Efficacy of bortezomib to intensify the conditioning regimen and the graft-versus-host disease prophylaxis for high-risk myeloma patients undergoing transplantation.

This multicenter phase I trial was designed to evaluate the safety and efficacy of bortezomib (Bz) as part of both the conditioning regimen and the graft-versus-host disease (GvHD) prophylaxis. Patients received fludarabine, melphalan and Bz (days -9 and -2). GVHD prophylaxis consisted of Bz (days +1, +4, and +7), sirolimus (Siro) from day -5 and tacrolimus (Tk) from -3 (except the first five patients that did not receive Tk). Twenty-five patients with poor prognostic multiple myeloma were included. Eleven out of the 19 patients had high-risk features. Out of the 21 patients evaluable at day +100, 14 were in CR (67%) and 7 (33%) in PR. Cumulative incidence (CI) of nonrelapse mortality at 1 year was 24%. CI of grades 2-4 and 3-4 acute GvHD was 35% and 10%, respectively; CI of chronic GvHD was 35% and 55% at 1 and 2 years, respectively. Overall and event free survival at 2 years were 64% and 31%, respectively. Bz as part of the conditioning regimen and in the combination with Siro/tacrolimus for GvHD prophylaxis is safe and effective allowing an optimal disease control early after transplant and reducing the risk of GvHD.

Determination of soluble dietary fibre content of Okara treated with high hydrostatic pressure and enzymes: a comparative evaluation of two methods (AOAC and HPLC-ELSD).

ABSTRACT: Okara is a promising by-product from soybean and a rich source of dietary fibre, chiefly insoluble (IDF). To increase its solubility and functionality, a treatment with high hydrostatic pressure (HHP) assisted by food grade enzymes -Ultraflo® L or Viscozyme® L- has been performed. To monitor the effectiveness, an analysis of dietary fibre, mainly the soluble fraction (SDF), was accomplished by the AOAC enzymatic-gravimetric method with dialysis followed by both, spectrophotometric methods and High Performance Liquid Chromatography with Evaporative Light Scattering Detector (HPLC-ELSD) analysis of the soluble fraction. A significant increase in SDF (≈1.5-times) to the expense of a decrease in IDF was shown and chromatograms revealed two peaks of 95 and 22 kDa. Thus, treated Okara possessed a more balanced and convenient ratio of soluble to insoluble dietary fibre, which could have health benefits as prebiotic. Inbuilt interferences of the official AOAC's method for dietary fibre were confirmed and the direct HPLC-ELSD approach was about twice more sensitive than spectrophotometric methods. Consequently, the direct HPLC-ELSD analysis of the supernatant is proposed as a cheaper, faster and reliable method. Combined HHP-treatments plus specific enzymes represent a promising alternative for the valorisation and preservation of agrofood by-products.

In vitro fermentability and prebiotic potential of soyabean Okara by human faecal microbiota.

At present, there is a huge interest in finding new prebiotics from agrofood industrial waste, such as the soyabean by-product Okara, rich in insoluble dietary fibre. A previous treatment of Okara with high hydrostatic pressure assisted by the food-grade enzyme Ultraflo ® L achieved a 58·2 % increment in its soluble dietary fibre (SDF) contents. Therefore, potential prebiotic effect of both treated and native Okara was assayed using 48 h, pH-controlled, anaerobic batch cultures inoculated with human faecal slurries, which simulate the human gut. Changes in faecal microbiota were evaluated using 16S rRNA-based fluorescence in situ hybridisation, whereas release of SCFA and lactic acid was assessed by HPLC. Both Okara samples exhibited potential prebiotic effects but Okara treated to maximise its SDF content showed higher SCFA plus lactic acid, better growth promotion of beneficial bacteria, including bifidobacteria after 4 and 48 h and lactobacilli after 4 h of fermentation, and a greater inhibition of potentially harmful bacterial groups such as clostridia and Bacteroides. Differences found between fructo-oligosaccharides and Okara substrates could be attributed to the great complexity of Okara's cell wall, which would need longer times to be fermented than other easily digested molecules, thus allowing an extended potential prebiotic effect. These results support an in vitro potential prebiotic effect of Okara.

Potential protective effect of Helicobacter pylori on the development of gastrointestinal GvHD.

