Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation.

Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic stem-cell transplantation. Because of the small number of results from well designed, large-scale, clinical studies there is considerable variability in the prevention and treatment of GVHD worldwide. In 2014, to standardise treatment approaches the European Society of Blood and Marrow Transplantation published recommendations on the management of GVHD in the setting of HLA-identical sibling or unrelated donor transplantation in adult patients with haematological malignancies. Here we update these recommendations including the results of study published after 2014. Evidence was searched in three steps: first, a widespread scan of published trials, meta-analyses, and systematic reviews; second, expert opinion was added for specific issues following several rounds of debate; and third, a refined search to target debated or rapidly updating issues. On the basis of this evidence and the 2014 recommendations, five members of the EBMT Transplant Complications Working Party created 38 statements on GVHD prophylaxis, drug management, and treatment of acute and chronic GVHD. Subsequently, they created the EBMT GVHD management recommendation expert panel by recruiting 20 experts with expertise in GVHD management. An email-based, two-round Delphi panel approach was used to manage the consensus. Modified National Comprehensive Cancer Network categories for evidence and consensus were applied to the approved statements. We reached 100% consensus for 29 recommendations and 95% consensus for nine recommendations. Key updates to these recommendations include a broader use of rabbit anti-T-cell globulin; lower steroid doses for the management of grade 2 acute GVHD with isolated skin or upper gastrointestinal tract manifestations; fluticasone, azithromycin, and montelukast should be used for bronchiolitis obliterans syndrome; and the addition of newer treatment options for resteroid-refractory acute and chronic GVHD. In addition, we discuss specific aspects of GVHD prophylaxis and management in the setting of haploidentical transplantation and in paediatric patients, but no formal recommendations on those procedures have been provided in this Review. The European Society of Blood and Marrow Transplantation proposes to use these recommendations as a basis for the routine management of GVHD during stem-cell transplantation.

Use of rivaroxaban for the prevention of stroke in patients with nonvalvular atrial fibrillation in Spain.

AIM: To analyze the clinical profile and rates of stroke, major bleeding and intracranial hemorrhage of patients with atrial fibrillation (AF) treated with rivaroxaban in clinical practice. METHODS: Retrospective study of AF patients anticoagulated with rivaroxaban in a Healthcare Area of Valencia, Spain. Patients started treatment with rivaroxaban from July 2012 to December 2015. RESULTS: A total of 230 patients (mean age 76.9 ± 9.9 years; CHA2DS2-VASc 4.3 ± 1.7; HAS-BLED 1.7 ± 0.9) were included. Rates of stroke, major bleeding and intracranial bleeding were 0.4, 1.9 and 0.5 events per 100 patient-years, respectively. CONCLUSION: In this cohort of AF patients anticoagulated with rivaroxaban, despite patients being older and having a high thromboembolic risk, rates of stroke, major bleeding and intracranial bleeding were low.

Efecto de la suplementación con vitamina D en monodosis en niños con parálisis cerebral: Estudio preliminar controlado y aleatorizado / Effect of supplementation with a single dose of vitamin D in children with cerebral palsy: Preliminary randomised controlled study

Introducción: Los niños con parálisis cerebral (PC) tienen mayor riesgo de deficiencia de vitamina D (VD). Aunque existen bastantes estudios sobre VD en PC, hay limitada información sobre suplementación con VD en estos pacientes. Objetivo: Evaluar el efecto de la suplementación con VD en monodosis en las concentraciones plasmáticas de 25-hidroxi-vitamina-D (25OHD) en niños con PC. Pacientes y método: Estudio controlado, prospectivo y aleatorizado. Se estudiaron 30 niños chilenos (19 varones) con PC, mediana de edad de 9,9 años (6,2-13,5). Se registraron las variables clínicas y bioquímicas incluyendo 25OHD (tiempo 0 y 8 semanas). El grupo suplementado (S) recibió 100.000 UI D3 oral (tiempo 0), comparado con el grupo placebo (P). Resultados: Entre las características clínicas destaca: gastrostomizados (60%), desnutrición (30%), postración (93,3%), uso de antiepilépticos (70%) y uso de antiepilépticos inductores del metabolismo de VD (43,3%). Las mediciones basales de variables bioquímicas fueron normales. La 25OHD fue insuficiente en 4/30 y deficiente en 6/30. No hubo asociación de 25OHD con las variables estudiadas. Completaron el estudio 8 pacientes en el grupo S y 10 en el P. En ambos grupos no se observaron diferencias significativas en las variables basales. A las 8 semanas la calcemia, la fosfemia y la fosfatasa alcalina fueron normales en ambos grupos, la 25OHD en el grupo P fue normal en 6/10 e insuficiente + deficiente en 4/10 y normal en 8/8 en el grupo S (test exacto de Fisher, p = 0,07). Conclusiones: Una monodosis de 100.000 UI de VD podría normalizar las concentraciones de 25OHD en niños con PC. Se necesitan más estudios para confirmar estos resultados.

