COVID-19 retinal microangiopathy as an in vivo biomarker of systemic vascular disease?

IMPORTANCE: COVID-19 is caused by SARS-CoV-2, a betacoronavirus that uses the angiotensin-converting enzyme-related carboxypeptidase (ACE2) receptor to gain entry into cells. ACE2 receptor is widely expressed in multiple organs, including the retina, an extension of the central nervous system. The ACE2 receptor is involved in the diabetic and hypertensive retinopathy. Additionally, coronaviruses cause ocular infections in animals, including retinitis, and optic neuritis. OBJECTIVE: To assess whether there is any retinal disease associated with COVID-19. DESIGN: We have evaluated 27 asymptomatic subjects, with retinal fundoscopic, optical coherence tomography (OCT) and OCT angiography fourteen days after hospital discharge due to COVID-19 bilateral pneumonia. RESULTS: Cotton wool exudates were evident in six out of 27 patients evaluated, a 22%. Cotton wool exudates are a marker vascular disease severity in other medical context, that is diabetes and hypertension, and are associated with increased risk for acute vascular events. Whether antiaggregation therapy may play a role on fundoscopic-selected patients with COVID-19 requires prospective trials.

Autoimmune interstitial lung disease in Latin-America.

Information about the prognosis and natural history of autoimmune interstitial lung diseases (Ai-ILD) is limited. The aim of the study was to evaluate the characteristics of patients diagnosed with Ai-ILD in Latin-America. We conducted an ambispective multicenter cohort study in 25 centers of Argentina, Colombia, and Uruguay between January 2015 and April 2018. Participants were included in the study if they had diagnosis of Ai-ILD performed by a multidisciplinary team. Patients were classified into the following sub-groups: connective tissue disease-associated ILD (ILD-CTD), interstitial pneumonia with autoimmune features (IPAF), and positive antineutrophils cytoplasmatic antibodies associated ILD (ILD-ANCA). All images were reviewed by a blinded thoracic radiologist. Out of the 381 patients included during the study period, 282 (74%; 95% CI; 69.39-78.16) were women. Mean age was 58 years old (SD 16). Three-hundred and twenty-five (85.1%; 95% CI 81.39-88.5) patients were classified as ILD-CTD (rheumatoid arthritis 31%, systemic sclerosis 29%, dermatomyositis 15%). Thirty-six patients were classified as IPAF (9.5%; 95% CI 6.9-12.8), and 13 (3.5%; 95% CI 2-5.75) as ILD-ANCA. Fifty percent of patients (95% CI 45.12-55.43) had a mild decrease of the forced vital capacity at the time of diagnosis. The most common treatment strategy was the combination of steroids and cyclophosphamide (30.1%; 95% CI 25.32-35.34) followed by azathioprine (20,3%; 95% CI 16.32-25.14). In conclusion, to the best of our knowledge, this is the first study to evaluate the characteristics and treatment strategies used in patients affected by Ai-ILD in Latin-America. Future studies should to evaluate the prognosis and impact of current treatment strategies in patients with Ai-ILD.

A prospective study of Rivaroxaban for central venous catheter associated upper extremity deep vein thrombosis in cancer patients (Catheter 2).

INTRODUCTION: Patients with cancer are at increased risk of thrombosis, particularly those with central venous catheter (CVC) placement, which may predispose to the development of upper extremity deep vein thrombosis (UEDVT). Standard treatment includes low molecular weight heparin (LMWH) or LMWH bridged to warfarin. The direct oral anticoagulants (DOACs) have become standard of care for uncomplicated venous thromboembolism (VTE), but research in patients with cancer is ongoing. OBJECTIVES: To assess rivaroxaban monotherapy in patients with cancer who develop UEDVT due to CVC for preservation of line function, and safety outcomes of VTE recurrence, bleeding risk and death. MATERIALS AND METHODS: Patients ≥18years of age with active malignancy and symptomatic proximal UEDVT with or without pulmonary embolism (PE), associated with a CVC, were eligible. Treatment included rivaroxaban 15mg oral twice daily for 3weeks, followed by 20mg oral daily for 9weeks. Patients were followed clinically for 12weeks to assess for line function, recurrent VTE and bleeding. RESULTS: Seventy patients (47 women) were included, with mean age 54.1years. The most common malignancy was breast cancer (41%). Preservation of line function was 100% at 12weeks. The risk of recurrent VTE at 12weeks was 1.43%, with one episode of fatal PE. 9 patients (12.9%) experienced 11 total bleeding episodes. CONCLUSIONS: Rivaroxaban showed promise in treating CVC-UEDVT in cancer patients, resulting in preserved line function. However, bleeding rates and a fatal pulmonary embolism on treatment are concerning safety outcomes necessitating further study before rivaroxaban can be recommended.

