Systemic inflammation in COVID-19 patients may induce various types of venous and arterial thrombosis: A systematic review.

COVID-19 is a global pandemic with a daily increasing number of affected individuals. Thrombosis is a severe complication of COVID-19 that leads to a worse clinical course with higher rates of mortality. Multiple lines of evidence suggest that hyperinflammation plays a crucial role in disease progression. This review compiles clinical data of COVID-19 patients who developed thrombotic complications to investigate the possible role of hyperinflammation in inducing hypercoagulation. A systematic literature search was performed using PubMed, Embase, Medline and Scopus to identify relevant clinical studies that investigated thrombotic manifestations and reported inflammatory and coagulation biomarkers in COVID-19 patients. Only 54 studies met our inclusion criteria, the majority of which demonstrated significantly elevated inflammatory markers. In the cohort studies with control, D-dimer was significantly higher in COVID-19 patients with thrombosis as compared to the control. Pulmonary embolism, deep vein thrombosis and strokes were frequently reported which could be attributed to the hyperinflammatory response associated with COVID-19 and/or to the direct viral activation of platelets and endothelial cells, two mechanisms that are discussed in this review. It is recommended that all admitted COVID-19 patients should be assessed for hypercoagulation. Furthermore, several studies have suggested that anticoagulation may be beneficial, especially in hospitalized non-ICU patients. Although vaccines against SARS-CoV-2 have been approved and distributed in several countries, research should continue in the field of prevention and treatment of COVID-19 and its severe complications including thrombosis due to the emergence of new variants against which the efficacy of the vaccines is not yet clear.

Unveiling the Chemistry of Citrus Peel: Insights into Nutraceutical Potential and Therapeutic Applications.

The recent millennium has witnessed a notable shift in consumer focus towards natural products for addressing lifestyle-related disorders, driven by their safety and cost-effectiveness. Nutraceuticals and functional foods play an imperative role by meeting nutritional needs and offering medicinal benefits. With increased scientific knowledge and awareness, the significance of a healthy lifestyle, including diet, in reducing disease risk is widely acknowledged, facilitating access to a diverse and safer diet for longevity. Plant-based foods rich in phytochemicals are increasingly popular and effectively utilized in disease management. Agricultural waste from plant-based foods is being recognized as a valuable source of nutraceuticals for dietary interventions. Citrus peels, known for their diverse flavonoids, are emerging as a promising health-promoting ingredient. Globally, citrus production yields approximately 15 million tons of by-products annually, highlighting the substantial potential for utilizing citrus waste in phyto-therapeutic and nutraceutical applications. Citrus peels are a rich source of flavonoids, with concentrations ranging from 2.5 to 5.5 g/100 g dry weight, depending on the citrus variety. The most abundant flavonoids in citrus peel include hesperidin and naringin, as well as essential oils rich in monoterpenes like limonene. The peel extracts exhibit high antioxidant capacity, with DPPH radical scavenging activities ranging from 70 to 90%, comparable to synthetic antioxidants like BHA and BHT. Additionally, the flavonoids present in citrus peel have been found to have antioxidant properties, which can help reduce oxidative stress by 30% and cardiovascular disease by 25%. Potent anti-inflammatory effects have also been demonstrated, reducing inflammatory markers such as IL-6 and TNF-α by up to 40% in cell culture studies. These findings highlight the potential of citrus peel as a valuable source of nutraceuticals in diet-based therapies.

Women and stroke: disparities in clinical presentation, severity, and short- and long-term outcomes.

Objectives: There are limited data from the Middle East on sex-related differences in short- and long-term stroke outcomes. We present 8 years of experience based on the Qatar stroke database. Setting: The Qatar stroke database prospectively collects data on all stroke patients admitted to Hamad General Hospital. For this study, we compared female and male acute ischemic stroke patients on their characteristics at admission, short-term outcomes [modified Rankin Scale (mRS) score], and long-term outcomes [incidence of major adverse cardiovascular events (MACEs)]. Participants: A total of 7,300 patients [F: 1,406 (19.3%), M: 5,894 (80.7%); mean age 55.1 ± 13.3 (F: 61.6 ± 15.1, M: 53.5 ± 12.3; p < 0.001)] were admitted with acute ischemic stroke. Results: Significantly fewer women presented within 4.5 h of onset (F: 29% vs. M: 32.8%; p = 0.01). Although women were more likely to experience severe stroke (NIHSS >10; F: 19.9% vs. M: 14.5%; p < 0.001), fewer were treated with thrombolysis (F: 9.8% vs. M: 12.1%; p = 0.02). Women experienced more medical complications (F: 11.7% vs. M: 7.4%; p < 0.001) and tended to have a more prolonged length of stay in the hospital (F: 6.4 ± 7.6 days vs. M: 5.5 ± 6.8 days; p < 0.001). Primary and secondary outcome measures: Good outcomes at 90 days (mRS score of 0-2) were less frequent in women (F: 53.3% vs. M: 71.2%; p < 0.001). Fewer female patients were taking antiplatelets (F: 78% vs. M: 84.8%; p < 0.001) or statins (F: 81.2% vs. M: 85.7%; p < 0.001). Significantly more female patients experienced a MACE (F: 12.6% vs. M: 6.5%; p < 0.001). Conclusion: Older age at presentation contributes to poor outcomes following acute stroke in women. Other contributing factors include delays in admission to the hospital, lower rates of thrombolysis, and lower rates of provision of preventative treatments.

