Systemic Inflammation Differences in Brain-vs. Circulatory-Dead Donors: Impact on Lung Transplant Recipients.

Brain death triggers a systemic inflammatory response. Whether systemic inflammation is different in lung donors after brain- (DBD) or circulatory-death (DCD) is unknown, but this may potentially increase the incidence of primary graft dysfunction (PGD) after lung transplantation. We compared the plasma levels of interleukin (IL)-6, IL-8, IL-10 and TNF-α in BDB and DCD and their respective recipients, as well as their relationship with PGD and mortality after LT. A prospective, observational, multicenter, comparative, cohort-nested study that included 40 DBD and 40 DCD lung donors matched and their respective recipients. Relevant clinical information and blood samples were collected before/during lung retrieval in donors and before/during/after (24, 48 and 72 h) LT in recipients. Incidence of PGD and short-term mortality after LT was recorded. Plasma levels of all determined cytokines were numerically higher in DBD than in DCD donors and reached statistical significance for IL-6, IL-10 and IL-8. In recipients with PGD the donor's plasma levels of TNF-α were higher. The post-operative mortality rate was very low and similar in both groups. DBD is associated with higher systemic inflammation than DCD donors, and higher TNF-α plasma levels in donors are associated with a higher incidence of PGD.

Chronic critical illness after trauma injury: outcomes and experience in a trauma center.

OBJECTIVE: To determine the prevalence, risk factors and functional results of chronic critical illness (CCI) in polytrauma patients. DESIGN: Single-center observational retrospective study. SETTING: ICU at a tertiary hospital in Santander, Spain, between 2015 and 2019. PATIENTS: Adult trauma patients who survived beyond 48 h after injury. CCI was defined as the need for mechanical ventilation for at least 14 days or tracheostomy for difficult weaning. MEASUREMENTS AND MAIN RESULTS: About 62/575 developed CCI. These patients were characterized by higher ISS score [17 (SD 10) vs. 13.8 (SD 8.2); p < 0.001] and higher NISS (26 (SD 11) vs. 19.2 (SD 10.5); p = 0.001). CCI group had greater proportion of hospital-acquired infections (100% vs. 18.1%; p < 0.001), and acute kidney failure (33.9% vs. 22.8% p < 0.001). During the first 24 h of admission, CCI group required in a greater proportion surgical intervention (50% vs. 29%; p = 0.001), and blood products (31.3% vs. 20.5%; p < 0.047). Hospital ward stay was longer in CCI patients [9.5 days (IQR 5-16.9) vs. 43.9 (IQR 30.3-53) p < 0.001]. The CCI mortality was higher (19.5% vs. 8.1%; p = 0.004). Surgical intervention in the first 24 h (OR 2.5 95% CI 1.1-4.1), age (> 55 years) (OR 2.1 95%CI 1.1-4.2), ISS score (OR 1.1 95%CI 1.02-1.3), GCS score (OR 0.8 95%CI 0.4-23.2) and multiple organ failure (OR 9.5 95%CI 3.9-23.2) were predictors of CCI in the multivariate analysis. CONCLUSIONS: CCI after severe trauma appears in a considerable proportion of patients. Early identification and implementation of specific interventions could change the evolution of this process.

Lung transplantation from controlled donation after circulatory death using simultaneous abdominal normothermic regional perfusion: A single center experience.

Despite the benefits of abdominal normothermic regional perfusion (A-NRP) for abdominal grafts in controlled donation after circulatory death (cDCD), there is limited information on the effect of A-NRP on the quality of the cDCD lungs. We aimed to study the effect of A-NRP in lungs obtained from cDCD and its impact on recipients´ outcomes. This is a study comparing outcomes of lung transplants (LT) from cDCD donors (September 2014 to December 2021) obtained using A-NRP as the abdominal preservation method. As controls, all lung recipients transplanted from donors after brain death (DBD) were considered. The primary outcomes were lung recipient 3-month, 1-year, and 5-year survival. A total of 269 LT were performed (60 cDCD and 209 DBD). There was no difference in survival at 3 months (98.3% cDCD vs. 93.7% DBD), 1 year (90.9% vs. 87.2%), and 5 years (68.7% vs. 69%). LT from the cDCD group had a higher rate of primary graft dysfunction grade 3 at 72 h (10% vs. 3.4%; p <  .001). This is the largest experience ever reported with the use of A-NRP combined with lung retrieval in cDCD donors. This combined method is safe for lung grafts presenting short-term survival outcomes equivalent to those transplanted through DBD.

