Synthesis of controlled-size silver nanoparticles for the administration of methotrexate drug and its activity in colon and lung cancer cells.

A controlled synthesis of methotrexate (MTX) silver nanoparticles (AgNPs-MTX) using borohydride and citrate as reduction and reduction/capping agents, respectively, was performed in order to obtain AgNPs-MTX conjugates with a narrow size distribution. Their characterization showed polydispersed spherical shape nanoparticles with a mean size around 13 nm and distribution range between 7-21 nm. The presence of MTX was confirmed by FTIR and EDX analysis. Spectroscopic determinations suggest the chemisorption of MTX through a carboxylic group (-COOH) onto AgNPs via the exchange with a citrate molecule. Drug loading capacities calculated for AgNPs synthesized using different amounts of MTX were 28, 31 and 40%. In vitro drug release tests depicted similar release profiles for all conjugated amounts releasing between 77 to 85% of the initial MTX loaded into the AgNPs. With respect to free MTX, the addition of the nanocarrier delayed its release and also changed its pharmacokinetics. Free MTX is released after 3 hours following a first order kinetic model, whereas in the presence of AgNPs, a fast initial release is observed during the first 5 hours, followed by a plateau after 24 hours. In this case, AgNPs-MTX fitted a Higuchi model, where its solubilization is controlled by a diffusion process. Results obtained from flow cytometry of different cell lines treated with AgNPs-MTX demonstrated the combined anticancer effect of both reagents, decreasing the percentage of living cells in a colon cancer cell line (HTC-116) down to 40% after 48 hours of exposure. This effect was weaker but still significant for a lung cancer cell line (A-549). Finally, a zebrafish assay with AgNPs-MTX did not show any significant cytotoxic effect, confirming thereby the reduction of systemic drug toxicity achieved by coupling MTX to AgNPs. This observed toxicity reduction in the zebrafish model implies also a probable improvement of the usage of AgNPs-MTX in chemotherapy against human cancers.

Degradation of the diuretic hydrochlorothiazide by UV/Solar radiation assisted oxidation processes.

The objective of this study was to analyse the effectiveness of advanced oxidation processes (AOPs) with Solar and UV radiation (UV/H2O2, UV/K2S2O8) for the degradation of hydrochlorothiazide (HCTZ), a widely used diuretic drug, in aqueous solution focusing on the influence of four experimental parameters: initial concentration of HCTZ, solution pH, nature of the water matrix, and initial concentration of radicals. The obtained results showed that using both kinds of direct photolysis (UV and Solar), the percentage of degraded HCTZ was low, but there was a decrease in the degradation rate favored by the increase of the initial concentration of this pollutant. In addition, the degradation rates were higher at acid pHs. With regard to the nature of water, the degradation rate varied in the order: ultrapure > superficial > tap water. This is due to the presence of organic and inorganic matter (bicarbonates, nitrates, and chlorides) in surface and tap water, that react with the radicals generated, which reduces the availability of radical species, generating competitive kinetics. The presence of radical-promoter species increased the degradation rate of the pollutant, reaching a degradation of 100% of HCTZ after 20 min of treatment. The results obtained point out that the degradation rate was higher in the presence of HO radicals. This behavior was attributed to the higher oxidation power of HO versus radicals. The determination of the degradation by-products led to structures very similar to the parent compound. For example, the corresponding hydroxylated dechlorinated derivative of HCTZ was found in all the systems used. The cytotoxicity test showed that these byproducts have a lower toxicity than the original product. Finally, the economic viability study confirmed that the UV/K2S2O8 system has the lowest cost.

Lactose drives Enterococcus expansion to promote graft-versus-host disease.

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.