Introduction: Children with cerebral palsy (CP) have an increased risk of vitamin D (VD) deficiency. Although there are many studies on VD and CP, there is limited information about VD supplementation in these patients. Objective: To evaluate the effect of supplementation with a single dose of VD on the plasma concentrations of 25-hydroxy-vitamin-D (25OHD) in children with CP. Patients and method: Prospective-randomised-controlled-trial, including 30 Chilean children (19 males) with CP, median age 9.9 years (6.2-13.5). Clinical and biochemical variables including 25OHD, were recorded (time 0 and 8 weeks). Patients were allocated to the supplemented (S) group receiving 100,000 IU oral D3 at baseline, and compared with the placebo (P) group. Results: Among clinical features are highlighted: gastrostomy (60%), underweight (30%), bedridden (93.3%), antiepileptic drugs (70%), and 43.3% used VD metabolism inducing antiepileptics. Baseline biochemical measurements were normal. The 25OHD was insufficient in 4/30 and deficient in 6/30. 25OHD levels were not associated with the variables studied. Eight patients completed the study in the S group, and 10 in P group. The placebo and supplementation groups had no significant difference in baseline variables. Serum calcium, phosphate, and alkaline phosphatase levels at 8 weeks were normal in both groups, with no statistically significant differences. 25OHD in the P group was normal in 6/10, and insufficient + deficient in 4/10, and the S group was normal in all (8/8) (exact Fisher test P = .07). Conclusions: A single dose of 100,000 IU VD could normalise the concentrations of 25OHD after 8 weeks of supplementation in Children with CP, but more studies are required to confirm these results.

[Effect of supplementation with a single dose of vitamin D in children with cerebral palsy. Preliminary randomised controlled study]. / Efecto de la suplementación con vitamina D en monodosis en niños con parálisis cerebral. Estudio preliminar controlado y aleatorizado.

INTRODUCTION: Children with cerebral palsy (CP) have an increased risk of vitamin D (VD) deficiency. Although there are many studies on VD and CP, there is limited information about VD supplementation in these patients. OBJECTIVE: To evaluate the effect of supplementation with a single dose of VD on the plasma concentrations of 25-hydroxy-vitamin-D (25OHD) in children with CP. PATIENTS AND METHOD: Prospective-randomised-controlled-trial, including 30 Chilean children (19 males) with CP, median age 9.9 years (6.2-13.5). Clinical and biochemical variables including 25OHD, were recorded (time 0 and 8 weeks). Patients were allocated to the supplemented (S) group receiving 100,000 IU oral D3 at baseline, and compared with the placebo (P) group. RESULTS: Among clinical features are highlighted: gastrostomy (60%), underweight (30%), bed-ridden (93.3%), antiepileptic drugs (70%), and 43.3% used VD metabolism inducing antiepileptics. Baseline biochemical measurements were normal. The 25OHD was insufficient in 4/30 and deficient in 6/30. 25OHD levels were not associated with the variables studied. Eight patients completed the study in the S group, and 10 in P group. The placebo and supplementation groups had no significant difference in baseline variables. Serum calcium, phosphate, and alkaline phosphatase levels at 8 weeks were normal in both groups, with no statistically significant differences. 25OHD in the P group was normal in 6/10, and insufficient+deficient in 4/10, and the S group was normal in all (8/8) (exact Fisher test P=.07). CONCLUSIONS: A single dose of 100,000 IU VD could normalise the concentrations of 25OHD after 8 weeks of supplementation in Children with CP, but more studies are required to confirm these results.

Alemtuzumab as treatment of steroid-refractory acute graft-versus-host disease: results of a phase II study.

We conducted a phase II trial to investigate the safety and efficacy of alemtuzumab in treating steroid-refractory acute graft-versus-host disease (aGVHD) grade II or higher after stem cell transplantation. Ten adult patients (6 with aGVHD grade III and 4 with aGVHD grade IV) were included in the study. Nine patients had gastrointestinal tract involvement, 7 had skin involvement, and 5 had liver involvement. Five patients responded to treatment, 2 with complete response and 3 with partial response. Eight infectious events (4 of grade 3-4) and 7 cytomegalovirus (CMV) reactivations were observed. Six patients had grade 3-4 cytopenia. All 10 patients died (7 resulting from aGVHD progression, 2 from severe infection, and 1 from to leukemia relapse), at a median of 40 days (range, 4 to 88 days) after alemtuzumab treatment. Overall, our findings suggest that steroid-refractory aGVHD may be improved by treatment with alemtuzumab, but that this treatment does not overcome the dismal prognosis of patients with severe aGVHD, demonstrating the need for alternative therapies to treat this complication.

La Medicina Tradicional Preisphánica, Vertebrados Terrestres y Productos Medicinales de tres Mercados del Valle de México / Traditional Prehispanic Medicine, Terrestrial Vertebrates and Medicinal Products from three markets in the Valley of Mexico

En México, la utilización de los animales y sus derivados como productos terapéuticos para curar afecciones del cuerpo y del alma, ha sido una práctica cotidiana desde tiempos prehispánicos. Dicha práctica, en cierta medida se ha conservado en la actualidad. Sin embargo, son pocos los estudios en nuestro país dedicados a explorar este tema. La presente investigación tiene como objetivo identificar a los vertebrados (anfibios, reptiles, aves y mamíferos) que se expenden en diversos comercios especializados, analizando las características de dichos animales que son tomadas en cuenta en las prácticas medicinales. Mediante entrevistas informales en los mercados de Sonora y Xochimilco, Distrito Federal y Chalco, Estado de México, se registraron 17 vertebrados cuyos productos se presentan de diversas formas. Asimismo, se hace una comparación de dichas prácticas con las que se han documentado para el México antiguo en el Códice De la Cruz-Badiano, el cual permite ver que se ha conservado el uso de una buena parte de animales utilizados en el pasado, aunque han variado tanto en el tratamiento como en la enfermedad que curan. Se discuten los posibles factores involucrados en estos cambios.