Deploying unsupervised clustering analysis to derive clinical phenotypes and risk factors associated with mortality risk in 2022 critically ill patients with COVID-19 in Spain.

BACKGROUND: The identification of factors associated with Intensive Care Unit (ICU) mortality and derived clinical phenotypes in COVID-19 patients could help for a more tailored approach to clinical decision-making that improves prognostic outcomes. METHODS: Prospective, multicenter, observational study of critically ill patients with confirmed COVID-19 disease and acute respiratory failure admitted from 63 ICUs in Spain. The objective was to utilize an unsupervised clustering analysis to derive clinical COVID-19 phenotypes and to analyze patient's factors associated with mortality risk. Patient features including demographics and clinical data at ICU admission were analyzed. Generalized linear models were used to determine ICU morality risk factors. The prognostic models were validated and their performance was measured using accuracy test, sensitivity, specificity and ROC curves. RESULTS: The database included a total of 2022 patients (mean age 64 [IQR 5-71] years, 1423 (70.4%) male, median APACHE II score (13 [IQR 10-17]) and SOFA score (5 [IQR 3-7]) points. The ICU mortality rate was 32.6%. Of the 3 derived phenotypes, the A (mild) phenotype (537; 26.7%) included older age (< 65 years), fewer abnormal laboratory values and less development of complications, B (moderate) phenotype (623, 30.8%) had similar characteristics of A phenotype but were more likely to present shock. The C (severe) phenotype was the most common (857; 42.5%) and was characterized by the interplay of older age (> 65 years), high severity of illness and a higher likelihood of development shock. Crude ICU mortality was 20.3%, 25% and 45.4% for A, B and C phenotype respectively. The ICU mortality risk factors and model performance differed between whole population and phenotype classifications. CONCLUSION: The presented machine learning model identified three clinical phenotypes that significantly correlated with host-response patterns and ICU mortality. Different risk factors across the whole population and clinical phenotypes were observed which may limit the application of a "one-size-fits-all" model in practice.

Convalescent plasma treatment for patients of 80 years and older with COVID-19 pneumonia.

BACKGROUND: Older patients, frequently with multiple comorbidities, have a high mortality from COVID-19 infection. Convalescent plasma (CP) is a therapeutic option for these patients. Our objective is to retrospectively evaluate the efficacy and adverse events of CP treatment in this population group. METHODS: Forty one patients over 80 years old with COVID-19 pneumonia received CP added to standard treatment, 51.2% with high anti-SARS-CoV-2 IgG titers and 48.8% with low titers. Median time between the onset of symptoms and the infusion of plasma was 7 days (IQR 4-10). A similar group of 82 patients who received only standard treatment, during a period in which CP was not available, were selected as a control group. RESULTS: In-hospital mortality was 26.8% for controls and 14.6% for CP patients (P = 0.131) and ICU admission was 8.5% for controls and 4.9% for CP patients (P = 0.467). Mortality tended to be lower in the high-titer group (9.5%) than in the low-titer group (20%), and in patients transfused within the first 7 days of symptom onset (10%) than in patients transfused later (19.1%), although the differences were not statistically significant (P = 0.307 and P = 0.355 respectively). There was no difference in the length of hospitalization. No significant adverse events were associated with CP treatment. CONCLUSIONS: Convalescent plasma treatment in patients over 80 years old with COVID-19 pneumonia was well tolerated but did not present a statistically significant difference in hospital mortality, ICU admission, or length of hospitalization. The results should be interpreted with caution as only half the patients received high-titer CP and the small number of patients included in the study limits the statistical power to detect significant differences. TRIAL REGISTRATION: CEIm Cantabria # 2020.127.

Strict selection criteria in uncontrolled donation after circulatory death provide excellent long-term kidney graft survival.