Guías clínicas para el ejercicio físico durante el embarazo / Clinical guidelines for physical exercise during pregnancy

De forma tradicional e histórica, las recomendaciones referidas al ejercicio físico durante el embarazo han estado basadas en cuestiones culturales y sociales, más que en evidencias científicas. De tal forma, la información científica disponible a través de guías de actuación profesional ha sido escasa o prácticamente inexistente. Ante esta situación, y con el ejercicio físico insertado en nuestra sociedad como un elemento básico de promoción de la salud, se hace importante disponer de unas guías prácticas que permitan a los profesionales, especialmente los sanitarios, disponer de recomendaciones para el ejercicio físico durante el embarazo basadas en sólidas evidencias científicas. El objetivo del presente estudio ha sido la elaboración de las primeras guías españolas de práctica clínica para el ejercicio físico durante el embarazo. El equipo de trabajo se formó producto de la solicitud de la Sociedad Española de Ginecología y Obstetricia (SEGO) al grupo de investigación Actividad Físico-deportiva en Poblaciones Específicas (AFIPE), de la Universidad Politécnica de Madrid; para la elaboración de las presentes guías estuvo formado por profesionales sanitarios, de las ciencias de la actividad física y del deporte y de la biblioteconomía y la documentación. El proceso metodológico desarrollado estuvo basado en el utilizado en las guías canadienses para la actividad física durante el embarazo, recientemente publicadas. Los resultados obtenidos permitieron elaborar unas recomendaciones básicas para el ejercicio físico durante la gestación, así como factores y situaciones que se deben tener en cuenta durante la práctica física en mujeres gestantes

Traditionally and historically, recommendations regarding physical exercise during pregnancy have been based on cultural and social issues, rather than on scientific evidence. Thus, the scientific information available through professional guidelines has been scarce or virtually non-existent. In this situation, with the physical exercise inserted in our society as a basic element of health promotion, it is important to have practical guidelines for professionals, especially health practitioners, with recommendations for physical exercise during pregnancy based in solid scientific evidence. The objective of this study has been the elaboration of the first Spanish clinical practice guidelines for physical exercise during pregnancy. The work team was formed based on the request of the Spanish Society of Gynecology and Obstetrics (SEGO) to the research group "Physical-sport activity in specific populations" (AFIPE), of the Universidad Politécnica de Madrid for the elaboration of the present guidelines, the work team was composed by health professionals, the physical activity and sports sciences professionals and one professional from the library and documentation science. The methodological process developed was based on the Canadian guidelines for physical activity during pregnancy, recently published. The obtained results allowed to establish basic recommendations for physical exercise during pregnancy, as well as factors and situations that should be considered during exercise in pregnant women

Valoración del flujo de la fístula arteriovenosa en pacientes en tratamiento con quelantes con calcio / Evaluation of arteriovenous fistula blood flow in patients with calcium chelation therapy

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Circulating microparticles are associated with clinical severity of persistent ST-segment elevation myocardial infarction complicated with cardiogenic shock.

BACKGROUND: Cardiogenic shock (CS) is the leading cause of death in patients admitted for acute myocardial infarction (MI). Despite the recent advances in reperfusion and medical treatment mortality remains unacceptably high. Whether cells of the blood compartment in CS-patients are activated and release microparticles (cMPs) that may be both messengers and biomarkers of cell damage is not known. We aimed to investigate the cMP subtypes and parental activated cells of ST-elevation MI (STEMI)-patients complicated by CS and that of non-CS STEMI-patients (non-CS) in order to identify a cMP signature that could aid CS patient's risk stratification. METHODS: Clinically-characterized STEMI-patients with and without CS (36/group) were included. Treatment was delivered according to guidelines and included primary percutaneous coronary intervention. cMPs were characterized by triple-labeling flow cytometry using Annexin V and cell surface-specific monoclonal antibodies. RESULTS: Increased levels of leukocyte-derived (neutrophil and granulocyte origin) and platelet-derived cMPs were detected in CS compared to non-CS patients. A signature of cMPs derived from platelets, leukocytes, and endothelium discriminated CS-patients (AUC of 0.743±0.059 [95% CI: 0.628-0.859], P<0.0001) and predicted mortality in CS (AUC of 0.869±0.06 [95% CI: 0.750-0.988], P<0.0001). In CS-patients, a higher number of platelet- and monocyte-cMPs and of tissue factor-rich cMPs associated to worse myocardial blush grade and thrombolysis in myocardial infarction flow. CONCLUSIONS: cMPs derived from proinflammatory and prothrombotic cells were found to be elevated in CS-patients. In treated as per guidelines CS patients, granulocytes and neutrophils remained activated and actively shed cMPs. These cMPs were biomarkers of adverse prognosis in CS. TRANSLATIONAL ASPECT: Increased levels of leukocyte and platelet-derived circulating microparticles (cMPs) are found in cardiogenic shock (CS) patients as compared to non-CS patients. In CS-patients, a higher number of platelet- and monocyte-cMPs and a higher number of tissue factor-rich cMPs were associated to worse myocardial reperfusion. A specific prothrombotic and proinflammatory cMPs signature in cardiogenic shock (CS) patients is a potential discriminator and survival prognostic biomarker for CS, which could aid management and improve clinical outcomes.

