Pronóstico de la enfermedad tromboembólica venosa en cirugía ortopédica o pacientes traumatológicos y uso de tromboprofilaxis / Prognosis of venous thromboembolism in orthopaedic surgery or trauma patients and use of thromboprophylaxis

Antecedentes: Hay escasa evidencia sobre el pronóstico de la tromboembolia venosa en pacientes sometidos a cirugía ortopédica y en pacientes que sufren un trauma no quirúrgico. Métodos: Utilizamos la base de datos RIETE (Registro Informatizado de pacientes con Enfermedad TromboEmbólica) para comparar el pronóstico del tromboembolismo venoso y el uso de tromboprofilaxis en pacientes sometidos a diferentes procedimientos ortopédicos y en pacientes con traumatismo que no requiere cirugía. Resultados: Desde marzo de 2001 a marzo de 2015, se inscribieron un total de 61.789 pacientes en RIETE. De estos, 943 (1.52%) desarrollaron tromboembolismo venoso después de artroplastia electiva, 445 (0.72%) después de fractura de cadera, 1.045 (1.69%) después de cirugía ortopédica no mayor y 2,136 (3.46%) después de trauma no quirúrgico. En general, 2.283 pacientes (50%) presentaron inicialmente embolia pulmonar. En los primeros 90 días de tratamiento, 30 pacientes (0.66%, IC 95% 0.45-0.93) murieron por embolia pulmonar. La tasa de embolia pulmonar fatal fue significativamente mayor después de cirugía de fractura de cadera (n = 9 [2.02%]) que después de la artroplastia electiva (n = 5 [0.53%]), cirugía ortopédica no mayor (n = 5 [0.48%]) o traumatismo no quirúrgico (n = 11 [0,48%]). La tromboprofilaxis se utilizó con mayor frecuencia para la fractura de cadera (93%) o la artroplastia electiva (94%) que para la cirugía ortopédica no mayor (71%) o traumatismo no quirúrgico (32%). La hemorragia mayor fue significativamente mayor después de la cirugía de fractura de cadera (4%) que después de artroplastia electiva (1,6%), cirugía ortopédica no mayor (1,5%) o traumatismo no quirúrgico (1,4%). Conclusiones: La tromboprofilaxis se utilizó con menos frecuencia en los procedimientos de menor riesgo a pesar del número absoluto de embolia pulmonar fatal después de cirugía ortopédica no mayor o traumatismo no quirúrgico, excedieron los observados después de procedimientos de alto riesgo

Background: There is scarce evidence about the prognosis of venous thromboembolism in patients undergoing orthopedic surgery and in patients suffering non-surgical trauma. Methods: We used the RIETE database (Registro Informatizado de pacientes con Enfermedad Trombo Embólica) to compare the prognosis of venous thromboembolism and the use of thromboprophylaxis in patients undergoing different orthopedic procedures and in trauma patients not requiring surgery. Results: From March 2001 to March 2015, a total of 61,789 patients were enrolled in RIETE database. Of these, 943 (1.52%) developed venous thromboembolism after elective arthroplasty, 445 (0.72%) after hip fracture, 1,045 (1.69%) after non-major orthopedic surgery and 2,136 (3.46%) after non-surgical trauma. Overall, 2,283 patients (50%) initially presented with pulmonary embolism. Within the first 90 days of therapy, 30 patients (0.66%; 95% CI 0.45-0.93) died from pulmonary embolism. The rate of fatal pulmonary embolism was significantly higher after hip fracture surgery (n = 9 [2.02%]) than after elective arthroplasty (n = 5 [0.53%]), non-major orthopedic surgery (n = 5 [0.48%]) or non surgical trauma (n = 11 [0.48%]). Thromboprophylaxis was more commonly used for hip fracture (93%) or elective arthroplasty (94%) than for non-major orthopedic surgery (71%) or non-surgical trauma (32%). Major bleeding was significantly higher after hip fracture surgery (4%) than that observed after elective arthroplasty (1.6%), non-major orthopedic surgery (1.5%) or non-surgical trauma (1.4%). Conclusions: Thromboprophylaxis was less frequently used in lower risk procedures despite the absolute number of fatal pulmonary embolism after non-major orthopedic surgery or non-surgical trauma, exceeded that observed after high risk procedures

Management of venous thromboembolism in patients with cancer.