BACKGROUND: We aimed to report our experience in uncontrolled donation after circulatory death (uDCD) kidney transplantation applying a strict donor selection and preservation criteria. METHODS: All kidney recipients received a graft from a local uDCD. As controls, we included all renal transplants from local standard criteria donation after brain death (SDBD) donors. Normothermic regional perfusion was the preservation method in all cases. RESULTS: A total of 19 kidneys from uDCD donors were included and 67 controls. Delayed graft function (DGF) was higher in the uDCD group (42.1% vs 17.9%; P = .033), whereas no differences were observed in primary nonfunction (0% cases vs 3% controls; P = .605). The estimated glomerular filtration rate was identical in both groups. No differences were observed in graft survival censored for death between the uDCD and the SDBD groups at 1-year (100% vs 95%) or 5-year follow-up (92% vs 91%). uDCD kidney recipients did not have higher risk of graft loss in the multivariate analysis adjusted by recipient age, cold ischemic time, presence of DGF, and second kidney transplant (HR: 0.4; 95% CI 0.02-6; P = .509). CONCLUSIONS: Obtaining renal grafts from uDCD is feasible in a small city and provides similar outcomes compared to standard DBD donors.

Excellent long-term outcome with lungs obtained from uncontrolled donation after circulatory death.

We aimed to propose a simple and effective preservation method in lungs procured for transplantation from uncontrolled donation after circulatory death (uDCD) associated with excellent long-term results. Outcome measures for lung recipients were survival and primary graft dysfunction (PGD) grade 3. Survival was estimated using the Kaplan-Meier method. A total of 9 lung uDCDs were evaluated and 8 lung transplants were performed. Mean no-flow time was 9.8 minutes (standard deviation [SD] 8.6). Mean time from cardiac arrest to topical cooling was 96.8 minutes (SD 16.8). Preservation time was 159 minutes (SD 31). Ex vivo lung perfusion was used to assess lung function prior to transplantation in 2 cases. Mean recipient age was 60.8 years (SD 3.1), and mean total ischemic time was 678 minutes (SD 132). PGD grade 3 was observed in 2 cases (25%). The 1-month, 1-year, and 5-year survival rates were 100%, 87.5%, and 87.5%, respectively. Mean follow-up was 52 months. The logistic complexity of procuring lungs from uDCDs for transplantation requires the development of new strategies designed to facilitate this type of donation. A program based on strict selection criteria, using a simple and effective preservation technique, may recover lung grafts with excellent long-term posttransplant outcomes.

Within-host transition to GES-55 during a GES-6-producing Serratia marcescens outbreak: Emergence of ceftazidime-avibactam resistance and increased susceptibility to carbapenems.

OBJECTIVES: To describe the in vivo emergence of ceftazidime-avibactam resistance in GES-type carbapenemases and to characterize an unusual outbreak of GES-6-producing Serratia marcescens during the COVID-19 pandemic in Spain. METHODS: Retrospective study to describe a GES-CPSM outbreak based on whole genome sequencing and antimicrobial susceptibility testing (AST). Transferability of blaGES-carrying plasmid was assessed by conjugation experiments. RESULTS: In December 2020, we identified a cluster of S. marcescens harbouring blaGES-6 involving 9 patients. Whole-genome sequence analysis revealed a clonal relationship (≤3 SNPs) between the first isolates identified in each of the evolved patients and environmental samples with GES-CPSM detection. Plasmid analysis showed that the blaGES-6 gene was located in an IncQ3-type plasmid. Triparental mating experiments using a helper plasmid demonstrated mobilization of the blaGES-6-carrying plasmid. Our results also demonstrate within-host evolution in S. marcescens isolates, leading to a transition from blaGES-6 to the new blaGES-55, caused by the P162S mutation, in a subsequent infection in one of the affected patients. In blaGES-55 we identified emergence of ceftazidime-avibactam resistance along with an increase of carbapenems susceptibility. This patient had been treated with a 14-day course of ceftazidime-avibactam. AST of the transformants bearing blaGES-6 and blaGES-55 plasmids, confirmed susceptibility variation affecting ceftazidime-avibactam and carbapenems. CONCLUSIONS: We report an unusual outbreak of GES-6 whose incidence is becoming increasing. Transition from GES-6 to GES-55 may readily occur in vivo leading to ceftazidime-avibactam resistance, which brings to the fore the critical need for developing more accurate diagnosis tools for detection of GES ß-lactamases and optimise the use of antimicrobials.

