Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis.

OBJECTIVES: Host responses to infection are a major determinant of outcome. However, the existence of different response profiles in patients with endocarditis has not been addressed. Our objective was to apply transcriptomics to identify endotypes in patients with infective endocarditis. METHODS: A total of 32 patients with infective endocarditis were studied. Clinical data and blood samples were collected at diagnosis and RNA sequenced. Gene expression was used to identify two clusters (endocarditis endotype 1 [EE1] and endocarditis endotype 2 [EE2]). RNA sequencing was repeated after surgery. Transcriptionally active cell populations were identified by deconvolution. Differences between endotypes in clinical data, survival, gene expression, and molecular pathways involved were assessed. The identified endotypes were recapitulated in a cohort of COVID-19 patients. RESULTS: A total of 18 and 14 patients were assigned to EE1 and EE2, respectively, with no differences in clinical data. Patients assigned to EE2 showed an enrichment in genes related to T-cell maturation and a decrease in the activation of the signal transducer and activator of transcription protein family pathway, with higher counts of active T cells and lower counts of neutrophils. A total of 14 patients (nine in EE1 and five in EE2) were submitted to surgery. Surgery in EE2 patients shifted gene expression toward a EE1-like profile. In-hospital mortality was higher in EE1 (56% vs 14%, P = 0.027), with an adjusted hazard ratio of 12.987 (95% confidence interval 3.356-50). Translation of these endotypes to COVID-19 and non-COVID-19 septic patients yielded similar results in cell populations and outcome. CONCLUSIONS: Gene expression reveals two endotypes in patients with acute endocarditis, with different underlying pathogenetic mechanisms, responses to surgery, and outcomes.

Infective endocarditis in HIV-infected patients. Analysis of a national cohort.

BACKGROUND: There is limited recent evidence about infective endocarditis (IE) in HIV-infected patients. Our aim was to compare IE according to HIV infection presence. METHODS: Consecutive inclusion of IE patients at 46 Spanish hospitals between 2008 and 2021. RESULTS: From 5667 patients, 99 were HIV-infected (1·7%; 50 intravenous drugs users). Compared to patients without HIV, HIV-infected patients were more frequently male (84% vs. 67%), had younger median age (46 vs. 69 years), and less comorbidities, except liver disease (52% vs. 9%) and intravenous drug use (51% vs. 1%). They had more common tricuspid location (36% vs. 5%) and community-acquired IE (82% vs. 63%), vascular (29% vs. 17%) and cutaneous (22% vs. 7%) foci of infection, and Staphylococcus aureus aetiology (46% vs. 22%). Vegetations (84% vs. 72%), vascular phenomena (17% vs. 9%), splenomegaly (30% vs. 11%), and embolisation (41% vs 21%) were also more common. Surgical indication and surgery were less frequent in HIV-infected patients (54% vs 67%, 28% vs 47%, respectively). Median CD4 count in HIV-infected patients was 318 cells/mm3. In-hospital mortality (23% vs. 26%) and one-year mortality (25% vs. 32%) were similar in both groups. HIV infection was not independently associated with in-hospital (odds ratio 1·1, 95% CI 0·6-1·9) nor one-year mortality (hazard ratio 0·8, 95% CI 0·4-1·3). CONCLUSIONS: In the combined antiretroviral therapy era, less than 2% of IE patients have HIV infection. HIV-infected patients have a different clinical profile than those without HIV, but the presence of HIV does not seem to impact on IE prognosis.

The medical treatment of cardiogenic shock.

Cardiogenic shock is characterized by tissue hypoperfusion due to the inadequate cardiac output to maintain the tissue oxygen demand. Despite some advances in cardiogenic shock management, extremely high mortality is still associated with this clinical syndrome. Its management is based on the immediate stabilization of hemodynamic parameters through medical care and the use of mechanical circulatory supports in specialized centers. This review aims to understand the cardiogenic shock current medical treatment, consisting mainly of inotropic drugs, vasopressors and coronary revascularization. In addition, we highlight the relevance of applying measures to other organ levels based on the optimization of mechanical ventilation and the appropriate initiation of renal replacement therapy.

