Publications by authors named "Miquel Ferrer"

117 Publications

Prediction of ventilator-associated pneumonia outcomes according to the early microbiological response: a retrospective observational study.

Eur Respir J 2021 Sep 2. Epub 2021 Sep 2.

August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona; Biomedical Research Networking Centres in Respiratory Diseases (CIBERES), Barcelona, Spain

Ventilator-associated pneumonia is a leading infectious cause of morbidity in critically ill patients; yet current guidelines offer no indications for follow-up cultures.We aimed to evaluate the role of follow-up cultures and microbiological response 3 days after diagnosing ventilator-associated pneumonia as predictors of short- and long-term outcomes.We performed a retrospective analysis of a cohort prospectively collected from 2004 to 2017. Ventilator-associated pneumonia was diagnosed based on clinical, radiographic, and microbiological criteria. For microbiological identification, a tracheobronchial aspirate was performed at diagnosis and repeated after 72 h. We defined three groups when comparing the two tracheobronchial aspirate results: persistence, superinfection, and eradication of causative pathogens.One-hundred-fifty-seven patients were enrolled in the study, among whom microbiological persistence, superinfection, and eradication was present in 67 (48%), 25 (16%), and 65 (41%), respectively, after 72hs. Those with superinfection had the highest mortalities in the intensive care unit (p=0.015) and at 90 days (p=0.036), while also having the fewest ventilation-free days (p=0.024). Multivariable analysis revealed shock at VAP diagnosis (odds ratios [OR] 3.43; 95% confidence interval [CI] 1.25 to 9.40), isolation at VAP diagnosis (OR 2.87; 95%CI 1.06 to 7.75), and hypothermia at VAP diagnosis (OR 0.67; 95%CI 0.48 to 0.95, per +1°C) to be associated with superinfection.Our retrospective analysis suggests that ventilator-associated pneumonia short-term and long-term outcomes may be associated with superinfection in follow-up cultures. Follow-up cultures may help guiding antibiotic therapy and its duration. Further prospective studies are necessary to verify our findings.
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http://dx.doi.org/10.1183/13993003.00620-2021DOI Listing
September 2021

Role of respiratory intermediate care units during the SARS-CoV-2 pandemic.

BMC Pulm Med 2021 Jul 13;21(1):228. Epub 2021 Jul 13.

Servei de Pneumologia i Al·lèrgia Respiratòria, Institut Clínic Respiratori, Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, Barcelona, Spain.

Rationale: The SARS-CoV2 pandemic increased exponentially the need for both Intensive (ICU) and Intermediate Care Units (RICU). The latter are of particular importance because they can play a dual role in critical and post-critical care of COVID-19 patients. Here, we describe the setup of 2 new RICUs in our institution to face the SARS-CoV-2 pandemic and discuss the clinical characteristics and outcomes of the patients attended.

Methods: Retrospective analysis of the characteristics and outcomes of COVID-19 patients admitted to 2 new RICUs built specifically in our institution to face the first wave of the SARS-CoV-2 pandemic, from April 1 until May 30, 2020.

Results: During this period, 106 COVID-19 patients were admitted to these 2 RICUs, 65 of them (61%) transferred from an ICU (step-down) and 41 (39%) from the ward or emergency room (step-up). Most of them (72%) were male and mean age was 66 ± 12 years. 31% of them required support with oxygen therapy via high-flow nasal cannula (HFNC) and 14% non-invasive ventilation (NIV). 42 of the 65 patients stepping down (65%) had a previous tracheostomy performed and most of them (74%) were successfully decannulated during their stay in the RICU. Length of stay was 7 [4-11] days. 90-day mortality was 19% being significantly higher in stepping up patients than in those transferred from the ICU (25 vs. 10% respectively; p < 0.001).

Conclusions: RICUs are a valuable hospital resource to respond to the challenges of the SARS-CoV-2 pandemic both to treat deteriorating and recovering COVID-19 patients.
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http://dx.doi.org/10.1186/s12890-021-01593-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275902PMC
July 2021

Impact of Cardiovascular Failure in Intensive CareUnit-Acquired Pneumonia: A Single-Center, Prospective Study.

Antibiotics (Basel) 2021 Jun 30;10(7). Epub 2021 Jun 30.

Hospital Clinic, IDIBAPS, Universidad de Barcelona, CIBERes, 08036 Barcelona, Spain.

Background: Cardiovascular failure (CVF) may complicate intensive care unit-acquired pneumonia (ICUAP) and radically alters the empirical treatment of this condition. The aim of this study was to determine the impact of CVF on outcome in patients with ICUAP.

Methods: A prospective, single-center, observational study was conducted in six medical and surgical ICUs at a University Hospital. CVS was defined as a score of 3 or more on the cardiovascular component of the Sequential Organ Failure Assessment (SOFA) score. At the onset of ICUAP, CVF was reported as absent, transient (if lasting ≤ 3 days) or persistent (>3 days). The primary outcome was 90-day mortality modelled through a Cox regression analysis. Secondary outcomes were 28-day mortality, hospital mortality, ICU length of stay (LOS) and hospital LOS.

Results: 358 patients were enrolled: 203 (57%) without CVF, 82 (23%) with transient CVF, and 73 (20%) with persistent CVF. Patients with transient and persistent CVF were more severely ill and presented higher inflammatory response than those without CVF. Despite having similar severity and aetiology, the persistent CVF group more frequently received inadequate initial antibiotic treatment and presented more treatment failures than the transient CVF group. In the persistent CVF group, at day 3, a bacterial superinfection was more frequently detected. The 90-day mortality was significantly higher in the persistent CVF group (62%). The 28-day mortality rates for patients without CVF, with transient and with persistent CVF were 19, 35 and 41% respectively and ICU mortality was 60, 38 and 19% respectively. In the multivariate analysis chronic pulmonary conditions, lack of Pa0/FiO improvement at day 3, pulmonary superinfection at day 3 and persistent CVF were independently associated with 90-day mortality in ICUAP patients. : Persistent CVF has a significant impact on the outcome of patients with ICUAP. Patients at risk from persistent CVF should be promptly recognized to optimize treatment and outcomes.
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http://dx.doi.org/10.3390/antibiotics10070798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300830PMC
June 2021

A 3D Finite Element Analysis Model of Single Implant-Supported Prosthesis under Dynamic Impact Loading for Evaluation of Stress in the Crown, Abutment and Cortical Bone Using Different Rehabilitation Materials.

Materials (Basel) 2021 Jun 24;14(13). Epub 2021 Jun 24.