A Machine Learning Approach to Determine Risk Factors for Respiratory Bacterial/Fungal Coinfection in Critically Ill Patients with Influenza and SARS-CoV-2 Infection: A Spanish Perspective.

Background: Bacterial/fungal coinfections (COIs) are associated with antibiotic overuse, poor outcomes such as prolonged ICU stay, and increased mortality. Our aim was to develop machine learning-based predictive models to identify respiratory bacterial or fungal coinfections upon ICU admission. Methods: We conducted a secondary analysis of two prospective multicenter cohort studies with confirmed influenza A (H1N1)pdm09 and COVID-19. Multiple logistic regression (MLR) and random forest (RF) were used to identify factors associated with BFC in the overall population and in each subgroup (influenza and COVID-19). The performance of these models was assessed by the area under the ROC curve (AUC) and out-of-bag (OOB) methods for MLR and RF, respectively. Results: Of the 8902 patients, 41.6% had influenza and 58.4% had SARS-CoV-2 infection. The median age was 60 years, 66% were male, and the crude ICU mortality was 25%. BFC was observed in 14.2% of patients. Overall, the predictive models showed modest performances, with an AUC of 0.68 (MLR) and OOB 36.9% (RF). Specific models did not show improved performance. However, age, procalcitonin, CRP, APACHE II, SOFA, and shock were factors associated with BFC in most models. Conclusions: Machine learning models do not adequately predict the presence of co-infection in critically ill patients with pandemic virus infection. However, the presence of factors such as advanced age, elevated procalcitonin or CPR, and high severity of illness should alert clinicians to the need to rule out this complication on admission to the ICU.

Applicability of an unsupervised cluster model developed on first wave COVID-19 patients in second/third wave critically ill patients.

OBJECTIVE: To validate the unsupervised cluster model (USCM) developed during the first pandemic wave in a cohort of critically ill patients from the second and third pandemic waves. DESIGN: Observational, retrospective, multicentre study. SETTING: Intensive Care Unit (ICU). PATIENTS: Adult patients admitted with COVID-19 and respiratory failure during the second and third pandemic waves. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Collected data included demographic and clinical characteristics, comorbidities, laboratory tests and ICU outcomes. To validate our original USCM, we assigned a phenotype to each patient of the validation cohort. The performance of the classification was determined by Silhouette coefficient (SC) and general linear modelling. In a post-hoc analysis we developed and validated a USCM specific to the validation set. The model's performance was measured using accuracy test and area under curve (AUC) ROC. RESULTS: A total of 2330 patients (mean age 63 [53-82] years, 1643 (70.5%) male, median APACHE II score (12 [9-16]) and SOFA score (4 [3-6]) were included. The ICU mortality was 27.2%. The USCM classified patients into 3 clinical phenotypes: A (n = 1206 patients, 51.8%); B (n = 618 patients, 26.5%), and C (n = 506 patients, 21.7%). The characteristics of patients within each phenotype were significantly different from the original population. The SC was -0.007 and the inclusion of phenotype classification in a regression model did not improve the model performance (0.79 and 0.78 ROC for original and validation model). The post-hoc model performed better than the validation model (SC -0.08). CONCLUSION: Models developed using machine learning techniques during the first pandemic wave cannot be applied with adequate performance to patients admitted in subsequent waves without prior validation.

Relationship between volume and survival in closed intensive care units is weak and apparent only in mechanically ventilated patients.

BACKGROUND: Recent studies have found an association between increased volume and increased intensive care unit (ICU) survival; however, this association might not hold true in ICUs with permanent intensivist coverage. Our objective was to determine whether ICU volume correlates with survival in the Spanish healthcare system. METHODS: Post hoc analysis of a prospective study of all patients admitted to 29 ICUs during 3 months. At ICU discharge, the authors recorded demographic variables, severity score, and specific ICU treatments. Follow-up variables included ICU readmission and hospital mortality. Statistics include logistic multivariate analyses for hospital mortality according to quartiles of volume of patients. RESULTS: The authors studied 4,001 patients with a mean predicted risk of death of 23% (range at hospital level: 14-46%). Observed hospital mortality was 19% (range at hospital level: 11-35%), resulting in a standardized mortality ratio of 0.81 (range: 0.5-1.3). Among the 1,923 patients needing mechanical ventilation, the predicted risk of death was 32% (14-60%) and observed hospital mortality was 30% (12-61%), resulting in a standardized mortality ratio of 0.96 (0.5-1.7). The authors found no correlation between standardized mortality ratio and ICU volume in the entire population or in mechanically ventilated patients. Only mechanically ventilated patients in very low-volume ICUs had slightly worse outcome. CONCLUSION: In the currently studied healthcare system characterized by 24/7 intensivist coverage, the authors found wide variability in outcome among ICUs even after adjusting for severity of illness but no relationship between ICU volume and outcome. Only mechanically ventilated patients in very low-volume centers had slightly worse outcomes.

