https://journal.chestnet.org/article/S0012-3692(12)60129-9/pdf

Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Background Obesity is associated with increased mortality. Weight loss improves cardiovascular risk factors, but no prospective interventional studies have reported whether weight loss decreases overall mortality. In fact, many observational studies suggest that weight reduction is associated with increased mortality. Methods The prospective, controlled Swedish Obese Subjects study involved 4047 obese subjects. Of these subjects, 2010 underwent bariatric surgery (surgery group) and 2037 received conventional treatment (matched control group). We report on overall mortality during an average of 10.9 years of follow-up. At the time of the analysis (November 1, 2005), vital status was known for all but three subjects (follow-up rate, 99.9%). Results The average weight change in control subjects was less than ±2% during the period of up to 15 years during which weights were recorded. Maximum weight losses in the surgical subgroups were observed after 1 to 2 years: gastric bypass, 32%; vertical-banded gastropl...

/pdf/effects-of-bariatric-surgery-on-mortality-in-swedish-obese-1hxcpfu6t3.pdf

Effects of bariatric surgery on mortality in Swedish obese subjects.

https://www.chpso.org/sites/main/files/file-attachments/chest-2008-geerts-381s-453s.pdf

Prevention of Venous Thromboembolism* American College of Chest Physicians Evidence- Based Clinical Practice Guidelines (8th Edition)

Deep vein thrombosis (DVT) and pulmonary embolism are common mortal/morbid diseases worldwide, and improvements in prophylaxis and therapy have been elusive. The basic pathophysiology of how a thrombus forms in vivo and how it resolves are now better understood through experiments with animal models. Inflammation can both cause and incite venous thrombosis. Leukocytes, platelets, and coagulation factors coalesce locally after a thrombogenic stimulus occurs. Cell adhesion molecules, such as P-selectin, bridge the interface of thrombosis and inflammation, and are both biomarkers for, and pathogenic in DVT. Once DVT forms, natural thrombolysis occurs primarily via the urokinase-type plasminogen activator (uPA)–plasmin system. Alternative pathways also exist for venous thrombus resolution, including the matrix metalloproteinases. A new concept in DVT resolution related to sterile inflammation is clearance of procoagulant necrotic leukocytes and platelets, in part mediated by TLR9 signaling. A consequence of DVT is the proximate vein wall injury, which is dependent on the mechanism and duration of the thrombus-vein wall contact. Both vascular smooth muscle cells and endothelial cells maintain normal vein homeostasis, but adopt an injury response after thrombosis that may lead to vein fibrosis. In humans, multiple biomarkers are now available, but increased specificity for venous thrombosis is still elusive. Some of these biomarkers such as P-selectin may also play a causative role, and be attractive therapeutic targets for nonanticoagulant DVT prophylaxis and treatment.

Recent Insights into the Molecular and Cellular Contributions to Venous Thrombosis

E-Selectin Inhibition: A New Way to Treat Proximal Deep Venous Thrombosis

Venous Thromboembolism Risk Assessment Scoring in the Critically Ill: The Impact of Misclassification

https://deepblue.lib.umich.edu/bitstream/handle/2027.42/41366/10016_2003_Article_13.pdf;sequence=1

Carotid Embolectomy in the Treatment of a Paradoxical Embolus

Background: The incidence of deep venous thrombosis (DVT) significantly increases 45 years of age. Our objective was to identify the direct relationship between aging and adhesion molecule activation during venous thrombosis in mice of varying ages. A mixed patient population was also evaluated for age-related effects during DVT. Methods: DVT was induced in 4 and 18 month old C57BL/6 mice using the electrolytic inferior vena cava model (EIM). Mice were euthanized at baseline (non-thrombosed, TC), 6 hours (6H), and 2 days (2D) postthrombosis. Blood and tissue samples were collected for the following analysis: thrombus weight (TW), soluble P (sP) and soluble E-selectin (sE) by ELISA, vein wall Pand E-selectin protein by ELISA, vein wall Pand E-selectin gene expression, vein wall inflammatory cell analysis by light microscopy, and hematology. In a patient population (n335), the relationship between patients with and without DVT, sP levels, and age (above and below 45 years) was evaluated. Results: Older mice had significantly larger venous thrombi versus younger mice at the 6H and 2D (x10-3 grams, P < .01; Fig 1). These same mice had significantly higher sP-selectin levels versus younger mice at 6 hours and 2 days (ng/mg, P < .01). Older mouse sE levels were significantly lower versus younger animals at baseline (pg/mg, P < .05). Older animals had significantly elevated vein wall P-selectin versus younger mice at 6H and 2D post-thrombosis (P < .01). Post-thrombosis, significantly increased vein wall E-selectin in younger mice versus older animals at 6H (P < .05). All mice showed active vein wall inflammatory cell extravasation post thrombosis. Older animals had significantly more circulating platelets versus younger mice at baseline, 6H, and 2D post-thrombosis (K/mL, P < .01). DVT-positive patients greater than 45 years (n 1⁄4 135) of age had significantly higher levels of soluble P-selectin versus patients positive for DVT less than 45 years (n 1⁄4 51) of age (ng/mL sP, P < .05; Fig 2). Conclusions: Aging significantly increased vein wall P-selectin, sP, and circulating platelets that amplified venous thrombosis in mice. For the first time, we have documented the translational role of soluble P-selectin as a biomarker for thrombosis in aged rodents and DVT-positive patients. These important findings will provide supporting evidence for the use of selectin targeted therapeutics in future clinical trials for the prophylaxis and treatment of DVT in the aged population.

Thomas W. Wakefield

Papers

Recent Insights into the Molecular and Cellular Contributions to Venous Thrombosis

E-Selectin Inhibition: A New Way to Treat Proximal Deep Venous Thrombosis

Venous Thromboembolism Risk Assessment Scoring in the Critically Ill: The Impact of Misclassification

Carotid Embolectomy in the Treatment of a Paradoxical Embolus

Vein Wall and Circulating P-selectin Promote Venous Thrombogenesis During Aging in a Rodent Model.