Measurement of multiple biomarkers in advanced stage heart failure patients treated with pulmonary artery catheter guided therapy

ABSTRACT: INTRODUCTION: This study was carried out to investigate the prognostic utility of biomarkers in advanced stage heart failure (HF) patients requiring ICU admission for pulmonary artery catheter (PAC) guided therapy. METHODS: Thirty patients admitted to an ICU for PAC guided HF therapy were enrolled; concentrations of soluble ST2 (sST2), highly sensitive troponin I, an experimental ultrasensitive troponin I, amino-terminal pro-B type natriuretic peptide, cystatin C, and myeloperoxidase were measured over the first 48 hours. Outcomes included response of filling pressures and hemodynamics to tailored therapy and 90-day event-free survival (death, left ventricular assist device implantation, transplant). RESULTS: Of the biomarkers evaluated, only sST2 concentrations were higher in those who failed to achieve goals for central venous pressure ((CVP), 225.3 versus 104.6 ng/mL; P = 0.003) and pulmonary capillary wedge pressure ((PCWP), 181.7 versus 88.2 ng/mL; P = 0.05). Only sST2 concentrations were associated with adverse events (186.7 versus 92.2 ng/mL; P = 0.01). In age-adjusted Cox proportional hazards analysis, an elevated sST2 during the first 48 hours following ICU admission independently predicted 90-day outcomes (Hazard Ratio = 5.53; P = 0.03) superior to the Simplified Acute Physiology Score for this application; in Kaplan-Meier analysis the risk associated with elevated sST2 concentrations was present early and sustained through the duration of follow-up (log rank P = 0.01). CONCLUSIONS: In patients undergoing HF therapy guided by invasive monitoring, sST2 concentrations were associated with impending failure to reduce filling pressures and predicted impending events. Elevated sST2 values early in the ICU course theoretically could assist therapeutic decision-making in advanced stage HF patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00595738.     

MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells

The MYC genes are the most frequently activated oncogenes in human tumors and are hence attractive therapeutic targets. MYCN amplification leads to poor clinical outcome in childhood neuroblastoma, yet strategies to modulate the function of MYCN do not exist. Here we show that 10058-F4, a characterized c-MYC/Max inhibitor, also targets the MYCN/Max interaction, leading to cell cycle arrest, apoptosis, and neuronal differentiation in MYCN-amplified neuroblastoma cells and to increased survival of MYCN transgenic mice. We also report the discovery that inhibition of MYC is accompanied by accumulation of intracellular lipid droplets in tumor cells as a direct consequence of mitochondrial dysfunction. This study expands on the current knowledge of how MYC proteins control the metabolic reprogramming of cancer cells, especially highlighting lipid metabolism and the respiratory chain as important pathways involved in neuroblastoma pathogenesis. Together our data support direct MYC inhibition as a promising strategy for the treatment of MYC-driven tumors.     

The clinicopathologic spectrum of segmental membranous glomerulopathy

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Ocena skuteczności Lactobacillus rhamnosus ATC A07FA w zapobieganiu martwiczego zapalenia jelit wcześniaków z bardzo małą urodzeniową masą ciała: badanie z randomizacją (wstępne wyniki)

BackgroundEvidence suggests that probiotics, as a group, are reducing the risk of necrotizing enterocolitis (NEC). The efficacy of each probiotic strain needs to be evaluated separately.ObjectiveTo evaluate the efficacy of administering Lactobacillus rhamnosus ATC A07FA (L. rhamnosus) for the prevention of necrotizing enterocolitis (NEC) ≥2 by the criteria of Bell in very low-birth-weight preterm infants.MethodPreterm infants children fulfillingthe inclusion criteria (gestational age <32 weeks and birth weight <1500 g and partial orfull enteral feeding) were enrolled in a randomized, double-blind, placebo-controlled trial. They received L. rhamnosus (commercially available as Lakcid) at a dose of 1.2 × 10¹⁰ CFU or a placebo orally, twice daily, for the duration of the hospital stay. The primary outcome measures were NEC ≥2 by the criteria of Beli, sepsis and death.ResultsThe study was stopped prematurely because of slow recruitment. Data from 55 preterm infants were included in the fina? analysis. In the experimental group, compared with the placebo group, the risk of developing NEC ≥2 by the criteria of Beli was reduced, however the difference was not statistically significant (1/30; 3.3% versus A/25; 16%, RR 0.2, 95% Cl 0.02 do 1.75). L. rhamnosus did not significantly affect the risk of developing sepsis or death. There was also no difference between the probiotic and placebo groups for any of the other secondary outcomes. No adverse events were reported.ConclusionThe administration of L. rhamnosus ATC A07FA compared with placebo had no effect on the incidence of NEC. Further studies with sufficient sample size are warranted.     

Stuck in time – a new Chaenothecopsis species with proliferating ascomata from Cunninghamia resin and its fossil ancestors in European amber

Resin protects wounded trees from microbial infection, but also provides a suitable substrate for the growth of highly specialized fungi. Chaenothecopsis proliferatus is described growing on resin of Cunninghamia lanceolata from Hunan Province, China. The new fungus is compared with extant species and two new fossil specimens from Eocene Baltic and Oligocene Bitterfeld ambers. The Oligocene fossil had produced proliferating ascomata identical to those of the newly described species and to other extant species of the same lineage. This morphology may represent an adaptation to growing near active resin flows: the proliferating ascomata can effectively rejuvenate if partially overrun by fresh, sticky exudate. Inward growth of fungal hyphae into resin has only been documented from Cenozoic amber fossils suggesting comparatively late occupation of resin as substrate by fungi. Still, resinicolous Chaenothecopsis species were already well adapted to their special ecological niche by the Eocene, and the morphology of these fungi has since remained remarkably constant.