PLASMA DYNAMICS OF NEUTROPHIL EXTRACELLULAR TRAPS AND CELL-FREE DNA IN SEPTIC AND NONSEPTIC VASOPLEGIC SHOCK: A PROSPECTIVE COMPARATIVE OBSERVATIONAL COHORT STUDY.

ABSTRACT: Background: The association between neutrophil extracellular traps (NETs) and the requirement for vasopressor and inotropic support in vasoplegic shock is unclear. This study aimed to investigate the dynamics of plasma levels of NETs and cell-free DNA (cfDNA) up to 48 h after the admission to the intensive care unit (ICU) for management of vasoplegic shock of infectious (SEPSIS) or noninfectious (following cardiac surgery, CARDIAC) origin. Methods: This is a prospective, observational study of NETs and cfDNA plasma levels at 0H (admission) and then at 12H, 24H, and 48H in SEPSIS and CARDIAC patients. The vasopressor inotropic score (VIS), the Sequential Organ Failure Assessment (SOFA) score, and time spent with invasive ventilation, in ICU and in hospital, were recorded. Associations between NETs/cfDNA and VIS and SOFA were analyzed by Spearman's correlation (rho), and between NETs/cfDNA and ventilation/ICU/hospitalization times by generalized linear regression. Results: Both NETs and cfDNA remained elevated over 48 h in SEPSIS (n = 46) and CARDIAC (n = 30) patients, with time-weighted average concentrations greatest in SEPSIS (NETs median difference 0.06 [0.02-0.11], P = 0.005; cfDNA median difference 0.48 [0.20-1.02], P < 0.001). The VIS correlated to NETs (rho = 0.3-0.60 in SEPSIS, P < 0.01, rho = 0.36-0.57 in CARDIAC, P ≤ 0.01) and cfDNA (rho = 0.40-0.56 in SEPSIS, P < 0.01, rho = 0.38-0.47 in CARDIAC, P < 0.05). NETs correlated with SOFA. Neither NETs nor cfDNA were independently associated with ventilator/ICU/hospitalization times. Conclusion: Plasma levels of NETs and cfDNA correlated with the dose of vasopressors and inotropes administered over 48 h in patients with vasoplegic shock from sepsis or following cardiac surgery. NETs levels also correlated with organ dysfunction. These findings suggest that similar mechanisms involving release of NETs are involved in the pathophysiology of vasoplegic shock irrespective of an infectious or noninfectious etiology.

Volume status and volume responsiveness in postoperative cardiac surgical patients: An observational, multicentre cohort study.

BACKGROUND: The best strategy to identify patients in whom fluid loading increases cardiac output (CO) following cardiac surgery remains debated. This study examined the utility of a calculated mean systemic filling pressure analogue (Pmsa ) and derived variables to explain the response to a fluid bolus. METHODS: The Pmsa was calculated using retrospective, observational cohort data in the early postoperative period between admission to the intensive care unit and extubation within 6 hours. The venous return pressure gradient (VRdP) was calculated as Pmsa  - central venous pressure. Concurrent changes induced by a fluid bolus in the ratio of the VRdP over Pmsa , the volume efficiency (Evol ), were studied to assess fluid responsiveness. Changes between Pmsa and derived variables and CO were analysed by Wilcoxon rank-sum test, hierarchial clustering and multiple linear regression. RESULTS: Data were analysed for 235 patients who received 489 fluid boluses. The Pmsa increased with consecutive fluid boluses (median difference [range] 1.3 [0.5-2.4] mm Hg, P = .03) with a corresponding increase in VRdP (median difference 0.4 [0.2-0.6] mm Hg, P = .04). Hierarchical cluster analysis only identified Evol and the change in CO within one cluster. The multiple linear regression between Pmsa and its derived variables and the change in CO (overall r2  = .48, P < .001) demonstrated the best partial regression between the continuous change in CO and the concurrent Evol (r = .55, P < .001). CONCLUSION: The mean systemic filling Pmsa enabled a comprehensive interpretation of fluid responsiveness with volume efficiency useful to explain the change in CO as a continuous phenomenon.

Associations between mean systemic filling pressure and acute kidney injury: An observational cohort study following cardiac surgery.

