Ana Alfonso

Screening for occult malignancy with FDG-PET/CT in patients with unprovoked venous thromboembolism

Extensive screening strategies to detect occult cancer in patients with unprovoked venous thromboembolism (VTE) are complex and no benefit in terms of survival has been reported. FDG‐PET/CT (2‐[F‐18] fluoro‐2‐deoxy‐D‐glucose positron emission tomography combined with computed tomography), a noninvasive technique for the diagnosis and staging of malignancies, could be useful in this setting. Consecutive patients ≥ 50 years with a first unprovoked VTE episode were prospectively included. Screening with FDG‐PET/CT was performed 3–4 weeks after the index event. If positive, appropriate diagnostic work‐up was programmed. Clinical follow‐up continued for 2 years. Blood samples were collected to assess coagulation biomarkers. FDG‐PET/CT was negative in 68/99 patients (68.7%), while suspicious FDG uptake was detected in 31/99 patients (31.3%). Additional diagnostic work‐up confirmed a malignancy in 7/31 patients (22.6%), with six of them at early stage. During follow‐up, two patients with negative FDG‐PET/CT were diagnosed with cancer. Sensitivity (S), positive (PPV) and negative predictive values (NPV) of FDG‐PET/CT as single tool for the detection of occult malignancy were 77.8% (95% CI: 0.51–1), 22.6% (95% CI: 0.08–0.37) and 97.1% (95% CI: 0.93–1), respectively. Median tissue factor (TF) activity in patients with occult cancer was 5.38 pM vs. 2.40 pM in those without cancer (p = 0.03). Limitation of FDG‐PET/CT screening to patients with TF activity > 2.8 pM would improve the PPV to 37.5% and reduce the costs of a single cancer diagnosis from 20,711€ to 11,670€. FDG‐PET/CT is feasible for the screening of occult cancer in patients with unprovoked VTE, showing high S and NPV. The addition of TF activity determination may be useful for patient selection.

High incidence of venous thromboembolism despite electronic alerts for thromboprophylaxis in hospitalised cancer patients

Many cancer patients are at high risk of venous thromboembolism (VTE) during hospitalisation; nevertheless, thromboprophylaxis is frequently underused. Electronic alerts (e-alerts) have been associated with improvement in thromboprophylaxis use and a reduction of the incidence of VTE, both during hospitalisation and after discharge, particularly in the medical setting. However, there are no data regarding the benefit of this tool in cancer patients. Our aim was to evaluate the impact of a computer-alert system for VTE prevention in patients with cancer, particularly in those admitted to the Oncology/Haematology ward, comparing the results with the rest of inpatients at a university teaching hospital. The study included 32,167 adult patients hospitalised during the first semesters of years 2006 to 2010, 9,265 (28.8%) with an active malignancy. Appropriate prophylaxis in medical patients, significantly increased over time (from 40% in 2006 to 57% in 2010) and was maintained over 80% in surgical patients. However, while e-alerts were associated with a reduction of the incidence of VTE during hospitalisation in patients without cancer (odds ratio [OR] 0.31; 95% confidence interval [CI], 0.15-0.64), the impact was modest in cancer patients (OR 0.89; 95% CI, 0.42-1.86) and no benefit was observed in patients admitted to the Oncology/Haematology Departments (OR 1.11; 95% CI, 0.45-2.73). Interestingly, 60% of VTE episodes in cancer patients during recent years developed despite appropriate prophylaxis. Contrary to the impact on hospitalised patients without cancer, implementation of e-alerts for VTE risk did not prevent VTE effectively among those with malignancies.