Preferred Management of Primary Deep Arm Vein Thrombosis.

OBJECTIVE: Given its rarity, the management of primary upper extremity deep vein thrombosis is controversial. Although anticoagulation alone is commonly advocated for its treatment, it is unclear if this will reduce the risk of developing post-thrombotic syndrome (PTS). The aim of this "Evidence Driven" Clinical Scenario is to evaluate whether more aggressive treatments (including catheter directed thrombolysis or surgery) might help reduce the risk of PTS or recurrent venous thromboembolism in patients with primary upper extremity deep vein thrombosis (DVT). METHODS: An electronic systematic review of Ovid MEDLINE and Embase was conducted. Randomised controlled trials and observational studies were eligible. The primary outcome was PTS. RESULTS: The initial search identified 146 articles, and 36 more were identified during a secondary search. In total, 25 studies, reporting the outcome of 1271 patients, were included. None of the studies included was a randomised controlled trial and the large majority of studies were retrospective cohorts. The use of anticoagulation alone was associated with a significant risk of PTS. In patients treated with surgery with or without thrombolysis the incidence of PTS was significantly reduced. CONCLUSION: Current evidence, albeit with some methodological limitations, suggests that anticoagulation may not be sufficient to prevent PTS in patients with primary upper extremity DVT and that surgery with or without thrombolysis to repair the anatomical defects is needed.

Net clinical benefit of hospitalization versus outpatient management of patients with acute pulmonary embolism.

Essentials Clinical benefit of hospitalization vs. outpatient treatment in pulmonary embolism (PE) is unknown. We performed a propensity matched cohort study of hemodynamically stable PE patients. Regardless of the risk assessment, hospitalized patients had the highest rate of adverse event. If confirmed, ambulatory care of normotensive PE patients may be preferred whenever possible. SUMMARY: Background The decision to hospitalize or not patients with acute pulmonary embolism (PE) is controversial. Despite the advantages of close monitoring, hospitalization by itself may lead to in-hospital complications and potentially worsen the prognosis of PE patients. Objectives To determine the net clinical benefit of hospitalization vs. outpatient management of normotensive patients with acute pulmonary embolism (PE). Methods Retrospective cohort propensity score analysis (radius marching with replacement). Hemodynamically stable PE patients treated as outpatients or inpatients were matched to balance out differences for 28 patient characteristics and known risk factors for adverse events. The primary outcome was the rate of adverse events at 14 days, including recurrent venous thromboembolism, major bleeding or death. Results Among 1127 eligible patients, 1081 were included in the matched cohort, 576 treated as inpatients and 505 as outpatients. The 14-day rate of adverse events was 13.0% for inpatients and 3.3% for outpatients (adjusted OR, 5.07; 95% CI, 1.68-15.28). The 3-month rate was 21.7% for inpatients and 6.9% for outpatients (OR, 4.90; 95% CI, 2.62-9.17). In the high-risk subgroup (Pulmonary Embolism Severity Index class III-V; n = 597), the 14-day rate of adverse events was 16.5% for hospitalized patients vs. 4.5% for outpatients (OR, 4.16; 95% CI, 1.2-14.35). Conclusion Outpatient treatment of hemodynamically stable PE patients seems to be associated with a lower rate of adverse events than hospitalization and, if confirmed, may be considered as first-line management in patients not requiring specific in-hospital care, regardless of their initial risk stratification, if proper outpatient care can be provided.

Leachate from microplastics impairs larval development in brown mussels.

