Introduction : The SARS-CoV-2 pandemic has been affecting the health and economic, as well as social, life of the entire globe since the end of 2019. The virus causes COVID-19, with a wide range of symptoms among the infected individuals, from asymptomatic infection to mortality. This, along with a high infection rate, prompted efforts to investigate the potential mechanisms of the different clinical manifestations caused by SARS-CoV-2 among the infected populations. Hypothesis : One of the possible mechanisms that has been reported is the ABO blood system polymorphism. Indeed, one of the major proposed mechanisms is the presence of naturally occurring anti-A antibodies in individuals of groups O and B, which could be partially protective against SARS-CoV-2 virions. Objective and Method : This article aimed to review the published data on the potential effect of the ABO blood group system on the susceptibility to COVID-19 and the disease progression and outcomes. Results : The reviewed data suggest that individuals of blood group A are at a higher risk of infection with SARS-CoV-2 and may develop severe COVID-19 outcomes, whereas blood group O is considered protective against the infection, to some extent. However, some of the available studies seem to have been influenced by unaccounted confounders and biases. Conclusion : Therefore, further appropriately controlled studies are warranted to fully investigate the possible association between the ABO blood groups and COVID-19 susceptibility and severity.

The current COVID-19 pandemic emerged in December 2019, in China, affecting millions of people worldwide. COVID-19 is mainly a disease of the respiratory system, yet systematic complications have also been reported among SARS-CoV-2 infected patients. Thrombotic complications are one of the severe clinical outcomes of COVID-19, especially among critically ill patients, and are associated with poor prognosis. To date, many studies have concluded that COVID-19 increases the incidence of thrombotic events and coagulopathies; however, the exact mechanism behind such a disease outcome is not well known. Various pathophysiological mechanisms for thrombotic events in COVID-19 have been proposed, these include virus-induced endothelial cell damage, inflammation, and excess production of pro-inflammatory cytokines. As a result, most critically diseased COVID-19 patients are managed with prophylactic anticoagulant, yet some still develop thrombotic episodes. Therefore, better understanding of the mechanisms behind the thrombotic complications is needed to develop treatments that specifically target such pathways, which may aid in better disease management and improve the prognosis.

This clinical trial (ACTRN12619001296123) investigated the impact of silymarin (Legalon®) on circulating bilirubin concentration, lipid status, systemic inflammation, and antioxidant status. The study design was a randomized, placebo‐controlled, single‐blind crossover trial of healthy men (18‐65 years), conducted at Griffith University, Gold Coast, Australia. Participants were recruited from Griffith University and were randomized to silymarin (140 mg silymarin capsules thrice daily) or placebo (3 capsules containing mannitol taken daily) for 14 days followed by a ≥4‐week washout and crossover to the other arm. The main outcomes were whether silymarin treatment would increase serum bilirubin concentration by >0.29 mg/dL, change serum lipid status (cholesterol and triglycerides), inflammation (c‐reactive protein), and antioxidant capacity (ferric reducing ability of plasma) compared with baseline. Silymarin consumption (n = 17) did not affect serum concentrations of unconjugated bilirubin (0.73 versus 0.67 mg/dL, P = .79), cholesterol (185 versus 189 mg/dL, P = .19), triglycerides (94.2 versus 92.3 mg/dL, P = .79), c‐reactive protein (0.17 versus 0.09 mg/dL, P = .23), or antioxidant status (6.61 versus 6.67 mg Fe2+/dL, P = .40). These findings challenge previous reports and manufacturer claims of hyperbilirubinemia following silymarin treatment and are critical to guiding researchers toward an effective means to mildly elevate bilirubin, which evidence suggests could protect from cardiovascular disease.

