 15% (p < 0.0001), respectively of younger patients. Baseline NIHSS≥16 correlated with poor prognosis in elderly (OR 16.4; 95% CI 4.49–59.91, p < 0.001) and younger (OR 8.73;95% CI 3.35–22.80, p < 0.001) patients. Prior rt-PA was associated with favorable outcome in younger (OR 2.90; 95%CI 1.29–6.52, p = 0.01) patients only.Conclusion: EVT has less favorable outcomes in elderly patients. However, results are better than outcomes in historical controls not treated with thrombectomy providing further support for EVT in the elderly

Health service management study for stroke : A randomized controlled trial to evaluate two models of stroke care

Background: The most effective and efficient model for providing organized stroke care remains uncertain. This study aimed to compare the effect of two models in a randomized controlled trial. Methods: Patients with acute stroke were randomized on day one of admission to combined, co-located acute/rehabilitation stroke care or traditionally separated acute/rehabilitation stroke care. Outcomes measured at baseline and 90 days post-discharge included functional independence measure, length of hospital stay, and functional independence measure efficiency (change in functional independence measure score ÷ total length of hospital stay). Results: Among 41 patients randomized, 20 were allocated co-located acute/rehabilitation stroke care and 21 traditionally separated acute/rehabilitation stroke care. Baseline measurements showed no significant difference. There was no significant difference in functional independence measure scores between the two groups at discharge and again at 90 days postdischarge (co-located acute/rehabilitation stroke care: 103·6 ± 22·2 vs. traditionally separated acute/rehabilitation stroke care: 99·5 ± 27·7; P = 0·77 at discharge; co-located acute/rehabilitation stroke care: 109·5 ± 21·7 vs. traditionally separated acute/rehabilitation stroke care: 104·4 ± 27·9; P= 0·8875 at 90 days post-discharge). Total length of hospital stay was 5·28 days less in co-located acute/rehabilitation stroke care compared with traditionally separated acute/rehabilitation stroke care (24·15 ± 3·18 vs. 29·42 ± 4·5, P = 0·35). There was significant improvement in functional independence measure efficiency score among participants assigned to co-located acute/rehabilitation stroke care compared with traditionally separated acute/rehabilitation stroke care (co-located acute/rehabilitation stroke care: median 1·60, interquartile range: 0·87–2·81; traditionally separated acute/rehabilitation stroke care: median 0·82, interquartile range: 0·27–1·57, P = 0·0393). Linear regression analysis revealed a high inverse correlation (R2 = 0·89) between functional independence measure efficiency and time spent in the acute stroke unit. Conclusion: This proof-of-concept study has shown that co-located acute/rehabilitation stroke care was just as effective as traditionally separated acute/rehabilitation stroke care as reflected in functional independence measure scores, but significantly more efficient as shown in greater functional independence measure efficiency. Co-located acute/rehabilitation stroke care has potential for significantly improved hospital bed utilization with no patient disadvantage

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

The role of thymoquinone, a major constituent of Nigella sativa, in the treatment of inflammatory and infectious diseases

Nigella sativa (N. sativa) is an annual flowering plant that has been used as a traditional remedy for many centuries. The seed possesses a large variety of compounds with thymoquinone (TQ) considered its major but not sole bioactive constituent. Supercritical fluid extraction, geographical location, and oxidative status of N. sativa produces the highest yield of essential oil content including TQ. Thymoquinone is lipophilic, heat and light sensitive with low oral bioavailability and rapid elimination that have significantly inhibited its pharmacological development. Novel developments in nanoparticulate-based oral administration, nasal spray and transdermal delivery may allow the clinical development of N. sativa and TQ as therapeutic agents. Animal and human studies indicate a potential role of N. sativa seed oil and TQ for a diverse range of disease processes including hypertension, dyslipidaemia, type 2 diabetes mellitus, arthritis, asthma, bacterial and viral infections, neurological and dermatological disorders, as it belongs to the group of pan-assay interference compounds. This review outlines the pharmacological properties of N. sativa and TQ and their potential wide application for a large variety of human diseases. The paper will focus on recent studies of the anti-inflammatory and antiviral properties that make N. sativa and TQ promising therapeutic agents targeting contemporary inflammatory and infectious diseases including Covid 19

An electromyographic study of parkinsonian swallowing and its response to levodopa

Background: Few studies have investigated the effect of levodopa on parkinsonian swallowing with findings thus far being equivocal. Methods: We used surface electromyography and accelerometry to investigate submental and laryngeal muscle activation during swallowing in 14 parkinsonian subjects before and after levodopa and in 22 age-matched controls. Our aims were (1) to demonstrate the clinical utility of noninvasive electromyography, (2) to identify electromyographic features of parkinsonian swallowing, and (3) to investigate the effect of levodopa on parkinsonian swallowing. Results: The parkinsonian group showed increased burst amplitudes and durations and increased swallow duration, clearing activity and latency between submental and laryngeal bursts (P <.05) and used more swallows than did controls to consume water boluses (P <.001). Levodopa decreased the latency between submental and laryngeal bursts (P <.05) but did not produce effects on individual muscle bursts. Conclusions: The clinical utility of electrophysiological and biomechanical methods of swallowing assessment was demonstrated. Levodopa tended to normalize the timing of the combined swallow response but not the activity of individual muscles.5 page(s