Factors influencing the use of thromboprophylaxis in cancer outpatients in clinical practice: A prospective study

INTRODUCTION Current clinical practice guidelines do not recommend routine pharmacological thromboprophylaxis in cancer outpatients receiving chemotherapy. However, a high proportion of cancer-associated venous thromboembolism (VTE) events occur in this setting. There are scarce data on the use of thromboprophylaxis in ambulatory cancer patients in real clinical practice. MATERIAL AND METHODS We conducted a single-center prospective study aimed to evaluate the use and factors influencing pharmacological prophylaxis in consecutive cancer patients receiving ambulatory chemotherapy. Patients were followed for 90 days after inclusion. RESULTS A total of 1108 patients were included. According to the Khorana score, 45.8% patients were classified as low-risk, 47.4% intermediate-risk and 6.8% as high-risk. Outpatient pharmacological prophylaxis was administered at any time during follow-up to 157 patients (14.2%) with a median duration of 42 days (range 1-90). Main factors influencing thromboprophylaxis were: previous history of VTE (odds ratio [OR], 19.11; 95% CI, 9.61-37.98), intercurrent hospitalization (OR, 5.40; 95% CI, 3.57-8.16), and gastrointestinal or gynecologic cancer (OR, 1.76; 95% CI, 1.11-2.80 and OR, 2.34; 95% CI, 1.05-5.26, respectively). During follow-up 58 (5.2%) VTE events were observed. Independent predictors of VTE were the site of malignancy (OR, 3.04; 95%CI, 1.20-7.71 and OR, 2.47; 95%CI, 1.21-5.01 for pancreas and lung cancer, respectively) and previous VTE (OR, 4.23; 95%CI, 1.26-14.27). Outpatient prophylaxis was associated with a lower risk of VTE during follow-up (OR, 0.30; 95%CI, 0.10-0.95). CONCLUSIONS Although the type of malignancy appears as the most relevant variable for decision-making, additional efforts are required to identify patients at particular high thrombosis risk.

Implementation of a management protocol for massive bleeding reduces mortality in non-trauma patients: Results from a single centre audit

OBJECTIVE To audit the impact upon mortality of a massive bleeding management protocol (MBP) implemented in our center since 2007. DESIGN A retrospective, single-center study was carried out. Patients transfused after MBP implementation (2007-2012, Group 2) were compared with a historical cohort (2005-2006, Group 1). BACKGROUND Massive bleeding is associated to high mortality rates. Available MBPs are designed for trauma patients, whereas specific recommendations in the medical/surgical settings are scarce. PATIENTS After excluding patients who died shortly (<6h) after MBP activation (n=20), a total of 304 were included in the data analysis (68% males, 87% surgical). INTERVENTIONS Our MBP featured goal-directed transfusion with early use of adjuvant hemostatic medications. VARIABLES OF INTEREST Primary endpoints were 24-h and 30-day mortality. Fresh frozen plasma-to-red blood cells (FFP:RBC) and platelet-to-RBC (PLT:RBC) transfusion ratios, time to first FFP unit and the proactive MBP triggering rate were secondary endpoints. RESULTS After MBP implementation (Group 2; n=222), RBC use remained stable, whereas FFP and hemostatic agents increased, when compared with Group 1 (n=82). Increased FFP:RBC ratio (p=0.053) and earlier administration of FFP (p=0.001) were also observed, especially with proactive MBP triggering. Group 2 patients presented lower rates of 24-h (0.5% vs. 7.3%; p=0.002) and 30-day mortality (15.9% vs. 30.2%; p=0.018) - the greatest reduction corresponding to non-surgical patients. Logistic regression showed an independent protective effect of MBP implementation upon 30-day mortality (OR=0.3; 95% CI 0.15-0.61). CONCLUSIONS These data suggest that the implementation of a goal-directed MBP for prompt and aggressive management of non-trauma, massive bleeding patients is associated to reduced 24-h and 30-day mortality rates.

