Prognosis factors and outcome of community-acquired pneumonia needing mechanical ventilation

PURPOSE: To evaluate the variables associated with mortality of patients with community-acquired pneumonia who require mechanical ventilation and to determine the attributable morbidity and intensive care unit (ICU) mortality of community-acquired pneumonia. MATERIAL AND METHODS: Retrospective cohort study carried out in 361 ICUs from 20 countries including 124 patients who required mechanical ventilation on the first day of admission to the hospital due to acute respiratory failure secondary to severe community-acquired pneumonia. To assess the factors associated with outcome, a forward stepwise logistic regression analysis was performed, and to determine the attributable mortality of community-acquired pneumonia, a matched study design was used. RESULTS: We found 3 independent variables significantly associated with death in patients with community-acquired pneumonia requiring mechanical ventilation: simplified acute physiological score greater than 45 (odds ratio, 5.5 [95% confidence interval, 1.7-12.3]), shock (odds ratio, 5.7 [95% confidence interval, 1.7-10.1]), and acute renal failure (odds ratio, 3.0 [95% confidence interval, 1.1-4.0]). There was no statistically significant difference in ICU mortality among patients with or without community-acquired pneumonia (32% vs 35%; P=.59). CONCLUSIONS: Community-acquired pneumonia needing mechanical ventilation is not a disease associated with higher mortality. The main determinants of patient outcome were initial severity of illness and the development of shock and/or acute renal failure.     

Nongenomic estrogen action regulates tyrosine phosphatase activity and tuberin stability

Estrogen action and tuberin function has been suggested to play a crucial role in the proliferation of lung smooth muscle-like cells and/or myofibroblasts in pulmonary lymphangioleiomyomatosis (LAM). Tuberin is a tumor suppressor phosphoprotein, which also regulates fluid phase endocytosis. Its activity, turnover and complex association with hamartin depends on its phosphorylation status. We have recently reported that nongenomic estrogen action regulates the phosphorylation status of several cytoplasmic proteins. Herein, we demonstrate that estrogen increases tyrosine phosphatase activity, which can be abrogated by antiestrogen ICI 182780 and tyrosine phosphatase inhibitor bpV(phen), but not by the protein synthesis inhibitor cyclohexamide. Furthermore, we show that estrogen transiently enhances the turnover of tuberin, which follows an inverse pattern to that observed for tyrosine phosphatase and endocytosis activity. We showed that tuberin phosphorylation protects it from degradation and induces its accumulation in female human lung fibroblasts and myofibroblasts. Our results suggest that nongenomic estrogen action induces tyrosine phosphatase activity that regulates stability of tyrosine phosphorylated proteins, including tuberin, which may play a crucial role in cellular specific functions such as endocytosis.     

Comparison of Caspofungin MICs by Means of EUCAST Method EDef 7.1 Using Two Different Concentrations of Glucose

According to the product insert for Cancidas (caspofungin acetate), the drug must not be diluted in solutions containing glucose as this decreases caspofungin stability. The aim of this study was to compare caspofungin MICs for a collection of yeasts by means of EUCAST method EDef7.1 but using two different concentrations of glucose: 2% versus 0.2%. MICs were identical or within one 2-fold dilution for 93 out of 95 strains (97.9%), showing that glucose does not interfere with susceptibility.In a previous work, a comparison of the major susceptibility testing methods for echinocandins was performed using a well-characterized panel of Candida strains (1). EUCAST method EDef 7.1 performed as one of the best methods for discriminating wild-type strains from isolates with mutations in FKS hot spot regions. However, for caspofungin the MICs obtained by EUCAST method EDef 7.1 were in general higher than those obtained using the CLSI M27A3 methodology. In addition, the number of very major errors (number of FSK hot spot mutants classified as susceptible according the wild-type upper limit values) was 50% for EUCAST method EDef 7.1 (1), while 7% of very major errors were obtained by means of CLSI M27A3 at 24 h (1, 2). Finally, this previous work also found that caspofungin MICs obtained by means of EUCAST method EDef 7.1 and CLSI M27A3 were, in general, higher than those obtained by Pfaller et al. in a previous work using CLSI M27A3 methodology (4), indicating a possible variability associated with caspofungin antifungal susceptibility testing (1). Thus, it was of interest to explore which variables influence the reproducibility of the susceptibility tests for caspofungin. Although it has been proven that both the EUCAST EDef 7.1 and CLSI M27 A3 (2, 5) methodologies generate similar results for amphotericin B and azole drugs (3, 6), this does not appear to be the case for caspofungin. The main differences between EUCAST method EDef 7.1 and CLSI M27A3 include different inocula (10⁵ versus 10³ CFU/ml, respectively) and glucose concentrations (2% versus 0.2%, respectively) (3, 6).The product insert for Cancidas states that the compound must not be diluted in solutions containing glucose because it decreases drug stability. As stated previously, the glucose concentration in the growth medium recommended for method EDef 7.1 in RPMI 1640 is 10 times higher than that recommended by the CLSI (5). As this concentration could have influenced the MIC values obtained by means of EUCAST method EDef 7.1 (5), the Antifungal Susceptibility Testing Subcommittee of EUCAST decided to set up a comparison test to examine whether the increased glucose concentration affects the MIC results. The test compared caspofungin MICs for a collection of well-characterized yeast isolates by means of EUCAST method EDef 7.1 (5) but using growth medium with two different concentrations of glucose: 2% versus 0.2%.     