Current guidelines for anticoagulant therapy do not so far suggest any form of differentiated approach to cancer patients with venous thromboembolism (VTE). This review article provides an overview of the published literature in cancer patients with VTE, mostly using data from the RIETE registry. Our findings provide some insights into what factors may be used to guide physicians in adapting recommended anticoagulant regimens to the individual patient, as oncologists are increasingly doing with cancer treatments. For instance, patients presenting with deep vein thrombosis (DVT) alone might benefit from curtailing treatment intensity as anticoagulant therapy progresses. The site of cancer also needs to be considered. In patients with incidental PE or splanchnic vein thrombosis, we should be more cautious before prescribing anticoagulant therapy. The optimal duration of anticoagulant therapy is unknown.

Prognosis of venous thromboembolism in orthopaedic surgery or trauma patients and use of thromboprophylaxis. / Pronóstico de la enfermedad tromboembólica venosa en cirugía ortopédica o pacientes traumatológicos y uso de tromboprofilaxis.

BACKGROUND: There is scarce evidence about the prognosis of venous thromboembolism in patients undergoing orthopedic surgery and in patients suffering non-surgical trauma. METHODS: We used the RIETE database (Registro Informatizado de pacientes con Enfermedad Trombo Embólica) to compare the prognosis of venous thromboembolism and the use of thromboprophylaxis in patients undergoing different orthopedic procedures and in trauma patients not requiring surgery. RESULTS: From March 2001 to March 2015, a total of 61,789 patients were enrolled in RIETE database. Of these, 943 (1.52%) developed venous thromboembolism after elective arthroplasty, 445 (0.72%) after hip fracture, 1,045 (1.69%) after non-major orthopedic surgery and 2,136 (3.46%) after non-surgical trauma. Overall, 2,283 patients (50%) initially presented with pulmonary embolism. Within the first 90 days of therapy, 30 patients (0.66%; 95% CI 0.45-0.93) died from pulmonary embolism. The rate of fatal pulmonary embolism was significantly higher after hip fracture surgery (n = 9 [2.02%]) than after elective arthroplasty (n = 5 [0.53%]), non-major orthopedic surgery (n = 5 [0.48%]) or non surgical trauma (n = 11 [0.48%]). Thromboprophylaxis was more commonly used for hip fracture (93%) or elective arthroplasty (94%) than for non-major orthopedic surgery (71%) or non-surgical trauma (32%). Major bleeding was significantly higher after hip fracture surgery (4%) than that observed after elective arthroplasty (1.6%), non-major orthopedic surgery (1.5%) or non-surgical trauma (1.4%). CONCLUSIONS: Thromboprophylaxis was less frequently used in lower risk procedures despite the absolute number of fatal pulmonary embolism after non-major orthopedic surgery or non-surgical trauma, exceeded that observed after high risk procedures.

Once versus twice daily enoxaparin for the initial treatment of acute venous thromboembolism.

Essentials In venous thromboembolism (VTE), it is uncertain if enoxaparin should be given twice or once daily. We compared the 15- and 30-day outcomes in VTE patients on enoxaparin twice vs. once daily. Patients on enoxaparin once daily had fewer major bleeds and deaths than those on twice daily. The rate of VTE recurrences was similar in both subgroups. SUMMARY: Background In patients with acute venous thromboembolism (VTE), it is uncertain whether enoxaparin should be administered twice or once daily. Methods We used the RIETE Registry data to compare the 15- and 30-day rates of VTE recurrence, major bleeding and death between patients receiving enoxaparin twice daily and those receiving it once daily. We used propensity score matching to adjust for confounding variables. Results The study included 4730 patients: 3786 (80%) received enoxaparin twice daily and 944 once daily. During the first 15 days, patients on enoxaparin once daily had a trend towards more VTE recurrences (odds ratio [OR], 1.79; 95% confidence interval [CI], 0.55-5.88), fewer major bleeds (OR, 0.42; 95% CI, 0.17-1.08) and fewer deaths (OR, 0.32; 95% CI, 0.13-0.78) than those on enoxaparin twice daily. At day 30, patients on enoxaparin once daily had more VTE recurrences (OR, 2.5; 95% CI, 1.03-5.88), fewer major bleeds (OR, 0.40; 95% CI, 0.17-0.94) and fewer deaths (OR, 0.58; 95% CI, 0.33-1.00). On propensity analysis, patients on enoxaparin once daily had fewer major bleeds at 15 (hazard ratio [HR], 0.30; 95% CI, 0.10-0.88) and at 30 days (HR, 0.16; 95% CI, 0.04-0.68) and also fewer deaths at 15 (HR, 0.37; 95% CI, 0.14-0.99) and at 30 days (HR, 0.19; 95% CI, 0.07-0.54) than those on enoxaparin twice daily. Conclusions Our findings confirm that enoxaparin prescribed once daily results in fewer major bleeds than enoxaparin twice daily, as suggested in a meta-analysis of controlled clinical trials.