First-line use of rituximab correlates with increased overall survival in late post-transplant lymphoproliferative disorders: retrospective, single-centre study

This retrospective study evaluates the impact of rituximab on PTLD response and survival in a single‐centre cohort. PTLD cases between 1984 and 2009, including heart, kidney, liver and lung transplant recipients, were included. Survival was analysed taking into account the type of PTLD (monomorphic vs. polymorphic), EBV infection status, IPI score, Ann Arbor stage and use of rituximab. Among 1335 transplanted patients, 24 developed PTLD. Median age was 54 yr (range 29–69), median time to diagnosis 50 months (range 0–100). PTLD type was predominantly late/monomorphic (79% and 75%), mostly diffuse large B‐cell type. Overall response rate (ORR) was 62% (66% rituximab vs. 50% non‐rituximab; P = 0.5). R‐CHOP‐like regimens were used most frequently (72% of patients treated with rituximab). Median overall survival was 64 months (CI 95% 31–96). OS was significantly increased in patients treated with rituximab (P = 0.01; CI 95% rituximab 58–79 months; non‐rituximab 1–30 months). Post‐transplant immunosuppression regimen had no effect on survival or time to PTLD, except for cyclosporine A (CyA), which associated with increased time to PTLD (P = 0.02). Rituximab was associated with increased survival in our single‐centre series, and it should be considered as first‐line therapy for PTLD patients. The possible protective effect of CyA for development of PTLD should be prospectively evaluated.

Papel de la nutrición en la prevención de la enfermedad aterosclerótica. Importancia de los suplementos dietéticos: nutracéuticos

RESUMEN La enfermedad cardiovascular, como la angina de pecho, el infarto agudo de miocardio, la hipertension arterial y la enfermedad vascular periferica, es la primera causa de mortalidad en paises desarrollados y en vias de desarrollo. Tiene su origen en la aparicion de aterosclerosis, esta directamente relacionada y afectada por una respuesta inflamatoria, como resultado directo de la obesidad, la mala nutricion, el sedentarismo y la mala respuesta adaptativa al estres y las tensiones psicoemocionales. Los factores de riesgo de las enfermedades cardiovasculares son multifactoriales y el tratamiento requiere con frecuencia cambios en los estilos de vida e intervenciones de cuerpo y mente. La medicina integrada holistica ofrece experiencia en nutricion, sustancias nutraceuticas, actividad fisica e intervenciones sobre el cuerpo y la mente que constituyen los pilares del tratamiento y la prevencion de la enfermedad cardiovascular. Un programa integral se dirige a todos los factores de riesgo y ofrece un entorno de apoyo centrado en el paciente.

Evaluation of Clinical and Biological Prognostic Factors in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Patients After Previous Treatment With Rituximab and Chemotherapy: Results of the PRO-R-IPI Study

INTRODUCTION Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity, showing a highly variable outcome. In patients with DLBCL relapsed/refractory to first-line treatment with rituximab the usefulness of the revised International Prognostic Index (R-IPI) as a prognostic tool remains unexplored. Some biological parameters (B-cell lymphoma 6 [Bcl-6], Bcl-2, p53, and multiple myeloma 1 [MUM1]) and blood populations (lymphocyte and monocyte counts) have been described as International Prognostic Index-independent prognostic factors. The objective was to evaluate the R-IPI to predict the outcome of DLBCL patients at the time of relapse after a front-line treatment with chemotherapy and rituximab and to establish in this population the relationship between biological parameters and outcome. PATIENTS AND METHODS We included patients with refractory/relapsed DLBCL after first-line treatment with rituximab-containing regimens; patients must have already finished a rescue treatment also including rituximab. Immunohistochemical assessment of Bcl-2, Bcl-6, p53, and MUM1 expression were undertaken in available biopsies. R-IPI factors were identified from the clinical data at diagnosis and at relapse. Response was assessed using National Cancer Institute-sponsored Working Group guidelines. RESULTS R-IPI prognosis at relapse was not significantly associated with overall response rate (ORR) after Rituximab-chemotherapy rescue therapy. None of the immunohistochemical parameters analyzed correlated with rescue therapy results. In contrast, patients with absolute lymphocyte count (ALC) ≥ 1 × 10(9)/L at relapse were more likely to respond than patients with ALC < 1 × 10(9)/L (P = .05). CONCLUSION The R-IPI score calculated at relapse could not predict the ORR to second-line treatment. Lymphopenia is a simple and useful predictor for outcome in relapsed/refractory DLBCL and the only prognostic factor that in our hands could predict the overall response to a second-line treatment with rituximab and chemotherapy.