Faculty of Dentistry, Universitat Internacional de Catalunya (UIC), 08017 Barcelona, Spain.

In the literature, many researchers investigated static loading effects on an implant. However, dynamic loading under impact loading has not been investigated formally using numerical methods. This study aims to evaluate, with 3D finite element analysis (3D FEA), the stress transferred (maximum peak and variation in time) from a dynamic impact force applied to a single implant-supported prosthesis made from different materials. A 3D implant-supported prosthesis model was created on a digital model of a mandible section using CAD and reverse engineering. By setting different mechanical properties, six implant-supported prostheses made from different materials were simulated: metal (MET), metal-ceramic (MCER), metal-composite (MCOM), carbon fiber-composite (FCOM), PEEK-composite (PKCOM), and carbon fiber-ceramic (FCCER). Three-dimensional FEA was conducted to simulate the collision of 8.62 g implant-supported prosthesis models with a rigid plate at a speed of 1 m/s after a displacement of 0.01 mm. The stress peak transferred to the crown, titanium abutment, and cortical bone, and the stress variation in time, were assessed.
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http://dx.doi.org/10.3390/ma14133519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269525PMC
June 2021

Predictive Performance of Risk Factors for Multidrug-Resistant Pathogens in Nosocomial Pneumonia.

Ann Am Thorac Soc 2021 05;18(5):807-814

August Pi i Sunyer Biomedical Research Institute, University of Barcelona, Biomedical Research Networking Centres in Respiratory Diseases (Ciberes), Barcelona, Spain.

In 2017, the International European Respiratory Society/European Society of Intensive Care Medicine/European Society of Clinical Microbiology and Infectious Diseases/Latin American Thoracic Society (European) guidelines defined new risk factors for multidrug-resistant (MDR) pathogens in patients with nosocomial pneumonia. To assess the predictive performance of these newly defined risk factors for MDR pathogens. We enrolled 507 adult patients with nosocomial pneumonia who were treated in six intensive care units at the Hospital Clinic of Barcelona in Spain. Of the 503 patients at high MDR pathogen and mortality risk, 275 (54%) had no septic shock and 228 (46%) had septic shock. Admission to hospital settings with high rates of MDR pathogens ( = 421; 83%) and prior antibiotic use ( = 399; 79%) showed the highest prevalence in the overall population, with sensitivities of 92% and 85% and negative predictive values of 85% and 82%, respectively. However, low specificities and low positive predictive values were found. Previous respiratory MDR pathogen isolation was less common ( = 17; 3%) but presented a specificity and positive predictive value of 100%. The area under the receiver operating characteristic curve was less than 0.6 for all risk factors and combinations. The risk factors proposed by the European Respiratory Society/European Society of Intensive Care Medicine/European Society of Clinical Microbiology and Infectious Diseases/Latin American Thoracic Society showed low accuracy for predicting MDR pathogens in intensive care unit acquired pneumonia (ICU-AP). Admission to hospital settings with high rates of MDR pathogens and prior antibiotic use were the most prevalent risk factors, with a high sensitivity for predicting these microorganisms; prior positive cultures for MDR pathogens showed high specificity but very low sensitivity. Combinations of risk factors did not show any great accuracy for predicting these microorganisms. Further studies assessing combined strategies of risk stratification and complementary methods are now warranted.
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http://dx.doi.org/10.1513/AnnalsATS.202002-181OCDOI Listing
May 2021

Characteristics and Outcomes in Patients with Ventilator-Associated Pneumonia Who Do or Do Not Develop Acute Respiratory Distress Syndrome. An Observational Study.

J Clin Med 2020 Oct 29;9(11). Epub 2020 Oct 29.

Department of Pneumology and Respiratory Intensive Care Unit, Institut Clinic de Respiratori, Hospital Clinic of Barcelona, 08036 Barcelona, Spain.

Ventilator-associated pneumonia (VAP) is a well-known complication of patients on invasive mechanical ventilation. The main cause of acute respiratory distress syndrome (ARDS) is pneumonia. ARDS can occur in patients with community-acquired or nosocomial pneumonia. Data regarding ARDS incidence, related pathogens, and specific outcomes in patients with VAP is limited. This is a cohort study in which patients with VAP were evaluated in an 800-bed tertiary teaching hospital between 2004 and 2016. Clinical outcomes, microbiological and epidemiological data were assessed among those who developed ARDS and those who did not. Forty-one (13.6%) out of 301 VAP patients developed ARDS. Patients who developed ARDS were younger and presented with higher prevalence of chronic liver disease. Pseudomonas aeruginosa was the most frequently isolated pathogen, but without any difference between groups. Appropriate empirical antibiotic treatment was prescribed to ARDS patients as frequently as to those without ARDS. Ninety-day mortality did not significantly vary among patients with or without ARDS. Additionally, patients with ARDS did not have significantly higher intensive care unit (ICU) and 28-day mortality, ICU, and hospital length of stay, ventilation-free days, and duration of mechanical ventilation. In summary, ARDS deriving from VAP occurs in 13.6% of patients. Although significant differences in clinical outcomes were not observed between both groups, further studies with a higher number of patients are needed due to the possibility of the study being underpowered.
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http://dx.doi.org/10.3390/jcm9113508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692126PMC
October 2020

Comparison between experimental digital image processing and numerical methods for stress analysis in dental implants with different restorative materials.

J Mech Behav Biomed Mater 2021 01 28;113:104092. Epub 2020 Sep 28.

Faculty of Dentistry, Universitat Internacional de Catalunya (UIC), Barcelona, Spain.

The aim of this study is to evaluate the stresses transferred to peri-implant areas from single implants restored with different restorative materials and subjected to a static vertical load with low eccentricity. A total of 12 crowns were made with four types of materials: carbon fiber-composite, metal-ceramic, metal-composite, and full-metal, all of them cemented over a titanium abutment. Three different ways of approaching the problem have been used independently to verify the robustness of the conclusions. The experimental results of stress distribution around the implant were obtained by two image processing techniques: Digital Photoelasticity and Digital Image Correlation (DIC). The tests have been modelled by 3D Finite Element Method (FEM). The FEM models have also been used to study the sensitivity of the results to slight changes in geometry or loads, so that the robustness of the experimental techniques can be analyzed. In addition, the realistic bone morphology of the mandible has also been modelled by FEM, including the cortical and trabecular bone property distinctions.
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http://dx.doi.org/10.1016/j.jmbbm.2020.104092DOI Listing
January 2021

Validation of a Prediction Score for Drug-Resistant Microorganisms in Community-acquired Pneumonia.