Previous reports ascribe a modulating capacity of the immune response to Helicobacter pylori (HP). Our hypothesis was to demonstrate in a prospective study that HP infection could have a protective effect against development of gastrointestinal GvHD in patients receiving allogeneic hematopoietic cell transplantation (HCT). Presence of HP before transplant was determined using C(13) urea breath test. Seventy-nine patients receiving an allogeneic HCT were included and 93.7% of them received PBSC; in 51.9%, the donor was unrelated. Acute gastrointestinal GvHD was diagnosed in 51.9% (n=41). In the multivariable analysis, HP infection was associated with a lower frequency of gastrointestinal GvHD (odds ratio (OR)=0.19 (95% confidence interval (CI): 0.05-0.67); in contrast, an unrelated donor was associated with a higher frequency of gastrointestinal GvHD (odds ratio=5.4 (95% confidence interval: 1.6-18.2). One year overall survival (OS) was 74%. In the multivariate Cox proportional-hazards regression analysis, stages 0-II gastrointestinal GvHD (hazards ratio (HR)=0.19), reduced intensity conditioning (HR=0.04) and tacrolimus-sirolimus GvHD prophylaxis (HR=0.06) were all associated with a better OS. In summary, HP infection could have a role in decreasing gastrointestinal GvHD in patients receiving allogeneic HCT from peripheral blood including related and unrelated donors.

Diagnostic utility of bone marrow examination for the assessment of patients with fever of unknown origin: a 10-year single-centre experience.

Bone marrow (BM) examination is included in the diagnostic algorithm of fever of unknown origin (FUO), although its role is not clearly determined. The purpose of this study was to assess the role of BM studies in patients with FUO. We retrospectively reviewed 45 consecutive patients (25% human immunodeficiency virus-positive) with FUO who underwent a BM study in the University Hospital of Salamanca from 2000 to 2010. We analysed the diagnostic role of BM smears, multiparameter flow cytometry analysis, histology and microbiological cultures. Five patients (11%) were finally diagnosed by BM study (three had an infectious disease and two were found to have haematological malignancies), all of whom were immunocompetent patients. Histology was the most useful study (diagnosis was obtained in 4/5 patients), while BM cultures did not establish the final diagnosis in any patient. Flow cytometry established the diagnosis in one patient, although this patient was also diagnosed by histology. In conclusion, BM study is useful for establishing the aetiology of FUO. BM biopsy for histological examination should be always mandatory if a BM examination is performed.

Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis has been suggested as a potential risk factor. However, the impact of tacrolimus (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n=68) or plus MTX (TAC/MTX)±ATG (n=34) for GVHD prophylaxis. No significant differences were observed in the incidence of TA-TMA between patients receiving TAC/SIR vs TAC/MTX±ATG (7.4% vs 8.8%, P=0.8). Only grade III-IV acute GVHD, previous HSCT and serum levels of TAC >25 ng/mL were associated with a greater risk of TA-TMA. Patients developing TA-TMA have significantly poorer survival (P<0.001); however, TA-TMA ceased to be an independent prognostic factor when it was included in a multivariate model. In conclusion, the combination of TAC/SIR does not appear to pose a higher risk of TA-TMA. By contrast, we identified three different risk groups for developing TA-TMA.

Influencia de la mutación C677T del gen de la metilentetrahidrofolato reductasa en la enfermedad tromboembólica venosa / Influence of the C677T mutation in methylenetetrahydrofolate reductase gene in venous thromboembolic disease

La enfermedad tromboembólica venosa (ETV) es considerada como una enfermedad multifactorial. Es necesaria la presencia de factores genéticos, que predisponen al individuo a la trombosis, y factores ambientales, que desencadenan la trombosis (interacción gen-ambiente). En los últimos años se han descrito numerosos polimorfismos asociados con un mayor o menor riesgo a padecer una enfermedad trombótica en sus distintas variantes. Una de estas mutaciones de interés es la C677T del gen metilentetrahidrofolato reductasa (MTHFR), que consiste en la sustitución de una citosina por una timina en el nucleótido 677. Este cambio de aminoácido genera una variante de MTHFR termolábil con capacidad reducida para metabolizar la homocisteína, pudiendo aparecer una hiperhomocisteinemia leve-moderada, factor de riesgo conocido en la ETV. Por tanto, C677T MTHFR podría predisponer a la aparición y recurrencia de la ETV. Este artículo pretende analizar el papel concreto desempeñado por este polimorfismo en la ETV, así como su aplicabilidad clínica(AU)

