Oxygen saturation or respiratory rate to improve risk stratification in hemodynamically stable patients with acute pulmonary embolism.

Essentials In acute pulmonary embolism (PE), risk stratification is essential to drive clinical management. Improving the 2014-ESC risk stratification strategy is crucial in hemodynamically stable patients. Oxygen saturation and respiratory rate improve risk stratification in hemodynamically stable PE. Simple and routine tests improve risk stratification of hemodynamically stable PE. SUMMARY: Background In patients with acute pulmonary embolism (PE), risk stratification for short-term death is recommended to drive clinical management. A risk stratification strategy combining the simplified Pulmonary Embolism Severity Index (PESI), echocardiography and troponin was proposed by the European Society of Cardiology (ESC) in 2014. The identification of hemodynamically stable patients at increased risk of death by this strategy needs improvement. Objective To assess whether further stratification by serial cut-off values of oxygen saturation or respiratory rate improves the accuracy of the ESC risk stratification strategy in hemodynamically stable PE patients. Methods Prospective cohorts of hemodynamically stable patients with PE were merged in a collaborative database. The accuracy of risk stratification for 30-day mortality by the original and a modified 2014 ESC strategy was assessed. Results Overall, 255 patients (27%) were categorized as low, 510 (54%) as intermediate-low and 181 (19%) as intermediate-high risk according to the original 2014 ESC strategy. Thirty-day mortality was 1.2% in low, 10% in intermediate-low and 11% in intermediate-high-risk patients. By adding oxygen saturation in air of < 88%, the discriminatory power of the 2014 ESC model improved for 30-day mortality (c-statistics, 0.71; 95% confidence interval [CI], 0.65-0.77 vs. 0.63, 95% CI, 0.56-0.69) and for PE-related death (c-statistics, 0.75; 95% CI, 0.69-0.81 vs. 0.63, 95% CI 0.56-0.69). Conclusions Simple and routine tests, such as oxygen saturation or respiratory rate, could be added to the 2014 ESC strategy for risk stratification to identify hemodynamically stable PE patients at increased risk of death who are potentially candidates for more aggressive treatment.

Variation of renal function over time is associated with major bleeding in patients treated with direct oral anticoagulants for atrial fibrillation.

Essential In patients on treatment with direct anticoagulants (DOACs) variation of renal function is common. The effect of variations of renal function over time on major bleeding is not well defined. Variation of renal function over time is an independent predictor of major bleeding. Identifying conditions associated with variation of renal function may increase safety of DOACs. SUMMARY: Background Chronic kidney disease is a risk factor for major bleeding in patients with atrial fibrillation (AF) treated with warfarin. Objective To assess the effect of variations in renal function over time on the risk of major bleeding during treatment with direct oral anticoagulants (DOACs) in patients with non-valvular AF. Methods Consecutive AF patients were prospectively followed after they had received the first DOAC prescription. Estimated glomerular filtration rate (eGFR) was periodically assessed, and the incidence of major bleeding was recorded. A joint survival model was used to estimate the association between variation in eGFR and the risk of major bleeding. Results During a mean follow-up of 575 days, 44 major bleeds occurred in 449 patients (6.1% per patient-year). eGFR over time was inversely and independently associated with the risk of major bleeding; every 1 mL min-1 absolute decrease in eGFR was associated with a 2% increase in the risk of major bleeding (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.01-1.04). A similar effect of the variation in eGFR over time was observed on the risk of clinically relevant non-major bleeding (HR 1.02, 95% CI 1.01-1.03). Deterioration of renal function leading to a change in eGFR staging was associated with an increase in the risk of major bleeding (HR 2.43, 95% CI 1.33-4.45). Conclusions Variation in renal function over time is associated with the risk of major bleeding in AF patients treated with DOACs in real life. Identification of intervening clinical conditions associated with variation in renal function is essential to reduce the risk of major bleeding and to make DOAC treatment more safe.

PO-40 - Real-life use of non-vitamin k antagonist oral anticoagulants in patients with cancer associated venous thromboembolism: data from a prospective cohort.