Características clínicas y evolución del paciente anciano mayor de 80 años en una Unidad de Cuidados Intensivos / Clinical features and disease progression of elderlypatients at the ICU setting

Objetivo Describir y caracterizar una cohorte de pacientes octogenarios ingresados en la UCI del Hospital Universitario Central de Asturias (HUCA). Diseño Estudio retrospectivo, observacional y descriptivo de 14 meses de duración. Ámbito Unidad de Cuidados Intensivos (UCI) Cardiaca y UCI Polivalente del Servicio de Medicina Intensiva del HUCA (Oviedo). Participantes Pacientes mayores de 80 años que ingresaron en la UCI durante más de 24 horas.Intervenciones Ninguna. Variables de interés principales Edad, sexo, comorbilidad, capacidad funcional, tratamiento, complicaciones, evolución, mortalidad. Resultados Los motivos de ingreso más frecuentes fueron la cirugía cardiaca y la neumonía. La estancia media de ingreso fue significativamente mayor en pacientes menores de 85 años (p=0,037). El 84,3% de estos últimos se benefició de ventilación mecánica invasiva (VMI) vs. 46,2% de los pacientes más mayores (p=<0,001). Los pacientes mayores de 85 años presentaron mayor fragilidad. El ingreso por intervención quirúrgica cardiaca se asoció con menor riesgo de mortalidad (hazard ratio [HR]=0,18; intervalo de confianza [IC] 95%, 0,062-0,527; p=0,002). Conclusiones Los resultados muestran una asociación entre el motivo de ingreso en UCI y el riesgo de mortalidad en pacientes octogenarios. La cirugía cardiaca se asoció con mejor pronóstico frente a la patología médica, donde la neumonía se asoció con mayor riesgo de mortalidad. Además, se observó una relación positiva significativa entre edad y fragilidad. (AU)

ObjectiveTo describe and characterize a cohort of octogenarian patients admitted to the ICU of the University Central Hospital of Asturias (HUCA). Design Retrospective, observational and descriptive study of 14 months’ duration. Setting Cardiac and Medical Intensive Care Units (ICU) of the HUCA (Oviedo). Participants Patients over 80 years old who were admitted to the ICU for more than 24hours. Interventions None. Main variables of interest Age, sex, comorbidity, functional dependence, treatment, complications, evolution, mortality. Results The most frequent reasons for admission were cardiac surgery and pneumonia. The average admission stay was significantly longer in patients under 85 years of age (p=0,037). 84,3% of the latter benefited from invasive mechanical ventilation compared to 46,2% of older patients (p=<0,001). Patients over 85 years of age presented greater fragility. Admission for cardiac surgery was associated with a lower risk of mortality (HR=0,18; 95% CI (0,062-0,527; p=0,002). Conclusions The results have shown an association between the reason for admission to the ICU and the risk of mortality in octogenarian patients. Cardiac surgery was associated with a better prognosis compared to medical pathology, where pneumonia was associated with a higher risk of mortality. Furthermore, a significant positive association was observed between age and frailty. (AU)

Prevalence and prognostic impact of stroke in a national cohort of infective endocarditis.

BACKGROUND: Stroke is a common complication of infective endocarditis (IE). Our aim was to describe the prevalence and prognostic impact of stroke in a national cohort of IE. METHODS: Consecutive inclusion at 46 Spanish hospitals between 2008 and 2021. RESULTS: Out of 5667 IE cases, 1125 had acute stroke (19.8%): 818 ischemic strokes (811 cardioembolic strokes (193 with hemorrhagic transformation), 4 transient ischemic attacks, 3 lacunar infarctions), 127 intracranial hemorrhages, and 27 other neurological complications (cerebral abscesses, encephalitis, and meningitis). Compared to patients without stroke, those with stroke had a similar mean age (69 years) but were more frequently female (68.2% vs 63.7%, p = 0.04) and had a higher incidence of intracardiac complications (35% vs 30%, p = 0.01), surgical indication (69.9% vs 65.9%, p = 0.001), in-hospital mortality (40.9% vs 22.0%, p < 0.001), and 1-year mortality (46.2% vs 27.9%, p < 0.001). The following variables were independently associated with stroke: mitral location (odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.34-1.8, p < 0.001), vascular phenomenon (OR = 2.9, 95% CI = 2.4-3.6, p = 0.0001), acute renal failure (OR = 1.2, 95% CI = 1.0-1.4, p = 0.021), septic shock (OR = 1.3, 95% CI = 1.1-1.6, p = 0.007), sepsis (OR = 1.3, 95% CI = 1.1-1.6, p = 0.005), surgery indicated but not performed (OR = 1.4, 95% CI = 1.2-1.7, p < 0.001), community-acquired IE (OR = 1.2, 95% CI = 1-1.4, p = 0.017), and peripheral embolization (OR = 1.6, 95% CI = 1.4-1.9, p < 0.001). Stroke was an independent predictor of in-hospital (OR = 2.1, 95% CI = 1.78-2.51, p < 0.001) and 1-year mortality (hazard ratio = 1.9, 95% CI = 1.6-2.5). CONCLUSION: One-fifth of patients with IE have concomitant stroke. Stroke is associated with mortality.