Managing the Next Wave of Influenza and/or SARS-CoV-2 in the ICU-Practical Recommendations from an Expert Group for CAPA/IAPA Patients.

The aim of this study was to establish practical recommendations for the diagnosis and treatment of influenza-associated invasive aspergillosis (IAPA) based on the available evidence and experience acquired in the management of patients with COVID-19-associated pulmonary aspergillosis (CAPA). The CAPA/IAPA expert group defined 14 areas in which recommendations would be made. To search for evidence, the PICO strategy was used for both CAPA and IAPA in PubMed, using MeSH terms in combination with free text. Based on the results, each expert developed recommendations for two to three areas that they presented to the rest of the group in various meetings in order to reach consensus. As results, the practical recommendations for the management of CAPA/IAPA patients have been grouped into 12 sections. These recommendations are presented for both entities in the following situations: when to suspect fungal infection; what diagnostic methods are useful to diagnose these two entities; what treatment is recommended; what to do in case of resistance; drug interactions or determination of antifungal levels; how to monitor treatment effectiveness; what action to take in the event of treatment failure; the implications of concomitant corticosteroid administration; indications for the combined use of antifungals; when to withdraw treatment; what to do in case of positive cultures for Aspergillus spp. in a patient with severe viral pneumonia or Aspergillus colonization; and how to position antifungal prophylaxis in these patients. Available evidence to support the practical management of CAPA/IAPA patients is very scarce. Accumulated experience acquired in the management of CAPA patients can be very useful for the management of IAPA patients. The expert group presents eminently practical recommendations for the management of CAPA/IAPA patients.

Ten Issues to Update in Nosocomial or Hospital-Acquired Pneumonia: An Expert Review.

Nosocomial pneumonia, or hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) are important health problems worldwide, with both being associated with substantial morbidity and mortality. HAP is currently the main cause of death from nosocomial infection in critically ill patients. Although guidelines for the approach to this infection model are widely implemented in international health systems and clinical teams, information continually emerges that generates debate or requires updating in its management. This scientific manuscript, written by a multidisciplinary team of specialists, reviews the most important issues in the approach to this important infectious respiratory syndrome, and it updates various topics, such as a renewed etiological perspective for updating the use of new molecular platforms or imaging techniques, including the microbiological diagnostic stewardship in different clinical settings and using appropriate rapid techniques on invasive respiratory specimens. It also reviews both Intensive Care Unit admission criteria and those of clinical stability to discharge, as well as those of therapeutic failure and rescue treatment options. An update on antibiotic therapy in the context of bacterial multiresistance, in aerosol inhaled treatment options, oxygen therapy, or ventilatory support, is presented. It also analyzes the out-of-hospital management of nosocomial pneumonia requiring complete antibiotic therapy externally on an outpatient basis, as well as the main factors for readmission and an approach to management in the emergency department. Finally, the main strategies for prevention and prophylactic measures, many of them still controversial, on fragile and vulnerable hosts are reviewed.

Controlled Donation After Circulatory Death Program: Analysis and Results at a Tertiary Care Hospital.