Acute and Chronic Glucose Control in Critically Ill Patients With Diabetes: The Impact of Prior Insulin Treatment

Background:Emerging data highlight the interactions of preadmission glycemia, reflected by admission HbA1c levels, glycemic control during critical illness, and mortality. The association of preadmission insulin treatment with outcomes is unknown.Methods:This observational cohort study includes 5245 patients admitted to the medical-surgical intensive care unit of a university-affiliated teaching hospital. Three groups were analyzed: patients with diabetes with prior insulin treatment (DM-INS, n = 538); patients with diabetes with no prior insulin treatment (DM-No-INS, n = 986); no history of diabetes (NO-DM, n = 3721). Groups were stratified by HbA1c level: <6.5%; 6.5%-7.9% and >8.0%.Results:Among the three strata of HbA1c, mean blood glucose (BG), coefficient of variation (CV), and hypoglycemia increased with increasing HbA1c, and were higher for DM-INS than for DM-No-INS. Among patients with HbA1c < 6.5%, mean BG ≥ 180 mg/dL and CV > 30% were associated with lower severity-adjusted mortality in DM-INS compared to patients with mean BG 80-140 mg/dL and CV < 15%, (P = .0058 and < .0001, respectively), but higher severity-adjusted mortality among DM-No-INS (P = .0001 and < .0001, respectively) and NON-DM (P < .0001 and < .0001, respectively). Among patients with HbA1c ≥ 8.0%, mean BG ≥ 180 mg/dL was associated with lower severity-adjusted mortality for both DM-INS and DM-No-INS than was mean BG 80-140 mg/dL (p < 0.0001 for both comparisons).Conclusions:Significant differences in mortality were found among patients with diabetes based on insulin treatment and HbA1c at home and post-admission glycemic control. Prospective studies need to confirm an individualized approach to glycemic control in the critically ill.     

How has the COVID-19 pandemic influenced prostate cancer?—a tertiary single-centre analysis of oncological results,diagnosis and treatment times

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has affected care for diseases like cancer. The aim was to evaluate the impact of COVID-19 on waiting times for diagnosis and treatment of prostate cancer (PC), as well as the possible effect on the treatment results in PC patients undergoing radical prostatectomy.MethodsWe compared the results of 497 patients who underwent biopsy prior to the COVID-19 pandemic (1 January–31 December 2019) with those of 290 patients biopsied during the COVID-19 pandemic (1 January–31 December 2020). Demographic data, tumour characteristics, type of treatment and diagnosis times were comparable. Prostate specific antigen (PSA) levels were recorded at consultation prior to biopsy and after treatment. Mann-Whitney and chi-square tests were used to compare continuous variables and percentages, respectively.ResultsIn 2020, there were fewer urology consultations (35,160 vs. 40,225 in 2019). The median PSA in 2020 was significantly higher (14.3 vs. 9.9 ng/dL in 2019). In 2019, 53.1% (N=264) of the biopsies were positive for cancer vs. 47.2% (N=137) in 2020 (P=0.104). In 2020, more patients presented with metastatic disease (7.3% vs. 1.9%, P=0.009). Also, in 2020 there was a longer waiting time for prostate biopsy (42.1 vs. 35.3 days in 2019, P=0.019). A total of 132 patients underwent laparoscopic radical prostatectomy (LARP). The median time until surgery was similar in both years (71.9 vs. 58.29 days). During 2020, a higher percentage of patients had ISUP grade 4 in the surgical specimen (34.3% vs. 17.5%, P=0.07). Furthermore, a higher percentage of aggressive (pT3) tumours were diagnosed (37.2% vs. 27.2%, P=0.08), and the percentage of patients with involvement of surgical margins was also higher (48.6% vs. 29.3%, P=0.027). There were no differences between the groups in terms of biochemical recurrence or persistent PSA at one year (P=0.711).ConclusionsDelayed biopsy during the COVID-19 period did not appear to adversely impact biopsy results. Patients biopsied in 2020 had higher PSA, possibly due to proper triaging. A higher rate of adverse pathology outcomes was observed in patients undergoing radical prostatectomy during the pandemic, probably due to understaging of the biopsy. This study serves to raise awareness of the risk of deterioration of care of PC patients due to possible underdiagnosis.     

Determination of TTT Diagrams of Ni-Al Binary Using Neural Networks

The heat treatment of a metal is a set of heating and cooling cycles that a metal undergoes to change its microstructure and, therefore, its properties. Temperature–time–transformation (TTT) diagrams are an essential tool for interpreting the resulting microstructures after heat treatments. The present work describes a novel proposal to predict TTT diagrams of the γ′ phase for the Ni-Al alloy using artificial neural networks (ANNs). The proposed methodology is composed of five stages: (1) database creation, (2) experimental design, (3) ANNs training, (4) ANNs validation, and (5) proposed models analysis. Two approaches were addressed, the first to predict only the nose point of the TTT diagrams and the second to predict the complete curve. Finally, the best models for each approach were merged to compose a more accurate hybrid model. The results show that the multilayer perceptron architecture is the most efficient and accurate compared to the simulated TTT diagrams. The prediction of the nose point and the complete curve showed an accuracy of 98.07% and 86.41%, respectively. The proposed final hybrid model achieves an accuracy of 96.59%.     

Eine neue Methode für kineplastische Operationen

Ohne Zusammenfassung Mit 9 Abbildungen im Text.