Correction: "Acute kidney injury in critically ill patients with COVID-19: The AKICOV multicenter study in Catalonia".

[This corrects the article DOI: 10.1371/journal.pone.0284248.].

"Acute kidney injury in critically ill patients with COVID-19: The AKICOV multicenter study in Catalonia".

This study describes the incidence, evolution and prognosis of acute kidney injury (AKI) in critical COVID-19 during the first pandemic wave. We performed a prospective, observational, multicenter study of confirmed COVID-19 patients admitted to 19 intensive care units (ICUs) in Catalonia (Spain). Data regarding demographics, comorbidities, drug and medical treatment, physiological and laboratory results, AKI development, need for renal replacement therapy (RRT) and clinical outcomes were collected. Descriptive statistics and logistic regression analysis for AKI development and mortality were used. A total of 1,642 patients were enrolled (mean age 63 (15.95) years, 67.5% male). Mechanical ventilation (MV) was required for 80.8% and 64.4% of these patients, who were in prone position, while 67.7% received vasopressors. AKI at ICU admission was 28.4% and increased to 40.1% during ICU stay. A total of 172 (10.9%) patients required RRT, which represents 27.8% of the patients who developed AKI. AKI was more frequent in severe acute respiratory distress syndrome (ARDS) ARDS patients (68% vs 53.6%, p<0.001) and in MV patients (91.9% vs 77.7%, p<0.001), who required the prone position more frequently (74.8 vs 61%, p<0.001) and developed more infections. ICU and hospital mortality were increased in AKI patients (48.2% vs 17.7% and 51.1% vs 19%, p <0.001) respectively). AKI was an independent factor associated with mortality (IC 1.587-3.190). Mortality was higher in AKI patients who required RRT (55.8% vs 48.2%, p <0.04). Conclusions There is a high incidence of AKI in critically ill patients with COVID-19 disease and it is associated with higher mortality, increased organ failure, nosocomial infections and prolonged ICU stay.

HIV/AIDS infection in critical care: epidemiological profile and risk factors for mortality in a Colombian cohort.

INTRODUCTION: Outcomes of human immunodeficiency virus (HIV) infected patients admitted to intensive care units (ICU) have improved with antiretroviral therapy (ART). However, whether the outcomes have improved in low- and middle-income countries, paralleling those of high-income countries is unknown. The objective of this study was to describe a cohort of HIV-infected patients admitted to ICU in a middle-income country and identify the risk factors associated with mortality. METHODOLOGY: A cohort study of HIV-infected patients admitted to five ICUs in Medellín, Colombia, between 2009 and 2014 was done. The association of demographic, clinical and laboratory variables with mortality was analyzed using a Poisson regression model with random effects. RESULTS: During this time period, 472 admissions of 453 HIV-infected patients were included. Indications for ICU admission were: respiratory failure (57%), sepsis/septic shock (30%) and central nervous system (CNS) compromise (27%). Opportunistic infections (OI) explained 80% of ICU admissions. Mortality rate was 49%. Factors associated with mortality included hematological malignancies, CNS compromise, respiratory failure, and APACHE II score ≥ 20. CONCLUSIONS: Despite advances in HIV care in the ART era, half of HIV-infected patients admitted to the ICU died. This elevated mortality was associated to underlying disease severity (respiratory failure and APACHE II score ≥ 20), and host conditions (hematological malignancies, admission for CNS compromise). Despite the high prevalence of OIs in this cohort, mortality was not directly associated to OIs.

Environmental and health risk implications of unregulated emissions from advanced biofuels in a Euro 6 engine.