BACKGROUND: The objective of the study was to evaluate the impact in organs obtained and transplanted from controlled donation after circulatory death (cDCD). METHODS: Transplants from cDCD donors performed at the Hospital Universitario Marqués de Valdecilla from the beginning of the program (December 2013) to December 2020 were evaluated. All procedures were performed with normothermic regional perfusion. Donors after brain death (DBDs) during the same period were used as a control group. RESULTS: A total of 95 donors after cardiac death and 152 DBDs were included. Age was similar in both groups (60 years [IQR, 53-68 years vs 62 years {IQR, 51-79 years]; P = .390). The number of organs recovered per donor was higher in the DBD group (4 [IQR, 3-5] vs 3 [IQR, 2-4], P < .001], as well as the number of transplanted organs (4 [IQR, 2-4] vs 2 [IQR, 2-4]; P = .002]. However, the number of noneffective donors was similar. DBDs presented a higher rate of liver donation (30.5% vs 46.7%; P = .012), lung donation (25.3% vs 38.2%; P = .036), and cardiac donation (1.1% vs 21.7%; P < .001) with respect to the donors after cardiac death group, but kidney and pancreatic donation were similar. CONCLUSIONS: The cDCD with normothermic regional perfusion program is fully established in our center. The age of the cDCD donor has increased with experience and it is currently identical to the control group (DBD). After overcoming the learning curve, cDCD is a multiorgan donation that presents an excellent profitability in the number of organs extracted and transplanted.

Immunomodulatory therapy for the management of critically ill patients with COVID-19: A narrative review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. AIM: To describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of hyperinflammation and abnormal immune responses to disease progression together with a complete narrative review of the different immunoadjuvant treatments used so far in COVID-19 and their indication in severe and life-threatening subsets. METHODS: A comprehensive literature search was developed. Authors reviewed the selected manuscripts following the PRISMA recommendations for systematic review and meta-analysis documents and selected the most appropriate. Finally, a recommendation of the use of each treatment was established based on the level of evidence of the articles and documents reviewed. This recommendation was made based on the consensus of all the authors. RESULTS: A brief rationale on the SARS-CoV-2 pathogenesis, immune response, and inflammation was developed. The usefulness of 10 different families of treatments related to inflammation and immunopathogenesis of COVID-19 was reviewed and discussed. Finally, based on the level of scientific evidence, a recommendation was established for each of them. CONCLUSION: Although several promising therapies exist, only the use of corticosteroids and tocilizumab (or sarilumab in absence of this) have demonstrated evidence enough to recommend its use in critically ill patients with COVID-19. Endotypes including both, clinical and biological characteristics can constitute specific targets for better select certain therapies based on an individualized approach to treatment.

Impact of early oseltamivir treatment on outcome in critically ill patients with 2009 pandemic influenza A.

OBJECTIVES: 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 the timing 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) with oseltamivir, 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 required mechanical ventilation (MV; mortality 32.6%). Among them, 385 received effective antiviral therapy and were included in the study group. All patients received oseltamivir for a median duration of 10 days (interquartile range 8-14 days). Seventy-nine (20.5%) ET patients were compared with 306 LT patients. The two groups were comparable in terms of main clinical variables. ICU length of stay (22.7 ±â€Š16.7 versus 18.4 ±â€Š14.2 days; P = 0.03), hospital length of stay (34.0 ±â€Š20.3 versus 27.2 ±â€Š18.2 days; P = 0.001) and MV days (17.4 ±â€Š15.2 versus 14.0 ±â€Š12.4; P = 0.04) were higher in the LT group. ICU mortality was also higher in LT (34.3%) than in ET (21.5%; OR = 1.9; 95% CI 1.06-3.41). A multivariate model identified ET (OR = 0.44; 95% CI 0.21-0.87) as an independent variable associated with reduced ICU mortality. These results were confirmed by propensity score analysis (OR = 0.44; 95% CI 0.22-0.90; P < 0.001). CONCLUSIONS: Our findings suggest that early oseltamivir administration was associated with favourable outcomes among critically ill ventilated patients with 2009 H1N1 virus infection.

[Clinical safety of liposomal amphotericin B]. / Seguridad clínica de la anfotericina B liposomal.

This article reviews the safety profile of liposomal amphotericin B, emphasizing the renal toxicity; the risk factors for its presentation, incidence, severity, and potential reversibility are expounded.

Usefulness of the COVID-GRAM and CURB-65 scores for predicting severity in patients with COVID-19.

