BackgroundThe elderly patients affected by candidemia are growing in proportion to inpatients, but available data are limited. We aimed to determine the epidemiology, antifungal management and clinical risk factors of death in the elderly population with candidemia in China.MethodsThis retrospective study included 63 elderly (≥65 years) and 84 younger patients (16–60 years) at 4 tertiary hospitals. Multivariable logistic regression model was used to identify independent risk factors of death in elderly patients.ResultsThe distribution of Candida species did not differ between elderly and younger patients (p >0.05). Resistance to fluconazole and voriconazole for non-Candida albicans species in elderly patients was approximately double that in younger patients. Host-related risk factors (e.g., underlying solid tumour, diabetes mellitus and chronic renal failure) and hospital-related factors (e.g., prior stay in an intensive care unit, mechanical ventilation, central vascular and urethral catheters placement) were identified more common in elderly patients. Elderly patients less often received triazoles and were less likely to receive antifungal therapies mostly because elderly or their guardians quit antifungal therapies. APACHE II scores and 30-day mortality were higher for elderly than younger patients (31.7% vs. 16.7%, p =0.032). For elderly patients, antifungal therapy administered before microbiological documentation was the only protective factor for death, whereas absence of antifungal therapies, receipt of mechanical ventilation and APACHE II score ≥20 were independent predictors of death.ConclusionsElderly patients with candidemia had poor prognoses characterized by certain host and hospital-related risk factors and special pathogen resistance features. More awareness of the burden of this disease is required, and the absence of antifungal therapies should be avoided to improve the prognoses of elderly patients with this severe infection.

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Cardiac fibrosis is a key factor to determine the prognosis in patient with myocardial infarction (MI). The aim of this study is to investigate whether the transcriptional factor paired-related homeobox 2 (Prrx2) regulates Wnt5a gene expression and the role in myocardial fibrosis following MI. The MI surgery was performed by ligation of left anterior descending coronary artery. Cardiac remodelling was assessed by measuring interstitial fibrosis performed with Masson staining. Cell differentiation was examined by analysis the expression of alpha-smooth muscle actin (α-SMA). Both Prrx2 and Wnt5a gene expressions were up-regulated in mice following MI, accompanied with increased mRNA and protein levels of α-SMA, collagen I and collagen III, compared to mice with sham surgery. Adenovirus-mediated gene knock down of Prrx2 increased survival rate, alleviated cardiac fibrosis, decreased infarction sizes and improved cardiac functions in mice with MI. Importantly, inhibition of Prrx2 suppressed ischaemia-induced Wnt5a gene expression and Wnt5a signalling. In cultured cardiac fibroblasts, TGF-β increased gene expressions of Prrx2 and Wnt5a, and induced cell differentiations, which were abolished by gene silence of either Prrx2 or Wnt5a. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Bai W-W, Tang Z-Y, Shan T-C, et al. Up-regulation of paired-related homeobox 2 promotes cardiac fibrosis in mice following myocardial infarction by targeting of Wnt5a.

Objective The burden of candidemia is shifting from intensive care units (ICU) to non-ICU settings. This study aimed to define the differences in epidemiology and predictors of death between ICU-acquired candidemia (ICUAC) and non-ICUAC. Methods We conducted a retrospective study of 80 patients with ICUAC and 147 patients with non-IUCAC at five hospitals. Results The distribution of Candida species and resistance to antifungal agents did not differ between the ICUAC and non-ICUAC groups. ICUAC patients received more echinocandins and less triazoles, as well as more adequate antifungal therapy than non-ICUAC patients (all p<0.05). ICUAC patients had a significantly higher average acute physiology and chronic health evaluation (APACHE) II score (21.0±7.9 vs. 17.8±8.6; p<0.01), Sequential Organ Failure Assessment score (9.2±5.5 vs. 7.4±3.9; p<0.05) and day-90 mortality rate (52.5% vs. 36.7%; p<0.05) when compared to non-ICUAC patients. Using a multivariate logistic analysis, adequate antifungal therapy was found to be the only protective factor for death in both groups. Respiratory failure supported with invasive mechanical ventilation, renal failure supported with replacement therapy and an APACHE II score ! 20 were independent predictors of death in ICUAC patients, while age ! 60 years, concurrent bacteremia and APACHE II score ! 20 were independent predictors of death in non-ICUAC patients. ConclusionThe Candida species and antifungal resistance profiles in patients with ICUAC were similar to non-ICUAC patients, but led to worse outcomes. The protective and risk factors for death may therefore be relevant for the clinical management of patients with candidemia in ICU and non-ICU settings.

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model except for the TaperGuard: while leak rate was on average approximately 65x higher than the novel device, fluid this result failed to reach statistical significance (p=0.3). While clear limitations exist due to the approximative nature of a bench-top setup, the novel device provided significantly better results in reducing leak rate in all but one of 8 comparisons, and non-significantly better results in one. While these results are promising, future studies are required for a more accurate and in-vivo comparison in order to evaluate the real benefit of this novel tool.Introduction: Increased prevalence of Extended-Spectrum Beta-Lactamase-producing enterobacteriaceae (ESBL-E) is becoming a clinical concern especially in UTI. The initial antibiotics selection needs to be taken into account for severity of UTI. Methods: This is a prospective cohort study in which patients with UTI were prospectively enrolled in a tertiary university-affiliated hospital in Japan from May 2012 to March 2013. UTI was defined as positive UTI symptoms, urine culture >=105 CPF/ml, and urine white blood cells >=10/HPF or apparent phagocytosis in Gram stain. UTI with ESBL-E were categorized into two groups: urosepsis vs. non-urosepsis. Clinical outcomes in the two groups were compared. Results: 338 consecutive cases of positive urine culture were registered. Chart review revealed 236 cases with UTI. Among 236 cases of UTI, 28.8% (68/236) met SIRS criteria ("urosepsis") and 71.2% (168/236) did not meet SIRS criteria ("non-urosepsis"). 16.2% (11/68) of urosepsis and 13.1% (22/168) of non-urosepsis had ESBL-E (p=0.53). Analysis among urosepsis cases, SAPS-II scores were higher in cases with ESBL-E (n=11 SAPS-II average 53.0) compared to the cases with non-ESBL-E (n=57, SAPS-II average 40.65, p=0.047). Among 22 cases of non-urosepsis with ESBL-E, causative pathogens were all E.coli. 9 cases were managed as inpatients and 13 cases as outpatients. About 50% cases of non-urosepsis with ESBL-E were treated with non-sensitive antibiotics. However all cases but 1 clinically improved successfully. Among 11 cases of urosepsis with ESBL-E, causative pathogens were as follows: 8 cases with E.coli, 2 with P.miralibis and 1 with K.pneumonia. 7 cases improved and 4 died. 5 out of 7 survived cases of urosepsis with ESBL-E were treated with carbapenem. Conclusions: Our study has demonstrated that the prognosis of non-urosepsis with ESBL-E is quite favorable and most of the cases do not necessarily need administration of carbapenems or inpatient management.