The use of conventional and advanced biofuels is part of the efforts to reduce greenhouse gases and harmful exhaust gaseous emissions. This study investigates the unregulated emissions in gas and particles from a Euro 6b diesel engine, operated with four unconventional and advanced biofuels (two hydrogenated terpenic biofuels, a polyoxymethylene dimethyl ether, and a glycerol-derived biofuel), blended with diesel fuel and pure hydrotreated vegetable oil as base biofuel. The engine was operated following WLTC starting from cold-engine conditions. Gas phase samples were collected at each phase of the driving cycle and particulate matter (PM) samples were collected from a dilution tunnel at the end of the driving cycle. A total of 16 PAH and 13 carbonyls were analyzed. In addition, the apoptotic index induced by gas and particle emissions was determined. In the gaseous phase, the total PAH and carbonyl emission factors were higher at the low-speed phase for all fuels. Gas-phase PAH emission factors exceeded particle-bound PAH. Carbonyl emission factors ranged from 0.12 ± 0.012 to 25.3 ± 4.2 mg/km, markedly exceeding gaseous PAH emissions, which ranged from 20.7 ± 1.5 to 51.7 ± 8.9 µg/km. Diesel fuel exhibited the highest carbonyl emissions and its blend with 20% of hydrogenated turpentine exhibited the highest PAH emissions at the end of the WLTC, both due to high emissions at the low-speed phase. Although particle-bound PAH comprise only a small fraction of total PAH emissions, both phases (gas and particles) contributed approximately equal to the toxicity associated with carcinogenic PAH. The apoptotic cells percentage increased in a dose-dependent manner and was significantly higher in cells exposed to gas phase-derived samples. The apoptotic index induced by particulate matter samples did not show a concentration-response effect for any of the fuels.

Comparison of gastric reactance with commonly used perfusion markers in a swine hypovolemic shock model.

BACKGROUND: The gut has been hypothesized to be a protagonist tissue in multiple organ dysfunction syndrome (MODS) for the past three decades. Gastric reactance (XL) is a potential perfusion marker derived from gastric impedance spectroscopy (GIS), which is an emerging tool through which living tissue can be continuously measured to determine its pathophysiological evolution. This study aimed to compare the performance of XL [positive predictive values (PPV), negative predictive values (NPV), and area under the curve (AUC)] against commonly used perfusion markers before and during hypovolemic shock in swine subjects. METHODS: Prospective, controlled animal trial with two groups, control group (CG) N = 5 and shock (MAP ≤ 48 mmHg) group (SG) N = 16. Comparison time points were defined as T-2 (2 h before shock), T-1 (1 h before shock), T0 (shock), T1 (1 h after shock), and T2 (2 h after shock). Shock severity was assessed through blood gases, systemic and hemodynamic variables, and via histological examination for assessing inflammation-edema and detachment in the gastric mucosa. Macroscopic assessment of the gastric mucosa was defined in five levels (0-normal mucosa, 1-stippling or epithelial hemorrhage, 2-pale mucosa, 3-violet mucosa, and 4-marmoreal mucosa). Receiver Operating Characteristic (ROC) curves of perfusion markers and XL were calculated to identify optimal cutoff values and their individual ability to predict hypovolemic shock. RESULTS: Comparison among the CG and the SG showed statistically significant differences in XL measurements at T-1, T0, T1, and T2, while lactate showed statistically significant differences until T1 and T2. Statistically significant differences were detected in mucosa class (p < 0.001) and in inflammation-edema in the gastric body and the fundus (p = 0.021 and p = 0.043). The performance of the minimum XL value per subject  per event (XL_Min) was better (0.81 ≤ AUC ≤ 0.96, 0.93 ≤ PPV ≤ 1.00, 0.45 ≤ NPV ≤ 0.83) than maximum lactate value (Lac_Max) per subject per event (0.29 ≤ AUC ≤ 0.82, 0.82 ≤ PPV ≤ 0.91, 0.24 ≤ NPV ≤ 0.82). Cutoff values for XL_Min show progressive increases at each time point, while cutoff values for Lac_Max increase only at T2. CONCLUSIONS: XL proved to be an indirect and consistent marker of inadequate gastric mucosal perfusion, which shows significant and detectable changes before commonly used markers of global perfusion under the hypovolemic shock conditions outlined in this work.

Biological toxicity risk assessment of two potential neutral carbon diesel fuel substitutes.

