Search

Epidemiology; Preventive medicine Epidemiologia, Medicina preventiva Epidemiología; Medicina preventiva Using categorical principal component analysis, we aimed to determine the relationship between health care-associated infections (HAIs) and diagnostic categories (DCs) in patients with acute heart disease using data collected in the Spanish prospective ENVIN-HELICS intensive care registry over a 10-year period (2005–2015). A total of 69,876 admissions were included, of which 5597 developed HAIs. Two 2-component CATPCA models were developed. In the first model, all cases were included; the first component was determined by the duration of the invasive devices, the ICU stay, the APACHE II score and the HAIs; the second component was determined by the type of admission (medical or surgical) and by the DCs. No clear association between DCs and HAIs was found. Cronbach’s alpha was 0.899, and the variance accounted for (VAF) was 52.5%. The second model included only admissions that developed HAIs; the first component was determined by the duration of the invasive devices and the ICU stay; the second component was determined by the inflammatory response, the mortality in the ICU and the HAIs. Cronbach’s alpha value was 0.855, and VAF was 46.9%. These findings highlight the role of exposure to invasive devices in the development of HAIS in patients with acute heart disease.

A subgroup of patients with SARS-CoV-2 infection was thought to have developed cytokine release syndrome and were treated with tocilizumab; however, a significant percentage of patients evolved. This study aimed to determine the usefulness of anakinra as a rescue treatment for patients with tocilizumab-refractory COVID-19 disease. A prospective cohort of patients with COVID-19 pneumonia who received anakinra as salvage therapy after failure of tocilizumab were compared (1:1) with selected controls in a historical cohort of patients treated with tocilizumab. Cases and controls were matched by age, comorbidities, pulse oximetry oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio at baseline, and time elapsed since the initiation of treatment with tocilizumab. The primary outcome was the improvement in clinical status measured by a 6-point ordinal scale, from baseline to day 21. The study included 20 cases and 20 controls (mean age 65.3 ± 12.8 years, 65% males). No differences were found in the clinical improvement rates at 7, 14 and 21 days of follow-up. The in-hospital mortality rate for patients receiving anakinra was 55% vs. 45% in the control group (P = 0.527). Treatment with anakinra was not useful in improving the prognosis of patients with tocilizumab-refractory severe COVID-19. This work was supported by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COV20/00181) — co‐financed by European Development Regional Fund “A way to achieve Europe”. M.F.R. holds a research contract “Miguel Servet” (CP18/00073) from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III. Sí

BackgroundThe role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear.MethodsWe conducted a retrospective single-center study including consecutive patients ≥65 years that developed severe COVID-19 between March 3 and May 1, 2020 and were treated with corticosteroids at various doses (methylprednisolone [0.5 mg/Kg/12 hours to 250 mg/24 hours]), either alone (“CS group”) or associated to intravenous tocilizumab (400-600 mg, one to three doses) (“CS-TCZ group”). Primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2-point decrease on a six-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied.ResultsOverall, 181 and 80 patients were included in the CS and CS-TCZ groups. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17 – 0.68;P-value = 0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21 – 0.68;P-value = 0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21 – 0.72;P-value = 0.003). Clinical improvement by day +14 was higher in the CS-TCZ group in the IPTW analysis only (OR: 2.26; 95% CI: 1.49 – 3.41;P-value ConclusionsThe combination of corticosteroids and TCZ was associated with better outcomes among patients ≥65 years with severe COVID-19.

