Effects of Early Changes in Organ Dysfunctions on the Outcomes of Critically Ill Patients in Need of Renal Replacement Therapy

INTRODUCTION: Acute kidney injury usually develops in critically ill patients in the context of multiple organ dysfunctions. OBJECTIVE: To evaluate the effect of changes in associated organ dysfunctions over the first three days of renal replacement therapy on the outcomes of patients with acute kidney injury. METHODS: Over a 19-month period, we evaluated 260 patients admitted to the intensive care units of three tertiary-care hospitals who required renal replacement therapy for > 48 h. Organ dysfunctions were evaluated by SOFA score (excluding renal points) on the first (D1) and third (D3) days of renal replacement therapy. Absolute (A-SOFA) and relative (D-SOFA) changes in SOFA scores were also calculated. RESULTS: Hospital mortality rate was 75%. Organ dysfunctions worsened (A-SOFA>0) in 53%, remained unchanged (A-SOFA=0) in 17% and improved (A-SOFA<0) in 30% of patients; and mortality was lower in the last group (80% vs. 84% vs. 61%, p=0.003). SOFA on D1 (p<0.001), SOFA on D3 (p<0.001), A-SOFA (p=0.019) and D-SOFA (p=0.016) were higher in non-survivors. However, neither A-SOFA nor D-SOFA discriminated survivors from non-survivors on an individual basis. Adjusting for other covariates (including SOFA on D1), A-SOFA and D-SOFA were associated with increased mortality, and patients in whom SOFA scores worsened or remained unchanged had poorer outcomes. CONCLUSIONS: In addition to baseline values, early changes in SOFA score after the start of renal replacement therapy were associated with hospital mortality. However, no prognostic score should be used as the only parameter to predict individual outcomes

Acceleration of methane production by carbon nanotubes

Book of Abstracts of CEB Annual Meeting 2017[Excerpt] Carbon nanotubes and other conductive materials have been found to influence the rates of several anaerobic reactions. A range of different conductive carbon materials (CM) were reported to enhance methane production by anaerobic microbial communities. In most studies, the improvement of the overall process is attributed to the ability of these compounds to promote direct interspecies electron transfer (DIET) between bacteria, degrading more complex substrates, and methanogens, producing methane. The occurrence of DIET in the majority of these systems is not, however, proved and the effect of such conductive compounds on the activity of individual members, inside complex microbial communities, was never investigated. Thus, we herein present the results obtained when incubating pure cultures of methanogens, without any other microbial partner, in the presence of increasing concentrations of carbon nanotubes (CNT). Methane production from acetate, by the acetoclastic methanogens Methanosaeta concilii and Methanosarcina mazei, and from hydrogen plus carbon dioxide, by the hydrogenotrophic methanogens Methanospirillum hungatei and Methanobacterium formicicum, was accelerated, up to 17 times, in the presence of CNT [1]. Physical/chemical properties of the growth media changed in the presence of CNT, with redox potential decreasing with increasing CNT concentrations, and thus favouring methanogenesis. These findings show that CNT influences the microbial activity of methanogens in pure cultures and most likely this effect is extended to methanogens in complex communities as well, occurring in anaerobic bioreactors and in the environment. [...]info:eu-repo/semantics/publishedVersio

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Religião e patriotismo: o anticomunismo católico nos Estados Unidos e no Brasil nos anos da Guerra Fria

O artigo analisa e compara o anticomunismo católico no Brasil e nos Estados Unidos no período da Guerra Fria. Depois de situar o campo de estudos constituído no Brasil sobre o tema, discute as relações entre americanismo e anticomunismo, procurando situar o catolicismo norte-americano neste meio. Utiliza-se de uma produção recente sobre cultura da Guerra Fria nos Estados Unidos. Levanta, finalmente, uma série de elementos de comparação sobre a forma que o anticomunismo católico assumiu nos dois países.<br>This article analyses and compares the Catholic anticommunism in the Brazil and in United States during the Cold War years. After showing the recent studies produced in Brazil about the fight against communism, it discusses the relationship between Americanism, anticommunism and Catholicism. This step is based on recent historical research about the Cold War culture in the United States. Finally, it makes comparisons between the forms that anticommunism assumed in each country

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p&lt;0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p&lt;0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status