We investigated the biological response of soluble organic fraction (SOF) and water-soluble fraction (WSF) extracted from particulate matter (PM) emitted by an automotive diesel engine operating in a representative urban driving condition. The engine was fueled with ultra-low sulfur diesel (ULSD), and its binary blends by volume with 13% of butanol (Bu13), and with hydrotreated vegetable oil (HVO) at 13% (HVO13) and 20% (HVO20). Cytotoxicity, genotoxicity, oxidative DNA damage and ecotoxicity tests were carried out, and 16 polycyclic aromatic hydrocarbons (PAH) expressed as tbenzo(a)pyrene total toxicity equivalent (BaP-TEQ) were also analyzed. The Hepatocarcinoma epithelial cell line (HepG2) was exposed to SOF for 24 h and analyzed using comet assay, with the inclusion of formamidopyrimidine DNA glycosylase (FPG) and endonuclease III (Endo III) to recognize oxidized DNA bases. The WSF was evaluated through acute ecotoxicity tests with the aquatic microcrustacean Daphnia pulex (D. Pulex). Results showed that there was no cytotoxic activity for all tested SOF concentrations. Genotoxic responses by all the SOF samples were at same level, except for the HVO13 which was weaker in the absence of the enzymes. The addition of the FPG and Endo III enzymes resulted in a significant increase in the comet tail, indicating that the DNA damage from SOF for all tested fuel blends involves oxidative damage including a higher level of oxidized purines for ULSD and Bu13 in comparison with HVO blends, but the oxidized pyrimidines for HVO blends were slightly higher compared to Bu13. The WSF did not show acute ecotoxicity for any of the fuels. Unlike other samples, Bu13-derived particles significantly increase the BaP-TEQ. The contribution to the genotoxic activity and oxidative DNA from SOF was not correlated to BaP-TEQ, which means that the biological activity of PM might be affected also by other toxic compounds present in particulate phase.

Adverse events in critical care: Search and active detection through the Trigger Tool.

AIM: To investigate the incidence of disadvantageous events by using the Global Trigger Tool in an intensive care unit (ICU). METHODS: A retrospective descriptive study was performed in a 12-bed university ICU in the city of Medellin, Colombia. Clinical charts of hospitalized patients were reviewed, between January 1 and December 31, 2016, with the following inclusion criteria: subjects aged over 18 years, with at least 24 h of hospitalization and who had a complete medical history that could be accessed. Interventions: Trained reviewers conducted a retrospective examination of medical charts searching for clue events that elicit investigation, in order to detect an unfavorable event. Measurements: Information was processed through SPSS software version 21; for numerical variables, the mean was reported with standard deviation (SD). Percentages were calculated for qualitative variables. RESULTS: Two hundred and forty-four triggers occurred, with 82.4% of subjects having presented with at least one and an average of 3.37 (SD 3.47). A total of 178 adverse events (AEs) took place in 48 individuals, with an incidence of 52.1%. On average, four events per patient were recorded, and for each unfortunate event, 1.98 triggers were presented. The most frequent displeasing issues were: pressure ulcers (17.6%), followed by complications or reactions to medical devices (4.3%), and lacerations or skin defects (3.7%); the least frequent was delayed diagnosis or treatment (0.56%). Thirty-eight point four percent of mishap events caused temporary damage that required intervention, and 48.9% of AEs were preventable. Comparison between AEs and admission diagnoses found that hypertension and sepsis were the only diagnoses that had statistical significance (P = 0.042 and 0.022, respectively). CONCLUSION: Almost half of the unfavorable issues were classified as avoidable, which leaves a very wide field of work in terms of preventative activities.

The Mediterranean Overflow in the Gulf of Cadiz: A rugged journey.

The pathways and transformations of dense water overflows, which depend on small-scale interactions between flow dynamics and erosional-depositional processes, are a central piece in the ocean's large-scale circulation. A novel, high-resolution current and hydrographic data set highlights the intricate pathway travelled by the saline Mediterranean Overflow as it enters the Atlantic. Interaction with the topography constraints its spreading. Over the initial 200 km west of the Gibraltar gateway, distinct channels separate the initial gravity current into several plunging branches depth-sorted by density. Shallow branches follow the upper slope and eventually detach as buoyant plumes. Deeper branches occupy mid slope channels and coalesce upon reaching a diapiric ridge. A still deeper branch, guided by a lower channel wall marked by transverse furrows, experiences small-scale overflows which travel downslope to settle at mid-depths. The Mediterranean salt flux into the Atlantic has implications for the buoyancy balance in the North Atlantic. Observations on how this flux enters at different depth levels are key to accurately measuring and understanding the role of Mediterranean Outflow in future climate scenarios.

Thermoconformity strategy in the freshwater turtle Hydromedusa tectifera (Testudines, Chelidae) in its southern distribution area.

