Predictive Role of Blood Cellular Indices and Their Relationship with Endogenous Glycosaminoglycans as Determinants of Inflammatory Biomarkers in Pulmonary Embolism.

INTRODUCTION: In this study, we profiled the levels of blood cellular indices, endogenous glycosaminoglycans (GAGs) and inflammatory biomarkers in a cohort comprised of pulmonary embolism (PE) patients, to determine their inter-relationships. Identification of this relationship may provide insight to the complex pathophysiology of PE and the predictive role of blood cellular indices in acute PE patients. MATERIALS AND METHODS: Plasma samples from PE patients and healthy controls were analyzed for thrombo-inflammatory biomarkers (IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFN-É£, TNF-α, IL-1α, IL-1ß, MCP-1, EGF, D-dimer, CRP and MMP-9) using biochip array and ELISA methods. The endogenous GAG levels were quantified using a fluorescence quenching method. The data regarding the blood cellular indices were collected through the review of patient medical records and analyzed to demonstrate their relationship. RESULTS: The levels of inflammatory biomarkers and endogenous GAGs were elevated in acute PE patients compared to controls (P < .05). Most of the blood cellular indices have shown significant differences in acute PE patients compared to controls (P < .05). The levels of inflammatory biomarkers, endogenous GAGs and the blood cellular indices have shown significant associations in correlation and multivariable analysis. While NLR, PLR and SII were significantly predicting the 30-day mortality, PNR, ELR and EMR were not sufficient to predict 30-day mortality in acute PE. CONCLUSION: Our results show that the increased thrombo-inflammatory response is associated with the release of GAGs and the changes in blood cellular indices. The predictive role of the blood cellular indices for mortality is dependent on their relationship with the inflammatory response.

Safety and efficacy of currently used COVID‐19 vaccines: Results of a pilot survey

Introduction After its emergence in China, the COVID‐19 pandemic has spread rapidly around the world, affecting all of our lives. Over the past few months, different vaccines have been issued to the public following FDA approval. Since their release, the number of COVID‐19 cases in the United States have gone down significantly. However, there is a long way to go until the eradication of the virus. There has also been a strong emergence of delta variants across the world, which (for the most part) can still be partially blocked by vaccines. This is why it is so important everyone gets a vaccine for COVID‐19. Purpose The purpose of this project was to determine the public’s opinion of COVID‐19 and the COVID‐19 vaccines, while also determining correlation between different demographics and these opinions. Hypothesis There are many different factors within various demographics that cause a correlation to a certain belief regarding COVID‐19 and COVID‐19 vaccines. Materials and Methods This study was conducted in collaboration with Loyola University Chicago. Survey questions about COVID‐19 and COVID‐19 vaccinations have been sent electronically to the respondents. Initial results based on a pilot study where the answers from 250 respondents were compiled. Basic descriptive statistics were used to characterize the sample and study variables. Univariate analysis of associations between categorical variables and vaccination intent and acceptance were assessed by chi‐square statistics. Multivariate analysis performed by regression analysis to determine significant independent predictors. A p‐value of less than 0.05 was considered to indicate statistical significance;all tests were 2‐tailed. Results In our study population vaccine willingness have been found as 94,4%, the rate of receiving at least one dose of vaccination have been found as 90,8%. In univariate analysis, gender, believing that vaccinations protect others and having enough information about safety and efficacy of vaccines have been found significant factors for vaccine willingness. For receiving at least one dose of vaccination, gender, previous COVID‐19 infection, believing that vaccinations protect others, having enough information about safety and efficacy of vaccines, the degree of COVID‐19 related effects on person’s life, knowledge that COVID‐19 can cause blood clots and the degree of concerns about delta variant have been found significant factors for vaccine willingness. In multivariate analysis only believing that vaccinations protect others have been found as an independent factor for vaccine willingness. For receiving at least one dose of vaccination, believing that vaccinations protect others, the degree of COVID‐19 related effects on person’s life and having enough information about safety and efficacy of vaccines have been found independent factors in multivariate analysis. Conclusion There are several vaccines currently available in the United States. All of these vaccines provide immunity against COVID‐19 and its variants which have been identified in 2020 and 2021. The level of immunity and the reported adverse events vary with each of the vaccines. Despite minor issues the vaccination outweighs the benefits and provides a clear approach to control this pandemic.