A prognostic score to identify low-risk outpatients with acute deep vein thrombosis in the upper extremity.

BACKGROUND: No studies have identified which patients with upper-extremity deep vein thrombosis (DVT) are at low risk for adverse events within the first week of therapy. METHODS: We used data from Registro Informatizado de la Enfermedad TromboEmbólica to explore in patients with upper-extremity DVT a prognostic score that correctly identified patients with lower limb DVT at low risk for pulmonary embolism, major bleeding, or death within the first week. RESULTS: As of December 2014, 1135 outpatients with upper-extremity DVT were recruited. Of these, 515 (45%) were treated at home. During the first week, three patients (0.26%) experienced pulmonary embolism, two (0.18%) had major bleeding, and four (0.35%) died. We assigned 1 point to patients with chronic heart failure, creatinine clearance levels 30-60 mL min(-1) , recent bleeding, abnormal platelet count, recent immobility, or cancer without metastases; 2 points to those with metastatic cancer; and 3 points to those with creatinine clearance levels < 30 mL min(-1) . Overall, 759 (67%) patients scored ≤ 1 point and were considered to be at low risk. The rate of the composite outcome within the first week was 0.26% (95% confidence interval [CI] 0.004-0.87) in patients at low risk and 1.86% (95% CI 0.81-3.68) in the remaining patients. C-statistics was 0.73 (95% CI 0.57-0.88). Net reclassification improvement was 22%, and integrated discrimination improvement was 0.0055. CONCLUSIONS: Using six easily available variables, we identified outpatients with upper-extremity DVT at low risk for adverse events within the first week. These data may help to safely treat more patients at home.

Valor pronóstico de la proteína fijadora de lipopolisácaridos y la procalcitonina en pacientes consepsis grave y shock séptico ingresados en una unidad de cuidados intensivos / Prognostic value of lipopolysaccharide binding protein and procalcitonin in patients with severe sepsis and septic shock admitted to intensive care

OBJETIVOS: 1) Valorar la utilidad pronóstica de la determinación inicial y seriada de la proteína fijadora de lipopolisacáridos (LBP) y de la procalcitonina (PCT) y 2) evaluar si su adicción a los scores de gravedad mejoraría su valor pronóstico. DISEÑO: Estudio prospectivo observacional. ÁMBITO: Unidad de Cuidados Intensivos de un hospital general universitario. PACIENTES: Se incluyó a 100 pacientes ingresados por sepsis grave/shock séptico. Variables de interés Datos demográficos, APACHE II y SOFA, concentración de PCT y LBP inicial y a las 48 h y mortalidad hospitalaria. RESULTADOS: Los scores APACHE II al ingreso y SOFA a las 48 h presentaron el mayor rendimiento como predictores de mortalidad hospitalaria (AUC ROC: 0,75 para ambos). La concentración inicial de PCT y LBP y el aclaramiento de LBP fueron similares en pacientes supervivientes y fallecidos. Solo el aclaramiento de PCT fue superior en supervivientes respecto a los fallecidos (AUC ROC: 0,66). La combinación de los scores de gravedad con el aclaramiento de PCT no mejoró su valor pronóstico. CONCLUSIONES: La concentración inicial de LBP y de PCT y el aclaramiento de LBP no presentaron valor pronóstico en pacientes con sepsis grave/shock séptico. Solo el aclaramiento de PCT se comportó como predictor de mortalidad hospitalaria. El rendimiento de los scores APACHE II al ingreso y SOFA a las 48 h fue superior al de los biomarcadores analizados y la adición del aclaramiento de PCT no aumentó su valor pronóstico

