Differential protein expression in endothelial cells exposed to serum from patients with acute graft-vs-host disease, depending on steroid response.

Graft-versus-host disease (GVHD) is a complication of allogeneic haematopoietic cell transplantation. Endothelial injury is crucial as pathophysiological substrate for GVHD. GVHD first-line treatment is high-dose corticosteroids, although some patients are steroid-refractory. Through the present study, we compared the endothelial proteomic profiles in response to serum from steroid-refractory acute GVHD (SR-aGVHD) and steroid-sensitive acute GVHD (SS-aGVHD) patients. Blood samples from SR-aGVHD (n = 4) and SS-aGVHD (n = 8) patients were collected at aGVHD diagnosis. Endothelial cell cultures were exposed (48 h) to patients' serum. Protein extraction and proteomic analysis were performed. Differences were statistically evaluated by multivariate analysis. Forty-four proteins contributed to separate all samples into the two study groups, among which 15 participated significantly (p < 0.05), 10 exhibiting a fold change >1.2. Differentially expressed proteins were mainly associated with oxidative phosphorylation (Cytochrome C oxidase subunit 6B1, CX6B1), inflammation and angiogenesis (Apolipoprotein D, APOD), cell survival (Rapamycin-insensitive companion of mTOR, RICTR), and oxidative stress (Riboflavin kinase, RIFK). This pilot study used a novel approach to distinguish the aGVHD response to steroid treatment. The proteins differentially expressed could constitute potential biomarkers for steroid-treatment response. These findings signify a step forward to identify the mechanisms of response to steroids, of high clinical relevance considering the SR-aGVHD elevated mortality.

Treatment of invasive fungal infections in high-risk haematological patients: what have we learnt in the past 10 years?

La infección fúngica invasora (IFI) por hongos filamentosos (HF) sigue constituyendo una complicación infecciosa muy grave en los pacientes con enfermedades onco-hematológicas. Las últi¬mas aportaciones en el campo del diagnóstico y la terapéutica, hoy sabemos que son limitadas. Algo parecido se puede decir de los ensayos clínicos, en especial por algunos cambios en las características del huésped. La aparición de técnicas diagnós¬ticas esperanzadoras y la relativa ampliación en el número de antifúngicos, dio lugar a una diversificación de las estrategias terapéuticas (profilaxis y tratamiento anticipado). Pero la falta de sensibilidad del AGA bajo algunas circunstancias y el poten¬cial retraso en el inicio del tratamiento por motivos logísticos en su realización, se ha traducido en una mayor mortalidad en determinados tipos de pacientes y en un aumento significativo de los días de tratamiento. Todas estas circunstancias han vuelto a colocar el abordaje empírico como una estrategia central en los pacientes de alto riesgo. El objetivo de este artículo es revisar la experiencia clínica en el tratamiento de las IFI en el paciente onco-hematológico publicada en el curso de la última década y hacer unas recomendaciones en base a ésta (AU)

Invasive fungal infection (IFI) caused by filamentous fungi remains a very severe infectious complication in patients with onco-haema¬tological diseases. Last advances in the diagnostic and therapeu¬tic fields, today we know that their contributions are limited. So¬mething similar can be said of clinical trials especially in relation to some changes in the characteristics of the host. The development of promising diagnostic techniques and the relative expansion in the number of antifungal agents has been associated with diversifica¬tion of therapeutic strategies (prophylaxis with extended-spectrum azoles and preemptive antifungal treatment). However, the low sen¬sitivity of AGA testing in some circumstances, and the potential de¬lay in starting treatment due to logistic reasons, has been reflected by a greater mortality in certain type of patients and a significant increase in the days of treatment. All these circumstances has once again focus attention to the empirical approach as a central strate¬gy in high-risk patients. The objective of this article is to review the clinical experience in the treatment of IFI in onco-haematological patients according to data published in the literature in the last de¬cade and to present a set of recommendations (AU)