The Relevance of Anti-PF4 Antibody Isotypes and Endogenous Glycosaminoglycans and their Relationship with Inflammatory Biomarkers in Pulmonary Embolism Patients.

INTRODUCTION: Previous studies have shown that inflammation may contribute to the interplay of endogenous glycosaminoglycans (GAGs) and anti-PF4 antibodies. In this study, we quantified the levels of anti-PF4 antibody isotypes and endogenous GAGs together with inflammatory biomarkers in pulmonary embolism (PE) patients to determine whether there is a relationship in between. Identification of this relationship may provide insight to the complex pathophysiology of PE and HIT and may also be useful for development of potential prognostic, diagnostic and therapeutic interventions. MATERIALS AND METHODS: Plasma samples from PE patients (n: 210) were analyzed for anti-PF4 antibody isotypes and various thrombo-inflammatory cytokines utilizing commercially available biochip array and ELISA methods. The endogenous GAG levels in PE patients' plasma were quantified using a fluorescence quenching method. The collected data analyzed to demonstrate the relationship between various parameters. RESULTS: The endogenous GAG levels were increased in the PE group (P < .05). The levels of anti-PF4 antibody isotypes were higher in varying levels in comparison to the normal group (P < .05). Inflammatory cytokines have shown varying levels of increase with IL-6, IL-8 and IL-10 showing the most pronounced values. Mortality outcome was related to increased GAGs and some of the cytokines. CONCLUSION: In this study, we demonstrated increased levels of anti-PF4 antibody isotypes, endogenous GAGs, and inflammatory biomarkers in a large patient cohort in PE. The levels of the endogenous GAGs and inflammatory biomarkers were associated with PE severity and mortality. More studies are needed to understand this complex pathophysiology.

Public Perceptions of Current COVID-19 Vaccinations. Results of a Pilot Survey.

INTRODUCTION: We conducted a cross-sectional survey as a part of an educational program in collaboration with the Global Thrombosis Forum (GTF), an affiliate of North American Thrombosis Forum (NATF), and Loyola University about public perceptions of COVID-19 and COVID-19 vaccinations in the US. In this study, we are reporting the results of this survey. MATERIALS AND METHODS: The survey, in the form of a questionnaire, has been developed by GTF and faculty members. A prepared questionnaire was sent to the members of the Georgia and Illinois communities. RESULTS: In our current study, the COVID-19 vaccine willingness rate was 94.5% and vaccination rate was 90.9%. In multivariate analysis believing to have enough information about the safety and efficacy of COVID-19 vaccines (OR: 3.730, 95% CI: 1.199-11.603, p: 0.023) and gender (OR: 0.123, 95% CI: 0.016-0.967, p: 0.046) were significant predictors for vaccine willingness. Previous COVID-19 infection (OR: 0.215, 95% CI: 0.061-0.758, p: 0.017), moderate and severe effects of COVID-19 pandemic on participant's life (OR: 4.631, 95% CI 1.681-12.760, p: 0.003) and believing to have enough information about the safety and efficacy of COVID-19 vaccines (OR: 4.119, 95% CI: 1.508-11.253, p: 0.006) were significant predictors for final vaccination status. CONCLUSION: In conclusion, currently vaccination remains one of the most effective tools in the fight against the COVID-19 pandemic. The vaccine hesitancy is a complex phenomenon that is driven by individuals' perceptions of safety, and efficiency of the vaccines. We must continue to educate the public and communities that vaccines are safe, that they are effective and that they are still required even after a COVID-19 infection.