INTRODUCTION: Cancer associated thrombosis (CAT) has an increased risk of recurrent venous thromboembolism (VTE). Type, stage of cancer and chemotherapy (CHT) influence thromboembolic risk. The use of novel oral anticoagulants (NOACs) is controversial in patients with CAT. AIM: The aim of this study is to assess mortality, recurrent VTE and bleeding complications in patients with CAT and in patients without cancer receiving NOACs. MATERIALS AND METHODS: Consecutive patients with acute objectively confirmed VTE receiving NOACs within 1 month from diagnosis are included from September 2013 in an ongoing prospective cohort study. Characteristics of patients and outcome are reported according to the presence of CAT. Chi-squared test and Student' t-test are used. RESULTS: As for November 10(th) 2015, 472 patients were included in the study: 78 with CAT (16.5%). Lung, breast, gastrointestinal and genitourinary cancer was observed in 16%, 24%, 20% and 24% of patients with CAT, respectively. 31 patients with CAT (40%) were on CHT or radiotherapy (RT). 10 patients with CAT (13%) had at least an additional risk factor for VTE (4 had a CVC related thrombosis) and 34 (43.5%) were inpatients. Baseline characteristics of patients with and without CAT are reported in the Table. Pulmonary embolism was index VTE in 152 patients: 24.4% of patients with CAT and in 33.8% of those without cancer (p=0.10). DVT only was present in 320 patients and 78 had both DVT and PE. Among NOACs patients, 312 (66%) received initial loading dose: 61% of those with CAT and 67% without. 53 (11%) received reduced maintenance doses (10% with CAT, 11% without). As for nowadays, 272 patients had at least 3 months of follow-up, the mean follow-up being 8.6 months. 20 patients died (7.3%): 17 were cancer related deaths. Non cancer related death occurred in 1 patient with CAT (2%) and in 2 patients without (0.9%). No fatal bleedings or fatal VTE recurrences occurred. Patients recruitment and follow-up is currently ongoing aimed at assessing mortality, recurrent VTE and bleeding complications. Updated results on clinical outcomes will be presented at the congress. CONCLUSIONS: Patients with CAT receiving NOACs are treated as patients without CAT in terms of use of loading doses and maintenance treatment. Upper arm thrombosis is more frequently involved in CAT patients and proximal lower vein in patients without CAT. Non cancer related mortality was higher in CAT patients but no fatal recurrences or fatal bleedings were observed so far.

To drain or not to drain extraperitoneal colorectal anastomosis? A systematic review and meta-analysis.

AIM: Anastomotic leakage is the one of the most serious complications in rectal cancer surgery and is associated with high mortality, morbidity and an increased incidence of local recurrence. Although many studies have compared drained and undrained colorectal anastomoses, to date the role of pelvic drainage in extraperitoneal colorectal anastomosis remains undefined. METHOD: We carried out a systematic review of the literature, performing an unrestricted search in MEDLINE and Embase up to 30 October 2012. Reference lists of retrieved articles and review articles were manually searched for other relevant studies. We performed a meta-analysis of the data currently available on the incidence of extraperitoneal anastomotic leakage, according to the presence or absence of pelvic drainage. RESULTS: Overall, eight studies - three randomized clinical trials (RCTs) and five non-RCTs, comprising a total of 2277 patients - were included in the meta-analysis. Pelvic drainage was demonstrated to reduce both the leak rate and the rate of reintervention in patients who underwent anterior rectal resection with extraperitoneal colorectal anastomosis (OR = 0.51, 95% CI: 0.36-0.73; and OR = 0.29, 95% CI: 0.18-0.46, respectively) compared with patients without drainage. Overall mortality and infection rates were also evaluated, but a nonsignificant correlation was found with the presence of drainage. CONCLUSION: The meta-analysis shows that the presence of a pelvic drain reduces the incidence of extraperitoneal colorectal anastomotic leakage and the rate of reintervention after anterior rectal resection.

Prognostic role of embolic burden assessed at computed tomography angiography in patients with acute pulmonary embolism: systematic review and meta-analysis.

BACKGROUND: In patients with acute pulmonary embolism (PE), risk stratification is indicated for tailoring of both diagnostic strategies and acute treatment. Whether embolic burden assessed at computed tomography (CT) angiography has a role in risk stratification in these patients is debated. OBJECTIVE: To systematically review and perform a meta-analysis to evaluate the role of CT-assessed burden associated with embolic obstruction and embolic localization in the prognostic stratification of patients with acute PE. METHODS: We performed a systematic search in EMBASE and MEDLINE up until 30 June 2013. Studies reporting on the 30-day outcome of patients with confirmed PE and CT-assessed embolic burden were included. The study outcome was death. RESULTS: Thirty studies reporting on the prognostic value of CT-assessed embolic burden met the inclusion criteria for this systematic review; of these, 19 were included in the meta-analysis. Five studies (2215 patients) were included in the analysis of localization: an association between embolus localization in the central arteries and 30-day mortality was found after heterogeneity was resolved (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.29-3.89, I(2)  = 0%). No correlation was observed between obstruction index (according to the Qanadli scoring system) and 30-day mortality after heterogeneity was reduced (16 studies, 3884 patients, OR 1.22, 95% CI 0.99-1.51, I(2)  = 27%). CONCLUSION: Localization of emboli assessed at CT angiography can be used for risk stratification in patients with acute PE. Moreover, no correlation was observed between obstruction index and prognosis.

