The records of 239 immunosuppressed patients receiving amphotericin B for suspected or proven aspergillosis were reviewed to determine rates of nephrotoxicity, dialysis, and fatality. The mean and median durations of treatment were 20.4 and 15.0 days, respectively. The creatinine level doubled in 53% of patients and exceeded 2.5 mg/dL in 29%; 14.5% underwent dialysis; and 60% died. A multivariate Cox proportional hazards analysis showed that patients whose creatinine level exceeded 2.5 mg/dL (hazard ratio [HR], 42.02; P<.001), allogeneic bone marrow transplantation (BMT) patients (HR, 6.34; P<. 001), and autologous BMT patients (HR, 5.06; P=.024) were at greatest risk for requiring hemodialysis. Use of hemodialysis (HR, 3. 089; P<.001), duration of amphotericin B use (HR, 1.03 per day; P=. 015), and use of nephrotoxic agents (HR, 1.96; P=.017) were associated with greater risk of death, whereas patients undergoing solid organ transplantation were at lowest risk (HR, 0.46; P=.002). These data indicate that elevated creatinine levels during amphotericin B treatment are associated with a substantial risk for hemodialysis and a higher mortality rate, but the risks vary in different patient groups.
Metabolic reprogramming has been described in rapidly growing tumors, which are thought to mostly contain fast‐cycling cells (FCCs) that have impaired mitochondrial function and rely on aerobic glycolysis. Here, we characterize the metabolic landscape of glioblastoma (GBM) and explore metabolic specificities as targetable vulnerabilities. Our studies highlight the metabolic heterogeneity in GBM, in which FCCs harness aerobic glycolysis, and slow‐cycling cells (SCCs) preferentially utilize mitochondrial oxidative phosphorylation for their functions. SCCs display enhanced invasion and chemoresistance, suggesting their important role in tumor recurrence. SCCs also demonstrate increased lipid contents that are specifically metabolized under glucose‐deprived conditions. Fatty acid transport in SCCs is targetable by pharmacological inhibition or genomic deletion of FABP7, both of which sensitize SCCs to metabolic stress. Furthermore, FABP7 inhibition, whether alone or in combination with glycolysis inhibition, leads to overall increased survival. Our studies reveal the existence of GBM cell subpopulations with distinct metabolic requirements and suggest that FABP7 is central to lipid metabolism in SCCs and that targeting FABP7‐related metabolic pathways is a viable therapeutic strategy.
Age at onset of clinical abnormalities, duration of clinical abnormalities prior to surgery, and preoperative neurologic status are risk factors for success of surgical management of AAS in dogs.
The loggerhead sea turtle (Caretta caretta) nests on sand beaches, has both oceanic and neritic life stages, and migrates internationally. We analyzed an 18-year time series of Index Nesting Beach Survey (Index) nest-count data to describe spatial and temporal trends in loggerhead nesting on Florida (USA) beaches. The Index data were highly resolved: 368 fixed zones (mean length 0.88 km) were surveyed daily during annual 109-day survey seasons. Spatial and seasonal coverage averaged 69% of estimated total nesting by loggerheads in the state. We carried out trend analyses on both annual survey-region nest-count totals (N = 18) and annual zone-level nest densities (N = 18 x 368 = 6624). In both analyses, negative binomial regression models were used to fit restricted cubic spline curves to aggregated nest counts. Between 1989 and 2006, loggerhead nest counts on Florida Index beaches increased and then declined, with a net decrease over the 18-year period. This pattern was evident in both a trend model of annual survey-region nest-count totals and a mixed-effect, "single-region" trend model of annual zone-level nest densities that took into account both spatial and temporal correlation between counts. We also saw this pattern in a zone-level model that allowed trend line shapes to vary between six coastal subregions. Annual mean zone-level nest density declined significantly (-28%; 95% CI: -34% to -21%) between 1989 and 2006 and declined steeply (-43%; 95% CI: -48% to -39%) during 1998-2006. Rates of change in annual mean nest density varied more between coastal subregions during the "mostly increasing" period prior to 1998 than during the "steeply declining" period after 1998. The excellent fits (observed vs. expected count R2 > 0.91) of the mixed-effect zone-level models confirmed the presence of strong, positive, within-zone autocorrelation (R > 0.93) between annual counts, indicating a remarkable year-to-year consistency in the longshore spatial distribution of nests over the survey region. We argue that the decline in annual loggerhead nest counts in peninsular Florida can best be explained by a decline in the number of adult female loggerheads in the population. Causes of this decline are explored.
Pretreatment CT measurements of tumor volume permits stratification of patients with supraglottic SCC treated with RT alone (which allows preservation of laryngeal function) into groups in which local control is more likely and less likely. Pre-epiglottic space spread is not a contraindication to using RT as the primary treatment for supraglottic SCC.
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