Venous thromboembolism (VTE) is a multifactorial disease in which both environmental and genetic factors are involved. The presence of mutations in genes coding for haemostatic, fibrinolytic and, also, inflammatory proteins is associated with an increased risk of first episode and recurrence of venous thrombosis. So, in the last years, several polymorphisms associated with thrombosis have been reported. Recently, the 677C > T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene (a C > T substitution at base pair 677 leading to the exchange of alanine to valine) has been proposed by some studies to be a thrombophilic risk factor. This mutation causes moderate hyper-Hcy, and Hyper-Hcy is well known to cause VTE. We analysed the role of C677T MTHFR in VTE, as well as its clinical applicability(AU)

El farmacéutico en el control sanitario local en Andalucía: evolución y actualidad del cuerpo de farmacéuticos titulares / The pharmacist in the local health control in Andalucía: evolution and body of pharmaceutical news headlines

Hasta mediados del siglo XIX no hubo en España una organización sanitaria municipal estable. El Cuerpo de Farmacéuticos Titulares nace en pleno bienio progresista del General Espartero, conociendo posteriormente periodos tan distintos como el reinado de Isabel II bajo el cual se inicia una organización racional de la sanidad española1. En la época actual, con el traspaso de competencias hacia las Comunidades Autónomas el Cuerpo de Farmacéuticos Titulares a sufrido una modificación importante y se ha integrado en los Servicios Autonómicos de Salud en la mayoría de las CCAA. El presente trabajo tiene como objetivo, analizar la evolución histórica del Cuerpo y definir su consideración como funcionarios dentro del Cuerpo Superior Facultativo de Instituciones Sanitarias de la Junta de Andalucía, concretando sus funciones dentro de las competencias que le son atribuidas en la Comunidad Autónoma Andaluza(AU)

Until the mid-nineteenth century in Spain there was a stable municipal health organization. Pharmacists Corps was created in full biennium General Espartero progressive, knowing later periods as diverse as the reign of Isabel II, under which initiates a rational organization of the Spanish health. At the present time, with the transfer of powers to the Autonomous Communities Corps pharmacists has undergone significant changes and has been integrated into regional health services in most regions. This study aims to analyze the historical evolution of the body and define its consideration as officers with in the Senior Corps Optional Health Institutions of the Government of Andalusia, specifying their duties within the powers conferred on it in the Autonomous Community of Andalusia(AU)

Carcinoma adenoide quístico de mama: a propósito de un caso / Adenoid cystic carcinoma of the breast. Apropos of a case

Objetivo: Describir un tipo de carcinoma mamario inusual y poco frecuente, con características definitorias propias. Caso clínico: Se presenta el caso de una mujer diagnosticada de este tipo de neoplasia y se realiza un comentario sobre los datos publicados hasta el momento. Resultados: Se analiza el comportamiento de este tumor en relación con otros tumores mamarios, su manejo clínico y tratamiento. Conclusiones: El carcinoma adenoide quístico es una entidad clinicopatológica diferente del carcinoma ductal o lobulillar infiltrante. Su tratamiento no se realiza según los parámetros determinantes en otros cánceres mamarios. Su evolución y comportamiento biológico parecen más favorables

Objective: To describe an unusual and infrequent type of breast carcinoma with specific defining characteristics. Case report: We present the case of a woman with cystic adenoid carcinoma and review the literature published on this entity to date. Results: The behavior of this tumor in relation to other breast tumors, and its clinical management and treatment are analyzed. Conclusions: Cystic adenoma of the breast is a distinct clinicopathological entity from infiltrating ductal or lobular breast carcinoma. Its treatment is not based on parameters that are determinant in other breast cancers. Its outcome and biological behavior seem more favorable

Disección aguda de aorta torácica o infarto agudo de miocardio. Necesidad de diferenciación precoz / Acute dissection of the thoracic aorta or acute myocardial infarction. The need for early differentiation

Presentamos un caso clínico de un paciente con dolor torácico típico que acudió a Urgencias y que, tras realizarle radiografía de tórax, analítica y electrocardiograma, se diagnosticó de infarto agudo de miocardio, siendo sometido a tratamiento con rTPA y que resultó ser posteriormente una disección aguda de aorta torácica. Destacamos que el dato de mayor sensibilidad es la sospecha clínica. La presencia de la radiografía simple de tórax, en este caso, era indicativa de disección aórtica, sin embargo, el electrocardiograma y la clínica pesaron más al hacer el diagnóstico. Igualmente subrayamos que la precocidad en el diagnóstico de disección aórtica y en su tratamiento específico mejoran la mortalidad. Asimismo, tras revisar en la literatura, hemos comprobado los pocos casos descritos (AU)