Long-term prognosis for 1-year relapse-free survivors of CD34+ cell-selected allogeneic hematopoietic stem cell transplantation: a landmark analysis.

CD34+ cell selection significantly improves GvHD-free survival in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, specific information regarding long-term prognosis and risk factors for late mortality after CD34+ cell-selected allo-HSCT is lacking. We conducted a single-center landmark analysis in 276 patients alive without relapse 1 year after CD34+ cell-selected allo-HSCT for AML (n=164), ALL (n=33) or myelodysplastic syndrome (n=79). At 5 years' follow-up after the 1-year landmark (range 0.03-13 years), estimated relapse-free survival (RFS) was 73% and overall survival (OS) 76%. The 5-year cumulative incidence of relapse and non-relapse mortality (NRM) were 11% and 16%, respectively. In multivariate analysis, Hematopoietic Cell Transplantation Comorbidity Index score⩾3 correlated with marginally worse RFS (hazard ratio (HR) 1.78, 95% confidence interval (CI) 0.97-3.28, P=0.06) and significantly worse OS (HR 2.53, 95% CI 1.26-5.08, P=0.004). Despite only 24% of patients with acute GvHD within 1 year, this also significantly correlated with worse RFS and OS, with increasing grades of acute GvHD associating with increasingly poorer survival on multivariate analysis (P<0.0001). Of 63 deaths after the landmark, GvHD accounted for 27% of deaths and was the most common cause of late mortality, followed by relapse and infection. Although prognosis is excellent for patients alive without relapse 1 year after CD34+ cell-selected allo-HSCT, risks of late relapse and NRM persist, particularly due to GvHD.

Autoimmune hemolysis and immune thrombocytopenic purpura after cord blood transplantation may be life-threatening and warrants early therapy with rituximab.

Autoimmune hemolysis (AH) and immune thrombocytopenic purpura (ITP) are recognized complications after cord blood transplantation (CBT). We evaluated the incidence and characteristics of AH/ITP after double-unit CBT in a day 100 landmark analysis of 152 patients (median age 36 years, range 0.9-70 years) transplanted for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor (CNI)/mycophenolate mofetil. With a median 5.2-year (range 1.6-9.7 years) survivor follow-up, 10 patients developed autoimmune cytopenias (8 AH, 1 ITP, 1 both) at a median of 10.4 months (range 5.8-24.5) post CBT for a 7% cumulative incidence 3 years after the day 100 landmark. Six patients presented with severe disease (hemoglobin ⩽6 g/dL and/or platelets <20 × 109/L). All AH patients were direct antiglobulin test positive. All 10 cases developed during immunosuppression taper with 8 having prior acute GVHD. All 10 patients received rituximab 2-18 days after diagnosis, and corticosteroids combined with rituximab within <7 days was the most effective. No patient died of AH/ITP. AH/ITP occurs infrequently after CBT but may be life-threatening requiring emergency therapy. Rituximab combined with corticosteroids at diagnosis is warranted in patients with severe disease.

Development of composite outcomes for individual patient data (IPD) meta-analysis on the effects of diet and lifestyle in pregnancy: a Delphi survey.