Ann Am Thorac Soc 2021 02;18(2):257-265

Centro de Investigacíon Biomédica en Red de Enfermedades Respiratorias (CB06/06/0028), Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universidad de Barcelona, Barcelona, Spain.

Recommended initial empiric antimicrobial treatment covers the most common bacterial pathogens; however, community-acquired pneumonia (CAP) may be caused by microorganisms not targeted by this treatment. Developed in 2015, the PES (, extended-spectrum β-lactamase-producing , and methicillin-resistant ) score was developed in 2015 to predict the microbiological etiology of CAP caused by PES microorganisms. To validate the usefulness of the PES score for predicting PES microorganisms in two cohorts of patients with CAP from Valencia and Mataró. We analyzed two prospective observational cohorts of patients with CAP from Valencia and Mataró. Patients in the Mataró cohort were all admitted to an intensive care unit (ICU). Of the 1,024 patients in the Valencia cohort, 505 (51%) had a microbiological etiology and 31 (6%) had a PES microorganism isolated. The area under the receiver operating characteristic curve was 0.81 (95% confidence interval [95% CI], 0.74-0.88). For a PES score ≥5, sensitivity, specificity, the negative and positive predictive values as well as the negative and positive likelihood ratios were 72%, 74%, 98%, 14%, 0.38, and 2.75, respectively. Of the 299 patients in the Mataró cohort, 213 (71%) had a microbiological etiology and 11 (5%) had a PES microorganism isolated. The area under the receiver operating characteristic curve was 0.73 (95% CI 0.61-0.86). For a PES score ≥ 5, sensitivity, specificity, the negative and positive predictive values, and the negative and positive likelihood ratios were 36%, 83%, 96%, 11%, 0.77, and 2.09, respectively. The best cutoff for patients admitted to the ICU was 4 points, which improved sensitivity to 86%. The hypothetical application of the PES score showed high rates of overtreatment in both cohorts (26% and 35%, respectively) and similar rates of undertreatment. The PES score showed good accuracy in predicting the risk for microorganisms that required different empirical therapy; however, its use as a single strategy for detecting noncore pathogens could lead to high rates of overtreatment. Given its high negative predictive value, the PES score may be used as a first step of a wider strategy that includes subsequent advanced diagnostic tests.
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http://dx.doi.org/10.1513/AnnalsATS.202005-558OCDOI Listing
February 2021

Diagnostic accuracy of Gram staining when predicting staphylococcal hospital-acquired pneumonia and ventilator-associated pneumonia: a systematic review and meta-analysis.

Clin Microbiol Infect 2020 Nov 19;26(11):1456-1463. Epub 2020 Aug 19.

Department of Pneumology, Institut Clinic de Respiratori Hospital Clinic, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomedica En Red-Enfermedades Respiratorias (CIBERES), Barcelona, Spain; University of Barcelona, Barcelona, Spain. Electronic address:

Background: There is no clear guidance on empirical antibiotic coverage against Staphylococcus aureus for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP).

Objective: To evaluate whether the presence of clusters of Gram-positive cocci in Gram staining of respiratory samples predicts S. aureus as HAP/VAP pathogen.

Methods: Data sources were MEDLINE, PubMed, Embase, Scielo, CINAHL and Scopus, from inception to 15/07/2017 (update on 31/10/2019), and original data from a single-centre database (PROSPERO: CRD42017072138). We included studies reporting the diagnostic accuracy of a Gram-staining evaluation suggestive of Staphylococcus compared with a positive culture for S. aureus in any type of lower respiratory tract sample. Participants were adult patients with HAP/VAP. The index test was morphological evaluation of Gram staining of respiratory samples. We followed PRISMA guidelines and assessed risk of bias and applicability with the QUADAS-2 tool. We conducted a meta-analysis using a bivariate random effects model.

Results: We selected five studies that included only VAP and data from a single-centre database including VAP and HAP. We pooled six studies for VAP and analysed 1665 respiratory samples. Pooled sensitivity was 68% (95%CI 49-83 and specificity 95% (95%CI 86-98). The pooled positive likelihood ratio was 12.7 (95%CI 5.1-31.6), negative likelihood ratio 0.34 (95%CI 0.20-0.57), diagnostic odds ratio 38 (95%CI 13-106) and area under the summary receiver operating curve (SROC) 0.91 (95%CI 0.88-0.93). There was great heterogeneity between sensitivity and specificity. In scenarios in which the prevalence of S. aureus was between 5% and 20%, the positive and negative predictive values were 62% (95%CI 47-77) and 95% (95%CI 82-100), respectively.

Conclusions: Detection of Gram-positive cocci in clusters in respiratory samples of patients with VAP has the potential to guide risk assessments of S. aureus for more personalized antibiotic coverage. Randomized clinical trials with patient-centred outcomes are needed for strong clinical recommendations.
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http://dx.doi.org/10.1016/j.cmi.2020.08.015DOI Listing
November 2020

Pneumonic versus Nonpneumonic Exacerbations of Chronic Obstructive Pulmonary Disease.

Semin Respir Crit Care Med 2020 Dec 29;41(6):817-829. Epub 2020 Jul 29.

Department of Pneumology, Respiratory Institute, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERES (CB06/06/0028), University of Barcelona, Barcelona, Spain.

Patients with chronic obstructive pulmonary disease (COPD) often suffer acute exacerbations (AECOPD) and community-acquired pneumonia (CAP), named nonpneumonic and pneumonic exacerbations of COPD, respectively. Abnormal host defense mechanisms may play a role in the specificity of the systemic inflammatory response. Given the association of this aspect to some biomarkers at admission (e.g., C-reactive protein), it can be used to help to discriminate AECOPD and CAP, especially in cases with doubtful infiltrates and advanced lung impairment. Fever, sputum purulence, chills, and pleuritic pain are typical clinical features of CAP in a patient with COPD, whereas isolated dyspnea at admission has been reported to predict AECOPD. Although CAP may have a worse outcome in terms of mortality (in hospital and short term), length of hospitalization, and early readmission rates, this has only been confirmed in a few prospective studies. There is a lack of methodologically sound research confirming the impact of severe AECOPD and COPD + CAP. Here, we review studies reporting head-to-head comparisons between AECOPD and CAP + COPD in hospitalized patients. We focus on the epidemiology, risk factors, systemic inflammatory response, clinical and microbiological characteristics, outcomes, and treatment approaches. Finally, we briefly discuss some proposals on how we should orient research in the future.
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http://dx.doi.org/10.1055/s-0040-1702196DOI Listing
December 2020

Noninvasive Ventilation and High-Flow Nasal Therapy Administration in Chronic Obstructive Pulmonary Disease Exacerbations.