Long-term outcomes of patients with cerebral vein thrombosis: a multicenter study.

BACKGROUND: Little information is available on the long-term clinical outcome of cerebral vein thrombosis (CVT). OBJECTIVES AND METHODS: In an international, retrospective cohort study, we assessed the long-term rates of mortality, residual disability and recurrent venous thromboembolism (VTE) in a cohort of patients with a first CVT episode. RESULTS: Seven hundred and six patients (73.7% females) with CVT were included. Patients were followed for a total of 3171 patient-years. Median follow-up was 40 months (range 6, 297 months). At the end of follow-up, 20 patients had died (2.8%). The outcome was generally good: 89.1% of patients had a complete recovery (modified Rankin Score [mRS] 0-1) and 3.8% had a partial recovery and were independent (mRS 2). Eighty-four per cent of patients were treated with oral anticoagulants and the mean treatment duration was 12 months. CVT recurred in 31 patients (4.4%), and 46 patients (6.5%) had a VTE in a different site, for an overall incidence of recurrence of 23.6 events per 1000 patient-years (95% confidence Interval [CI] 17.8, 28.7) and of 35.1 events/1000 patient-years (95% CI, 27.7, 44.4) after anticoagulant therapy withdrawal. A previous VTE was the only significant predictor of recurrence at multivariate analysis (hazard ratio [HR] 2.70; 95% CI 1.25, 5.83). CONCLUSIONS: The long-term risk of mortality and recurrent VTE appears to be low in patients who survived the acute phase of CVT. A previous VTE history independently predicts recurrent events.

Prognostic role of sentinel node biopsy in patients with thick melanoma: a meta-analysis.

OBJECTIVES: Sentinel lymph node (SLN) biopsy is a prognostic tool for patients with intermediate-thickness melanomas. However, controversies exist regarding its role in patients with thick melanomas (tumour thickness greater than 4.0 mm). We performed a meta-analysis to assess the prognostic role of SLN in thick melanoma in terms of disease-free survival (DFS) and overall survival (OS). METHODS: An electronic search in MEDLINE and EMBASE databases using the terms 'melanoma' and 'sentinel lymph node' was performed. Studies were considered if they reported data on thick melanoma and SLN biopsy results (positive and negative) and outcomes (DFS or OS). A proportion meta-analysis was used to calculate weighted means and an incidence rate ratio meta-analysis was used to compare outcomes according to SLN biopsy results. RESULTS: Nine studies were included. The weighted mean thickness of melanoma was 4.4 mm, 42% of patients had ulcerated melanoma. SLN was positive in 36% of the patients. Overall, DFS was 71% in patients with a negative SLN and 39% in patients with a positive SLN after a median follow-up of 33 months (IRR 1.83, 95% CI = 1.56-2.14). OS was 71% in patients with a negative SLN and 49% in patients with a positive SLN (IRR 1.44, 95% CI = 1.25-1.65). CONCLUSIONS: The results of this analysis showed that thick melanoma patients with a positive SLN had a significantly worse survival compared with SLN negative patients, thus supporting the routine adoption of SLN biopsy as a prognostic tool also for this subgroup of patients.

The sentinel node biopsy in patients with thick melanoma: outcome analysis from a single-institution database.