OBJECTIVE: To develop maternal, fetal, and neonatal composite outcomes relevant to the evaluation of diet and lifestyle interventions in pregnancy by individual patient data (IPD) meta-analysis. DESIGN: Delphi survey. SETTING: The International Weight Management in Pregnancy (i-WIP) collaborative network. Sample Twenty-six researchers from the i-WIP collaborative network from 11 countries. METHODS: A two-generational Delphi survey involving members of the i-WIP collaborative network (26 members in 11 countries) was undertaken to prioritise the individual outcomes for their importance in clinical care. The final components of the composite outcomes were identified using pre-specified criteria. MAIN OUTCOME MEASURES: Composite outcomes considered to be important for the evaluation of the effect of diet and lifestyle in pregnancy. RESULTS: Of the 36 maternal outcomes, nine were prioritised and the following were included in the final composite: pre-eclampsia or pregnancy-induced hypertension, gestational diabetes mellitus (GDM), elective or emergency caesarean section, and preterm delivery. Of the 27 fetal and neonatal outcomes, nine were further evaluated, with the final composite consisting of intrauterine death, small for gestational age, large for gestational age, and admission to a neonatal intensive care unit (NICU). CONCLUSIONS: Our work has identified the components of maternal, fetal, and neonatal composite outcomes required for the assessment of diet and lifestyle interventions in pregnancy by IPD meta-analysis.

El ejercicio físico supervisado durante el embarazo mejora la respuesta cardiaca fetal / Supervised physical activity during pregnancy improves fetal cardiac response

Objetivo: Valorar la influencia de un programa de ejercicio físico durante la gestación en la adaptación de la frecuencia cardiaca fetal (FCF). Se espera encontrar una mejor adaptación de la FCF especialmente en cuanto a recuperaciones más rápidas. Método: 45 gestantes participantes en un ensayo clínico aleatorizado sin complicaciones ni contraindicaciones para el ejercicio fueron estudiadas durante el tercer trimestre de embarazo. Se midieron las siguientes variables: FCF en reposo, FCF post-ejercicio y tiempo de recuperación de la FCF a los niveles de reposo. Resultados: La FCF en reposo fue similar en ambos grupos. La FCF post-ejercicio fue significativamente mayor en el grupo control (GC) que en el grupo ejercicio (GE) en ambas pruebas, al 40% GE=138,5±6,4GE vs 141±7,5 GC (p=0,001), al 60% 141,6±10,8 GE vs 150,3±16,8GC. Lo mismo ocurre en los tiempos de recuperación, al 40% 78,2±95,7GE vs 328,4±315,2GC (p=0,001), al 60% 193,3±257,8 GE vs 542,6±482,9GC (p=0,003). Conclusión: El ejercicio físico desarrollado durante el embarazo tiene como consecuencia una mejor adaptación de la FCF post-ejercicio, así como recuperaciones más rápidas (AU)

Objective: To assess the influence of a physical activity program during pregnancy on the adaptation of the fetal heart rate (FHR). Greater adaptations and faster recovery are expected to find. Methods: 45 pregnant women included in a randomized control trial, all with uncomplicated pregnancies for exercise were studied in their third trimester of pregnancy. Rest FHR, post-exercise FHR and recovery time were assessed. Results: Rest FHR was similar in both groups. Post-exercise FHR were significantly higher in control group (CG) than in exercise group (EG) in both test, 40% 138,5±6,4EG vs 141±7,5CG (p=0,001), 60% 141,6±10,8EG vs 150,3±16,8CG. The same was found in recovery time, 40% 78,2±95,7EG vs 328,4±315,2CG (p=0,001), al 60% 193,3±257,8EG vs 542,6±482,9CG (p=0,003). Conclusion: Greater adaptation in post-exercise FHR and faster recovery to rest FHR have been found as a result of a physical activity program carried out during pregnancy (AU)

Comparison of outcomes at two institutions of patients with ALL receiving ex vivo T-cell-depleted or unmodified allografts.