Semin Respir Crit Care Med 2020 Dec 28;41(6):786-797. Epub 2020 Jul 28.

Respiratory Intensive and Intermediate Care Unit, Department of Pneumology, Respiratory Institute, Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.

Noninvasive ventilation (NIV) is considered to be the standard of care for the management of acute hypercapnic respiratory failure in patients with chronic obstructive pulmonary disease exacerbation. It can be delivered safely in any dedicated setting, from emergency rooms to high dependency or intensive care units and wards. NIV helps improving dyspnea and gas exchange, reduces the need for endotracheal intubation, and morbidity and mortality rates. It is therefore recognized as the gold standard in this condition. High-flow nasal therapy helps improving ventilatory efficiency and reducing the work of breathing in patients with severe chronic obstructive pulmonary disease. Early studies indicate that some patients with acute hypercapnic respiratory failure can be managed with high-flow nasal therapy, but more information is needed before specific recommendations for this therapy can be made. Therefore, high-flow nasal therapy use should be individualized in each particular situation and institution, taking into account resources, and local and personal experience with all respiratory support therapies.
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http://dx.doi.org/10.1055/s-0040-1712101DOI Listing
December 2020

Association between sepsis at ICU admission and mortality in patients with ICU-acquired pneumonia: An infectious second-hit model.

J Crit Care 2020 10 25;59:207-214. Epub 2020 Jun 25.

Servei de Pneumologia, Institut del Torax, Hospital Clinic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Biomedica En Red-Enfermedades Respiratorias (CibeRes). Spain; Fellow of European Respiratory Society, United States.

Purpose: We explore the hypothesis that critically ill patients developing ICU-acquired pneumonia (ICU-AP) have worse outcomes and an altered inflammatory response if their ICU admission was sepsis-related.

Methods: Prospective cohort study in two centers. Patients with ICU-AP were evaluated according to their previous exposure to sepsis at ICU-admission. Demographic variables, comorbidities, severity scores at admission and at the time of acquisition of ICU-AP, and serum biomarkers of the inflammatory response were evaluated.

Primary Outcome: 90-day mortality.

Secondary Outcomes: ICU and hospital length of stay, mortality at days 28 and 180, in-hospital mortality, ventilator-free days (day-28), and inflammatory response. Propensity scoring weighted the risk of previously-acquired sepsis. Multivariate analysis evaluated the risk of mortality by day-90. Sensitivity analyses evaluated the primary outcome in different subgroups.

Results: Of 341 patients enrolled, 147 had sepsis on ICU-admission. Adjusted risk of mortality at 90 days did not differ overall [hazard ratio (HR) = 0.94(CI:0.65-1.37)], nor in subpopulations with a confirmed etiology of pneumonia [HR = 0.93(CI:0.57-1.53)] or sepsis [HR = 0.91(0.54-1.55)], ventilator-associated pneumonia (VAP) [HR = 1.01(CI:0.61-1.68)], nor non-VAP ICU-AP [HR = 0.83(CI:0.40-1.71)]. No differences were found in clinical secondary outcomes, the inflammatory response was similar.

Conclusions: Previous sepsis does not appear to predispose to higher mortality nor worse outcomes in patients who develop ICU-acquired pneumonia.
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http://dx.doi.org/10.1016/j.jcrc.2020.06.012DOI Listing
October 2020

Mechanism of action of SNF472, a novel calcification inhibitor to treat vascular calcification and calciphylaxis.

Br J Pharmacol 2020 10 23;177(19):4400-4415. Epub 2020 Aug 23.

Sanifit Therapeutics, Palma, Spain.

Background And Purpose: No therapy is approved for vascular calcification or calcific uraemic arteriolopathy (calciphylaxis), which increases mortality and morbidity in patients undergoing dialysis. Deposition of hydroxyapatite (HAP) crystals in arterial walls is the common pathophysiologic mechanism. The mechanism of action of SNF472 to reduce HAP deposition in arterial walls was investigated.

Experimental Approach: We examined SNF472 binding features (affinity, release kinetics and antagonism type) for HAP crystals in vitro, inhibition of calcification in excised vascular smooth muscle cells from rats and bone parameters in osteoblasts from dogs and rats.

Key Results: SNF472 bound to HAP with affinity (K ) of 1-10 μM and saturated HAP at 7.6 μM. SNF472 binding was fast (80% within 5 min) and insurmountable. SNF472 inhibited HAP crystal formation from 3.8 μM, with complete inhibition at 30.4 μM. SNF472 chelated free calcium with an EC of 539 μM. Chelation of free calcium was imperceptible for SNF472 1-10 μM in physiological calcium concentrations. The lowest concentration tested in vascular smooth muscle cells, 1 μM inhibited calcification by 67%. SNF472 showed no deleterious effects on bone mineralization in dogs or in rat osteoblasts.

Conclusion And Implications: These experiments show that SNF472 binds to HAP and inhibits further HAP crystallization. The EC for chelation of free calcium is 50-fold greater than a maximally effective SNF472 dose, supporting the selectivity of SNF472 for HAP. These findings indicate that SNF472 may have a future role in the treatment of vascular calcification and calcific uraemic arteriolopathy in patients undergoing dialysis.
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http://dx.doi.org/10.1111/bph.15163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484563PMC
October 2020

The Effect of Hospital Discharge with Empiric Noninvasive Ventilation on Mortality in Hospitalized Patients with Obesity Hypoventilation Syndrome. An Individual Patient Data Meta-Analysis.

Ann Am Thorac Soc 2020 05;17(5):627-637

Department of Medicine, Boston University School of Medicine, Boston, Massachusetts; and.

