COVID-19 infection has protean systemic manifestations. Experience from previous coronavirus outbreaks, including the current SARS-CoV-2, has shown an augmented risk of thrombosis of both macrovasculature and microvasculature. The former involves both arterial and venous beds manifesting as stroke, acute coronary syndrome and venous thromboembolic events. The microvascular thrombosis is an underappreciated complication of SARS-CoV-2 infection with profound implications on the development of multisystem organ failure. The telltale signs of perpetual on-going coagulation and fibrinolytic cascades underscore the presence of diffuse endothelial damage in the patients with COVID-19. These parameters serve as strong predictors of mortality. While summarizing the alterations of various components of thrombosis in patients with COVID-19, this review points to the emerging evidence that implicates the prominent role of the extrinsic coagulation cascade in COVID-19-related coagulopathy. These mechanisms are triggered by widespread endothelial cell damage (endotheliopathy), the dominant driver of macro- and micro-vascular thrombosis in these patients. We also summarize other mediators of thrombosis, clinically relevant nuances such as the occurrence of thromboembolic events despite thromboprophylaxis (breakthrough thrombosis), current understanding of systemic anticoagulation therapy and its risk–benefit ratio. We conclude by emphasizing a need to probe COVID-19-specific mechanisms of thrombosis to develop better risk markers and safer therapeutic targets.

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Data on the status of iodine deficiency in the Arabian peninsula is scarce. We have conducted a cross-sectional national epidemiological survey in Saudi Arabia to study the iodine status of Saudi schoolchildren, between eight and ten years, who were randomly selected, after taking into consideration the gender, provincial population and area distribution. Casual urine samples were collected and sent to the central laboratory for analysis. Clinical assessment for the presence of goiter was conducted in four areas with different geographical natures. The survey included 4638 subjects, and their median and mean (SD) of urinary iodine concentration was 18 and 17 μg/dL, respectively. We found provincial differences with respect to urinary iodine concentration and the percentage of subjects with urinary iodine concentration <10 μg/dL. The Southern province had the lowest median (11 μg/dL) and the highest percentage (45%) of subjects with urinary iodine concentration <10 μg/dL. On the other hand, subjects of the Western province had the highest median (24 μg/dL) and the lowest percentage (8%) of subjects with urinary iodine concentration <10 μg/dL. The clinical assessment revealed that the highest prevalence and more advanced grade of goiter (22%, 95% CI 19-25, grade 1; 8%, 95% CI 6-10, grade 2) was found in the Asir region, a highaltitude area in the Southern province. The lowest prevalence of goiter (4%, 95% CI 0.8-7.2, grade 1) was found in Gizan, an urban coastal community. There was a significant relationship between the prevalence of goiter and the urinary iodine concentration. The survey for iodine deficiency disorder (IDD) in Saudi Arabia has shown a mild degree of iodine deficiency in the Southern province. Odds ratio (OR) was used to study the statistical relationship between the prevalence of goiter and the urinary iodine concentration. There is a need to launch a control program to ensure the exclusive availability of iodized salt in

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Chronic kidney disease (CKD) imposes a strong and independent risk for peripheral artery disease (PAD). While solutes retained in CKD patients (uremic solutes) inflict vascular damage, their role in PAD remains elusive. Here, we show that the dietary tryptophan-derived uremic solutes including indoxyl sulfate (IS) and kynurenine (Kyn) at concentrations corresponding to those in CKD patients suppress β-catenin in several cell types, including microvascular endothelial cells (ECs), inhibiting Wnt activity and proangiogenic Wnt targets in ECs. Mechanistic probing revealed that these uremic solutes downregulated β-catenin in a manner dependent on serine 33 in its degron motif and through the aryl hydrocarbon receptor (AHR). Hindlimb ischemia in adenine-induced CKD and IS solute–specific mouse models showed diminished β-catenin and VEGF-A in the capillaries and reduced capillary density, which correlated inversely with blood levels of IS and Kyn and AHR activity in ECs. An AHR inhibitor treatment normalized postischemic angiogenic response in CKD mice to a non-CKD level. In a prospective cohort of PAD patients, plasma levels of tryptophan metabolites and plasma’s AHR-inducing activity in ECs significantly increased the risk of future adverse limb events. This work uncovers the tryptophan metabolite/AHR/β-catenin axis as a mediator of microvascular rarefaction in CKD patients and demonstrates its targetability for PAD in CKD models.