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.

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.

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.

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.

Management of hyperinflammation in COVID-19 patients

In response to SARS-CoV-2 infection, the immune system physiologically upregulates to try to clear the virus from the body; failure to compensate for this inflammatory response with an anti-inflammatory response leads to dysregulation of the immune system that ultimately leads to a situation of uncontrolled hyperinflammation called cytokine storm. This cytokine storm can cause ARDS or multi-organ failure leading to patient death. This review exposes the different mechanisms of the inflammatory response in COVID-19 infection and the therapeutic options to treat this process. (AU)

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.

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.

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.

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.

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.

[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.

Tratamiento farmacológico de la covid-19: revisión narrativa de los grupo de trabajo de enfermedades infecciosas y sepsis (gteis) y del grupo de trabajo de transfusiones y hemoderivados (gtth) / Pharmacological treatment of covid-19: narrative review of the working group in infectious diseases and sepsis (gteis) and the working groups in transfusions and blood products(gtth)

La infección por el virus SARS-CoV-2, denominada COVID-19 (COronaVIrus Disease 19), fue detectada inicialmente en China en diciembre 2019, y posteriormente se ha diseminado rápidamente por todo el mundo, hasta el punto de que el 11 de marzo la OMS declaró que el brote podría definirse como pandemia. La COVID-19 presenta un cuadro que oscila desde episodios leves pseudogripales a otros graves e incluso potencialmente mortales debido, sobre todo, a insuficiencia respiratoria aguda. Es frecuente el ingreso de estos pacientes en nuestros Servicios de Medicina Intensiva en relación con un Síndrome de Distrés Respiratorio Agudo (SDRA). La falta de un tratamiento con evidencia científica ha llevado al empleo de diferentes pautas terapéuticas, en muchas ocasiones, con modificaciones rápidas de los protocolos. Recientes revisiones en revistas de prestigio han destacado la falta de terapias probadas y la necesidad de ensayo clínicos que permitan establecer pautas de tratamiento claras y objetivas. Este documento tiene por objeto ofrecer una actualización de la terapia que se está aplicando en la actualidad, y una ayuda en la asistencia diaria, sin pretender sustituir los protocolos adoptados en cada centro

Infection by the SARS-CoV-2 virus, known as COVID-19 (Corona VIrus Disease-19) was initially detected in China in December 2019, and has subsequently spread rapidly throughout the world, to the point that on March 11 the World Health Organization (WHO) reported that the outbreak could be defined as a pandemic. COVID-19 disease ranges from mild flu-like episodes to other serious and even life-threatening conditions, mainly due to acute respiratory failure. These patients are frequently admitted to our Intensive Care Units in relation to acute respiratory distress syndrome (ARDS). The lack of a treatment based on scientific evidence has led to the use of different management guidelines, in many cases with rapid changes in the applied protocols. Recent reviews in reputed journals have unders cored the lack of proven therapies and the need for clinical trials to establish clear and objective treatment guidelines. The present study provides an update on the currently applied treatment, and intends to offer help in relation to daily care, without seeking to replace the protocols adopted in each individual center

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.

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.

Vitamin D binding protein, but not vitamin D or vitamin D-related peptides, is associated with septic shock mortality / La proteína transportadora de vitamina D, pero no la vitamina D ni los péptidos derivados de ella se asocia con la mortalidad de los pacientes en shock séptico

BACKGROUND: The aim of this study was to assess the prognostic value of vitamin D, vitamin D binding protein (VDBP) and vitamin D-related peptides in septic shock patients in relation to hospital mortality. METHODS: This is a single-center, prospective, observational study that included all consecutive patients meeting criteria for septic shock who were admitted to the ICU. VDBP, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, cathelicidin and beta-defensin levels were determined in blood samples obtained on admission to the ICU. RESULTS: Seventy-five patients were studied. The best area under the curve (AUC) for prediction of in-hospital mortality was for VDBP (0.78), with a negative predictive value of 85.45% for the optimal cut-off point. VDBP was also the only variable that had a statistically significant association with a higher risk of in-hospital mortality, regardless of other assessed variables and pre-determined confounders: adjusted odds ratio of 5.20 (95% confidence interval: 1.21-22.36). When restricted to patients with vitamin D insufficiency (n = 54), the AUC was 0.77, and the adjusted OR 12.22 (95% CI: 1.46-102.14; p = 0.021) for in-hospital mortality. CONCLUSIONS: VDBP levels showed a statistically significant association with in-hospital mortality, supporting the clinical utility of VDBP as a good prognostic marker in septic shock patients. Vitamin D and vitamin D-related peptides are not associated with in-hospital mortality. These results should be confirmed in a multicentre study with a larger sample size