Clinical features and disease progression of elderly patients at the ICU setting.

OBJECTIVE: To describe and characterize a cohort of octogenarian patients admitted to the ICU of the University Central Hospital of Asturias (HUCA). DESIGN: Retrospective, observational and descriptive study of 14 months' duration. SETTING: Cardiac and Medical intensive care units (ICU) of the HUCA (Oviedo). PARTICIPANTS: Patients over 80 years old who were admitted to the ICU for more than 24 h. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Age, sex, comorbidity, functional dependence, treatment, complications, evolution, mortality. RESULTS: The most frequent reasons for admission were cardiac surgery and pneumonia. The average admission stay was significantly longer in patients under 85 years of age (p = 0,037). 84,3% of the latter benefited from invasive mechanical ventilation compared to 46,2% of older patients (p = <0,001). Patients over 85 years of age presented greater fragility. Admission for cardiac surgery was associated with a lower risk of mortality (HR = 0,18; 95% CI (0,062-0,527; p = 0,002). CONCLUSIONS: The results have shown an association between the reason for admission to the ICU and the risk of mortality in octogenarian patients. Cardiac surgery was associated with a better prognosis compared to medical pathology, where pneumonia was associated with a higher risk of mortality. Furthermore, a significant positive association was observed between age and frailty.

Epidemiology and Risk Factors of Mycotic Aneurysm in Patients With Infective Endocarditis and the Impact of its Rupture in Outcomes. Analysis of a National Prospective Cohort.

Background: Several aspects of the occurrence and management of mycotic aneurysm (MA) in patients with infective endocarditis (IE) have not been studied. Objectives: To determine the incidence and factors associated with MA presence and rupture and to assess the evolution of those initially unruptured MA. Methods: Prospective multicenter cohort including all patients with definite IE between January 2008 and December 2020. Results: Of 4548 IE cases, 85 (1.9%) developed MA. Forty-six (54.1%) had intracranial MA and 39 (45.9%) extracranial MA. Rupture of MA occurred in 39 patients (45.9%). Patients with ruptured MA had higher 1-year mortality (hazard ratio, 2.33; 95% confidence interval, 1.49-3.67). Of the 55 patients with initially unruptured MA, 9 (16.4%) presented rupture after a median of 3 days (interquartile range, 1-7) after diagnosis, being more frequent in intracranial MA (32% vs 3.3%, P = .004). Of patients with initially unruptured MA, there was a trend toward better outcomes among those who received early specific intervention, including lower follow-up rupture (7.1% vs 25.0%, P = .170), higher rate of aneurysm resolution in control imaging (66.7% vs 31.3%, P = .087), lower MA-related mortality (7.1% vs 16.7%, P = .232), and lower MA-related sequalae (0% vs 27.8%, P = .045). Conclusions: MA occurred in 2% of the patients with IE. Half of the Mas occurred in an intracranial location. Their rupture is frequent and associated with poor prognosis. A significant proportion of initially unruptured aneurysms result from rupture during the first several days, being more common in intracranial aneurysms. Early specific treatment could potentially lead to better outcomes.

Clinical presentation, microbiology, and prognostic factors of prosthetic valve endocarditis. Lessons learned from a large prospective registry.