Microplastic debris is a pervasive type of contaminant in marine ecosystems, being considered a major threat to marine biota. One of the problems of microplastics is that they can adsorb contaminants in extremely high concentrations. When released from the particle, these contaminants have the potential to cause toxic effects in the biota. So far, reports of toxic effects are mostly linked with the direct exposure of organisms through ingestion of contaminated microplastics. There is little information on the toxicity of leachates from microplastics to marine organisms. In this study, we conducted experiments to evaluate the toxicity of leachates from virgin and beached plastic pellets to embryo development of the brown mussel (Perna perna). We compared the efficiency of two test procedures, and evaluated the toxicity of beached pellets collected in a coastal marine protected area. We observed that mussel embryo is sensitive to leachate from both virgin and beached pellets. However, the toxicity of the leachate from beached pellets was much higher than that of virgin pellets. We suggest contaminants adsorbed onto the surface of beached pellets were responsible for the high toxicity of leachate from beached pellets, while the toxicity of leachate from virgin pellets was mainly due to plastic additives. Our results suggest microplastic debris may be harmful even if ingestion is not the only or main pathway of interaction of marine organisms with contaminated plastic debris.

Role of Vitamin K Antagonists in the Prevention of Thrombotic Bypass Occlusion After Infrainguinal Venous Bypass.

CLINICAL VIGNETTE: Despite being the most common antithrombotic strategy in trials comparing venous with prosthetic grafts, the use of vitamin K antagonists (VKAs) to improve the outcome of venous bypass remains the subject of debate. In this systematic review, evidence supporting the use of VKAs for improving venous patency following infrainguinal venous bypass is provided. CLINICAL QUESTION: A 67 year old man with lifestyle limiting claudication underwent a successful infrainguinal venous bypass. Can VKAs help preserve patency after venous bypass surgery? METHODS: A systematic review of electronic databases, including MEDLINE and Embase, was conducted. Only randomized controlled studies comparing VKAs with aspirin (ASA) were included. The main outcome was bypass patency. RESULTS: Four studies using different intensities of anticoagulation ± ASA were identified. All but one showed a benefit of VKAs over ASA with respect to primary patency. However, this benefit was also accompanied by an increased risk of bleeding. The Dutch Bypass Oral Anticoagulants, or ASA, study was the largest included and showed that VKAs (without concomitant ASA) were superior to ASA alone for the prevention of graft occlusion (hazard ratio 0.69, 95% confidence interval 0.54-0.88). CONCLUSION: Current evidence suggests that VKAs are superior to ASA for the prevention of infrainguinal autologous venous graft thrombosis.

Prothrombin G20210A mutation and lower extremity peripheral arterial disease: a systematic review and meta-analysis.

OBJECTIVE/BACKGROUND: Despite being an important risk factor for venous thromboembolism, the role of the prothrombin G20210A mutation in patients with arterial disease remains unclear. The aim of this review was to evaluate the association of prothrombin G20210A and lower extremity peripheral arterial disease (PAD). METHODS: This was a systematic review and meta-analysis of case-control studies. A systematic review of electronic databases, including MEDLINE and Embase, was conducted to assess the prevalence of prothrombin G20210A in patients with lower extremity PAD. The main outcome was the prevalence of prothrombin G20210A in patients with lower extremity PAD. The random effects model odds ratio (OR) was used as the primary outcome measure. RESULTS: The initial electronic search identified 168 relevant abstracts of which five studies evaluating 1,524 cases of PAD and 1,553 controls were included. Prothrombin G20210A was found in 70 of 1,524 patients with lower extremity PAD and 44 of 1,553 of the controls (random effects OR 1.68, 95% confidence interval [CI] 0.8-3.2). In those with critical limb ischemia (CLI), the prevalence of prothrombin G20210A was 23 of 302 compared with 31 of 1,253 of the controls (OR 3.2, 95% CI 1.6-6.1). CONCLUSION: Despite finding no significant association between lower extremity PAD and prothrombin G20210A, the meta-analysis suggests that the prevalence of prothrombin G20210A is significantly elevated in those with atherosclerotic occlusive disease of the lower extremities presenting with CLI. Well-designed prospective cohort studies evaluating the role of prothrombin G20210A as a predictor of disease progression or adverse vascular events are highly needed.

Accumulation of six metals in the mangrove crab Ucides cordatus (Crustacea: Ucididae) and its food source, the red mangrove Rhizophora mangle (Angiosperma: Rhizophoraceae).