AIMS: 1) To assess the prognostic value of levels on admission and serial measurements of lipopolysaccharide binding protein (LBP) and procalcitonin (PCT) in relation to in-hospital mortality; and 2) to determine whether the addition of these parameters to severity scores (APACHE II and SOFA) is able to improve prognostic accuracy. DESIGN: A single-center, prospective observational study was carried out. Setting Intensive Care unit of a university hospital. PATIENTS: One hundred severe sepsis and septic shock patients were included. Data collected Demographic data, APACHE II and SOFA scores, PCT and LBP levels on admission and after 48hours, and in-hospital mortality. RESULTS: The best area under the curve for predicting in-hospital mortality corresponded to APACHE II on admission and SOFA after 48h (AUC ROC: 0.75 for both). PCT and LBP levels on admission and LBP clearance were not statistically different between in-hospital survivors and non-survivors. Only PCT clearance was higher among in-hospital survivors than in non-survivors (AUC ROC: 0.66). The combination of severity scores and PCT clearance did not result in superior areas under the curve. CONCLUSIONS: LBP and PCT levels on admission and LBP clearance showed no prognostic value in severe sepsis and septic shock patients. Only PCT clearance was predictive of in-hospital mortality. The prognostic accuracy was significantly better for APACHE on admission and SOFA after 48h than for any of the analyzed biomarkers, and the addition of PCT clearance did not improve their prognostic value

Trend and seasonality in hospitalizations for pulmonary embolism: a time-series analysis.

BACKGROUND: The existence of seasonal variability in patients with acute pulmonary embolism (PE) has been debated for years, with contradictory results. The aim of this study was to identify the trend and possible existence of a seasonal pattern in hospitalizations for PE in Spain. METHODS: We analyzed the hospital discharge database of the Spanish National Health System from 2001 to 2010. Patients aged > 14 years diagnosed with PE were selected and a time series was constructed considering mean daily admissions for PE by month. The trend and seasonality factor of the series were determined using time-series analysis, and time-series modeling was used for analysis. Exponential smoothing models and the autoregressive integrated moving average test were used to generate a predictive model. RESULTS: From 2001 to 2010, there were 162,032 diagnoses of PE (5.07 per 1000 hospitalizations). In 105,168 cases, PE was the reason for admission. The PE diagnosis rate ranged from 4.14 per 1000 in 2001 to 6.56 per 1000 in 2010; and hospital admissions due to PE ranged from 2.67 to 4.28 per 1000 hospital discharges. Time-series analysis showed a linear increase in the incidence and a significant seasonal pattern with 17% more admissions in February and 12% fewer in June-July with respect to the central tendency (difference from February to June, 29%). CONCLUSIONS: The incidence of hospitalizations for PE showed a linear increase and a seasonal pattern, with the highest number of admissions in winter and the lowest number in summer.

[Prognostic value of lipopolysaccharide binding protein and procalcitonin in patients with severe sepsis and septic shock admitted to intensive care]. / Valor pronóstico de la proteína fijadora de lipopolisácaridos y la procalcitonina en pacientes con sepsis grave y shock séptico ingresados en una unidad de cuidados intensivos.

AIMS: 1) To assess the prognostic value of levels on admission and serial measurements of lipopolysaccharide binding protein (LBP) and procalcitonin (PCT) in relation to in-hospital mortality; and 2) to determine whether the addition of these parameters to severity scores (APACHE II and SOFA) is able to improve prognostic accuracy. DESIGN: A single-center, prospective observational study was carried out. SETTING: Intensive Care unit of a university hospital. PATIENTS: One hundred severe sepsis and septic shock patients were included. DATA COLLECTED: Demographic data, APACHE II and SOFA scores, PCT and LBP levels on admission and after 48 hours, and in-hospital mortality. RESULTS: The best area under the curve for predicting in-hospital mortality corresponded to APACHE II on admission and SOFA after 48 h (AUC ROC: 0.75 for both). PCT and LBP levels on admission and LBP clearance were not statistically different between in-hospital survivors and non-survivors. Only PCT clearance was higher among in-hospital survivors than in non-survivors (AUC ROC: 0.66). The combination of severity scores and PCT clearance did not result in superior areas under the curve. CONCLUSIONS: LBP and PCT levels on admission and LBP clearance showed no prognostic value in severe sepsis and septic shock patients. Only PCT clearance was predictive of in-hospital mortality. The prognostic accuracy was significantly better for APACHE on admission and SOFA after 48 h than for any of the analyzed biomarkers, and the addition of PCT clearance did not improve their prognostic value.