Appropriate use of antiplatelet medications following transient ischemic attacks and stroke: a 9-year study from the Middle East.

Background and purpose: Guidelines recommend that patients with high-risk TIAs and minor strokes presenting within 1-3 days from onset should be offered dual antiplatelet therapy (DAPT). There are little data on real-world adherence to these recommendations. We evaluated the appropriateness of DAPT use in TIA and stroke patients in a prospective database. Methods: The Qatar Stroke Database began the enrollment of patients with TIAs and acute stroke in 2014 and currently has ~16,000 patients. For this study, we evaluated the rates of guideline-adherent use of antiplatelet treatment at the time of discharge in patients with TIAs and stroke. TIAs were considered high-risk with an ABCD2 score of 4, and a minor stroke was defined as an NIHSS of 3. Patient demographics, clinical features, risk factors, previous medications, imaging and laboratory investigations, final diagnosis, discharge medications, and discharge and 90-day modified Rankin Scale (mRS) were analyzed. Results: After excluding patients with ICH, mimics, and rare secondary causes, 8,082 patients were available for final analysis (TIAs: 1,357 and stroke: 6,725). In high-risk TIAs, 282 of 666 (42.3%) patients were discharged on DAPT. In patients with minor strokes, 1,207 of 3,572 (33.8%) patients were discharged on DAPT. DAPT was inappropriately offered to 238 of 691 (34.4%) low-risk TIAs and 809 of 3,153 (25.7%) non-minor stroke patients. Conclusion: This large database of prospectively collected patients with TIAs and stroke shows that, unfortunately, despite several guidelines, a large majority of patients with TIAs and stroke are receiving inappropriate antiplatelet treatment at discharge from the hospital. This requires urgent attention and further investigation.

Systemic Inflammation May Induce Cardiac Injury in COVID-19 Patients Including Children and Adolescents Without Underlying Cardiovascular Diseases: A Systematic Review.

Coronavirus disease 2019(COVID-19) is an ongoing global pandemic with a daily increasing number of affected individuals and a relatively high mortality rate. COVID-19 patients that develop cardiac injury are at increased risk of a worse clinical course with higher rates of mortality. Increasing amounts of evidence suggest that a system-wide inflammatory response and a cytokine storm mediated type syndrome plays a crucial role in disease progression. This systematic review investigates the possible role of hyperinflammation in inducing cardiac injury as one of the severe complications of COVID-19. A systematic literature search was performed using PubMed, Embase and Scopus databases to identify relevant clinical studies that investigated cardiovascular injury manifestations and reported inflammatory and cardiac biomarkers in COVID-19 patients. Only 29 studies met our inclusion criteria and the majority of these studies demonstrated significantly elevated inflammatory and cardiac blood markers. It was evident that underlying cardiovascular diseases may increase the risk of developing cardiac injury. However, many COVID-19 patients included in this review, developed different types of cardiac injury without having any underlying cardiovascular diseases. Furthermore, many of these patients were either children or adolescents. Therefore, age and comorbidities may not always be the two main risk factors that dictate the severity and outcome of COVID-19. Further investigations are required to understand the underlying mechanisms of pathogenicity as an urgent requirement to develop the appropriate treatment and prevention strategies. These strategies may specifically target hyperinflammation as a suspected driving factor for some of the severe complications of COVID-19.

The Interplay Between the Immune System, the Renin-Angiotensin-Aldosterone System (RAAS), and RAAS Inhibitors May Modulate the Outcome of COVID-19: A Systematic Review.

Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), numerous research has been undertaken to delineate the various effects of the virus which manifests in many ways all over the body. The association between the SARS-CoV-2 invasion mechanism and the renin-angiotensin-aldosterone system (RAAS) receptors, created many debates about the possible consequences of using RAAS-modulating drugs including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) during the pandemic. Many clinical studies were conducted to assess the outcomes of coronavirus disease 2019 (COVID-19) in patients who use ACEi/ARBs following the arguments claiming to discontinue these drugs as a precautionary measure. Although several studies mainly analyzed the outcomes of the disease, this review aimed to compare specific blood markers in both groups of COVID-19 patients to gain better insight into the interaction of ACEi/ARBs with different body functions during the infection. Several databases were searched using a combination of keywords followed by screening and data extraction. Only 28 studies met our inclusion criteria, the majority of which showed no significant difference between the inflammation markers of COVID-19 patients who used or did not use ACEi/ARBs. Interestingly, 6 studies reported lower inflammatory markers in COVID-19 patients who used ACEi/ARBs, and 6 studies reported better outcomes among the same group. We therefore concluded that the use of ACEi/ARBs may not lead to worse prognosis of COVID-19 and may even play a protective role against the hyperinflammatory response associated with COVID-19.