The crab Ucides cordatus and the red mangrove Rhizophora mangle are endemic mangrove species and potential bio-accumulators of metals. This study quantified the accumulation of six metals (Cd, Cr, Cu, Hg, Mn and Pb) in different organs (claw muscle, hepatopancreas and gills) of U. cordatus, as well as in different maturation stages of the leaves (buds, green mature, and pre-abscission senescent) of R. mangle. Samples were collected from mangrove areas in Cubatão, state of São Paulo, a heavily polluted region in Brazil. Data for metal contents in leaves were evaluated by one-way ANOVA; while for crabs a factorial ANOVA was used to investigate the effect of different tissues, animal size and the interactions between them. Means were compared by Tukey test at five percent, and the association between the metal concentrations in each crab organ, depending on the size, was evaluated by Pearson's linear correlation coefficient (r). Concentrations of Pb and Hg were undetectable for the different leaf stages and crab tissues, while Cd concentrations were undetectable in the leaf stages. In general, the highest accumulation of metals in R. mangle leaves occurred in pre-abscission senescent and green mature leaves, except for Cu, which was found in the highest concentrations in buds and green mature leaves. For the crab, Cd, Cu, Cr and Mn were present in concentrations above the detection limit, with the highest accumulation in the hepatopancreas, followed by the gills. Cu was accumulated mostly in the gills. Patterns of bioaccumulation between the crab and the mangrove tree differed for each metal, probably due to the specific requirements of each organism for essential metals. However, there was a close and direct relationship between metal accumulation in the mangrove trees and in the crabs feeding on them. Tissues of R. mangle leaves and U. cordatus proved effective for monitoring metals, acting as important bioindicators of mangrove areas contaminated by various metals.

Safety of outpatient treatment in acute pulmonary embolism.

INTRODUCTION: Data regarding outpatient treatment of pulmonary embolism (PE) is scarce. This study evaluates the safety of outpatient management of acute PE. METHODS: This is a retrospective cohort study of consecutive patients presenting at the Ottawa Hospital with acute PE diagnosed between 1 January 2007 and 31 December 2008. PE was defined as an arterial filling defect on CTPA or a high probability V/Q scan. Patients were managed as outpatients if they were hemodynamically stable, did not require supplemental oxygenation and did not have contraindications to low-molecular-weight heparin therapy. RESULTS: In this cohort of 473 patients with acute PE, 260 (55.0%) were treated as outpatients and 213 (45.0%) were admitted to the hospital. The majority of the patients were admitted because of severe comorbidities (45.5%) or hypoxia (22.1%). No outpatient died of fatal PE during the 3-month follow-up period. At the end of follow-up, the overall mortality was 5.0% (95% CI, 2.7-8.4%). The rates of recurrent venous thromboembolism (VTE) in outpatients were 0.4% (95% CI, 0.0-2.1%) and 3.8% (95% CI, 1.9-7.0%) within 14 days and 3 months, respectively. The rates of major bleeding episodes were 0% (95% CI, 0-1.4%) and 1.5% (95% CI, 0.4-3.9%) within 14 days and 3 months, respectively. Four (1.5%) outpatients were admitted to the hospital within 14 days. CONCLUSIONS: A majority of patients with acute PE can be managed as outpatients with a low risk of mortality, recurrent VTE and major bleeding episodes.

Unprovoked venous thromboembolism: Short term or indefinite anticoagulation? Balancing long-term risk and benefit.

Whether to continue oral anticoagulant therapy indefinitely after completing 3 to 6 months of oral anticoagulant therapy for "unprovoked" venous thromboembolism (VTE), is one of the most important unanswered questions in VTE management. This long-term decision should be based on balancing the long-term mortality risk from recurrent VTE, largely preventable with oral anticoagulant therapy, against the long-term mortality risk of major bleeding, the principle complication of oral anticoagulant therapy. There exist important knowledge gaps in estimating the long-term mortality risk of recurrent VTE in patients with unprovoked VTE who discontinue therapy and the long-term mortality risk from major bleeding in those who continue oral anticoagulant therapy. These knowledge gaps, reviewed herein, are the source of uncertainty for patients and health care providers wrestling with this important question. One promising solution is recurrent VTE risk stratification where unprovoked VTE patients are categorised as low or high risk for recurrent VTE and clinical decision making is less ambiguous and ultimately will likely lead to better outcomes.