Coronavirus disease 2019 (COVID‐19) can lead to a massive cytokine release. The use of the anti‐interleukin‐6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID‐19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6‐point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6‐point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon‐β (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06‐0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06‐0.99; P = .048) were negatively associated with clinical improvement by day 7. All‐cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C‐reactive protein levels dropped by day 2. There were no TCZ‐attributable adverse events. In this observational single‐center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID‐19 pneumonia., Highlights COVID‐19 can lead to a hyperinflammatory state that mirrors the cytokine release syndrome.The off‐labeluse of the anti‐interleukin‐6 receptor monoclonal antibody tocilizumab has been proposed to abrogate this deleterious inflammatory response, although the supporting evidence is scarce.In the present single‐centre study comprising 88 consecutive patients with COVID‐19 pneumonia that received at least one dose of intravenous tocilizumab between March 16 and 27, 2020, the rates of clinical improvement (defined by discharge to home and/or a decrease of = 2 points on a six‐point ordinal scale) were 44.3% (39/88) and 73.9% (65/88) by days 7 and 14, respectively.The previous or concomitant use of interferon‐β and baseline serum lactate dehydrogenase levels >450 U/L were negatively associated with clinical improvement by day 7. All‐cause mortality was 6.8%, with no tocilizumab‐attributable adverse events.

Background Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic. Because the severity of the disease is highly variable, predictive models to stratify patients according to their mortality risk are needed. Objective Our aim was to develop a model able to predict the risk of fatal outcome in patients with COVID-19 that could be used easily at the time of patients' arrival at the hospital. Methods We constructed a prospective cohort with 611 adult patients in whom COVID-19 was diagnosed between March 10 and April 12, 2020, in a tertiary hospital in Madrid, Spain. The analysis included 501 patients who had been discharged or had died by April 20, 2020. The capacity of several biomarkers, measured at the beginning of hospitalization, to predict mortality was assessed individually. Those biomarkers that independently contributed to improve mortality prediction were included in a multivariable risk model. Results High IL-6 level, C-reactive protein level, lactate dehydrogenase (LDH) level, ferritin level, d -dimer level, neutrophil count, and neutrophil-to-lymphocyte ratio were all predictive of mortality (area under the curve >0.70), as were low albumin level, lymphocyte count, monocyte count, and ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2). A multivariable mortality risk model including the SpO2/FiO2 ratio, neutrophil-to-lymphocyte ratio, LDH level, IL-6 level, and age was developed and showed high accuracy for the prediction of fatal outcome (area under the curve 0.94). The optimal cutoff reliably classified patients (including patients with no initial respiratory distress) as survivors and nonsurvivors with 0.88 sensitivity and 0.89 specificity. Conclusion This mortality risk model allows early risk stratification of hospitalized patients with COVID-19 before the appearance of obvious signs of clinical deterioration, and it can be used as a tool to guide clinical decision making.

Diagnosis of invasive fungal disease (IFD) in patients under intensive care is challenging. Circulating biomarkers, (1,3)-β-D-glucan (BG) and galactomannan (GM), were prospectively assessed in 98 critically ill patients at risk of IFD. There were 11 cases of invasive aspergillosis (IA; 4 proven and 7 probable), 9 cases of proven invasive candidiasis (IC), 1 case of mixed proven IC and probable IA, 1 case of proven zygomycosis, and 1 case of mixed mycelial proven IFD. In all IA cases there was no significant difference when the area under the receiver operating characteristic curve (AUC) of GM (0.873 [95%CI, 0.75-0.99]) and BG (0.856 [95% CI, 0.71-0.99]) were compared (p = 0.871). The AUC for BG in IC and for the rest of the IFD cases was 0.605 (95% CI, 0.39-0.82) and 0.768 (95% CI, 0.63-0.90) respectively. Positive BG (40%) predated blood culture (n = 3) and abdominal pus (n = 1) a mean of 3.25 days before Candida was grown. In patients with IFD caused by molds, BG appeared a mean of 5.65 days before culture results. For the diagnosis of patients at risk of IC, BG has shown a high NPV (94.5%), with positive results also predating blood cultures in 30% of patients. In conclusion, early BG results permit a timely initiation of antifungal therapy in patients at risk of IFD.