We compared outcomes of adult patients receiving T-cell-depleted (TCD) hematopoietic SCT (HCT) without additional GVHD prophylaxis at Memorial Sloan Kettering Cancer Center (MSKCC, N=52), with those of patients receiving conventional grafts at MD Anderson Cancer Center (MDACC, N=115) for ALL in CR1 or CR2. Patients received myeloablative conditioning. Thirty-nine patients received anti-thymocyte globulin at MSKCC and 29 at MDACC. Cumulative incidence of grades 2-4 acute (P=0.001, 17.3% vs 42.6% at 100 days) and chronic GVHD (P=0.006, 13.5% vs 33.4% at 3 years) were significantly lower in the TCD group. The non-relapse mortality at day 100, 1 and 3 years was 15.4, 25.0 and 35.9% in the TCD group and 9.6, 23.6 and 28.6% in the unmodified group (P=0.368). There was no difference in relapse (P=0.107, 21.3% vs 35.5% at 3 years), OS (P=0.854, 42.6% vs 43.0% at 3 years) or RFS (P=0.653, 42.8% vs 35.9% at 3 years). In an adjusted model, age >50, cytogenetics and CR status were associated with inferior RFS (hazard ratio (HR)=2.16, P=0.003, HR=1.77, P=0.022, HR=2.47, P<0.001), whereas graft type was NS (HR=0.90, P=0.635). OS and RFS rates are similar in patients undergoing TCD or conventional HCT, but TCD effectively reduces the rate of GVHD.

Safety of voriconazole and sirolimus coadministration after allogeneic hematopoietic SCT.

Antifungal prophylaxis with azoles is considered standard in allogeneic hematopoietic SCT (allo-HSCT). Although sirolimus is being used increasingly for the prevention of GVHD, it is a substrate of CYP3A4, which is inhibited by voriconazole, and concurrent administration can lead to significantly increased exposure to sirolimus. We identified 67 patients with hematologic malignancies who underwent allo-HSCT with sirolimus, tacrolimus and low-dose MTX and received concomitant voriconazole prophylaxis from April 2008 to June 2011. All patients underwent a non-myeloablative or reduced-intensity conditioned allo-HSCT. Patients received sirolimus and voriconazole concurrently for a median of 113 days. The median daily dose reduction of sirolimus at the start of coadministration was 90%. The median serum sirolimus trough levels before and at steady state of coadministration were 5.8 ng/mL (range: 0-47.6) and 6.1 ng/mL (range: 1-14.2) (P=0.45), respectively. One patient with an average sirolimus level of 6 ng/mL developed sirolimus-related thrombotic microangiopathy that resolved after sirolimus discontinuation. No sinusoidal obstructive syndrome was reported. Seventeen patients (25%) prematurely discontinued voriconazole because of the adverse events. Only two patients (3%) presented with possible invasive fungal infections at day 100. We demonstrate that sirolimus and voriconazole coadministration with an empiric 90% sirolimus dose reduction and close monitoring of sirolimus trough levels is safe and well tolerated.

Exercise during pregnancy attenuates prenatal depression: a randomized controlled trial.

Recent studies have estimated the prevalence of depression during pregnancy to be between 10% and 30%, which is higher than that in the postpartum period. Pharmacological treatment during pregnancy is difficult because of the possible side effects of antidepressants on the mother and the fetus. The aim of this study was to examine whether a supervised exercise program (EP) reduces depressive symptoms in pregnant women. A randomized controlled trial was designed. One hundred eighty four healthy pregnant women from Fuenlabrada Hospital were included (31.37 ± 3.62 years). Women from the exercise group (EG) participated in a supervised EP consisting of three, 55- to 60-min sessions per week throughout pregnancy. The main outcome measure was the patients' depression level assessed by means of the Center for Epidemiologic Studies Depression Scale (CES-D). A total of 167 pregnant women were analyzed; 90 were allocated to the EG and 77 to the control group (CG). Significant differences were found between groups at the end of the study in CES-D scores (EG: 7.67 ± 6.30 vs. CG: 11.34 ± 9.74, p = .005) and in percentages of pregnant women depressed (EG: n = 11/12.2% vs. CG: n = 19/24.7%, p = .04). Our results show that supervised physical exercise during pregnancy reduces the level of depression and its incidence in pregnant women.