INTRODUCCIÓN: El objeto de este estudio fue evaluar el valor pronóstico de la vitamina D, la proteína transportadora de la vitamina D (PTVD) y de los péptidos derivados de la vitamina D en relación a la mortalidad hospitalaria de los pacientes en shock séptico. MÉTODOS: Se trata de un estudio prospectivo unicéntrico observacional que incluyo consecutivamente a todos los pacientes que ingresan en la UCI en shock séptico. Los valores de la PTVD, 25-hydroxy vitamina D, 1,25-dihydroxy vitamina D, catelicidina y beta-defensina se cuantificaron en muestras sanguíneas extraídas en el momento del ingreso en la UCI. RESULTADOS: Se incluyeron un total de 75 pacientes. La mejor área bajo la curva (AUC) para la predicción de mortalidad hospitalaria fue para la PTVD (0,78), con un valor predictivo negativo del 85,45% para el punto de corte óptimo. La PTVD fue además la única variable asociada estadísticamente con un mayor riesgo de mortalidad hospitalaria independientemente de las otras variables evaluadas y de los factores de confusión prestablecidos: odds ratio ajustada 5,20 (intervalo de confianza [IC] 95%: 1,21-22,36). Cuando el estudio se focalizó en los pacientes con insuficiencia de vitamina D (N = 54), el AUC fue de 0,77 y la odds ratio ajustada de 12,22 (IC 95%: 1,46-102,14; p = 0,021) en relación a la mortalidad hospitalaria. CONCLUSIONES: Los valores sanguíneos de la PTVD se asociaron de forma estadísticamente significativa con la mortalidad hospitalaria, apoyando la potencial utilidad clínica de la PTVD como un buen marcador pronóstico en los pacientes en shock séptico. La vitamina D y los péptidos derivados de ella no relacionaron con la mortalidad hospitalaria. Estos resultados deben ser confirmados en un estudio multicéntrico con mayor número de pacientes

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.

Vitamin D binding protein, but not vitamin D or vitamin D-related peptides, is associated with septic shock mortality.

BACKGROUND: The aim of this study was to assess the prognostic value of vitamin D, vitamin D binding protein (VDBP) and vitamin D-related peptides in septic shock patients in relation to hospital mortality. METHODS: This is a single-center, prospective, observational study that included all consecutive patients meeting criteria for septic shock who were admitted to the ICU. VDBP, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, cathelicidin and beta-defensin levels were determined in blood samples obtained on admission to the ICU. RESULTS: Seventy-five patients were studied. The best area under the curve (AUC) for prediction of in-hospital mortality was for VDBP (0.78), with a negative predictive value of 85.45% for the optimal cut-off point. VDBP was also the only variable that had a statistically significant association with a higher risk of in-hospital mortality, regardless of other assessed variables and pre-determined confounders: adjusted odds ratio of 5.20 (95% confidence interval: 1.21-22.36). When restricted to patients with vitamin D insufficiency (n=54), the AUC was 0.77, and the adjusted OR 12.22 (95% CI: 1.46-102.14; p=0.021) for in-hospital mortality. CONCLUSIONS: VDBP levels showed a statistically significant association with in-hospital mortality, supporting the clinical utility of VDBP as a good prognostic marker in septic shock patients. Vitamin D and vitamin D-related peptides are not associated with in-hospital mortality. These results should be confirmed in a multicentre study with a larger sample size.

Role of biomarkers in early infectious complications after lung transplantation.

BACKGROUND: Infections and primary graft dysfunction are devastating complications in the immediate postoperative period following lung transplantation. Nowadays, reliable diagnostic tools are not available. Biomarkers could improve early infection diagnosis. METHODS: Multicentre prospective observational study that included all centres authorized to perform lung transplantation in Spain. Lung infection and/or primary graft dysfunction presentation during study period (first postoperative week) was determined. Biomarkers were measured on ICU admission and daily till ICU discharge or for the following 6 consecutive postoperative days. RESULTS: We included 233 patients. Median PCT levels were significantly lower in patients with no infection than in patients with Infection on all follow up days. PCT levels were similar for PGD grades 1 and 2 and increased significantly in grade 3. CRP levels were similar in all groups, and no significant differences were observed at any study time point. In the absence of PGD grade 3, PCT levels above median (0.50 ng/ml on admission or 1.17 ng/ml on day 1) were significantly associated with more than two- and three-fold increase in the risk of infection (adjusted Odds Ratio 2.37, 95% confidence interval 1.06 to 5.30 and 3.44, 95% confidence interval 1.52 to 7.78, respectively). CONCLUSIONS: In the absence of severe primary graft dysfunction, procalcitonin can be useful in detecting infections during the first postoperative week. PGD grade 3 significantly increases PCT levels and interferes with the capacity of PCT as a marker of infection. PCT was superior to CRP in the diagnosis of infection during the study period.