Because of the organ shortage, non-heart-beating donors have been proposed as a possible source of grafts for orthotopic liver transplantation (OLT). Despite the widespread use of controlled non-heart-beating donors, there are only a few published studies reporting the outcomes with uncontrolled non-heart-beating donors (UNHBDs). A prospective case-control study on adult patients undergoing OLT was designed. We used normothermic extracorporeal membrane oxygenation (NECMO) in all UNHBDs. Matching 2:1 ratio comparison was performed between a study group (UNHBDs) and a brain death donor (BDD) control group. Between January 2006 and March 2008, a total of 60 patients were included: 20 in the UNHBD group and 40 in the control group. The incidence of ischemic cholangiopathy was 5% (n = 1) for the UNHBD group and 0% for the BDD group (P = 0.15). The rate of primary nonfunction was 10% (n = 2) in UNHBD recipients and 2.5% (n = 1) in BDD recipients (P = 0.21), with graft loss in all of them. Three patients were retransplanted in the UNHBD group (15%), 2 of them because of primary nonfunction and 1 because of ischemic cholangiopathy; no patient was retransplanted in the control group (P = 0.012). After a mean follow-up of 330.4 +/- 224.9 days, 1-year cumulative patient survival was 85.5% for the UNHBD group and 87.5% for the BDD group (P = 0.768). One-year cumulative graft survival was 80% in the UNHBD group and 87.5% in the BDD group (P = 0.774). In conclusion, UNHBDs under NECMO are a potential source of organs for OLT with encouraging outcomes potentially comparable to those obtained with BDDs.

Introduction. The aim of the study was to examine different antibiotic choices and their relation to outcomes. Methods. We reviewed patients with severe community-acquired pneumonia (SCAP) from two multicenter studies. Empirical antimicrobial regimens were classified as: macrolides alone (group M); macrolides plus betalactams (group MB); macrolides plus betalactam/betalactamase inhibitor (group MBI); every regimen including aminoglycosides (group A); non-pseudomonal third-generation cephalosporins alone (group C); another betalactam alone (first- and second-generation cephalosporins, or betalactam/betalactamase inhibitor) (group B); fluoroquinolones (group F); and other regimens (group Misc). Results. Initial distribution of regimens was: group MB: 261 patients; group A: 65 patients; group C: 31 patients; group B: 23 patients; group M: 18 patients; group MBI: 13 patients; group F: 11 patients; group Misc: 38 patients. The lowest overall mortality was associated with initial treatment with a macrolide plus other agent (or alone). No deaths were documented among the 13 patients receiving amoxicillin/clavulanate plus a macrolide. The excess mortality for initial treatment with group A was significantly higher (14.2%; CI 95% 27.3–1.1) than the overall mortality rate between patients receiving a macrolide plus other agents. No significant differences were documented when mortality was adjusted for intubated patients. Conclusion. Clinicians select the empirical antibiotic regimen after classifying patients according to likely pathogens and prognosis. The inclusion of a macrolide as part of the initial therapeutic regimen for SCAP appears to be as safe and effective as alternative options. Addition of a macrolide agent to a betalactam/betalactamase inhibitor or using a macrolide alone was a marker for less severe disease.

This study was designed to compare the effectiveness of liposomal amphotericin B (L-AmB) in ICU patients with and without renal replacement therapy (RRT).Observational, retrospective, comparative and multicenter study conducted in critically ill patients treated with L-AmB for 3 or more days, divided into two cohorts depending on the use of RRT before or within the first 48 hours after starting L-AmB. Clinical and microbiological response at the end of treatment was evaluated.A total of 158 patients met the inclusion criteria, 36 (22.8%) of which required RRT during the ICU stay. Patients with RRT as compared with those without RRT showed a higher APACHE II score on admission (21.4 vs 18.4, P = 0.041), greater systemic response against infection (P = 0.047) and higher need of supportive techniques (P = 0.002). In both groups, main reasons for the use of L-AmB were broad spectrum and hemodynamic instability. A higher daily dose of L-AmB was used in the RRT group (4.30 vs 3.84 mg/kg, P = 0.030) without differences in the total cumulative dose or treatment duration. There were no differences in the clinical response (61.1% vs 56.6%, P = 0.953) or microbiological eradication rate (74.1% vs 64.6%, P = 0.382). In patients with proven invasive fungal infection, satisfactory clinical response was obtained in 74.1% and microbiological eradication 85.7%.Although the study sample is small, this study shows that L-AmB is effective in critically ill patients admitted to the ICU requiring RRT.