Embarazo en pacientes con lesión medular / Pregnancy in patients with spinal cord injury

ANTECEDENTES: Las gestaciones en pacientes con daño medular representan un reto para la obstetricia. Las complicaciones más frecuentes son las infecciones de las vías respiratorias y de las vías urinarias, y la más grave la hiperreflexia autonómica. El parto vaginal es posible en lesiones por debajo de T5, pero por encima de ese nivel, la imposibilidad de percibir las contracciones, de identificar el trabajo de parto y realizar pujos lleva a la necesidad de una cesárea programada. OBJETIVO: Exponer nuestra experiencia y revisar el manejo más adecuado de la embarazada parapléjica. MÉTODOS: Estudio retrospectivo en el periodo 2003-2014. Hubo 10 pacientes con 24 gestaciones: 6 abortos espontáneos, un 1 aborto inducido, quedando para el análisis 17 gestaciones (1 embarazo gemelar). La evaluación es independiente a la etiología o localización de la lesión. Se analiza las complicaciones perinatales y maternas. Resultados: La edad media fue 33 años. La edad gestacional media al parto fue 37 semanas: 12 de término (70,59%), 4 de pretérmino (23,53%) y una desconocida (5,88%). Hubo 10 cesáreas (58,82%) y 7 partos vaginales (41,18%). Peso medio neonatal de 2940 g, ninguno con retraso de crecimiento intrauterino. CONCLUSIONES: Nuestra experiencia muestra una alta tasa de prematuridad y de cesáreas, pero con buenos resultados maternos y perinatales, que hace permisible que estas pacientes puedan cumplir su deseo genésico, superando su discapacidad.

BACKGROUND: The pregnancies in patients with spinal cord injury represent a challenge for obstetrics. The most common complications are infections of the respiratory and urinary tract, and the most severe is the autonomic hyperreflexia. Vaginal delivery is possible in lesions below T5, but above that level the inability to perceive contractions, to identify labor and perform straining leads to the need for a scheduled cesarean. OBJECTIVE: To describe our experience and review the most appropriate management of paraplegic pregnant. Methods: Retrospective study in the period 2003-2014. There were 10 patients with 24 pregnancies: 6 spontaneous abortions, 1 induced abortion, leaving 17 for analysis pregnancies (one twin pregnancy). The evaluation is independent of the etiology or location of the lesion. Perinatal and maternal complications were analyzed. RESULTS: The mean age was 33 years. The mean gestational age at delivery was 37 weeks: 12 to term (70.59%), 4 preterm deliveries (23.53%) and one unknow. There were 10 cesarean sections (58.82%) and 7 vaginal deliveries (41.18%). Average birth weight of 2940 g, none with intrauterine growth restriction. CONCLUSIONS: Our experience shows a high rate of prematurity and cesarean section, but with good maternal and perinatal outcomes, which makes it permissible for these patients can fulfill their procreative desire, overcoming his disability.

Tratamiento con hemodiálisis larga con filtros de alto cut-off en la nefropatía por cilindros del mieloma: nuestra experiencia / Treatment by long haemodialysis sessions with high cut-off filters in myeloma cast nephropathy: our experience

El mieloma múltiple (MM) consiste en la proliferación incontrolada de células plasmáticas con producción de cantidades variables de inmunoglobulinas o sus cadenas. La insuficiencia renal aguda puede ser un síntoma del MM, y a veces su forma de presentación. Las cadenas ligeras libres circulantes (CLL) pueden dar lugar al fallo renal por la precipitación intratubular de ellas, causando una nefropatía por cilindros. El tratamiento del mieloma, una adecuada hidratación y la eliminación de CLL mediante técnicas de aféresis son los tratamientos admitidos actualmente para esta entidad. Se han intentado diversas técnicas de aféresis para intentar eliminar las CLL, siendo la hemodiálisis de larga duración con filtros para eliminar dichas cadenas ligeras (alto cut-off) la que se postula como el tratamiento más eficaz para la nefropatía del mieloma. MÉTODOS: Presentamos cinco casos de nefropatía de mieloma: tres con nefropatía por cilindros (NC) diagnosticada por biopsia renal y dos con alta probabilidad de NC (niveles de CLL > 500 mg/l) tratados con hemodiálisis larga con membrana de alto cut-off. Todos presentaban insuficiencia renal aguda, en cuatro de ellos con necesidad de terapia sustitutiva y uno en situación de insuficiencia renal avanzada. En todos ellos los niveles de CLL fueron muy elevados. Recibieron tratamiento específico para el mieloma más hemodiálisis de alto cut-off hasta alcanzar niveles de CLL < 500 mg/l. RESULTADOS: Cuatro de los cinco pacientes recuperaron función renal, quedando independientes de diálisis. El tiempo de evolución del mieloma desde el inicio de la clínica fue variable (1-6 m). El número de sesiones varió entre 8-16. El paciente de más tiempo de evolución precisó más sesiones y no recuperó función renal. CONCLUSIONES: La hemodiálisis larga con filtros de alto cut-off más tratamiento con quimioterapia del mieloma parece ser un tratamiento eficaz en la insuficiencia renal aguda debida a nefropatía del mieloma. La precocidad en el inicio del tratamiento puede ser un factor determinante de la respuesta