Ectotherm species are not capable of generating metabolic heat; therefore, they present different strategies for regulating their body temperatures, ranging from a precise degree of thermoregulation to a passive thermoconformity with ambient temperatures. In reptiles, aerial basking is the most common mechanism for gaining heat. However, among aquatic reptiles, such as freshwater turtles, aquatic basking is also frequent. Hydromedusa tectifera is a turtle of exclusively aquatic and nocturnal habits widely distributed in South America. We studied the relationship between body temperature (Tb) of H. tectifera and its habitat, and explored the effects of sex, life stage and body size and mass on Tb. Fieldwork was conducted in two streams of a mountain area of central Argentina. We recorded cloacal temperature, size and mass of 84 turtles. We also determined individuals' sex and life stage (adult/juvenile). Regarding ambient temperatures, we measured water temperature on the surface (Tsurf) and at depth of turtle capture (Tdepth) and air temperature. Mean Tb was 18.58°C (Min = 10.20°C; Max = 25.70°C). Tsurf and Tdepth were highly correlated. Multi-model analysis using Akaike criterion indicated that Tb was strongly associated with water temperature, whereas air temperature and body size and mass did not show a significant effect. There was also no effect of turtle sex or life stage on Tb. Our results indicate that H. tectifera is a thermoconformer and eurythermal species. A nocturnal pattern of activity and a fully aquatic lifestyle are suggested as determinant factors.

Implications of observed PBDE diffusion coefficients in low density polyethylene and silicone rubber.

A film-stacking technique was used to estimate diffusion coefficients of polybrominated diphenyl ethers (PBDEs) in low density polyethylene (LDPE) and silicone rubber. Substantially higher PBDE diffusion coefficients were observed for silicone rubber (AlteSil™) than for LDPE. A much steeper decrease in LDPE diffusion coefficients was found with increasing PBDE molecular weight than that for silicone rubber. From a passive sampling point-of-view, this means that for equivalent polymer-water partition coefficients for these two materials, the mass transfer resistance for these substances in the LDPE will be significantly higher than that for silicone rubber. Boundary layer control of the uptake process for silicone rubber can be expected for PBDEs. With a microplastic perspective, the low diffusion coefficients of PBDEs and in particular of decabromo diphenyl ether (BDE 209) in LDPE imply that the polymer diffusion coefficients for these plastic additives used as flame retardants need to be taken into account when considering the risk posed by microplastic particle ingestion by marine organisms.

Surgical approach for tumours of the third and fourth part of the duodenum. Distal pancreas-sparing duodenectomy.

The anatomic complexity of the duodenum makes surgical resection challenging. We describe our experience with distal pancreas-sparing duodenectomy (PSD) for tumours that arise in the third and fourth parts of the duodenum. Between July 2008 and January 2012 eight patients underwent surgical resection for tumours in the distal parts of the duodenum. Short and long-term outcomes of treatment are retrospectively analyzed. We used the Cattell and Braash surgical approach in six patients. Seven patients underwent a segmental resection of the distal duodenum with a duodenojejunal anastomosis and in one case we performed a wedge local excision with primary closure. There were 5 gastrointestinal stromal tumours (GIST), 1 primary duodenal adenocarcinoma, 1 metastasis of a lung adenocarcinoma and 1 patient with malignant duodenocolic fistula caused by advanced sigmoid colon carcinoma. Median operating time was 200 min and median intraoperatory blood loss 162 mL. Three patients showed postoperative complications and one of them died. There was no reoperation. Median hospital stay was 10 days (range, 7-28 days). The patient with primary adenocarcinoma died after 12 months due to hepatic metastases. All of five patients with GIST are alive without recurrence (mean follow up of 65.6 months), as well as the patient with metastatic duodenal infiltration (45 months after surgery). Segmental resection of the third and fourth portions of the duodenum is reliable and feasible. The Cattell and Braash manoeuvre provides a good exposure and makes this kind of resection easier.

Five years of designing wireless sensor networks in the Doñana Biological Reserve (Spain): an applications approach.