Seguridad y eficacia de un concentrado de complejo protrombínico en pacientes con coagulopatía y hemorragia

Background. Prothrombin complex concentrates (PCC) are approved for urgent reversal of vitamin K antagonists (VKA). Recently, PCC have been used in the management of massive bleeding-associated coagulopathy. The present work evaluates safety and efficacy of PCC in a case series of both VKA reversal and massive bleeding. Methods. Retrospective review of cases treated with CCP (January 2010 to February 2013). Safety endpoints were infusion reactions and incidence of thromboembolic events. Efficacy endpoints were: 1) VKA reversal efficacy and 2) Massive bleeding coagulopathy reversal and 24h mortality. Results. Thirty-one patients were included (22 male), median age 61 years (range 30-86). No infusion reactions were detected, and only 1 thrombotic episode was observed. VKA reversal was effective in 100% of patients (6/6), all of them with complete reversal of INR value. In massive bleeding, 24-hour survival was 64% (16/25). Invasive hemostatic procedures were required in 28% of patients (7/25). CCP use was correlated with bleeding control in 44% of cases (11/25), and also significantly associated with survival (p=0.01). Conclusion. CCP are safe and effective for the novel indication of adjuvant treatment in massive bleeding patients, as well as for traditional urgent reversal of VKA.

Insights into venous thromboembolism prevention in hospitalized cancer patients: Lessons from a prospective study

Hospitalized cancer patients are at high risk of venous thromboembolism (VTE). Despite current recommendations in clinical guidelines, thromboprophylaxis with low molecular weight heparin (LMWH) is underused. We performed an observational prospective study to analyse factors influencing prophylaxis use, VTE events and mortality in cancer-hospitalized patients. 1072 consecutive adult cancer patients were included in an University Hospital from April 2014 to February 2017, and followed-up for 30 days after discharge. The rate of LMWH prophylaxis was 67.6% (95% confidence interval [CI] 64.7% to 70.4%), with a 2.8% rate of VTE events (95% CI 1.9% to 3.9%) and 3.5% rate of major bleeding events (95% CI 2.5% to 4.8%). 80% of VTE events occurred despite appropriate thromboprophylaxis. Overall, 30-day mortality rate was 13.2% (95% CI 11.2% to 15.3%). Active chemotherapy treatment, hospital stay ≥ 4 days, and metastatic disease were associated with a higher use of LMWH. On the contrary, patients with hematologic malignancies, anemia or thrombocytopenia were less prone to receive thromboprophylaxis. The main reasons for not prescribing LMWH prophylaxis were thrombocytopenia (23.9%) and active/recent bleeding (21.8%). The PRETEMED score, used for VTE risk stratification, correlated with 30-day mortality. There is room for improvement in thromboprophylaxis use among hospitalized-cancer patients, especially among those with hematologic malignancies. A relevant number of VTE events occurred despite prophylaxis with LMWH. Therefore, identification of risk factors for thromboprophylaxis failure is needed.

Short-term Heparin Re-exposure During Heart Transplantation in Patients With Ventricular Assist Devices and Acute Heparin-induced Thrombocytopenia.

a Facultad de Medicina, Universidad de Navarra, Pamplona, Navarra, Spain b Servicio de Hematologia, Clinica Universidad de Navarra, Pamplona, Navarra, Spain c Departamento de Anestesiologia, Clinica Universidad de Navarra, Pamplona, Navarra, Spain d Departamento de Cardiologia y Cirugia Cardiovascular, Clinica Universidad de Navarra, Pamplona, Navarra, Spain ___________________________________________________________________________