The incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years as a result of a combination of factors. More patients with severe underlying disease or immunosuppression from anti-neoplastic or anti-rejection chemotherapy and at risk from fungal infection are now admitted to the ICU. Improvements in supportive medical and surgical care have led to many patients who would previously have died as a result of trauma or disease surviving to receive intensive care. Moreover, some therapeutic interventions used in the ICU, most notably broad-spectrum antibiotics and intravascular catheters, are also associated with increased risks of candidiasis. Systemic Candida infections are associated with a high morbidity and mortality, but remain difficult to diagnose and ICU staff need to be acutely aware of this often insidious pathogen. A number of studies have identified risk factors for systemic Candida infection which may be used to identify those at highest risk. Such patients may be potential candidates for early, presumptive therapy. Here we review the epidemiology, pathogenesis, morbidity and mortality of systemic Candida infections in the ICU setting, and examine predisposing risk factors. Antifungal treatment, including the use of amphotericin B, flucytosine and fluconazole, and the roles of early presumptive therapy and prophylaxis, is also reviewed.

A prospective randomized clinical trial assessed the efficacy and tolerance of micafungin compared with that of standard fluconazole treatment in patients undergoing hematopoietic stem cell transplantation (HSCT). Adult patients (n = 106) were randomly assigned to receive prophylaxis with either micafungin 150 mg (n = 52), or fluconazole 400 mg (n = 52). Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and the absence of proven or probable IFI through the end of the 4-week period following treatment. The overall efficacy of micafungin was comparable to that of fluconazole (94 vs. 88%; difference 6.0%; 95% confidence interval, -5.4 to +17.4%; P = 0.295). A total of 2 (4.0%) of 50 patients in the micafungin arm and 6 (12.0%) of 50 patients in the fluconazole arm received empirical antifungal therapy (P = 0.06). Micafungin treatment did not result in increasing adverse effects and had a safe profile as fluconazole in neutropenic patients. This randomized trial indicates that the efficacy and tolerance of micafungin 150 mg was comparable to that of fluconazole 400 mg, suggesting that micafungin at 150 mg daily represents a valuable new treatment option for antifungal prophylaxis in HSCT recipients.

responses. 1 In vivo, NO has been reported to have pro-LPS stimulated NO formation in a dose-dependent manner and induced half-maximal effects at 30 pmol/L. Maxi-tective effects during the inflammation and endotoxemal stimulation was achieved at 12 to 16 hours after the mia associated with hepatic injury. 2 In contrast, NO addition of 1 nmol/L of IL-1b, and was 50-to 60-fold above has also been reported to induce hepatic mitochondrial basal levels in rat hepatocytes. The combined effect of dysfunction both in perfused liver and isolated hepatothese cytokines with LPS or IFN-g on NO formation was cytes. 3 Interleukin (IL)1b, tumor necrosis factor a also examined. Neither LPS nor IFN-g affected the IL-(TNF-a), and endotoxins have all been shown to stimu1b-induced NO formation. TNF-a, however, stimulated late NO formation in hepatocytes and in Kupffer cells IL-1b-induced NO formation, while IL-6 inhibited it, al-cultured from chronically endotoxemic rats 4 or turpenthough independently these cytokines had no effect on tine-injected rats. 5 NO is synthesized from L-arginine NO formation. None of the cytokines tested stimulated by NO synthases (NOS). These enzymes can be classi-NO formation in cultured rat Kupffer cells. In hepatocytes, the NO formation induced by IL-1b was blocked by fied into at least two distinct groups. Constitutive NOS both the NO synthase (NOS) inhibitor N G -monomethyl-L-is present in endothelium 6 and in brain. 7 Inducible arginine (L-NMMA) and by IL-1 receptor antagonist (IL-NOS (iNOS) is present in negligible quantities under 1ra). Furthermore, IL-1b markedly increased NOS activ-physiological conditions, but is highly expressed in reity, and this increase in activity was accompanied by sponse to stimuli such as endotoxins and cytokines, the expression of inducible NOS (iNOS) messenger RNA in a variety of cells including vascular smooth muscle (mRNA). This study clearly demonstrated that IL-1b cells, 8,9 macrophages, 10 and liver cells. [11][12][13] Within the markedly stimulates NO formation in hepatocytes, in the liver, however, it is not clear whether the Kupffer cells or the hepatocytes are the primary producers of NO. In order to elucidate the mechanism by which cytokines induce NO formation within the liver, a sensitive Abbreviations: IL, interleukin; TNF-a, tumor necrosis factor a; NOS, nitric oxide synthase; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; chemiluminescence system was employed for the mea-

The ACA index has the ability to stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of elderly patients with DLBCL treated with R-CHOP. 2017;22:554-560 IMPLICATIONS FOR PRACTICE: Currently, little is known regarding how to identify elderly patients with diffuse large B-cell lymphoma who may tolerate a full dose of chemotherapy or to what extent cytotoxic drugs should be reduced in some specific conditions. The Society of Lymphoma Treatment in Japan developed a host-dependent prognostic model consisting of higher age (>75 years), hypoalbuminemia (<3.7 g/dL), and higher Charlson Comorbidity Index score (≥3) for such elderly patients. This model can stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of these patients and thus help clinicians in formulating personalized treatment strategies for this growing patient population.

StllTlillaryThe etiopathogenesis of focal and segmental glomerular sclerosis (FGS) remains unknown. Using a new animal model for FGS (FGS mouse), we demonstrate here that bone marrow transplantation from normal mice to FGS mice with a high grade of proteinuria (+ + +) ameliorates FGS, and that the transplantation of bone marrow cells or purified hemopoietic stem cells (HSCs) from FGS mice induces FGS in normal mice. These findings strongly suggest that FGS is a stem cell disorder; the abnormalities may be genetically programmed at the level of HSCs.