Cirugía de la trombosis venosa profunda iliofemoral: postura en contra / Surgery of iliofemoral deep vein thrombosis: A stance agains

La localización iliofemoral de la trombosis venosa profunda (TVP) es especialmente grave dado que afecta al eje único de drenaje del miembro inferior. El tratamiento únicamente con anticoagulación suele ser insuficiente en la prevención del síndrome postrombótico severo debido a la frecuente incompleta resolución del trombo. Si bien las nuevas técnicas de trombectomía son capaces de conseguir una permeabilidad del eje venoso iliofemoral en un mayor porcentaje de casos que las anteriores técnicas, no se han comparado con el actual estándar de tratamiento que es la trombólisis dirigida por catéter. Esta técnica además se puede combinar con la trombólisis mecánica, aumentando su eficacia. Actualmente está en fase de reclutamiento un ensayo clínico que valorará la dosis de alteplasa más eficiente en la trombólisis dirigida por catéter en los pacientes con TVP iliofemoral y la posibilidad de aumentar su eficacia con métodos mecánicos

The iliofemoral location of a deep vein thrombosis (DVT) is particularly serious, as it affects the single drainage stem of the lower limb. Treatment with anticoagulatants alone is often insufficient in preventing severe post-thrombotic syndrome, due to frequent incomplete thrombus resolution. While new thrombectomy techniques are capable of achieving patency of the iliofemoral venous system in a higher percentage of cases than previous techniques, they have not been compared with the current standard of treatment, which is the catheter-directed thrombolysis. This catheter-directed thrombolysis also can be combined with mechanical thrombolysis, increasing its effectiveness. A clinical trial is currently in the recruiting phase and it will assess the most efficient dose of alteplase in catheter-directed thrombolysis in patients with iliofemoral DVT, and the possibility of increasing its effectiveness with mechanical methods

Historia natural de la enfermedad tromboembólica venosa en el área mediterránea. Una revisión sistemática / Natural history of venous thromboembolism in patients from the Mediterranean region. A systematic review

Antecedentes: El pronóstico de las enfermedades cardiovasculares es mejor en los países mediterráneos que en otras partes del mundo. Se desconoce si estas diferencias también acontecen en la enfermedad tromboembólica venosa (ETV) Métodos: En las bases de datos Medline y EMBASE se revisaron los ensayos clínicos y estudios de cohortes de pacientes con ETV que habían recibido tratamiento anticoagulante durante 3 meses. Dos revisores extrajeron independientemente los datos de forma reglada. Se seleccionaron 24 estudios con un total de 7.225 pacientes incluidos (2.414 del área mediterránea y 4.811 de otras regiones). Resultados: Entre los pacientes del área mediterránea predominaban las mujeres, tenían mayor edad, y la ETV idiopática fue menos frecuente que en otras regiones del mundo. Comparados con otros países, los pacientes del área mediterránea presentaron más recidivas de trombosis venosa profunda (4,35% frente a 2,68%; odds ratio [OR]: 1,65; intervalo de confianza al 95% [IC95%]: 1,27-2,15), recidivas mortales de ETV (0,75% frente a 0,35%; OR: 2,11; IC95%: 1,09-4,12) y sangrado mortal (0,25% frente a 0,06%; OR: 3,99; IC95%: 1-16). En el área mediterránea el porcentaje de recidivas de ETV mortal fue del 12,8%, IC95%: 7,99-19,1 frente al 8,41%, IC95%: 5,15-12,9 en otras zonas del mundo. El porcentaje de hemorragias mortales fue del 11,3%, IC95%: 4,72-22,1 frente al 3,22%, IC95%: 0,83-8,53 en otras zonas geográficas. Conclusiones: Los pacientes con ETV del área mediterránea tienen una mayor mortalidad durante los 3 primeros meses de tratamiento imputable a una mayor incidencia de ETV recidivante y de hemorragias graves (AU)