Background: Immunocompromised patients, including those with hematological malignancies, are at a high risk of developing severe coronavirus disease 2019 (COVID-19) complications. Currently, there is a limited number of systematic reviews into the efficacy of convalescent plasma therapy (CPT) use in the treatment of COVID-19 patients with hematological malignancies. Therefore, the aim of this review was to systematically appraise the current evidence for the clinical benefits of this therapy in COVID-19 patients with hematological malignancies. Methods: A comprehensive search was conducted up to April 2022, using four databases: PubMed, Web of Science, Science Direct, and Scopus. Two reviewers independently assessed the quality of the included studies. Data collection analysis was performed using Microsoft Excel 365 and GraphPad Prism software. Results: 18 studies met the inclusion criteria; these records included 258 COVID-19 patients who had hematological malignancies and were treated with CPT. The main findings from the reviewed data suggest that CPT may be associated with improved clinical outcomes, including (a) higher survival rate, (b) improved SARS-CoV-2 clearance and presence of detectable anti-SARS-CoV-2 antibodies post CP transfusion, and (c) improved hospital discharge time and recovery after 1 month of CPT. Furthermore, treatment with convalescent plasma was not associated with the development of adverse events. Conclusions: CPT appears to be an effective supportive therapeutic option for hematological malignancy patients infected with COVID-19. To our knowledge, this is one of the first systematic reviews of the clinical benefits of CPT in COVID-19 patients with hematological malignancies.

Background: Immunocompromised patients, including those with haematological malignancies, are among the high-risk group to develop severe coronavirus disease 2019 (COVID-19) complications. The effectiveness of passive immunotherapy with convalescent plasma (CP) on such patients diagnosed with COVID-19 has not been reviewed. Therefore, the aim of this review was to systematically appraise the current evidence for the efficacy of this therapy in haematological malignancies patients with COVID-19 infection. Methods: A comprehensive search was conducted up-to October 2021, using four databases: PubMed, Web of Science, Science Direct, and Scopus. Two reviewers independently assessed the quality of the included studies. Data collection analysis were performed using Microsoft Excel 365 and GraphPad Prism software. Results: 17 studies met the inclusion criteria; these records included 258 COVID-19 patients with haematological malignancies and treated with CP therapy (CPT). The main findings from the reviewed data suggests CPT may be associated with improved clinical outcomes including (a) higher survival rate, (b) improved SARS-CoV-2 clearance and presence of detectable anti-SARS-CoV-2 antibodies post CP transfusion, (c) improved hospital discharge time, and recovery after 1 month of CP therapy. Furthermore, treatment with convalescent plasma was not associated with development of adverse events. Conclusion: Owing to its safety and beneficial effects in improving clinical outcomes, CPT appears to be an effective supportive therapeutic option for haematological malignancy patients infected with COVID-19.

Lead is a heavy, toxic metal and its exposure to humans can lead to increased risk of cardiovascular disease development and mortality. Lead exposure has been shown to induce hyperhomocysteinemia (HHCy ) which further increases the risk of cardiovascular diseases. We aimed to investigate the mediation effect of blood lead induced HHCy on cardiovascular mortality in a national cohort. A total of 17,915 adults aged ≥ 20 who participated in the National Health and Nutrition Examination Survey (1999 to 2006). Information on mortality was ascertained via probabilistic matching to the death certificates from the National Death Index recorded up to December 31, 2015. Cox proportional hazards regression was performed to assess the association between blood lead levels and mortality. Mediation via HHCy was examined using a logit model. During a mean follow-up of 11.6 years, the incidences of CVD mortality were 0.73, 2.18, 3.03 and 4.94 per 1000 person-years across quarterlies of blood lead levels from low to high. Following multivariable adjustment, blood lead levels were strongly associated with CVD mortality in all mortality models (p trend < 0.001). This association remained statistically significant after further adjusting for quartiles of homocysteine (model 3; HR 1.38 (95% CI 1.01 - 1.89) p trend < 0.001). Furthermore, blood lead levels increased the odds of CVD mortality via homocysteine (indirect effect) (OR 1.42 (95% CI 1.30 - 1.55)), demonstrating the mediatory effect of homocysteine. This the first study that demonstrates that increased homocysteine mediates more than half of CVD mortality related to blood lead levels.