Hospitalized patients with acute-on-chronic hypercapnic respiratory failure due to obesity hypoventilation syndrome (OHS) have increased short-term mortality. It is unknown whether prescribing empiric positive airway pressure (PAP) at the time of hospital discharge reduces mortality compared with waiting for an outpatient evaluation (i.e., outpatient sleep study and outpatient PAP titration). An international, multidisciplinary panel of experts developed clinical practice guidelines on OHS for the American Thoracic Society. The guideline panel asked whether hospitalized adult patients with acute-on-chronic hypercapnic respiratory failure suspected of having OHS, in whom the diagnosis has not yet been made, should be discharged from the hospital with or without empiric PAP treatment until the diagnosis of OHS is either confirmed or ruled out. A systematic review with individual patient data meta-analyses was performed to inform the guideline panel's recommendation. Grading of Recommendations, Assessment, Development, and Evaluation was used to summarize evidence and appraise quality. The literature search identified 2,994 articles. There were no randomized trials. Ten studies met study selection criteria, including two nonrandomized comparative studies and eight nonrandomized noncomparative studies. Individual patient data on hospitalized patients who survived to hospital discharge were obtained from nine of the studies and included a total of 1,162 patients (1,043 discharged with PAP and 119 discharged without PAP). Empiric noninvasive ventilation was prescribed in 91.5% of patients discharged on PAP, and the remainder received empiric continuous PAP. Discharge with PAP reduced mortality at 3 months (relative risk 0.12, 95% confidence interval 0.05-0.30, risk difference -14.5%). Certainty in the estimated effects was very low. Hospital discharge with PAP reduces mortality following acute-on-chronic hypercapnic respiratory failure in patients with OHS or suspected of having OHS. Well-designed clinical trials are needed to confirm this finding.
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http://dx.doi.org/10.1513/AnnalsATS.201912-887OCDOI Listing
May 2020

The association of cardiovascular failure with treatment for ventilator-associated lower respiratory tract infection.

Intensive Care Med 2019 12 16;45(12):1753-1762. Epub 2019 Oct 16.

Critical Care Department, Hospital Universitario Joan XXIII, URV/IISPV/CIBERES, Tarragona, Spain.

Purpose: Ventilator associated-lower respiratory tract infections (VA-LRTIs), either ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), accounts for most nosocomial infections in intensive care units (ICU) including. Our aim was to determine if appropriate antibiotic treatment in patients with VA-LRTI will effectively reduce mortality in patients who had cardiovascular failure.

Methods: This was a pre-planned subanalysis of a large prospective cohort of mechanically ventilated patients for at least 48 h in eight countries in two continents. Patients with a modified Sequential Organ Failure Assessment (mSOFA) cardiovascular score of 4 (at the time of VA-LRTI diagnosis and needed be present for at least 12 h) were defined as having cardiovascular failure.

Results: VA-LRTI occurred in 689 (23.2%) out of 2960 patients and 174 (25.3%) developed cardiovascular failure. Patients with cardiovascular failure had significantly higher ICU mortality than those without (58% vs. 26.8%; p < 0.001; OR 3.7; 95% CI 2.6-5.4). A propensity score analysis found that the presence of inappropriate antibiotic treatment was an independent risk factor for ICU mortality in patients without cardiovascular failure, but not in those with cardiovascular failure. When the propensity score analysis was conducted in patients with VA-LRTI, the use of appropriate antibiotic treatment conferred a survival benefit for patients without cardiovascular failure who had only VAP.

Conclusions: Patients with VA-LRTI and cardiovascular failure did not show an association to a higher ICU survival with appropriate antibiotic treatment. Additionally, we found that in patients without cardiovascular failure, appropriate antibiotic treatment conferred a survival benefit for patients only with VAP.

Trial Registry: ClinicalTrials.gov, number NCT01791530.
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http://dx.doi.org/10.1007/s00134-019-05797-6DOI Listing
December 2019

Effect of Corticosteroids on C-Reactive Protein in Patients with Severe Community-Acquired Pneumonia and High Inflammatory Response: The Effect of Lymphopenia.

J Clin Med 2019 Sep 13;8(9). Epub 2019 Sep 13.

Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York 10065, NY, USA.

Background: Lymphopenic patients with community-acquired pneumonia (CAP) have shown high mortality rates. Corticosteroids have immunomodulatory properties and regulate cytokine storm in CAP. However, it is not known whether their modulatory effect on cytokine secretion differs in lymphopenic and non-lymphopenic patients with CAP. Therefore, we aimed to test whether the presence of lymphopenia may modify the response to corticosteroids (mainly in C reactive protein (CRP)) in patients with severe CAP and high inflammatory status).

Methods: A post hoc analysis of a randomized controlled trial [1] (NCT00908713) which evaluated the effect of corticosteroids in patients with severe CAP and high inflammatory response (CRP > 15 mg/dL). Patients were clustered according to the presence of lymphopenia (lymphocyte count below 1000 cell/mm).

Results: At day 1, 35 patients (59%) in the placebo group presented with lymphopenia, compared to 44 patients (73%) in the corticosteroid group. The adjusted mean changes from day 1 showed an increase of 1.19 natural logarithm (ln) cell/mm in the corticosteroid group and an increase of 0.67 ln cell/mm in the placebo group (LS mean difference of the changes in ln (methylprednisolone minus placebo) 0.51, 95%CI (0.02 to 1.01), = 0.043). A significant effect was also found for the interaction ( = 0.043) between corticosteroids and lymphopenia in CRP values at day 3, with lower values in patients without lymphopenia receiving corticosteroids after adjustments for potential confounders.

Conclusion: In this exploratory post hoc analysis from ramdomized controlled trial (RCT) data, the response to corticosteroids, measured by CRP, may differ according to lymphocyte count. Further larger studies are needed to confirm this data.
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http://dx.doi.org/10.3390/jcm8091461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780068PMC
September 2019

Ventilator-Associated Pneumonia and PaO/FO Diagnostic Accuracy: Changing the Paradigm?

J Clin Med 2019 Aug 14;8(8). Epub 2019 Aug 14.

Department of Pneumology, Hospital Clinic of Barcelona, August Pi i Sunyer Biomedical Research Institute - IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.

Background: Ventilator-associated pneumonia (VAP) is associated to longer stay and poor outcomes. Lacking definitive diagnostic criteria, worsening gas exchange assessed by PaO/FO ≤ 240 in mmHg has been proposed as one of the diagnostic criteria for VAP. We aim to assess the adequacy of PaO/FO ≤ 240 to diagnose VAP.

Methods: Prospective observational study in 255 consecutive patients with suspected VAP, clustered according to PaO/FO ≤ 240 vs. > 240 at pneumonia onset. The primary analysis was the association between PaO/FO ≤ 240 and quantitative microbiologic confirmation of pneumonia, the most reliable diagnostic gold-standard.

