Self-limited versus delayed resolution of acute inflammation: temporal regulation of pro-resolving mediators and microRNA.

Mechanisms underlying delays in resolution programs of inflammation are of interest for many diseases. Here, we addressed delayed resolution of inflammation and identified specific microRNA (miR)-metabolipidomic signatures. Delayed resolution initiated by high-dose challenges decreased miR-219-5p expression along with increased leukotriene B(4) (5-fold) and decreased (~3-fold) specialized pro-resolving mediators, e.g. protectin D1. Resolvin (Rv)E1 and RvD1 (1 nM) reduced miR-219-5p in human macrophages, not shared by RvD2 or PD1. Since mature miR-219-5p is produced from pre-miRs miR-219-1 and miR-219-2, we co-expressed in human macrophages a 5-lipoxygenase (LOX) 3'UTR-luciferase reporter vector together with either miR-219-1 or miR-219-2. Only miR-219-2 reduced luciferase activity. Apoptotic neutrophils administered into inflamed exudates in vivo increased miR-219-2-3p expression and PD1/NPD1 levels as well as decreased leukotriene B(4). These results demonstrate that delayed resolution undermines endogenous resolution programs, altering miR-219-2 expression, increasing pro-inflammatory mediators and compromising SPM production that contribute to failed catabasis and homeostasis.

ZYGOMYCOSIS: current approaches to management of patients with haematological malignancies.

Zygomycosis is an invasive infection that can occur particularly in patients with haematological malignancy. The causative fungi are members of the order Mucorales, and individual species within this group require a high level of laboratory skill to be identified. Zygomycosis can present as rhinocerebral, pulmonary, or disseminated disease, with a rapid clinical course. The optimal management of these cases requires early diagnosis, aggressive antifungal therapy and, when possible, surgical debridement. Founded on clinical experience, but without the benefit of comparative studies, liposomal amphotericin B has become the therapeutic agent of choice. Posaconazole is an orally administered triazole with a demonstrated in vitro and in vivo activity against most Zygomycetes that is comparable to that of amphotericin B. Studies on salvage therapy with posaconazole have yielded promising results, and successful case reports are also available. As an adjuvant approach, iron chelation with deferasirox has shown promising results, although clinical experience is still limited.

Infusion of a high number of CD34+ cells provides a rapid hematopoietic recovery and cost savings in autologous peripheral blood stem cell transplantation.

BACKGROUND: The objectives of this study were to evaluate the effect of the number of infused CD34+ cells on hematopoietic recovery and on the cost in autologous peripheral blood stem cell transplantation (PBSCT). METHODS: Sixty-nine patients who received autologous PBSCT (ABSCT) were divided into three groups defined by the number of infused CD34+ cells. The number of days until 0.5 x 10(9)/l neutrophils and 50 x 10(9)/l platelets, the number of transfused blood products, the febrile days, the duration of parenteral antibiotics and the cost of additional supportive care (transfusions of blood products and parenteral antibiotics) were analyzed. RESULTS: Twenty-three patients received <2.5 x 10(6)/kg of CD34+ cells (group A), 25 patients received > or = 2.5 to 5 x 10(6)/kg of CD34+ cells (group B) and 21 patients received > or = 5 x 10(6)/kg of CD34+ cells (group C). Patients in group C had rapid neutrophil (p < 0.01) and platelet (p < 0.05) recovery and required less platelet transfusions (p < 0.05) than patients in other groups. Transfusions of red blood cell concentrates, the duration of febrile days or parenteral antibiotics were not statistically different between the two groups. The patients in group C required significantly lower costs for platelet concentrates and additional supportive care (p < 0.05). CONCLUSION: Infusion of > or = 5 x 10(6)/kg of CD34+ cells in ABSCT shortens hematopoietic recovery and reduces costs for additional supportive care.