Association between recurrence of acute kidney injury and mortality in intensive care unit patients with severe sepsis.

BACKGROUND: Acute kidney injury (AKI) occurs in more than half critically ill patients admitted in intensive care units (ICU) and increases the mortality risk. The main cause of AKI in ICU is sepsis. AKI severity and other related variables such as recurrence of AKI episodes may influence mortality risk. While AKI recurrence after hospital discharge has been recently related to an increased risk of mortality, little is known about the rate and consequences of AKI recurrence during the ICU stay. Our hypothesis is that AKI recurrence during ICU stay in septic patients may be associated to a higher mortality risk. METHODS: We prospectively enrolled all (405) adult patients admitted to the ICU of our hospital with the diagnosis of severe sepsis/septic shock for a period of 30 months. Serum creatinine was measured daily. 'In-ICU AKI recurrence' was defined as a new spontaneous rise of ≥0.3 mg/dl within 48 h from the lowest serum creatinine after the previous AKI episode. RESULTS: Excluding 5 patients who suffered the AKI after the initial admission to ICU, 331 patients out of the 400 patients (82.8%) developed at least one AKI while they remained in the ICU. Among them, 79 (19.8%) developed ≥2 AKI episodes. Excluding 69 patients without AKI, in-hospital (adjusted HR = 2.48, 95% CI 1.47-4.19), 90-day (adjusted HR = 2.54, 95% CI 1.55-4.16) and end of follow-up (adjusted HR = 1.97, 95% CI 1.36-2.84) mortality rates were significantly higher in patients with recurrent AKI, independently of sex, age, mechanical ventilation necessity, APACHE score, baseline estimated glomerular filtration rate, complete recovery and KDIGO stage. CONCLUSIONS: AKI recurred in about 20% of ICU patients after a first episode of sepsis-related AKI. This recurrence increases the mortality rate independently of sepsis severity and of the KDIGO stage of the initial AKI episode. ICU physicians must be aware of the risks related to AKI recurrence while multiple episodes of AKI should be highlighted in electronic medical records and included in the variables of clinical risk scores.

The protective association of endogenous immunoglobulins against sepsis mortality is restricted to patients with moderate organ failure.

BACKGROUND: Pre-evaluation of endogenous immunoglobulin levels is a potential strategy to improve the results of intravenous immunoglobulins in sepsis, but more work has to be done to identify those patients who could benefit the most from this treatment. The objective of this study was to evaluate the impact of endogenous immunoglobulins on the mortality risk in sepsis depending on disease severity. METHODS: This was a retrospective observational study including 278 patients admitted to the ICU with sepsis fulfilling the SEPSIS-3 criteria, coming from the Spanish GRECIA and ABISS-EDUSEPSIS cohorts. Patients were distributed into two groups depending on their Sequential Organ Failure Assessment score at ICU admission (SOFA < 8, n = 122 and SOFA ≥ 8, n = 156), and the association between immunoglobulin levels at ICU admission with mortality was studied in each group by Kaplan-Meier and multivariate logistic regression analysis. RESULTS: ICU/hospital mortality in the SOFA < 8 group was 14.8/23.0%, compared to 30.1/35.3% in the SOFA ≥ 8 group. In the group with SOFA < 8, the simultaneous presence of total IgG < 407 mg/dl, IgM < 43 mg/dl and IgA < 219 mg/dl was associated with a reduction in the survival mean time of 6.6 days in the first 28 days and was a robust predictor of mortality risk either during the acute or during the post-acute phase of the disease (OR for ICU mortality: 13.79; OR for hospital mortality: 7.98). This predictive ability remained in the absence of prior immunosuppression (OR for ICU mortality: 17.53; OR for hospital mortality: 5.63). Total IgG < 407 mg/dl or IgG1 < 332 mg/dl was also an independent predictor of ICU mortality in this group. In contrast, in the SOFA ≥ 8 group, we found no immunoglobulin thresholds associated with neither ICU nor hospital mortality. CONCLUSIONS: Endogenous immunoglobulin levels may have a different impact on the mortality risk of sepsis patients based on their severity. In patients with moderate organ failure, the simultaneous presence of low levels of IgG, IgA and IgM was a consistent predictor of both acute and post-acute mortalities.