BACKGROUND: We examined the impact of sentinel lymph node (SLN) biopsy among patients with primary melanoma that exceeded 4.0 mm in Breslow thickness, treated in our Institution from 1998 until 2009. PATIENTS AND METHODS: According to Kaplan-Meier statistics, overall survival (OS) and disease-free survival (DFS) were assessed in patients with: i) disseminated disease at diagnosis with respect to patients undergoing SLN biopsy and ii) positive SLN and negative SLN. The effect of age, thickness and number of positive SLN on survival was also calculated. RESULTS: Forty-three patients with thick melanoma were included (29 men and 14 women; mean age 65 ± 17 years, tumor thickness ranging from 4 to 20 mm). Thirteen patients (30%) were not eligible for SLN biopsy due to metastatic disease or poor clinical condition. Biopsy was performed on 30 patients: 14 with positive SLN (46.7%, group A) and 16 with negative SLN (53.3%, group B). Seven patients (50%) died in group A and 2 patients (13%) in group B (mean follow-up 28 and 59 months, respectively); all 7 patients in group A and no patient in group B died because of melanoma. OS and DFS were both significantly higher in group B than group A. CONCLUSION: Our experience demonstrates a high rate of positive SLNs in patients with thick melanoma, and significant differences regarding the general outcomes between those with positive and negative SLNs, the latter group having a good prognosis despite the thick primary tumor. This observation stresses the importance of SLN biopsy as a staging tool in patients with thick melanoma.

Incidence of arterial cardiovascular events after venous thromboembolism: a systematic review and a meta-analysis.

SUMMARY BACKGROUND: Whether patients with unprovoked venous thromboembolism (VTE) have a higher risk of arterial cardiovascular events than the general population and patients with provoked VTE is a matter of debate. OBJECTIVE: To perform a systematic review and a meta-analysis aimed at assessing the risk of arterial cardiovascular events in patients with unprovoked VTE as compared with both patients with provoked VTE and controls. METHODS: A systematic search was performed. Studies reporting on (i) patients with confirmed VTE, (ii) a follow-up of at least 6 months and (iii) the incidence of arterial cardiovascular events (acute myocardial infarction and ischemic stroke) were included in the systematic review. Those studies reporting separate incidences of cardiovascular events in patients with unprovoked and provoked VTE or patients with unprovoked VTE and controls were included in the incidence rate meta-analysis. RESULTS: Overall, 17 studies were included in the systematic review. The weighted mean incidence of arterial cardiovascular events was 0.46% [95% confidence interval (CI) 0.34-0.59] and 0.35% (95% CI 0.24-0.49) per patient-year in patients with unprovoked and provoked VTE, respectively. Six studies were included in the meta-analysis. The risk of arterial cardiovascular events appeared to be higher in patients with unprovoked VTE than in controls [incidence rate ratio (IRR) 1.87, 95% CI 1.32-2.65] and than in patients with provoked VTE (IRR 1.86, 95% CI 1.19-2.89). CONCLUSIONS: Patients with unprovoked VTE have a higher risk of arterial cardiovascular events than patients with provoked VTE over long-term follow-up.

Patients with primary antiphospholipid antibody syndrome and without associated vascular risk factors present a normal endothelial function.

INTRODUCTION: Primary antiphospholipid antibody syndrome (PAPS) is characterized by venous or arterial thrombosis and positive antiphospholipid antibodies. It is controversial whether PAPS patients have early atherosclerosis. Endothelial dysfunction is an early event in the natural history of atherosclerosis. Aim of our study was to compare endothelial function of patients with PAPS and no associated risk factors with that of age- and sex-matched controls. MATERIALS AND METHODS: Patients with PAPS, carefully selected to exclude all known risk factors for cardiovascular diseases, estrogen therapy, pregnancy, intake of drugs affecting endothelial function, vitamins or antioxidants, were included in a case-control study. Controls were age- (+/-5 years) and sex-matched subjects with the same exclusion criteria but without PAPS. Flow-mediated dilation of the brachial artery and some plasmatic markers of endothelial and platelet activation were measured. Measures are expressed as mean+/-SEM. RESULTS: Twenty cases (mean age 42+/-4.0 years, 11 females) and 39 controls (mean age 41+/-2.9, 22 females) were studied. FMD was 5.7+/-0.8% in cases (95% CI: 4.1 to 7.3) and 6.8+/-0.5% (5.7 to 7.9) in controls (p=NS). Plasma von Willebrand factor was 128+/-11.3% and 134.2+/-16.1% in cases and controls, respectively (p=NS). Soluble P-selectin and soluble CD40L were 94.1+/-4.9 ng/ml and 0.7+/-0.1 ng/ml in cases and 87.7+/-4.0 ng/ml and 1.0+/-0.2 in controls, respectively (p=NS). In a substudy, circulating progenitor and mature endothelial cells were comparable between the two groups. CONCLUSIONS: Endothelial function in patients with PAPS and no associated risk factors is similar to that of age- and sex- matched controls. These data suggest that the alterations leading to thrombosis in PAPS concern primarily the clotting system.