Multiple myeloma (MM) is the uncontrolled proliferation of plasma cells with variable amounts of production of immunoglobulin or their chains. Acute renal failure can be a symptom of MM, and it is sometimes their presentation form. Circulating free light chains (FLC) could led to renal failure by intratubular precipitation of themselves causing a cast nephropathy. Myeloma's treatment, an adequate hydration and FLC's elimination by aphaeresis treatments are currently eligible therapy for this entity. Several aphaeresis techniques have been tried to eliminate the FLC being long-term hemodialysis with filters to remove these light chains (High Cut-Off filters). This treatment is postulated as the most effective treatment for myeloma nephropathy. METHODS: We report 5 cases of myeloma nephropathy: three of them with cast nephropathy (CN) diagnosed by renal biopsy and another two with high probability of NC (FLC levels >500mg/L). All of them were treated by hemodialysis with membrane high Cut-Off. The five patients had had an acute renal failure; in four of them need replacement renal therapy. The fifth patient only had an advanced renal failure. In all patients, FLC levels were very high. All patients received specific treatment for myeloma in addiction on hemodialysis high Cut-Off until the FLC levels were <500mg/ L. RESULTS: Four of the five patients recovered renal function, being independent of dialysis. The evolution time of myeloma since the first symptoms appeared was variable (1-6 months). The number of treatment sessions ranged from 8-16. The patient whose evolution time was the longest one required more sessions and did not recovered the renal function. CONCLUSIONS: Length hemodialysis with filters high cut-off plus specific myeloma chemotherapy seems to be an effective treatment in acute renal failure due to cast myeloma. The early initiation of treatment could be an important factor for the response

Treatment by long haemodialysis sessions with high cut-off filters in myeloma cast nephropathy: our experience.

UNLABELLED: Multiple myeloma (MM) is the uncontrolled proliferation of plasma cells with variable amounts of production of immunoglobulins or their chains. Acute renal failure can be a symptom of MM, and it is sometimes its form of presentation. Circulating free light chains (FLC) could lead to renal failure due to their intratubular precipitation, causing a cast nephropathy. The treatment of myeloma, adequate hydration and the removal of FLC by apheresis techniques are currently the treatments that are accepted for this disease. Several apheresis techniques have been attempted for the removal of FLC, with long haemodialysis sessions with filters for the removal of these light chains (high cut-off filters) being proposed as the most effective treatment for myeloma nephropathy. METHODS: We report 5 cases of myeloma nephropathy: three had cast nephropathy (CN) diagnosed by renal biopsy and the other two had a high probability of CN (FLC levels >500 mg/l). They were treated with long haemodialysis sessions with a high cut-off membrane. All patients had suffered acute renal failure; four required renal replacement therapy and one patient had advanced renal failure. In all patients, FLC levels were very high. They received specific treatment for myeloma in addition to high cut-off haemodialysis until they achieved FLC levels of <500 mg/l. RESULTS: Four of the five patients recovered renal function, and became independent of dialysis. The progression time for myeloma from the time the first symptoms appeared varied (1-6 months). The number of treatment sessions ranged from 8-16. The patient with the longest progression time required more sessions and did not recover renal function. CONCLUSIONS: Long haemodialysis sessions with high cut-off filters in addition to specific myeloma chemotherapy seems to be an effective treatment for acute renal failure due to myeloma nephropathy. The early initiation of treatment could be a determining factor for the response.