Search

It is unknown how lower-leg injury and knee arthroscopy, both associated with venous thromboembolism (VTE), affect coagulation. To study the effect of (1) lower-leg trauma and (2) knee arthroscopy on coagulation, plasma samples of the Prevention of Thrombosis following CAST immobilization (POT-CAST, #NCT01542762) and Prevention of Thrombosis following Knee Arthroscopy (POT-KAST, #NCT01542723) trials were used, which were collected shortly after lower-leg trauma and before/after (

Frozen shoulder (FS), also known as adhesive capsulitis, is a painful inflammatory fibrotic disease of the glenohumeral joint capsule. While it's frequently self-limiting, patients can be symptomatic for years. The clinical course is often divided into three phases: the freezing phase with predominantly pain, the frozen phase with mainly stiffness, and the thawing phase during which the complaints slowly resolve. Diagnosing FS can be challenging during the freezing phase as the symptoms in this phase are similar to other common shoulder conditions (such as subacromial pain syndrome). Treatment options include analgesia, physical therapy, corticosteroid injections, hydrodilatation, manipulation under anaesthesia, and arthroscopic release. Despite the many treatment options, there is no clear treatment guideline. Based on recent literature, conservative management is indicated as it can provide temporary symptom reduction. Due to significant risk of complications, surgical management should only be considered if patients retain complaints despite long-term conservative therapy.

Introduction Patients with lower-leg cast immobilization and patients undergoing knee arthroscopy have an increased risk of venous thrombosis (VT). Guidelines are ambiguous about thromboprophylaxis use, and individual risk factors for developing VT are often ignored. To assist in VT risk stratification and guide thromboprophylaxis use, various prediction models have been developed. These models depend largely on clinical factors and provide reasonably good C-statistics of around 70%. We explored using protein levels in blood plasma measured by multiplexed quantitative targeted proteomics to predict VT. Our aim was to assess whether a VT risk prediction model based on absolute plasma protein quantification is possible. Methods We used internal standards to quantify proteins in less than 10 mu l plasma. We measured 270 proteins in samples from patients scheduled for knee arthroscopy or with lower-leg cast immobilization. The two prospective POT-(K)CAST trails allow complementary views of VT signature in blood, namely pre and post trauma, respectively. From approximately 3000 patients, 31 patients developed VT who were included and matched with double the number of controls. Results Top discriminating proteins between cases and controls included APOC3, APOC4, APOC2, ATRN, F13B, and F2 in knee arthroscopy patients and APOE, SERPINF2, B2M, F13B, AFM, and C1QC in patients with lower-leg cast. A logistic regression model with cross-validation resulted in C-statistics of 88.1% (95% CI: 85.7-90.6%) and 79.6% (95% CI: 77.2-82.0%) for knee arthroscopy and cast immobilization groups respectively. Conclusions Promising C-statistics merit further exploration of the value of proteomic tests for predicting VT risk upon additional validation.

Background: Lower-leg injury and knee arthroscopy are both associated with venous thromboembolism (VTE). The mechanism of VTE in both situations is unknown, including the role of procoagulant microparticles. This may provide useful information for individualizing thromboprophylactic treatment in both patient groups. Objective: We aimed to study the effect of (1) lower-leg trauma and (2) knee arthroscopy on procoagulant phospholipid-dependent (PPL) activity plasma levels. Methods: POT-(K)CAST trial participants who did not develop VTE were randomly selected for the current study. Plasma was collected shortly after lower-leg trauma or before and after knee arthroscopy. For aim 1, samples of 67 patients with lowerleg injury were compared with control samples (preoperative samples of 74 patients undergoing arthroscopy). Linear regression was used to obtain mean ratios (natural logarithm retransformed data), adjusted for age, sex, body mass index, infections, and comorbidities. For aim 2, pre- and postoperative samples of 49 patients undergoing arthroscopy were compared using paired t tests. PPL activity was measured using modified activated factor X–dependent PPL clotting assay. Results: For aim 1, PPL activity levels were almost threefold higher in patients with lower-leg injury compared with controls, that is, mean ratio, 2.82 (95% confidence interval [CI], 1.98-4.03). For aim 2, postoperative PPL activity levels did not change significantly, that is, mean change, −0.72 mU/mL (95% CI, −2.03 to 0.59). Conclusion: Lower-leg trauma was associated with increased plasma levels of PPL activity, in contrast to knee arthroscopy. Lower-leg trauma triggers the release of procoagulant microparticles.