Wireless Sensor Networks (WSNs) are a technology that is becoming very popular for many applications, and environmental monitoring is one of its most important application areas. This technology solves the lack of flexibility of wired sensor installations and, at the same time, reduces the deployment costs. To demonstrate the advantages of WSN technology, for the last five years we have been deploying some prototypes in the Doñana Biological Reserve, which is an important protected area in Southern Spain. These prototypes not only evaluate the technology, but also solve some of the monitoring problems that have been raised by biologists working in Doñana. This paper presents a review of the work that has been developed during these five years. Here, we demonstrate the enormous potential of using machine learning in wireless sensor networks for environmental and animal monitoring because this approach increases the amount of useful information and reduces the effort that is required by biologists in an environmental monitoring task.

Assessment of candidemia-attributable mortality in critically ill patients using propensity score matching analysis.

INTRODUCTION: Candidemia in critically ill patients is usually a severe and life-threatening condition with a high crude mortality. Very few studies have focused on the impact of candidemia on ICU patient outcome and attributable mortality still remains controversial. This study was carried out to determine the attributable mortality of ICU-acquired candidemia in critically ill patients using propensity score matching analysis. METHODS: A prospective observational study was conducted of all consecutive non-neutropenic adult patients admitted for at least seven days to 36 ICUs in Spain, France, and Argentina between April 2006 and June 2007. The probability of developing candidemia was estimated using a multivariate logistic regression model. Each patient with ICU-acquired candidemia was matched with two control patients with the nearest available Mahalanobis metric matching within the calipers defined by the propensity score. Standardized differences tests (SDT) for each variable before and after matching were calculated. Attributable mortality was determined by a modified Poisson regression model adjusted by those variables that still presented certain misalignments defined as a SDT > 10%. RESULTS: Thirty-eight candidemias were diagnosed in 1,107 patients (34.3 episodes/1,000 ICU patients). Patients with and without candidemia had an ICU crude mortality of 52.6% versus 20.6% (P < 0.001) and a crude hospital mortality of 55.3% versus 29.6% (P = 0.01), respectively. In the propensity matched analysis, the corresponding figures were 51.4% versus 37.1% (P = 0.222) and 54.3% versus 50% (P = 0.680). After controlling residual confusion by the Poisson regression model, the relative risk (RR) of ICU- and hospital-attributable mortality from candidemia was RR 1.298 (95% confidence interval (CI) 0.88 to 1.98) and RR 1.096 (95% CI 0.68 to 1.69), respectively. CONCLUSIONS: ICU-acquired candidemia in critically ill patients is not associated with an increase in either ICU or hospital mortality.

Efficacy of corticosteroid therapy in patients with an acute exacerbation of chronic obstructive pulmonary disease receiving ventilatory support.

BACKGROUND: Randomized trials assessing the effect of systemic corticosteroids on chronic obstructive pulmonary disease (COPD) exacerbations excluded patients who were mechanically ventilated or admitted to the intensive care unit (ICU). Critically ill patients constitute a population of persons who are prone to develop complications that are potentially associated with the use of corticosteroids (eg, infections, hyperglycemia, ICU-acquired paresis) that could prolong the duration of mechanical ventilation and even increase mortality. METHODS: A double-blind placebo-controlled trial was conducted to evaluate the efficacy and safety of systemic corticosteroid treatment in patients with an exacerbation of COPD who were receiving ventilatory support (invasive or noninvasive mechanical ventilation). A total of 354 adult patients who were admitted to the ICUs of 8 hospitals in 4 countries from July 2005 through July 2009 were screened, and 83 were randomized to receive intravenous methylprednisolone (0.5 mg/kg every 6 hours for 72 hours, 0.5 mg/kg every 12 hours on days 4 through 6, and 0.5 mg/kg/d on days 7 through 10) or placebo. The main outcome measures were duration of mechanical ventilation, length of ICU stay, and need for intubation in patients treated with noninvasive mechanical ventilation. RESULTS: There were no significant differences between the groups in demographics, severity of illness, reasons for COPD exacerbation, gas exchange variables, and corticosteroid rescue treatment. Corticosteroid treatment was associated with a significant reduction in the median duration of mechanical ventilation (3 days vs 4 days; P = .04), a trend toward a shorter median length of ICU stay (6 days vs 7 days; P = .09), and significant reduction in the rate of NIV failure (0% vs 37%; P = .04). CONCLUSION: Systemic corticosteroid therapy in patients with COPD exacerbations requiring mechanical ventilation is associated with a significant increase in the success of noninvasive mechanical ventilation and a reduction in the duration of mechanical ventilation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01281748.