Background: Patients with cardiovascular diseases living in the Mediterranean area have a better outcome than those in other parts of the world, but it is not known whether these differences also occur with venous thromboembolism (VTE). Methods: We searched the Medline and EMBASE databases to identify clinical trials and cohort studies of patients with VTE who had been treated with anticoagulant therapy for 3 months. Two reviewers independently extracted the data in a standardized manner. A total of 24 studies that included 7,225 patients (2,414 from the Mediterranean region and 4,811 from other regions) were analyzed. Results: The patients from the Mediterranean area were predominately women and older, and the idiopathic VTE was less frequent than in other regions. Compared with patients from other regions, patients from the Mediterranean region had an increased rate of recurrent deep vein thrombosis (4.35% vs. 2.68%; odds ratio [OR], 1.65; 95% confidence interval [95% CI] 1.27-2.15), fatal recurrent VTE (0.75% vs. 0.35%; OR, 2.11; 95% CI 1.09-4.12) and fatal bleeding (0.25% vs. 0.06%; odds ratio: 3.99; 95% CI 1.00-16.0). The case-fatality rate (CFR) for recurrent VTE was 12.8% (95% CI 7.99-19.1) in the Mediterranean region and 8.41% (5.15-12.9) in other areas. The CFR for major bleeding was 11.3% (95% CI 4.72-22.1) and 3.22% (95% CI 0.83-8.53), respectively. Conclusions: Compared to other regions, patients with VTE from the Mediterranean region have greater mortality during the first 3 months of treatment due to a greater incidence of recurrent VTE and severe hemorrhaging (AU)

Natural history of venous thromboembolism in patients from the Mediterranean region. A systematic review.

BACKGROUND: Patients with cardiovascular diseases living in the Mediterranean area have a better outcome than those in other parts of the world, but it is not known whether these differences also occur with venous thromboembolism (VTE). METHODS: We searched the Medline and EMBASE databases to identify clinical trials and cohort studies of patients with VTE who had been treated with anticoagulant therapy for 3 months. Two reviewers independently extracted the data in a standardized manner. A total of 24 studies that included 7,225 patients (2,414 from the Mediterranean region and 4,811 from other regions) were analyzed. RESULTS: The patients from the Mediterranean area were predominately women and older, and the idiopathic VTE was less frequent than in other regions. Compared with patients from other regions, patients from the Mediterranean region had an increased rate of recurrent deep vein thrombosis (4.35% vs. 2.68%; odds ratio [OR], 1.65; 95% confidence interval [95% CI] 1.27-2.15), fatal recurrent VTE (0.75% vs. 0.35%; OR, 2.11; 95% CI 1.09-4.12) and fatal bleeding (0.25% vs. 0.06%; odds ratio: 3.99; 95% CI 1.00-16.0). The case-fatality rate (CFR) for recurrent VTE was 12.8% (95% CI 7.99-19.1) in the Mediterranean region and 8.41% (5.15-12.9) in other areas. The CFR for major bleeding was 11.3% (95% CI 4.72-22.1) and 3.22% (95% CI 0.83-8.53), respectively. CONCLUSIONS: Compared to other regions, patients with VTE from the Mediterranean region have greater mortality during the first 3 months of treatment due to a greater incidence of recurrent VTE and severe hemorrhaging.

Computed tomography-assessed right ventricular dysfunction and risk stratification of patients with acute non-massive pulmonary embolism: systematic review and meta-analysis.

BACKGROUND: The ability of computed tomography (CT)-assessed right ventricular dysfunction (RVD) to identify normotensive patients with acute pulmonary embolism (PE) at high risk of mortality or adverse outcome lacks clarity. METHODS AND RESULTS: We performed a systematic review and a meta-analysis of studies in normotensive patients with acute PE to assess the prognostic value of CT-assessed RVD for death and a predefined composite outcome of PE-related complications. We conducted unrestricted searches of MEDLINE and EMBASE from 1980 to March 2013, and used the terms 'computed tomography', 'pulmonary embolism', and 'prognos*'. We used a random-effects model to pool study results, funnel-plot inspection to evaluate for publication bias, and I(2) testing to assess for heterogeneity. The analysis included data from 10 studies (2288 patients). Overall, 99 of 1268 patients with RVD assessed by CT died (7.8%; 95% confidence interval [CI] 6.3-9.3) as compared with 52 of 1020 without RVD (5.1%; 95% CI 3.7-6.4). CT-assessed RVD had significant associations with mortality (odds ratio [OR] 1.8; 95% CI 1.3-2.6), with death resulting from PE (OR 7.4; 95% CI 1.4-39.5), and with PE-related complications (OR 2.4; 95% CI 1.2-4.7). Pooled likelihood ratios (LRs) were not extreme (negative LR 0.71; 95% CI 0.57-0.89; and positive LR 1.27; 95% CI 1.12-1.43). CONCLUSIONS: Although RVD assessed by CT showed an association with an increased risk of mortality in patients with hemodynamically stable PE, it resulted in only small increases in the ability to classify risk.