Background A small subgroup of patients treated with lower-leg cast immobilization develops venous thromboembolism (VTE). Objectives (1) Identify risk factors for VTE in patients with cast immobilization, (2) assess the effectiveness of thromboprophylaxis in low- and high-risk groups, and (3) validate the performance of the L-TRiP(cast) score. Methods Data from the POT-CAST trial were used. A total of 1,519 patients with lower-leg cast immobilization were randomized to a prophylactic dose of low-molecular-weight heparin or no treatment. Primary outcome: symptomatic VTE within 3 months. Absolute risks (ARs) were determined for low- and high-risk subgroups. For several risk factors, relative risks (RRs) for VTE were estimated with corresponding 95% confidence intervals (CIs). For validating the L-TRiP(cast) score, a discrimination and calibration analysis were performed. Results Patients with a body mass index of > 30 kg/m2 and those with a VTE in their family history had an increased VTE risk, RR 3.8 (95% CI, 1.5–9.4) and RR 2.4 (95% CI, 1.0–5.6), respectively. Concerning injury-specific risk factors, patients with an Achilles tendon rupture or those who were surgically treated had the highest risk of VTE, AR at 8.5% (95% CI, 3.7–16.1) and AR 3.5% (95% CI, 1.3–7.5), respectively. There were no subgroups in which thromboprophylaxis was effective for prevention of symptomatic VTE. The area under the curve for the L-TRiP(cast) score was 0.69 (95% CI, 0.58–0.80). Conclusion Thromboprophylaxis was not effective for VTE prevention following lower-leg cast immobilization in any risk category. Low- and high-risk individuals could be identified using the L-TRiP(cast) score. The best treatment strategy for these patients is yet to be determined.

Patients at high risk for venous thrombosis (VT) following knee arthroscopy could potentially benefit from thromboprophylaxis. We explored the predictive values of environmental, genetic risk factors and levels of coagulation markers to integrate these into a prediction model. Using a population-based case–control study into the aetiology of VT, we developed a Complete (all variables), Screening (easy to use in clinical practice) and Clinical (only environmental risk factors) model. The Clinical model was transformed into the Leiden-Thrombosis Risk Prediction (arthroscopy) score [L-TRiP(ascopy) score]. Model validation was performed both internally and externally in another case–control study. A total of 4,943 cases and 6,294 controls were maintained in the analyses, 107 cases and 26 controls had undergone knee arthroscopy. Twelve predictor variables (8 environmental, 3 haemorheological and 1 genetic) were selected from 52 candidates and incorporated into the Complete model (area under the curve [AUC] of 0.81, 95% confidence interval [CI], 0.76–0.86). The Screening model (9 predictors: environmental factors plus factor VIII activity) reached an AUC of 0.76 (95% CI, 0.64–0.88) and the Clinical (and corresponding L-TRiP(ascopy)) model an AUC of 0.72 (95% CI, 0.60–0.83). In the internal and external validation, the Complete model reached an AUC of 0.78 (95% CI, 0.52–0.98) and 0.75 (95% CI, 0.42–1.00), respectively, while the other models performed slightly less well.