Study of the nitric oxide system in the rat cerebellum during aging.

BACKGROUND: The cerebellum is the neural structure with the highest levels of nitric oxide, a neurotransmitter that has been proposed to play a key role in the brain aging, although knowledge concerning its contribution to cerebellar senescence is still unclear, due mainly to absence of integrative studies that jointly evaluate the main factors involved in its cell production and function. Consequently, in the present study, we investigate the expression, location, and activity of nitric oxide synthase isoenzymes; the protein nitration; and the production of nitric oxide in the cerebellum of adult and old rats. RESULTS: Our results show no variation in the expression of nitric oxide synthase isoforms with aging, although, we have detected some changes in the cellular distribution pattern of the inducible isoform particularly in the cerebellar nuclei. There is also an increase in nitric oxide synthase activity, as well as greater protein-nitration levels, and maintenance of nitrogen oxides (NOx) levels in the senescent cerebellum. CONCLUSIONS: The nitric oxide/nitric oxide synthases system suffers from a number of changes, mainly in the inducible nitric oxide synthase distribution and in overall nitric oxide synthases activity in the senescent cerebellum, which result in an increase of the protein nitration. These changes might be related to the oxidative damage detected with aging in the cerebellum.

Usefulness of the "Candida score" for discriminating between Candida colonization and invasive candidiasis in non-neutropenic critically ill patients: a prospective multicenter study.

OBJECTIVE: To assess the usefulness of the "Candida score" (CS) for discriminating between Candida species colonization and invasive candidiasis (IC) in non-neutropenic critically ill patients. A rate of IC <5% in patients with CS <3 was the primary end point. DESIGN: Prospective, cohort, observational study. SETTING: Thirty-six medical-surgical intensive care units of Spain, Argentina, and France. PATIENTS: A total of 1,107 non-neutropenic adult intensive care unit patients admitted for at least 7 days between April 2006 and June 2007. MEASUREMENTS AND MAIN RESULTS: Clinical data, surveillance cultures for fungal growth, and serum levels of (1-3)-beta-d-glucan and anti-Candida antibodies (in a subset of patients) were recorded. The CS was calculated as follows (variables coded as absent = 0, present = 1): total parenteral nutrition x1, plus surgery x1, plus multifocal Candida colonization x1, plus severe sepsis x2. A CS >or=3 accurately selected patients at high risk for IC. The colonization index was registered if >or=0.5. The rate of IC was 2.3% (95% confidence interval [CI] 1.06-3.54) among patients with CS <3, with a linear association between increasing values of CS and IC rate (p 7 days, with a CS <3 and not receiving antifungal treatment, the rate of IC was <5%. Therefore, IC is highly improbable if a Candida-colonized non-neutropenic critically ill patient has a CS <3.

Promoter hypermethylation of cancer-related genes: a strong independent prognostic factor in acute lymphoblastic leukemia.

Promoter hypermethylation plays an important role in the inactivation of cancer-related genes. This abnormality occurs early in leukemogenesis and seems to be associated with poor prognosis in acute lymphoblastic leukemia (ALL). To determine the extent of hypermethylation in ALL, we analyzed the methylation status of the CDH1, p73, p16, p15, p57, NES-1, DKK-3, CDH13, p14, TMS-1, APAF-1, DAPK, PARKIN, LATS-1, and PTEN genes in 251 consecutive ALL patients. A total of 77.3% of samples had at least 1 gene methylated, whereas 35.9% of cases had 4 or more genes methylated. Clinical features and complete remission rate did not differ among patients without methylated genes, patients with 1 to 3 methylated genes (methylated group A), or patients with more than 3 methylated genes (methylated group B). Estimated disease-free survival (DFS) and overall survival (OS) at 11 years were 75.5% and 66.1%, respectively, for the nonmethylated group; 37.2% and 45.5% for methylated group A; and 9.4% and 7.8% for methylated group B (P < .0001 and P = .0004, respectively). Multivariate analysis demonstrated that the methylation profile was an independent prognostic factor in predicting DFS (P < .0001) and OS (P = .003). Our results suggest that the methylation profile may be a potential new biomarker of risk prediction in ALL.