Colorectal serrated adenocarcinoma shows a different profile of oncogene mutations, MSI status and DNA repair protein expression compared to conventional and sporadic MSI-H carcinomas.

Molecular characterization has been extensively studied in serrated polyps but very little is known in serrated adenocarcinomas (SACs). We analyzed the incidence of KRAS, BRAF and PIK3CA mutations, microsatellite instability (MSI) status and loss of the DNA repair proteins MLH1, MSH2, MSH6 and MGMT in a series of 89 SAC, 81 matched conventional carcinomas (CC) and 13 sporadic colorectal cancer showing histological and molecular features of high-level MSI (sMSI-H). Our results demonstrate that KRAS are more prevalent than BRAF mutations in SAC (42.7% vs. 25.8%; p = 0.011) being the KRAS-mutated cases even more abundant in SAC displaying adjacent serrated adenomas (51%). G12D and E545K are the most common KRAS and PIK3CA mutations found in SAC, respectively. SAC show higher frequency of MGMT loss compared to CC (50.6% vs. 25.3%; p = 0.001) especially in distal colon/rectum (60.0% vs. 21.6%; p = 0.0009). SAC differ from sMSI-H in terms of KRAS and BRAF mutation prevalence, MSI status and MLH1 expression (p = 0.0003, p < 0.0001, p < 0.0001, p < 0.001, respectively). SACs are more often KRAS-mutated and microsatellite stable and display different molecular and immunohistochemical characteristics compared to CC and sMSI-H.

Venous thromboembolism during pregnancy, postpartum or during contraceptive use.

Venous thromboembolism (VTE) is a leading cause of maternal death during pregnancy or postpartum, and in women using hormonal contraceptives. However, important issues concerning its natural history and therapy remain unsolved, and most of the protocols for treatment of VTE in this patient population are based on data extrapolated from other populations. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute VTE. We examined the clinical characteristics and three-month outcome of all enrolled women with pregnancy, postpartum or using hormonal contraceptives. As of December 2008, 173 pregnant women, 135 postpartum, and 798 contraceptive users were enrolled. Of these, 438 (40%) presented with pulmonary embolism (PE) and 668 with deep-vein thrombosis (DVT). Most women with acute PE had dyspnea (72%) or chest pain (75%), but only 2.0% had hypoxaemia. During the three-month study period, five women (0.45%; 95% CI: 0.17-1.00) died (3 had fatal PE), 13 (1.18%; 95% CI: 0.66-1.95) had VTE recurrences, and seven (0.63%; 95% CI: 0.28-1.25) major bleeding. Two of the three women with fatal PE died during the first few hours after arriving at the emergency ward, with no time to start any therapy. The outcome of pregnant or postpartum women with VTE is similar to that in contraceptive users, even though the treatment is different. The non-specific nature of PE signs may have caused some delay in PE diagnosis.

Clinical outcome in patients with venous thromboembolism and hidden cancer: findings from the RIETE Registry.

INTRODUCTION: Although extensive screening in patients with venous thromboembolism (VTE) may result in early identification of hidden cancer, it is unknown whether the prognosis of these patients may be favorably influenced. PATIENTS AND METHODS: RIETE is an ongoing, prospective registry of consecutive patients with objectively confirmed, symptomatic, acute VTE. We compared the 3-month outcome of patients with hidden cancer with that in patients in whom no symptoms of cancer were noted. RESULTS: Of 17,475 patients with acute VTE, 2852 (16%) had cancer diagnosed before VTE or during admission. Hidden cancer was detected in 178 (1.2%) of the remaining 14,623 patients. The most common sites were lung, prostate, colorectum, or hematologic, and 51% had metastases. As compared with patients in whom no symptoms of cancer were noted, those with hidden cancer had an increased incidence of recurrent VTE (11.4% vs. 2.1%; P < 0.001), major bleeding (5.1% vs. 2.1%; P = 0.007), and mortality (20% vs. 5.4%; P < 0.001). In the multivariate analysis, patients aged 60-75 years [odds ratio 1.8; 95% CI 1.2-2.7], with idiopathic VTE (odds ratio 3.0; 95% CI 2.2-4.2), with bilateral thrombosis (odds ratio 2.3; 95% CI 1.3-4.1) or with anemia (odds ratio 1.9; 95% CI 1.4-2.6) were at an increased risk for hidden cancer. CONCLUSIONS: VTE patients with hidden cancer have an increased incidence of recurrences, major bleeding or death during the first 3 months of therapy. With four simple, easily obtainable variables, it is possible to identify a subgroup of VTE patients with a higher risk for hidden cancer.