HPLC MethodBriefly, HPLC-PDA analysis was performed using a Shimadzu Prominence HPLC system consisting of an online degassing unit (DGU20A5R), solvent delivery unit (LC-20AT), autosampler (SIL-20 AC), column oven (CTO-20) and photo diode-array (SPD-M20A), connected in series. Separation was achieved via reverse phase C18 column (GraceSmart™ RP-C18, 150mm x 4.6mm, 3µm; Grace Davidson, Australia), which was preceded by a guard column (GraceSmart™ RP-C18, 3µm; Grace Davidson, Australia) and an UltraLine HPLC in-line filter (Restek, 0.5µm; Shimadzu, Sydney, Australia), respectively. The column oven and autosampler were set to 45˚C and 4˚C, respectively, with an initial flow rate of 1.6mL•min −1 . Starting mobile phase consisted of 20% organic B (100% HPLC grade MeOH) and 80% aqueous A (10mM NH4OAc in 25% HPLC grade MeOH and 75% Milli-Q purified H2O). A linear gradient was applied, reaching 90% B at 4.5 minutes, remaining until 7 minutes. From 7 to 11.5 minutes, the mobile phase was set at 20% B. To assist equilibration, flow rate remained at 1.6mL•min −1 until 6 minutes where it increased to 2.3mL•min −1 at 6.35 minutes, remaining until 8.5 minutes. From 8.5 to 9.5 minutes, the flow rate decreased to 1.6mL•min −1 and remained until 11.5 minutes. The total run time including adequate column re-equilibration was 11.5 minutes. For UCB and BRT extraction, 160μL of extractant (1:4 DMSO:MeOH) was added to 40μL of PPM sample, mixed via vortex for 10 seconds before centrifugation (21 500RCF; 10 minutes) to pellet protein. The supernatant was diluted (2:1) with Milli-Q H2O upon addition to a HPLC vial, prior to being placed in the autosampler where 40µL was injected for analysis. Commercially prepared BRT and UCB (Frontier Scientific Inc. Logan, UT, USA) served as external standards with retention times of 4.1 and 5.1 minutes respectively. Extraction efficiencies of these compounds from PPM was 95% and 91% for BRT and UCB, with standard curves indicating great linearity over concentration ranges of 1.5625µM -100µM (r 2 =0.9993) and 0.15625µM -10µM (r 2 =0.9995)

Highlights Abstract Background: Peripheral intravenous venous catheters (PIVCs) are associated with a postinsertion failure incidence of 40%, yet the common maintenance and preventive strategy of saline flushing is poorly understood at a physiological level. Methods: We developed a human model of bilateral cephalic vein cannulation to study the impact of varied PIVC flushing frequency (high frequency, HF; low frequency, LF) over 5 hours on catheter failure (primary outcome), coagulation, platelet aggregation, and local tissue injury. Ultrasound was used in a subset to assess vascular diameter/catheter to vein, blood flow velocity, and thrombus formation. Results: Out of 34 catheters in 17 adult participants, 1/17 (6%) LF catheters failed, which was not significantly different from HF catheters (0/17). Platelet function, activated partial thromboplastin time, and tissue factor were also not different (P &gt; 0.05). However, prothrombin time (PT) increased with HF versus LF after 5 hours (P &lt; 0.05). Ultrasound demonstrated luminal thromboses in veins experiencing both HF (6/7) versus LF (5/7) conditions after 5 hours with nonsignificant changes in vascular diameter and blood flow velocity over time. Conclusions: Although no difference in PIVC failure was observed between HF and LF flushing conditions over 5 hours, greater flushing frequency increased PT time, suggesting delayed activation or consumption of extrinsic coagulation factors. This study also demonstrated feasibility in assessment of luminal thromboses, which were remarkably prevalent after PIVC placement, and changes in vascular diameter and blood flow. This manuscript illustrates that the development of a sensitive human model will be of great use for exploring the impact of interventions on reducing PIVC failure in the future.