Objectives Knowledge on the epidemiology and long-term course of rotator cuff calcific tendinitis (RCCT) is scarce. We assessed demographics, radiological characteristics, and their association with long-term outcomes in a large patient group. Methods Baseline demographics, radiological characteristics and treatment were recorded in 342 patients. Interobserver agreement of radiological measures was analyzed. Long-term outcome was evaluated with questionnaires (WORC, DASH). The association of baseline characteristics with outcome was assessed. Results Mean age was 49.0 (SD = 10.0), and 59.5 % were female. The dominant arm was affected in 66.0 %, and 21.3 % had bilateral disease. Calcifications were on average 18.7 mm (SD = 10.1, ICC = 0.84 (p

Background Guidelines and clinical practice vary considerably with respect to thrombosis prophylaxis during plaster cast immobilization of the lower extremity. Identifying patients at high risk for the development of venous thromboembolism (VTE) would provide a basis for considering individual thromboprophylaxis use and planning treatment studies. The aims of this study were (1) to investigate the predictive value of genetic and environmental risk factors, levels of coagulation factors, and other biomarkers for the occurrence of VTE after cast immobilization of the lower extremity and (2) to develop a clinical prediction tool for the prediction of VTE in plaster cast patients. Methods and Findings We used data from a large population-based case–control study (MEGA study, 4,446 cases with VTE, 6,118 controls without) designed to identify risk factors for a first VTE. Cases were recruited from six anticoagulation clinics in the Netherlands between 1999 and 2004; controls were their partners or individuals identified via random digit dialing. Identification of predictor variables to be included in the model was based on reported associations in the literature or on a relative risk (odds ratio) > 1.2 and p ≤ 0.25 in the univariate analysis of all participants. Using multivariate logistic regression, a full prediction model was created. In addition to the full model (all variables), a restricted model (minimum number of predictors with a maximum predictive value) and a clinical model (environmental risk factors only, no blood draw or assays required) were created. To determine the discriminatory power in patients with cast immobilization (n = 230), the area under the curve (AUC) was calculated by means of a receiver operating characteristic. Validation was performed in two other case–control studies of the etiology of VTE: (1) the THE-VTE study, a two-center, population-based case–control study (conducted in Leiden, the Netherlands, and Cambridge, United Kingdom) with 784 cases and 523 controls included between March 2003 and December 2008 and (2) the Milan study, a population-based case–control study with 2,117 cases and 2,088 controls selected between December 1993 and December 2010 at the Thrombosis Center, Fondazione IRCCS Ca’ Granda–Ospedale Maggiore Policlinico, Milan, Italy. The full model consisted of 32 predictors, including three genetic factors and six biomarkers. For this model, an AUC of 0.85 (95% CI 0.77–0.92) was found in individuals with plaster cast immobilization of the lower extremity. The AUC for the restricted model (containing 11 predictors, including two genetic factors and one biomarker) was 0.84 (95% CI 0.77–0.92). The clinical model (consisting of 14 environmental predictors) resulted in an AUC of 0.77 (95% CI 0.66–0.87). The clinical model was converted into a risk score, the L-TRiP(cast) score (Leiden–Thrombosis Risk Prediction for patients with cast immobilization score), which showed an AUC of 0.76 (95% CI 0.66–0.86). Validation in the THE-VTE study data resulted in an AUC of 0.77 (95% CI 0.58–0.96) for the L-TRiP(cast) score. Validation in the Milan study resulted in an AUC of 0.93 (95% CI 0.86–1.00) for the full model, an AUC of 0.92 (95% CI 0.76–0.87) for the restricted model, and an AUC of 0.96 (95% CI 0.92–0.99) for the clinical model. The L-TRiP(cast) score resulted in an AUC of 0.95 (95% CI 0.91–0.99). Major limitations of this study were that information on thromboprophylaxis was not available for patients who had plaster cast immobilization of the lower extremity and that blood was drawn 3 mo after the thrombotic event. Conclusions These results show that information on environmental risk factors, coagulation factors, and genetic determinants in patients with plaster casts leads to high accuracy in the prediction of VTE risk. In daily practice, the clinical model may be the preferred model as its factors are most easy to determine, while the model still has good predictive performance. These results may provide guidance for thromboprophylaxis and form the basis for a management study., Using three population-based case-control studies, Banne Nemeth and colleagues derive and validate a clinical prediction score (L-TRiP(cast)) for venous thrombosis risk., Editors' Summary Background Blood normally flows smoothly around the human body, but when a cut or other injury occurs, proteins called clotting factors make the blood gel (coagulate) at the