Haemodynamically unstable pulmonary embolism in the RIETE Registry: systolic blood pressure or shock index?

Patients with acute pulmonary embolism (PE) presenting with haemodynamic instability have the worst prognosis. However, what is understood by haemodynamic instability has not been clearly defined. The Registro Informatizado de la Enfermedad Tromboembólica (RIETE) is an ongoing registry of consecutive patients with symptomatic, objectively confirmed, acute deep vein thrombosis or PE. The present authors compared the predictive value of a systolic blood pressure (SBP) value of <100 mmHg and <90 mmHg and the shock index (cardiac frequency divided by SBP) on 30-day mortality in consecutive patients with PE. As of May 2006, 6,599 patients with PE were enrolled in the study. Of these, 417 (6.3%) died within 30 days: 153 of the initial PE, 29 of recurrent PE and 235 due to other causes. Of the 417 individuals who died, 127 (30%) had a positive shock index, 60 (14%) had SBP <100 mmHg and 33 (7.9%) had SBP <90 mmHg. On multivariate analysis any of the three parameters were independently associated with an increased mortality. The shock index had a higher sensitivity (30.5 versus 14.4 and 7.9% for SBP <100 mmHg and <90 mmHg, respectively) but lower specificity (86.3 versus 93.0 and 96.6). All three measures of haemodynamic instability are independent predictors of 30-day mortality. However, while the shock index had the highest sensitivity, a systolic blood pressure value <90 mmHg had the highest specificity.

Acute venous thromboembolism in patients with recent major bleeding. The influence of the site of bleeding and the time elapsed on outcome.

BACKGROUND: Patients with major bleeding who subsequently develop clinically apparent venous thromboembolism (VTE) present a particularly difficult therapeutic dilemma. METHODS: RIETE is a prospective registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We retrospectively studied those who had experienced recent major bleeding (<30 days prior to VTE) to assess the influence of the site of bleeding and the time elapsed to VTE on their 3 month outcome. RESULTS: Of 12,294 patients enrolled up to July 2005, 306 (2.5%) had recent major bleeding: gastrointestinal (GI) tract, 116 (38%); intracranial, 94 (31%); other, 96 (31%). During the study period, 19 patients [6.2%; 95% confidence interval (CI) 3.5-8.9] with recent bleeding rebled (eight died): 13 of them (68%) during the first 2 weeks. Multivariate analysis confirmed that patients with recent GI bleeding had an increased risk for both major rebleeding (hazard ratio 2.8; 95% CI 1.4-5.3) and death (hazard ratio 1.9; 95% CI 1.2-3.1) compared to those with no recent bleeding. Those who bled in other sites had an increased risk only for death (hazard ratio 2.0; 95% CI 1.2-3.3). An elapsed time of <2 weeks from bleeding to the index VTE event was also associated with an increased risk for major rebleeding (hazard ratio 2.4; 95% CI 1.2-5.0) and death (hazard ratio 2.8; 95% CI 1.8-4.5). CONCLUSION: The incidence of new bleeding or death depends on the site of prior bleeding and the time elapsed until VTE. This information may help to identify the best therapeutic approach for these high-risk patients.

[Effect of cyclosporine on plasma levels of uric acid in patients treated with bone marrow transplantation]. / Efecto de la ciclosporina sobre los niveles plasmáticos de ácido úrico en pacientes trasplantados de médula ósea.

In patients treated with cyclosporine, an increase in the incidence of goiter has been demonstrated. This agent produces changes in the lipidic metabolisms, among which the increase in VLDL stands put. Given that the hyperlipemia more frequently associated to hyperuricemia is the increase of such lipoprotein, we decided to study the behaviour of plasmatic uric acid in patients receiving treatment with cyclosporine. The study was conducted in patients with bone marrow transplant undergoing immunosuppressive therapy, considering the effect of cyclosporine as the only drug or following a scheme of mixed immunosuppression associated to prednisone. We observed a reversible increase in the plasmatic levels of uric acid in patients treated with cyclosporine, which was positively correlated to an increase in VLDL triglycerides. Hence, the cyclosporine produced an increase of uric acid which was neither observed when associated to prednisone nor in the group of self-transplanted patients.