To understand neutrophil impairment in the progression from MGUS through active MM, we investigated the function of mature, high-density neutrophils (HDNs), isolated from peripheral blood. In 7 MM, 3 MGUS and 3 healthy subjects by gene expression profile, we identified a total of 551 upregulated and 343 downregulated genes in MM-HDN, involved in chemokine signaling pathway and FC-gamma receptor mediated phagocytosis conveying in the activation of STAT proteins. In a series of 60 newly diagnosed MM and 30 MGUS patients, by flow-cytometry we found that HDN from MM, and to a lesser extend MGUS, had an up-regulation of the inducible FcγRI (also known as CD64) and a down-regulation of the constitutive FcγRIIIa (also known as CD16) together with a reduced phagocytic activity and oxidative burst, associated to increased immune-suppression that could be reverted by arginase inhibitors in co-culture with lymphocytes. In 43 consecutive newly-diagnosed MM patients, who received first-line treatment based on bortezomib, thalidomide and dexamethasone, high CD64 could identify at diagnosis patients with inferior median overall survival (39.5 versus 86.7 months, p = 0.04). Thus, HDNs are significantly different among healthy, MGUS and MM subjects. In both MGUS and MM neutrophils may play a role in supporting both the increased susceptibility to infection and the immunological dysfunction that leads to tumor progression.

SummaryTo date, no prospective study on Plerixafor 'on-demand' in combination with chemotherapy and granulocyte colony-stimulating factor (G-CSF) has been reported. We present an interim analysis of the first prospective study in which Plerixafor was administered on-demand in patients affected by multiple myeloma and lymphoma who received high dose cyclophosphamide or DHAP (dexamethasone, cytarabine, cisplatin) plus G-CSF to mobilize peripheral blood stem cells (PBSC). One hundred and two patients were evaluable for response. A cohort of 240 patients receiving the same mobilizing chemotherapy was retrospectively studied. Failure to mobilize CD34 + cells in peripheral blood was reduced by 'on-demand' strategy compared to conventional mobilization; from 13Á0 to 3Á0% (P = 0Á004). Failure to harvest CD34 + cells 2 9 10 6 /kg decreased from 20Á9 to 4Á0% (P = 0Á0001). The on-demand Plerixafor strategy also resulted in a lower rate of mobilization failure (P = 0Á03) and harvest failure (P = 0Á0008) when compared to a 'bias-adjusted set of controls'. Evaluation of economic costs of the two strategies showed that the overall cost of the two treatments were comparable when salvage mobilizations were taken into account. When in combination with cyclophosphamide or DHAP plus G-CSF, the 'on-demand' use of Plerixafor showed, in comparison to conventionally treated patients, a significant improvement in mobilization of PBSC with no increase in overall cost.

In critically ill patients, the analysis of nursing diagnoses, outcomes and interventions confirmed an intense activity in response to a broad spectrum of patient needs. The number of nursing diagnoses allowed to predict patient outcomes.

Introduction. Noninvasive blood pressure (NIBP) monitoring methods are widely used in critically ill patients despite poor evidence of their accuracy. The erroneous interpretations of blood pressure (BP) may lead to clinical errors. Objectives. To test the accuracy and reliability of aneroid (ABP) and oscillometric (OBP) devices compared to the invasive BP (IBP) monitoring in an ICU population. Materials and Methods. Fifty adult patients (200 comparisons) were included in a randomized crossover trial. BP was recorded simultaneously by IBP and either by ABP or by OBP, taking IBP as gold standard. Results. Compared with ABP, IBP systolic values were significantly higher (mean difference ± standard deviation 9.74 ± 13.8; P < 0.0001). Both diastolic (−5.13 ± 7.1; P < 0.0001) and mean (−2.14 ± 7.1; P=0.0033) IBP were instead lower. Compared with OBP, systolic (10.80 ± 14.9; P < 0.0001) and mean (5.36 ± 7.1; P < 0.0001) IBP were higher, while diastolic IBP (−3.62 ± 6.0; P < 0.0001) was lower. Bland-Altman plots showed wide limits of agreement in both NIBP-IBP comparisons. Conclusions. BP measurements with different devices produced significantly different results. Since in critically ill patients the importance of BP readings is often crucial, noninvasive techniques cannot be regarded as reliable alternatives to direct measurements.

The combined derangements in mitochondria network, function and dynamics can affect metabolism and ATP production, redox homeostasis and apoptosis triggering, contributing to cancer development in many different complex ways. In hematological malignancies, there is a strong relationship between cellular metabolism, mitochondrial bioenergetics, interconnections with supportive microenvironment and drug resistance. Lymphoma and chronic lymphocytic leukemia cells, e.g., adapt to intrinsic oxidative stress by increasing mitochondrial biogenesis. In other hematological disorders such as myeloma, on the contrary, bioenergetics changes, associated to increased mitochondrial fitness, derive from the adaptive response to drug-induced stress. In the bone marrow niche, a reverse Warburg effect has been recently described, consisting in metabolic changes occurring in stromal cells in the attempt to metabolically support adjacent cancer cells. Moreover, a physiological dynamic, based on mitochondria transfer, between tumor cells and their supporting stromal microenvironment has been described to sustain oxidative stress associated to proteostasis maintenance in multiple myeloma and leukemia. Increased mitochondrial biogenesis of tumor cells associated to acquisition of new mitochondria transferred by mesenchymal stromal cells results in augmented ATP production through increased oxidative phosphorylation (OX-PHOS), higher drug resistance, and resurgence after treatment. Accordingly, targeting mitochondrial biogenesis, electron transfer, mitochondrial DNA replication, or mitochondrial fatty acid transport increases therapy efficacy. In this review, we summarize selected examples of the mitochondrial derangements in hematological malignancies, which provide metabolic adaptation and apoptosis resistance, also supported by the crosstalk with tumor microenvironment. This field promises a rational design to improve target-therapy including the metabolic phenotype.