Management for motor and non-motor complications in late Parkinson's disease

The prevalence of neurodegenerative diseases such as Parkinson's disease (PD) increases with age. in an aging population, an understanding of the management of late complications of PD is becoming ever more important. Drug treatment for Parkinson's disease is largely symptomatic and relies primarily on levodopa (L-dopa) and adjuvant therapies including dopamine agonists and catechoi-0-methyitransferase (COMT) inhibitors. Rehabilitation and allied health input also constitutes a core part of successful management. Most subjects who are symptomatic for more than 5 years are prone to late complications of PD. Some of these are related to the treatment, such as motor fluctuations, including the "on-off" phenomenon and levodopa-related peak dose dyskinesia. Others, such as postural hypotension, falls, psychosis, and dementia, although well-recognized problems in the elderly, often require different treatment strategies if occurring in the context of PD. The practical evidence-based management of motor and non-motor complications in late PD is discussed

Reperfusion therapy in acute ischemic stroke: dawn of a new era?

Abstract Following the success of recent endovascular trials, endovascular therapy has emerged as an exciting addition to the arsenal of clinical management of patients with acute ischemic stroke (AIS). In this paper, we present an extensive overview of intravenous and endovascular reperfusion strategies, recent advances in AIS neurointervention, limitations of various treatment paradigms, and provide insights on imaging-guided reperfusion therapies. A roadmap for imaging guided reperfusion treatment workflow in AIS is also proposed. Both systemic thrombolysis and endovascular treatment have been incorporated into the standard of care in stroke therapy. Further research on advanced imaging-based approaches to select appropriate patients, may widen the time-window for patient selection and would contribute immensely to early thrombolytic strategies, better recanalization rates, and improved clinical outcomes

Review, comparison and meta-analysis of CYP2D6 polymorphism and association with Parkinson’s disease in Caucasian and Asian populations

Despite the recent advances in the discovery of a synuclein gene and parkin gene which help to elucidate the pathogenesis of hereditary Parkinson's disease in some families, the aetiology of Parkinson's disease remains unclear in the majority of the sporadic onset cases. Both environmental and genetic risk factors are thought to be involved and these factors are thought to interact in causing Parkinson's disease. The hypothesis that failure to metabolise xenobiotics is a putative risk factor in predisposed individuals with susceptible genetic defects remain an attractive possibility. This hypothesis is further supported by some drug addicts who developed parkinsonism after self-administrating synthetic meperidine analogues contaminated with 1-methyl-4-phenyl-1 ,2,3,6-tetrahydropyridine. This paper reviews and compares the evidence in literature of the cytochrome P450 2D6 (CYP2D6 debrisoquine 4-hydroxylase) genetic polymorphism in Caucasian and Asian populations and the association with Parkinson's disease. Furthermore, it also attempts to clarify the issue by using meta-analyses for analysing the results of genotypic studies of CYP2D6 and Parkinson's disease in the two populations. Interestingly, this latest and largest meta-analysis showed that there is a weak association of CYP2D6 poor metaboliser genotype and Parkinson 's disease in Caucasians (Odds ratio 1.3; 95% CI: 1.04 - 1.63). However, the situation is less clear in Asians as the poor metaboliser genotype is very rare and meta-analysis of heterozygotes in Asians carrying one mutant gene (instead of two) indicated an increased risk of2.07 (95% CI 1.33 - 3.24) compared to controls. However, the results of poor metaboliser genotypes in Caucasians and heterozygotes in Asians are clouded by the fact that there is significant heterogeneity amongst the studies used in the meta-analyses. Therefore, although the meta-analysis did overcome the sample size problems of allele association studies, other limitations remain including the lack of consideration of environmental factors, lack of consideration of interactions, diagnostic accuracy for Parkinson's disease and consideration of multiple genes being involved

Acute Ischaemic Stroke in Infective Endocarditis: Pathophysiology and Clinical Outcomes in Patients Treated with Reperfusion Therapy

Infective endocarditis in the setting of acute stroke poses a clinical challenge given the high mortality and morbidity associated with the condition. The pathophysiological mechanisms including clinical and imaging biomarkers that can provide insights into clinical trajectories of such patients are of immense interest. The current paper aims to provide a comprehensive overview of acute stroke with infective endocarditis and provide insights into various clinical factors mediating outcomes and therapeutic strategies, specifically in the setting of reperfusion therapy. Prognostic and therapeutic pathways to potentially improve functional outcomes in these patients are also discussed