BACKGROUND: Prosthetic valve endocarditis (PVE) is a serious infection associated with high mortality that often requires surgical treatment. METHODS: Study on clinical characteristics and prognosis of a large contemporary prospective cohort of prosthetic valve endocarditis (PVE) that included patients diagnosed between January 2008 and December 2020. Univariate and multivariate analysis of factors associated with in-hospital mortality was performed. RESULTS: The study included 1354 cases of PVE. The median age was 71 years with an interquartile range of 62-77 years and 66.9% of the cases were male. Patients diagnosed during the first year after valve implantation (early onset) were characterized by a higher proportion of cases due to coagulase-negative staphylococci and Candida and more perivalvular complications than patients detected after the first year (late onset). In-hospital mortality of PVE in this series was 32.6%; specifically, it was 35.4% in the period 2008-2013 and 29.9% in 2014-2020 (p = 0.031). Variables associated with in-hospital mortality were: Age-adjusted Charlson comorbidity index (OR: 1.15, 95% CI: 1.08-1.23), intracardiac abscess (OR:1.78, 95% CI:1.30-2.44), acute heart failure related to PVE (OR: 3. 11, 95% CI: 2.31-4.19), acute renal failure (OR: 3.11, 95% CI:1.14-2.09), septic shock (OR: 5.56, 95% CI:3.55-8.71), persistent bacteremia (OR: 1.85, 95% CI: 1.21-2.83) and surgery indicated but not performed (OR: 2.08, 95% CI: 1.49-2.89). In-hospital mortality in patients with surgical indication according to guidelines was 31.3% in operated patients and 51.3% in non-operated patients (p<0.001). In the latter group, there were more cases of advanced age, comorbidity, hospital acquired PVE, PVE due to Staphylococcus aureus, septic shock, and stroke. CONCLUSIONS: Not performing cardiac surgery in patients with PVE and surgical indication, according to guidelines, has a significant negative effect on in-hospital mortality. Strategies to better discriminate patients who can benefit most from surgery would be desirable.

Transcriptomic clustering of critically ill COVID-19 patients.

BACKGROUND: Infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a severe disease, termed coronavirus disease 2019 (COVID-19), with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms and their modulation has shown a mortality benefit. METHODS: In a cohort of 56 critically ill COVID-19 patients, peripheral blood transcriptomes were obtained at admission to an intensive care unit (ICU) and clustered using an unsupervised algorithm. Differences in gene expression, circulating microRNAs (c-miRNAs) and clinical data between clusters were assessed, and circulating cell populations estimated from sequencing data. A transcriptomic signature was defined and applied to an external cohort to validate the findings. RESULTS: We identified two transcriptomic clusters characterised by expression of either interferon-related or immune checkpoint genes, respectively. Steroids have cluster-specific effects, decreasing lymphocyte activation in the former but promoting B-cell activation in the latter. These profiles have different ICU outcomes, despite no major clinical differences at ICU admission. A transcriptomic signature was used to identify these clusters in two external validation cohorts (with 50 and 60 patients), yielding similar results. CONCLUSIONS: These results reveal different underlying pathogenetic mechanisms and illustrate the potential of transcriptomics to identify patient endotypes in severe COVID-19 with the aim to ultimately personalise their therapies.

Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the LUNG SAFE study.

BACKGROUND: Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality. METHODS: Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied. Relationships between ventilatory parameters and outcomes (ICU discharge/hospital mortality) were assessed using latent mixture analysis and a marginal structural model. RESULTS: From 4499 patients, 391 meeting CPE criteria (median age 70 [interquartile range 59-78], 40% female) were included. ICU and hospital mortality were 34% and 40%, respectively. ICU survivors were younger (67 [57-77] vs 74 [64-80] years, p < 0.001) and had lower driving (12 [8-16] vs 15 [11-17] cmH2O, p < 0.001), plateau (20 [15-23] vs 22 [19-26] cmH2O, p < 0.001) and peak (21 [17-27] vs 26 [20-32] cmH2O, p < 0.001) pressures. Latent mixture analysis of patients receiving invasive mechanical ventilation on ICU day 1 revealed a subgroup ventilated with high pressures with lower probability of being discharged alive from the ICU (hazard ratio [HR] 0.79 [95% confidence interval 0.60-1.05], p = 0.103) and increased hospital mortality (HR 1.65 [1.16-2.36], p = 0.005). In a marginal structural model, driving pressures in the first week (HR 1.12 [1.06-1.18], p < 0.001) and tidal volume after day 7 (HR 0.69 [0.52-0.93], p = 0.015) were related to survival. CONCLUSIONS: Higher airway pressures in invasively ventilated patients with CPE are related to mortality. These patients may be exposed to an increased risk of ventilator-induced lung injury. Trial registration Clinicaltrials.gov NCT02010073.