Incidence of venous thromboembolism after elective knee arthroscopic surgery: a historical cohort study.

BACKGROUND: The incidence of symptomatic venous thromboembolism (VTE) after knee arthroscopy is uncertain. OBJECTIVES: To estimate the incidence of symptomatic VTE after arthroscopic knee surgery. METHODS: In a population-based historical cohort study, all Olmsted County, MN, USA, residents undergoing a first arthroscopic knee surgery during the 18-year period of 1988-2005 were followed for incident deep venous thrombosis or pulmonary embolism. The cumulative incidence of VTE after knee arthroscopy was determined using the Kaplan-Meier product limit estimator. Patient age at surgery, sex, calendar year of surgery, body mass index, anesthesia characteristics, and hospitalization were tested as potential predictors of VTE using Cox proportional hazards modeling, both univariately and adjusted for age and sex. RESULTS: Among 4833 Olmsted County residents with knee arthroscopy, 18 developed postoperative VTE, all within the first 6 weeks after surgery. The cumulative incidence rates of symptomatic VTE at 7, 14, and 35 days were 0.2%, 0.3%, and 0.4%, respectively. The hazard for postoperative VTE was significantly increased for older patient age (hazard ratio = 1.34 for each 10-year increase in patient age; P = 0.03) and hospitalization either before or after knee arthroscopy (hazard ratio = 14.1; P < 0.001). CONCLUSIONS: The incidence of symptomatic VTE after arthroscopic knee surgery is very low. Older age and hospitalization are associated with increased risk. Routine prophylaxis to prevent symptomatic VTE is likely not needed in this patient population.

Cancer effect on periprocedural thromboembolism and bleeding in anticoagulated patients.

BACKGROUND: Patients with active cancer are often on chronic anticoagulation and frequently require interruption of this treatment for invasive procedures. The impact of cancer on periprocedural thromboembolism (TE) and major bleeding is not known. PATIENTS AND METHODS: Two thousand one hundred and eighty-two consecutive patients referred for periprocedural anticoagulation (2484 procedures) using a standardized protocol were followed forward in time to estimate the 3-month incidence of TE, major bleeding and survival stratified by anticoagulation indication. For each indication, we tested active cancer and bridging heparin therapy as potential predictors of TE and major bleeding. RESULTS: Compared with patients without cancer, active cancer patients (n=493) had more venous thromboembolism (VTE) complications (1.2% versus 0.2%; P=0.001), major bleeding (3.4% versus 1.7%; P=0.02) and reduced survival (95% versus 99%; P<0.001). Among active cancer patients, only those chronically anticoagulated for VTE had higher rates of periprocedural VTE (2% versus 0.16%; P=0.002) and major bleeding (3.7% versus 0.6%; P<0.001). Bridging with heparin increased the rate of major bleeding in cancer patients (5% versus 1%; P=0.03) without impacting the VTE rate (0.7% versus 1.4%, P=0.50). CONCLUSIONS: Cancer patients anticoagulated for VTE experience higher rates of periprocedural VTE and major bleeding. Periprocedural anticoagulation for these patients requires particular attention to reduce these complications.

Giant cell myocarditis as a manifestation of drug hypersensitivity.

Adverse drug effects on the myocardium are often classified into toxic and hypersensitivity forms of myocarditis, each with distinct histologic findings. In contrast, giant cell myocarditis (GCM) is generally not associated with adverse drug reactions and has unique histopathologic features. We report four cases of adverse drug reactions in which the histologic findings were characteristic of GCM. The clinical recognition that GCM may be a manifestation of an adverse drug reaction is important, since the prognosis and treatment of this entity may be different from that of other forms of myocarditis.

Characterization of the interactions of human papillomavirus type 16 E6 with p53 and E6-associated protein in insect and human cells.

Human papillomavirus (HPV) 16 E6 induces the degradation of the tumour suppressor protein p53 by the ubiquitin-dependent proteolysis pathway. In vitro, this process involves the formation of a trimolecular complex between E6, p53 and a cellular protein E6-associated protein (E6-AP). However, an analysis of their potential interactions in vivo has not been carried out. We have established a model for the expression and analysis of the interactions of these three proteins in insect cells, a eukaryotic system where potentially crucial modifications of the proteins will occur. In baculovirus-infected cells the degradation of p53 can occur. However, p53 is only degraded early in the infectious cycle due to a lack of ATP at later times. Consequently, substantial quantities of material can be produced in this system for further analysis. Evidence is also provided that, in vivo, E6 can interact with p53 in the absence of E6-AP and that E6-AP can interact with p53 in the absence of E6. Furthermore, analysis of the subcellular localization of the proteins using both biochemical fractionation and indirect immunofluorescence suggests that the degradation of p53 occurs in the perinuclear region of the cell.

Molecular analysis of the interaction between HPV type 16 E6 and human E6-associated protein.

The complex formed between the human papillomavirus type 16 E6 protein and human E6-associated protein, which combine to ubiquitylate and degrade p53, has been studied by chemical crosslinking. Analysis of the interactions of proteins purified from Escherichia coli as well as proteins expressed in insect cells indicates that, while E6 has the capacity to form dimers, E6 and E6-associated protein interact as two monomers to form a heterologous dimer.