Results: Mean PaO/FO at VAP onset was 195 ± 82; 171 (67%) cases had PaO/FO ≤ 240. Patients with PaO/FO ≤ 240 had a lower APACHE-II score at ICU admission; however, at pneumonia onset they had higher CPIS, SOFA score, acute respiratory distress syndrome criteria and incidence of shock, and less microbiological confirmation of pneumonia (117, 69% vs. 71, 85%, p = 0.008), compared to patients with PaO/FIO > 240. In multivariate logistic regression, PaO/FIO ≤ 240 was independently associated with less microbiological confirmation (adjusted odds-ratio 0.37, 95% confidence interval 0.15-0.89, = 0.027). The association between PaO/FO and microbiological confirmation of VAP was poor, with an area under the ROC curve 0.645. Initial non-response to treatment and length of stay were similar between both groups, while hospital mortality was higher in patients with PaO/FO ≤ 240.

Conclusion: Adding PaO/FO ratio ≤ 240 to the clinical and radiographic criteria does not help in the diagnosis of VAP. PaO/FO ratio > 240 does not exclude this infection. Using this threshold may underestimate the incidence of VAP.
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http://dx.doi.org/10.3390/jcm8081217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722826PMC
August 2019

Risk and Prognostic Factors in Very Old Patients with Sepsis Secondary to Community-Acquired Pneumonia.

J Clin Med 2019 Jul 2;8(7). Epub 2019 Jul 2.

Department of Pneumology, Hospital Clinic of Barcelona, 08036 Barcelona, Spain.

Background: Little is known about risk and prognostic factors in very old patients developing sepsis secondary to community-acquired pneumonia (CAP). We conducted a retrospective observational study of data prospectively collected at the Hospital Clinic of Barcelona over a 13-year period. Consecutive patients hospitalized with CAP were included if they were very old (≥80 years) and divided into those with and without sepsis for comparison. Sepsis was diagnosed based on the Sepsis-3 criteria. The main clinical outcome was 30-day mortality. Among the 4219 patients hospitalized with CAP during the study period, 1238 (29%) were very old. The prevalence of sepsis in this age group was 71%. Male sex, chronic renal disease, and diabetes mellitus were independent risk factors for sepsis, while antibiotic therapy before admission was independently associated with a lower risk of sepsis. Thirty-day and intensive care unit (ICU) mortality did not differ between patients with and without sepsis. In CAP-sepsis group, chronic renal disease and neurological disease were independent risk factors for 30-day mortality. In very old patients hospitalized with CAP, in-hospital and 1-year mortality rates were increased if they developed sepsis. Antibiotic therapy before hospital admission was associated with a lower risk of sepsis.
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http://dx.doi.org/10.3390/jcm8070961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678833PMC
July 2019

Lymphocytopenia as a Predictor of Mortality in Patients with ICU-Acquired Pneumonia.

J Clin Med 2019 Jun 13;8(6). Epub 2019 Jun 13.

Pneumology Department, Respiratory Institute (ICR), Hospital Clinic of Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) - University of Barcelona, Ciber de Enfermedades Respiratorias (CIBERES), ICREA Academia, 08036 Barcelona, Spain.

Background: Intensive care unit-acquired pneumonia (ICU-AP) is a severe complication in patients admitted to the ICU. Lymphocytopenia is a marker of poor prognosis in patients with community-acquired pneumonia, but its impact on ICU-AP prognosis is unknown. We aimed to evaluate whether lymphocytopenia is an independent risk factor for mortality in non-immunocompromised patients with ICU-AP.

Methods: Prospective observational cohort study of patients from six ICUs of an 800-bed tertiary teaching hospital (2005 to 2016).

Results: Of the 473 patients included, 277 (59%) had ventilator-associated pneumonia (VAP). Receiver operating characteristic (ROC) analysis of the lymphocyte counts at diagnosis showed that 595 cells/mm was the best cut-off for discriminating two groups of patients at risk: lymphocytopenic group (lymphocyte count <595 cells/mm, 141 patients (30%)) and non-lymphocytopenic group (lymphocyte count ≥595 cells/mm, 332 patients (70%)). Patients with lymphocytopenia presented more comorbidities and a higher sequential organ failure assessment (SOFA) score at the moment of pneumonia diagnosis. Also, 28-day mortality and 90-day mortality were higher in patients with lymphocytopenia (28-day: 38 (27%) versus 59 (18%), 90-day: 74 (53%) versus 111 (34%)). In the multivariable model, <595 cells/mm resulted to be an independent predictor for 90-day mortality (Hazard Ratio 1.41; 95% Confidence Interval 1.02 to 1.94).

Conclusion: Lymphocytopenia is an independent predictor of 90-day mortality in non-immunocompromised patients with ICU-AP.
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http://dx.doi.org/10.3390/jcm8060843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617552PMC
June 2019

Pure Viral Sepsis Secondary to Community-Acquired Pneumonia in Adults: Risk and Prognostic Factors.

J Infect Dis 2019 08;220(7):1166-1171

Department of Pneumology, Hospital Clinic of Barcelona, Spain.

We investigated the risk and prognostic factors of pure viral sepsis in adult patients with community-acquired pneumonia (CAP), using the Sepsis-3 definition. Pure viral sepsis was found in 3% of all patients (138 of 4028) admitted to the emergency department with a diagnosis of CAP, 19% of those with CAP (138 of 722) admitted to the intensive care unit, and 61% of those (138 of 225) with a diagnosis of viral CAP. Our data indicate that males and patients aged ≥65 years are at increased risk of viral sepsis.
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http://dx.doi.org/10.1093/infdis/jiz257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107497PMC
August 2019

Invasive and non-invasive diagnostic approaches for microbiological diagnosis of hospital-acquired pneumonia.

Crit Care 2019 Feb 18;23(1):51. Epub 2019 Feb 18.

Department of Pneumology, Institut Clinic de Respiratori, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), ICREA Academia award, Ciber de Enfermedades Respiratorias (Ciberes, CB06/06/0028), Barcelona, Spain.

Background: Data on the methods used for microbiological diagnosis of hospital-acquired pneumonia (HAP) are mainly extrapolated from ventilator-associated pneumonia. HAP poses additional challenges for respiratory sampling, and the utility of sputum or distal sampling in HAP has not been comprehensively evaluated, particularly in HAP admitted to the ICU.

Methods: We analyzed 200 patients with HAP from six ICUs in a teaching hospital in Barcelona, Spain. The respiratory sampling methods used were divided into non-invasive [sputum and endotracheal aspirate (EAT)] and invasive [fiberoptic-bronchoscopy aspirate (FBAS), and bronchoalveolar lavage (BAL)].

