ABSTRACT
As the Coronavirus disease 2019 (COVID-19) pandemic spread to the US, so too did descriptions of an associated coagulopathy and thrombotic complications. Hospitals created institutional protocols for inpatient management of COVID-19 coagulopathy and thrombosis in response to this developing data. We collected and analyzed protocols from 21 US academic medical centers developed between January and May 2020. We found greatest consensus on recommendations for heparin-based pharmacologic venous thromboembolism (VTE) prophylaxis in COVID-19 patients without contraindications. Protocols differed regarding incorporation of D-dimer tests, dosing of VTE prophylaxis, indications for post-discharge pharmacologic VTE prophylaxis, how to evaluate for VTE, and the use of empiric therapeutic anticoagulation. These findings support ongoing efforts to establish international, evidence-based guidelines.
Subject(s)
Anticoagulants/administration & dosage , Blood Coagulation/drug effects , COVID-19 Drug Treatment , Clinical Protocols , Pulmonary Embolism/prevention & control , Thrombophilia/prevention & control , Venous Thromboembolism/prevention & control , Venous Thrombosis/prevention & control , Academic Medical Centers , Anticoagulants/adverse effects , COVID-19/blood , COVID-19/complications , COVID-19/diagnosis , Consensus , Healthcare Disparities/trends , Humans , Practice Patterns, Physicians'/trends , Pulmonary Embolism/blood , Pulmonary Embolism/diagnosis , Pulmonary Embolism/etiology , Risk Assessment , Risk Factors , Thrombophilia/blood , Thrombophilia/diagnosis , Thrombophilia/etiology , Treatment Outcome , United States , Venous Thromboembolism/blood , Venous Thromboembolism/diagnosis , Venous Thromboembolism/etiology , Venous Thrombosis/blood , Venous Thrombosis/diagnosis , Venous Thrombosis/etiologyABSTRACT
Ligament heals in a synchronized and complex series of events. The remodeling process may last months or years. Experimental evidence suggests the damaged ligament does not recover its normal functional properties. Specific mechanisms to prevent scar formation and to regenerate the original mechanical function remain elusive but likely involve regulation of creeping substitution. Creeping substitution creates a larger hypercellular, hypervascular, and disorganized granulation tissue mass that results in an inefficient and nonregenerative wound healing process for the ligament. Control of creeping substitution may limit the extent of this tissue compromise and reduce the time necessary for healing. The objective of this study is to better understand the mechanism behind scar formation by identifying the extracellular matrix factors and other unique genes of interest differentially expressed during rat ligament healing via microarray. For this study, rat medial collateral ligaments were either surgically transected or left intact. Ligaments were collected at day 3 or 7 postinjury and used for microarray, quantitative PCR, and/or immunohistochemistry. Results were compared with the normal intact ligament. We demonstrate that early ligament healing is characterized by the modulation of several inflammatory and extracellular matrix factors during the first week of injury. Specifically, a number of matrix metalloproteinases and collagens are differentially and significantly expressed during early ligament healing. Additionally, we demonstrate the modulation of three novel genes, periostin, collagen-triple helix repeat containing-1, and serine protease 35 in our ligament healing model. Together, control of granulation tissue creeping substitution and subsequent downstream scar formation is likely to involve these factors.
Subject(s)
Collateral Ligaments/physiology , Gene Expression Profiling , Wound Healing/genetics , Animals , Cell Adhesion Molecules/metabolism , Collagen/biosynthesis , DNA Primers , Extracellular Matrix/enzymology , Extracellular Matrix/metabolism , Glycoproteins/genetics , Immunohistochemistry , In Situ Hybridization , Inflammation/enzymology , Inflammation/metabolism , Male , Matrix Metalloproteinases/biosynthesis , Microarray Analysis , RNA/biosynthesis , RNA/genetics , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Osteoarthritis of the knee has consistently been linked to obesity, defined as a body mass index (BMI) >30kg/m(2). It has been hypothesized that obesity may lead to osteoarthritis through increased joint pressure, accumulated microtrauma, and disruption of normal chondrocyte metabolism. These changes in chondrocyte metabolism have not been thoroughly investigated, and it is the purpose of this study to identify a relationship between BMI and altered chondrocyte metabolism in osteoarthritic tissue. Articular cartilage was harvested from the femoral condyles of patients after total knee arthroplasty, and analyzed in explant and alginate models. Glycosaminoglycan (GAG) content was measured using a dimethylmethylene blue assay and normalized to DNA content using a PicoGreen(R) assay. Studies have reported GAGs to be a reliable measurement of chondrocyte metabolism and osteoarthritis progression. Our results show a significant linear relationship of increasing BMI and increasing GAG content in both alginate and explant models (p<0.001 and p=0.001). Obese (BMI>/=30kg/m(2)) and non-obese (BMI<30kg/m(2)) comparisons also demonstrated significant differences with higher GAG/DNA content in obese individuals compared to non-obese (p=0.001 and p=0.015). The study results reveal significant relationships between GAG content and BMI in this population of osteoarthritic patients. The significant difference in GAG content between the obese and non-obese patients supports the connection between osteoarthritis and obesity previously reported. Higher patient BMI (>30kg/m(2)) may be similar to dynamic compression injuries which cause increased GAG synthesis in response to cartilage damage.