Acute liver failure has a high mortality and its most frequent cause in Spain is viral infection. In this article, we present a case of fulminant liver failure. The failure is secondary to an idiosyncratic reaction to ibuprofen, an entity included in the DRESS syndrome. This syndrome plays a key role in the differential diagnosis of acute liver failure, since its unfortunate course often requires liver transplantation as the only useful therapeutic weapon. This case illustrates the need for an efficient coordination between hospitals as a key factor for improving the prognosis.

Received 8 October 2010; returned 9 November 2010; revised 2 December 2010; accepted 6 December 2010Objectives: The impact of oseltamivir on mortality in critically ill patients with 2009 pandemic influenza A(2009 H1N1) is not clear. The main objective of this study was to investigate the relationship between thetiming of antiviral administration and intensive care unit (ICU) outcomes.Methods: Prospective, observational study of a cohort of ICU patients with confirmed 2009 H1N1 infection.Clinical data, treatment and outcome were compared between patients receiving early treatment (ET) withoseltamivir, initiated within 2 days, and patients administered late treatment (LT), initiated after this timepoint.Multivariate analysis and propensity score were used to determine the effect of oseltamivir on ICU mortality.Results: Six hundred and fifty-seven patients were enrolled. Four hundred and four (61.5%) patients requiredmechanical ventilation (MV; mortality 32.6%). Among them, 385 received effective antiviral therapy andwere included in the study group. All patients received oseltamivir for a median duration of 10 days (interquar-tile range 8–14 days). Seventy-nine (20.5%) ET patients were compared with 306 LT patients. The two groupswere comparable in terms of main clinical variables. ICU length of stay (22.7+16.7 versus 18.4+14.2 days;P¼0.03), hospital length of stay (34.0+20.3 versus 27.2+18.2 days; P¼0.001) and MV days (17.4+15.2versus 14.0+12.4; P¼0.04) were higher in the LT group. ICU mortality was also higher in LT (34.3%) than inET (21.5%; OR¼1.9; 95% CI 1.06–3.41). A multivariate model identified ET (OR¼0.44; 95% CI 0.21–0.87) asan independent variable associated with reduced ICU mortality. These results were confirmed by propensityscore analysis (OR¼0.44; 95% CI 0.22–0.90; P,0.001).Conclusions: Our findings suggest that early oseltamivir administration was associated with favourableoutcomes among critically ill ventilated patients with 2009 H1N1 virus infection.Keywords: antiviral treatment, prognosis, pneumonia

To assess the efficacy of the Molecular Adsorbent Recirculating System MARS (GAMBRO LUNDIA AB, Europe) in patients with acute liver failure waiting for liver transplantation.Case-control study in a medical-surgical ICU of a referral hospital. Patients admitted to ICU with severe acute liver failure of any etiology were included. Conventional treatment was applied in all cases according to patient's clinical condition. Patients were treated with MARS after the implementation of this therapy in the ICU. Patients without this treatment were the control group.Were included 45 patients (control group: 26, MARS group: 19). Comparison between groups showed only differences in plasma bilirrubin levels in the first 24 hours. ICU mortality was 52.63% in the treatment group and 42.3% in the control group (p = 0.49). In the control group 17 patients (65.4%) received a liver transplant and 11 (57.9%) in the MARS group. ICU mortality was lower for transplanted patients in the study group (27.27% vs. 87.5%) (p = 0.019). Kaplan-Meier survival curves indicate that MARS-treated patients before liver transplantation had better survival.Combination therapy with MARS and liver transplantation seems to be the more effective therapeutic option for patients with severe ALF.