Results: A median of three diagnostic methods were applied [range 2-4]. At least one respiratory sampling method was applied in 93% of patients, and two or more were applied in 40%. Microbiological diagnosis was achieved in 99 (50%) patients, 69 (70%) by only one method (42% FBAS, 23% EAT, 15% sputum, 9% BAL, 7% blood culture, and 4% urinary antigen). Seventy-eight (39%) patients underwent a fiberoptic-bronchoscopy when not receiving mechanical ventilation. Higher rates of microbiological diagnosis were observed in the invasive group (56 vs. 39%, p = 0.018). Patients with microbiological diagnosis more frequently presented changes in their empirical antibiotic scheme, mainly de-escalation.

Conclusions: A comprehensive approach might be undertaken for microbiological diagnosis in critically ill nonventilated HAP. Sputum sampling determined one third of microbiological diagnosis in HAP patients who were not subsequently intubated. Invasive methods were associated with higher rates of microbiological diagnosis.
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http://dx.doi.org/10.1186/s13054-019-2348-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379979PMC
February 2019

Determination of the Elasticity Modulus of 3D-Printed Octet-Truss Structures for Use in Porous Prosthesis Implants.

Materials (Basel) 2018 Nov 29;11(12). Epub 2018 Nov 29.

Escola Tècnica Superior d'Enginyeria Industrial de Barcelona (ETSEIB), Avinguda Diagonal, 647, 08028 Barcelona, Spain.

In tissue engineering, scaffolds can be obtained by means of 3D printing. Different structures are used in order to reduce the stiffness of the solid material. The present article analyzes the mechanical behavior of octet-truss microstructures. Three different octet structures with strut radii of 0.4, 0.5, and 0.6 mm were studied. The theoretical relative densities corresponding to these structures were 34.7%, 48.3%, and 61.8%, respectively. Two different values for the ratio of height (H) to width (W) were considered, H/W = 2 and H/W = 4. Several specimens of each structure were printed, which had the shape of a square base prism. Compression tests were performed and the elasticity modulus (E) of the octet-truss lattice-structured material was determined, both, experimentally and by means of Finite Element Methods (FEM). The greater the strut radius, the higher the modulus of elasticity and the compressive strength. Better agreement was found between the experimental and the simulated modulus of elasticity results for H/W = 4 than for H/W = 2. The octet-truss lattice can be considered to be a promising structure for printing in the field of tissue engineering.
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http://dx.doi.org/10.3390/ma11122420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317202PMC
November 2018

Effect of Combined β-Lactam/Macrolide Therapy on Mortality According to the Microbial Etiology and Inflammatory Status of Patients With Community-Acquired Pneumonia.

Chest 2019 04 22;155(4):795-804. Epub 2018 Nov 22.

Department of Pneumology, the Hospital Clinic of Barcelona, the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), the University of Barcelona (UB), SGR 911-CIBER de Enfermedades Respiratorias (CIBERES), and ICREA Academia, Barcelona, Spain. Electronic address:

Background: Antibiotic combinations that include macrolides have shown lower mortality rates than β-lactams in monotherapy or combined with fluoroquinolones in patients with community-acquired pneumonia (CAP). However, this effect has not been studied according to the levels of C-reactive protein in CAP with identified microbial cause. In patients with CAP and known microbial cause we aimed to evaluate 30-day mortality of a β-lactam plus macrolide (BL + M) compared with a fluoroquinolone alone or with a β-lactam (FQ ± BL).

Methods: We analyzed a prospective observational cohort of patients with CAP admitted to the Hospital Clinic of Barcelona between 1996 and 2016. We included only patients with known microbial cause.

Results: Of 1,715 patients (29%) with known etiology, a total of 932 patients (54%) received BL + M. Despite lower crude mortality in the BL + M group in the overall population (BL + M, 5% vs FQ ± BL, 8%; P = .015), after adjustment by a propensity score and baseline characteristics, the combination of BL + M had a protective effect on mortality only in patients with high inflammatory response (C-reactive protein, > 15 mg/dL) and pneumococcal CAP (adjusted OR, 0.28; 95% CI, 0.09-0.93). No benefits on mortality were observed for the population without high inflammatory response and pneumococcal CAP or with other etiologies.

Conclusions: The combination of a β-lactam with a macrolide was associated with decreased mortality in patients with pneumococcal CAP and in patients with high systemic inflammatory response. When both factors occurred together, BL + M was protective for mortality in the multivariate analysis.
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http://dx.doi.org/10.1016/j.chest.2018.11.006DOI Listing
April 2019

Adjunctive Therapies for Community-Acquired Pneumonia.

Clin Chest Med 2018 12;39(4):753-764

Pneumology Department, Respiratory Institute (ICR), Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), SGR 911 - Ciber de Enfermedades Respiratorias (CIBERES), ICREA Academia, Villarroel 170, Barcelona 08036, Spain; Department of Pneumology, Hospital Clinic of Barcelona, Villarroel 140, Barcelona 08036, Spain. Electronic address:

The use of adjuvant therapies for community-acquired pneumonia is still in development. Combinations of antibiotics with macrolides seem to be the best option when there is no risk of resistance. The use of corticosteroids is the treatment of choice in patients with severe pneumonia and a high inflammatory response who do not present contraindications for these drugs. Other drugs await confirmation of their benefit and should be used only on exceptional occasions at this time.
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http://dx.doi.org/10.1016/j.ccm.2018.07.008DOI Listing
December 2018

Assessment of in vivo versus in vitro biofilm formation of clinical methicillin-resistant Staphylococcus aureus isolates from endotracheal tubes.

Sci Rep 2018 08 9;8(1):11906. Epub 2018 Aug 9.