injury site. The resultant clot (thrombus) plugs the wound and prevents blood loss. Sometimes, however, a thrombus forms inside an uninjured blood vessel and partly or completely blocks the blood flow. Clot formation inside one of the veins deep in the body (usually in a leg) is called deep vein thrombosis (DVT). DVT, which can cause pain, swelling, and redness in the affected limb, is treated with anticoagulants, drugs that stop the clot growing. If left untreated, part of the clot can break off and travel to the lungs, where it can cause a life-threatening pulmonary embolism. DVT and pulmonary embolism are known collectively as venous thromboembolism (VTE). Risk factors for VTE include age, oral contraceptive use, having an inherited blood clotting disorder, and prolonged inactivity (for example, being bedridden). An individual’s lifetime risk of developing VTE is about 11%; 10%–30% of people die within 28 days of diagnosis of VTE. Why Was This Study Done? Clinicians cannot currently accurately predict who will develop VTE, but it would be very helpful to be able to identify individuals at high risk for VTE because the condition can be prevented by giving anticoagulants before a clot forms (thromboprophylaxis). The ability to predict VTE would be particularly useful in patients who have had a lower limb immobilized in a cast after, for example, breaking a bone. These patients have an increased risk of VTE compared to patients without cast immobilization. However, their absolute risk of VTE is not high enough to justify giving everyone with a leg cast thromboprophylaxis because this therapy increases the risk of major bleeds. Here, the researchers investigate the predictive value of genetic and environmental factors and levels of coagulation factors and other biomarkers on VTE occurrence after cast immobilization of the lower leg and develop a clinical tool for the prediction of VTE in patients with plaster casts. What Did the Researchers Do and Find? The researchers used data from the MEGA study, a study of risk factors for VTE, to build a prediction model for a first VTE in patients with a leg cast; the prediction model included 32 predictors (the full model). They also built a restricted model, which included only 11 predictors but had maximum predictive value, and a clinical model, which included 14 environmental predictors that can all be determined without drawing blood or undertaking any assays. They then determined the ability of each model to distinguish between patients with a leg cast who did and did not develop VTE using receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) for the full model was 0.85, for the restricted model it was 0.85, and for the clinical model it was 0.77. (A predictive test that discriminates perfectly between individuals who do and do not subsequently develop a specific condition has an AUC of 1.00; a test that is no better at predicting outcomes than flipping a coin has an AUC of 0.5.) Similar or higher AUCs were obtained for all the models using data collected in two independent studies. Finally, the researchers converted the clinical model into a risk score by giving each variable in the model a numerical score. The sum of these scores was used to stratify individuals into categories of low or high risk for VTE. With a cutoff of 9 points, the risk score correctly identified 80.8% of the patients in the MEGA study with a plaster cast who developed VTE and 60.8% of the patients who did not develop VTE. What Do These Findings Mean? Some aspects of this study may limit the accuracy of its findings. For example, no information was available about which patients with a plaster cast received thromboprophylaxis. Nevertheless, these findings suggest that information on environmental risk factors, coagulation factors, and genetic determinants can be used to predict VTE risk in patients with a leg cast with high accuracy. Importantly, the risk score derived and validated by the researchers, which includes only predictors that can be easily determined in clinical practice, may help clinicians decide which patients with a leg cast should receive thromboprophylaxis and which should not be exposed to the risk of anticoagulant therapy, until an unambiguous guideline for these patients becomes available. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001899. The US National Heart, Lung, and Blood Institute provides information on deep vein thrombosis (including an animation about how DVT causes pulmonary embolisms) and on pulmonary embolism The UK National Health Service Choices website has information on deep vein thrombosis (including personal stories) and on pulmonary embolism The US non-profit organization National Blood Clot Alliance provides detailed information about deep vein thrombosis and pulmonary embolism for patients and professionals and includes a selection of personal stories about these conditions MedlinePlus has links to further information about deep vein thrombosis and pulmonary embolism (in English and Spanish) Wikipedia has a page on ROC curve analysis (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) More information about the MEGA study is available