Aspergillus lentulus was first described in the year 2005, and since it cannot be phenotypically distinguished from Aspergillus fumigatus, it is conceivable that earlier descriptions (before 2005) could be attributed to this new species. Currently invasive infections caused by A. lentulus are rare and very few cases have been previously published in neutropenic patients, all of them with fatal outcome. Here we report a critically ill non neutropenic patient with chronic obstructive pulmonary disease (COPD) who was admitted to the medical intensive care unit with an exacerbation of COPD and who had been treated with long term corticosteroids. A. fumigatus was cultured from two bronchial aspirates and in a third bronchial aspirate both A. lentulus and A. fumigatus were isolated. On two consecutive days detection of galactomannan in serum was negative whilst detection of (1-3) beta-D glucan was positive (518 pg/ml). Minimal inhibitory concentrations (MIC) for itraconazole, voriconazole, caspofungin and amphotericin B were high for this strain of A. lentulus. Given the high MIC values of A. lentulus to available antifungals, the accurate identification of this new species is warranted. To our knowledge, this is the first report of the isolation of A. lentulus in a non-neutropenic critically ill patient, although we note that since it was isolated only once from respiratory specimens, its implication as an etiologic agent of infection for this patient remains to be established.

Diagnosis of fungal pneumonia (FP) in critically ill patients is challenging. Circulating biomarkers for the diagnosis of FP have limitations and the combination of different assays in serum samples and directly from the target organ may further improve the diagnosis of FP. We prospectively assessed the diagnostic utility of paired galactomannan (GM) in bronchoalveolar lavage fluid (BAL) and serum GM and (1→3)–β–d-glucan (BG) assays in critically ill patients at risk of FP. Patients with FP were classified according to European Organisation for Research and Treatment of Cancer-Mycoses Study Group criteria, with modifications. Out of 847 admissions, 51 patients were eligible. There were nine invasive aspergillosis (IA) cases (four proven, five probable), three proven Pneumocysitis jirovecii pneumonia (PJP) cases and one mixed FP case (probable IA and proven PJP). The diagnostic accuracy as given by the area under the receiver operating characteristic curve in IA cases (proven and probable) for GM in BAL was 0.98 (95% CI, 0.94–1.00), whilst for GM and BG in serum it was 0.85 (95% CI, 0.74–0.96) and 0.815 (95% CI, 0.66–0.96), respectively. For IA cases (proven and probable) AUC for GM in BAL was significantly higher than GM and BG in serum (p 0.025 and p 0.032, respectively). In one of four proven and one of six probable IA cases, GM in serum remained negative, whereas GM in BAL was positive. In patients with IA, GM (90%) and BG (80%) appeared a mean of 4.3 days (range, 1–10 days) before Aspergillus was cultured. GM detection in BAL appears to improve the diagnosis of IA in critical patients.

Objectives: To define which variables upon ICU admission could be related to the presence of coinfection using CHAID (Chi-squared Automatic Interaction Detection) analysis. Methods: A secondary analysis from a prospective, multicentre, observational study (2009 -2014) in ICU patients with confirmed A(H1N1)pdm09 infection. We assessed the potential of biomarkers and clinical variables upon admission to the ICU for coinfection diagnosis using CHAID analysis. Performance of cut-off points obtained was determined on the basis of the bi-nominal distributions of the true (+) and true (-) results. Results: Of the 972 patients included, 196 (20.3%) had coinfection. Procalcitonin (PCT; ng/mL 2.4 vs. 0.5, p < 0.001), but not C-reactive protein (CRP; mg/dL 25 vs. 38.5; p = 0.62) was higher in patients with coinfection. In CHAID analyses, PCT was the most important variable for coinfection. PCT < 0.29 ng/mL showed high sensitivity (Se = 88.2%), low Sp (33.2%) and high negative predictive value (NPV = 91.9%). The absence of shock improved classification capacity. Thus, for PCT < 0.29 ng/mL, the Se was 84%, the Sp 43% and an NPV of 94% with a post-test probability of coinfection of only 6%. Conclusion: PCT has a high negative predictive value (94%) and lower PCT levels seems to be a good tool for excluding coinfection, particularly for patients without shock. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.