Centro de Investigación Biomedica En Red-Enfermedades Respiratorias (CibeRes, CB06/06/0028) and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Our aim was to demonstrate that biofilm formation in a clinical strain of methicillin-resistant Staphylococcus aureus (MRSA) can be enhanced by environment exposure in an endotracheal tube (ETT) and to determine how it is affected by systemic treatment and atmospheric conditions. Second, we aimed to assess biofilm production dynamics after extubation. We prospectively analyzed 70 ETT samples obtained from pigs randomized to be untreated (controls, n = 20), or treated with vancomycin (n = 32) or linezolid (n = 18). A clinical MRSA strain (MRSA-in) was inoculated in pigs to create a pneumonia model, before treating with antibiotics. Tracheally intubated pigs with MRSA severe pneumonia, were mechanically ventilated for 69 ± 16 hours. All MRSA isolates retrieved from ETTs (ETT-MRSA) were tested for their in vitro biofilm production by microtiter plate assay. In vitro biofilm production of MRSA isolates was sequentially studied over the next 8 days post-extubation to assess biofilm capability dynamics over time. All experiments were performed under ambient air (O) or ambient air supplemented with 5% CO. We collected 52 ETT-MRSA isolates (placebo N = 19, linezolid N = 11, and vancomycin N = 22) that were clonally identical to the MRSA-in. Among the ETT-MRSA isolates, biofilm production more than doubled after extubation in 40% and 50% under 5% CO and O, respectively. Systemic antibiotic treatment during intubation did not affect this outcome. Under both atmospheric conditions, biofilm production for MRSA-in was at least doubled for 9 ETT-MRSA isolates, and assessment of these showed that biofilm production decreased progressively over a 4-day period after extubation. In conclusion, a weak biofilm producer MRSA strain significantly enhances its biofilm production within an ETT, but it is influenced by the ETT environment rather than by the systemic treatment used during intubation or by the atmospheric conditions used for bacterial growth.
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http://dx.doi.org/10.1038/s41598-018-30494-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085380PMC
August 2018

Epidemiology of ICU-acquired pneumonia.

Curr Opin Crit Care 2018 10;24(5):325-331

Department of Pneumology, Respiratory Institute, Hospital Clinic - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona.

Purpose Of Review: Review of the epidemiology of ICU-acquired pneumonia, including both ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) in nonventilated ICU patients, with critical review of the most recent literature in this setting.

Recent Findings: The incidence of ICU-acquired pneumonia, mainly VAP has decrease significantly in recent years possibly due to the generalized implementation of preventive bundles. However, the exact incidence of VAP is difficult to establish due to the diagnostic limitations and the methods employed to report rates. Incidence rates greatly vary based on the studied populations. Data in the literature strongly support the relevance of intubation, not ventilatory support, in the development of HAP in ICU patients, but also that the incidence of HAP in nonintubated patients is not negligible. Despite the fact of a high crude mortality associated with the development of VAP, the overall attributable mortality of this complication was estimated in 13%, with higher mortality rates in surgical patients and those with mid-range severity scores at admission. Mortality is consistently greatest in patients with HAP who require intubation, slightly less in VAP, and least for nonventilated HAP. The economic burden of ICU acquired pneumonia, particularly VAP, is important. The increased costs are mainly related to the longer periods of ventilatory assistance and ICU and hospital stays required by these patients. However, the different impact of VAP on economic burden among countries is largely dependent on the different costs associated with heath care.

Summary: VAP has significant impact on mortality mainly in surgical patients and those with mid-range severity scores at admission. The economic burden on ICU-acquired pneumonia depends mainly on the increased length of stay of these patients.
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http://dx.doi.org/10.1097/MCC.0000000000000536DOI Listing
October 2018

Acute respiratory distress syndrome in mechanically ventilated patients with community-acquired pneumonia.

Eur Respir J 2018 03 29;51(3). Epub 2018 Mar 29.

Dept of Pneumology, Institut Clinic de Respiratori, Hospital Clinic of Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Ciber de Enfermedades Respiratorias (Ciberes), Barcelona, Spain.

Our aim was to assess the incidence, characteristics, aetiology, risk factors and mortality of acute respiratory distress syndrome (ARDS) in intensive care unit (ICU) patients with community-acquired pneumonia (CAP) using the Berlin definition.We prospectively enrolled consecutive mechanically ventilated adult ICU patients with CAP over 20 years, and compared them with mechanically ventilated patients without ARDS. The main outcome was 30-day mortality.Among 5334 patients hospitalised with CAP, 930 (17%) were admitted to the ICU and 432 required mechanical ventilation; 125 (29%) cases met the Berlin ARDS criteria. ARDS was present in 2% of hospitalised patients and 13% of ICU patients. Based on the baseline arterial oxygen tension/inspiratory oxygen fraction ratio, 60 (48%), 49 (40%) and 15 (12%) patients had mild, moderate and severe ARDS, respectively. was the most frequent pathogen, with no significant differences in aetiology between groups. Higher organ system dysfunction and previous antibiotic use were independent risk factors for ARDS in the multivariate analysis, while previous inhaled corticosteroids were independently associated with a lower risk. The 30-day mortality was similar between patients with and without ARDS (25% 30%, p=0.25), confirmed by propensity-adjusted multivariate analysis.ARDS occurs as a complication of CAP in 29% of mechanically ventilated patients, but is not related to the aetiology or mortality.
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http://dx.doi.org/10.1183/13993003.02215-2017DOI Listing
March 2018

Severe community-acquired pneumonia: Characteristics and prognostic factors in ventilated and non-ventilated patients.

PLoS One 2018 25;13(1):e0191721. Epub 2018 Jan 25.

Department of Pneumology, Respiratory Institute, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Background: Patients with severe community-acquired pneumonia (SCAP) and life-threatening acute respiratory failure may require invasive mechanical ventilation (IMV). Since use of IMV is often associated with significant morbidity and mortality, we assessed whether patients invasively ventilated would represent a target population for interventions aimed at reducing mortality of SCAP.

Methods: We prospectively recruited consecutive patients with SCAP for 12 years. We assessed the characteristics and outcomes of patients invasively ventilated at presentation of pneumonia, compared with those without IMV, and determined the influence of risks factors on mortality with a multivariate weighted logistic regression using a propensity score.

Results: Among 3,719 patients hospitalized with CAP, 664 (18%) had criteria for SCAP, and 154 (23%) received IMV at presentation of pneumonia; 198 (30%) presented with septic shock. In 370 (56%) cases SCAP was diagnosed based solely on the presence of 3 or more IDSA/ATS minor criteria. Streptococcus pneumoniae was the main pathogen in both groups. The 30-day mortality was higher in the IMV, compared to non-intubated patients (51, 33%, vs. 94, 18% respectively, p<0·001), and higher than that predicted by APACHE-II score (26%). IMV independently predicted 30-day mortality in multivariate analysis (adjusted odds-ratio 3·54, 95% confidence interval 1·45-8·37, p = 0·006). Other independent predictors of mortality were septic shock, worse hypoxemia and increased serum potassium.

Conclusion: Invasive mechanical ventilation independently predicted 30-day mortality in patients with SCAP. Patients invasively ventilated should be considered a different population with higher mortality for future clinical trials on new interventions addressed to improve mortality of SCAP.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191721PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784994PMC
March 2018
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