AIM: The aim of this study was to determine the usefulness of COVID-GRAM and CURB-65 scores as predictors of the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Caucasian patients. METHODS: This was a retrospective observational study including all adults with SARS-CoV-2 infection admitted to Hospital Universitario Marqués de Valdecilla from February to May 2020. Patients were stratified according to COVID-GRAM and CURB-65 scores as being at low-medium or high risk of critical illness. Univariate analysis, multivariate logistic regression models, receiver operating characteristic curve, and area under the curve (AUC) were calculated. RESULTS: A total of 523 patients were included (51.8% male, 48.2% female; mean age 65.63 years (standard deviation 17.89 years)), of whom 110 (21%) presented a critical illness (intensive care unit admission 10.3%, 30-day mortality 13.8%). According to the COVID-GRAM score, 122 (23.33%) patients were classified as high risk; 197 (37.7%) presented a CURB-65 score ≥2. A significantly greater proportion of patients with critical illness had a high COVID-GRAM score (64.5% vs 30.5%; P < 0.001). The COVID-GRAM score emerged as an independent predictor of critical illness (odds ratio 9.40, 95% confidence interval 5.51-16.04; P < 0.001), with an AUC of 0.779. A high COVID-GRAM score showed an AUC of 0.88 for the prediction of 30-day mortality, while a CURB-65 ≥2 showed an AUC of 0.83. CONCLUSIONS: The COVID-GRAM score may be a useful tool for evaluating the risk of critical illness in Caucasian patients with SARS-CoV-2 infection. The CURB-65 score could be considered as an alternative.

Impact of the Surviving Sepsis Campaign protocols on hospital length of stay and mortality in septic shock patients: results of a three-year follow-up quasi-experimental study.

OBJECTIVES: To describe the effectiveness of the Surviving Sepsis Campaign bundles with regard to both implementation and outcome in patients with septic shock and to determine the contribution of the various elements of the bundles to the outcome. DESIGN: Quasi-experimental study with a historical comparison group. SETTING: The three medical-surgical intensive care units of an academic tertiary care center. PATIENTS: A total of 384 adult patients in septic shock were enrolled after the educational intervention (September 2005-August 2008) and 96 patients in the historical group (June 2004-May 2005). INTERVENTION: A hospital-wide quality improvement program based on the implementation of the Surviving Sepsis Campaign guidelines performed between June 2005 and August 2005. MEASUREMENTS AND RESULTS: In-hospital mortality was reduced from 57.3% in the historical group to 37.5% in the intervention group (p = .001). This difference remained significant after controlling for confounding factors (odds ratio, 0.50; 95% confidence interval, 0.28-0.89). The intervention group had also lower length of stay for survivors in the hospital (36.2 +/- 34.8 days vs. 41.0 +/- 26.3 days; p = .043) and in the intensive care units (8.4 +/- 9.8 days vs. 11.0 +/- 9.5 days; p = .004). Improvements in survival were related to the number of bundle interventions completed (p for trend <.001). Compliance with six or more interventions of the 6-hr resuscitation bundle was an independent predictor of survival (adjusted odds ratio, 0.30; 95% confidence interval, 0.17-0.53; p <.001). The only single intervention with impact on mortality was the achievement of ScvO2 > or =70% (adjusted odds ratio, 0.62; 95% confidence interval, 0.38-0.99; p = .048). CONCLUSIONS: The implementation of the Surviving Sepsis Campaign guidelines was associated with a significant decrease in mortality. The benefits depend on the number of interventions accomplished within the time limits. The 6-hr resuscitation bundle showed greater compliance and effectiveness than the 24-hr management bundle.

Pulmonary venous obstruction after lung transplantation. Diagnostic advantages of transesophageal echocardiography.

Pulmonary venous vascular complications after lung transplantation are rare and a major cause of morbidity and mortality unless diagnosed and treated early. The epidemiological, diagnostic, and management characteristics of 33 patients (two of them in our hospital) with post-transplant pulmonary vein obstruction published in the literature were reviewed. We consider of utmost importance to differentiate stenosis from thrombosis as the cause of the obstruction. The angiography, considered the gold standard for diagnosis, was replaced by transesophageal echocardiography (TEE) in 79% of the cases, but no echocardiographic diagnostic criteria were defined. A diameter of the pulmonary veins, with 2D/color TEE, <0.5 cm, peak systolic flow velocity (PSFV) >1 m/s, pulmonary vein-left atrial pressure gradient (PVLAG) >/=10-12 mmHg, non-permeable flow through the stenosis and the presence of thrombus at that level, must lead us to suspect this complication. Higher mortality rates were found in unilateral procedures and in women. We consider that TEE must be carried out as part of the intraoperative routine or within the first 24 h of the post-operative period.