The COVID-19 Pandemic and the Need for an Integrated and Equitable Approach: An International Expert Consensus Paper.

BACKGROUND: One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis. MANAGEMENT: Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population. The launch of a mass vaccination program in many countries in late December 2020 with mRNA vaccines, adenovirus-based vaccines, and inactivated virus vaccines has generated hope for the end of the pandemic. CURRENT ISSUES: The continuous appearance of new pathogenic viral strains and the ability of vaccines to prevent infection and transmission raise important concerns as we try to achieve community immunity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variants. The need of a second and even third generation of vaccines has already been acknowledged by the WHO and governments. PERSPECTIVES: There is a critical and urgent need for a balanced and integrated strategy for the management of the COVID-19 outbreaks organized on three axes: (1) Prevention of the SARS-CoV-2 infection, (2) Detection and early diagnosis of patients at risk of disease worsening, and (3) Anticipation of medical care (PDA). CONCLUSION: The "PDA strategy" integrated into state policy for the support and expansion of health systems and introduction of digital organizations (i.e., telemedicine, e-Health, artificial intelligence, and machine-learning technology) is of major importance for the preservation of citizens' health and life world-wide.

Comparative Anticoagulant and Thrombin Generation Inhibitory Profile of Heparin, Sulodexide and Its Components.

INTRODUCTION: Sulodexide represents a mixture of fast-moving heparin (FMH) and dermatan sulfate (DS) and has been used for the management of venous diseases such as DVT and related disorders. The purpose of this study is to compare sulodexide and its components with unfractionated heparin (UFH) to determine its suitability for the indications in which UFH is used. MATERIALS AND METHOD: Active pharmaceutical ingredients (API) versions of sulodexide, FMH and DS were obtained from Alfasigma. API versions of UFH were obtained from Medefil Inc. Normal human citrated plasma was obtained from blood bank of the Loyola University Medical Center. Each of the individual agents were supplemented in plasma at a graded concentration of 0.0-10 µg/mL. Clotting assays (PiCT, aPTT, PT and TT), anti-Xa and anti-IIa and thrombin generation studies were carried out. Results were compiled as mean ± SD of 3 individual determination. RESULT: In the clot based (PiCT, aPTT and TT), anti-Xa and IIa assays, both the UFH and FMH produced stronger activities in these assays followed by sulodexide. DS did not show any anticoagulant activity. In the thrombin generation assay, FMH and UFH produced comparable inhibition of thrombin generation as measured by various parameters. Sulodexide was slightly weaker in this assay, whereas DS produced relatively weaker effects. CONCLUSION: In comparison to sulodexide, both UFH and FMH exhibit comparable anticoagulant activity despite differences in their molecular weight. These results suggest that sulodexide can be developed as a parenteral anticoagulant for indications in which UFH is used.

Targeted, Site-Specific, Delivery Vehicles of Therapeutics for COVID-19 Patients. Brief Review.

Definitive pharmacological therapies for COVID-19 have yet to be identified. Several hundred trials are ongoing globally in the hope of a solution. However, nearly all treatments rely on systemic delivery but COVID-19 damages the lungs preferentially. The use of a targeted delivery approach is reviewed where engineered products are able to reach damaged lung tissue directly, which includes catheter-based and aerosol-based approaches. In this review we have outlined various target directed approaches which include microbubbles, extracellular vesicles including exosomes, adenosine nanoparticles, novel bio-objects, direct aerosol targeted pulmonary delivery and catheter-based drug delivery with reference to their relative effectiveness for the specific lesions. Currently several trials are ongoing to determine the effectiveness of such delivery systems alone and in conjunction with systemic therapies. Such approaches may prove to be very effective in the controlled and localized COVID-19 viral lesions in the lungs and potential sites. Moreover, localized delivery offered a safer delivery mode for such drugs which may have systemic adverse effects.

Viral Coagulopathy in Patients With COVID-19: Treatment and Care.

COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation-like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.