BACKGROUND: Venous congestion has been implied in cardiac surgery-associated acute kidney injury (CSA-AKI). The mean systemic filling pressure may provide a physiologically more accurate estimate of renal venous pressure and renal perfusion pressure but its association with CSA-AKI has not been reported. METHODS: Patients admitted to ICU following cardiac surgery without pre-operative renal dysfunction were included with monitoring of mean arterial pressure (MAP) and central venous pressure (CVP) and cardiac output (CO) to calculate the mean systemic filling pressure analogue (Pmsa ). The AKI-KDIGO guidelines were used to define CSA-AKI. Logistic regression models including CO, heart rate, MAP, CVP and Pmsa were used to ascertain the association with CSA-AKI and reported by odds ratio (OR) with 95% confidence interval (95%CI) and area under the curve (AUROC). RESULTS: One hundred and thirty patients (out of 221 screened) were included of whom 66 (51%) developed CSA-AKI. Patients with CSA-AKI were older, with greater weight and increased stay in ICU while the proportion of comorbidities, type of surgical procedures, APACHE III scores and fluid volumes administered were similar to patients without AKI. The Pmsa , but not CVP, was associated with CSA-AKI (OR 1.2 95%CI [1.16-1.25]). Renal perfusion pressure was associated with CSA-AKI estimated as MAP-Pmsa (OR 0.81 [0.76-0.86]) and MAP-CVP (OR 0.89 [0.85-0.93]) with the former generating a higher AUROC (median difference 0.10 [0.07-0.12], P < .001) in the regression model. CONCLUSIONS: The Pmsa in post-operative cardiac surgery patients was associated with the development of CSA-AKI also when incorporated into estimates of renal perfusion pressure.

Clinical characteristics and evolution of non-HIV-infected immunocompromised patients with an in-hospital diagnosis of tuberculosis.

OBJECTIVE: To investigate the characteristics of and risk factors for mortality among non-HIV-infected immunocompromised patients with an in-hospital diagnosis of tuberculosis. METHODS: This was a two-year, retrospective cohort study of patients with an in-hospital diagnosis of tuberculosis. The predictive factors for mortality were evaluated. RESULTS: During the study period, 337 hospitalized patients were diagnosed with tuberculosis, and 61 of those patients presented with immunosuppression that was unrelated to HIV infection. Extrapulmonary tuberculosis was found in 47.5% of cases. In the latter group, the in-hospital mortality rate was 21.3%, and the mortality rate after discharge was 18.8%. One-year survival was significantly higher among the immunocompetent patients than among the HIV patients (p = 0.008) and the non-HIV-infected immunocompromised patients (p = 0.015), although there was no such difference between the two latter groups (p = 0.848). Among the non-HIV-infected immunocompromised patients, the only factor statistically associated with mortality was the need for mechanical ventilation. Among the patients over 60 years of age, fibrosis/atelectasis on chest X-rays and dyspnea were more common, whereas fever and consolidations were less common. Fever was also less common among the patients with neoplasms. The time from admission to the initiation of treatment was significant longer in patients over 60 years of age, as well as in those with diabetes and those with end-stage renal disease. Weight loss was least common in patients with diabetes and in those using corticosteroids. CONCLUSIONS: The lower prevalence of classic symptoms, the occurrence of extrapulmonary tuberculosis, the delayed initiation of treatment, and the high mortality rate reflect the diagnostic and therapeutic challenges of tuberculosis in non-HIV-infected immunocompromised patients.

Características clínicas e evolução de pacientes imunocomprometidos não HIV com diagnóstico intra-hospitalar de tuberculose / Clinical characteristics and evolution of non-HIV-infected immunocompromised patients with an in-hospital diagnosis of tuberculosis

OBJETIVO: Investigar as características de pacientes imunocomprometidos não HIV com diagnóstico intra-hospitalar de tuberculose e determinar os fatores de risco para mortalidade. MÉTODOS: Durante um período de dois anos, foi realizado um estudo de coorte retrospectivo que incluiu os pacientes com diagnóstico de tuberculose após a internação. Os fatores preditores de mortalidade foram coletados. RESULTADOS: Durante o período do estudo, 337 pacientes foram internados e diagnosticados com TB, e desses, 61 apresentavam imunossupressão não decorrente da infecção pelo HIV. A tuberculose extrapulmonar estava presente em 47,5 por cento dos casos. Nesse grupo, a taxa de mortalidade intra-hospitalar foi de 21,3 por cento, e a mortalidade após a alta foi de 18,8 por cento. Os pacientes imunocompetentes tiveram sobrevida em um ano maior que os pacientes com HIV (p = 0,008) e que os imunocomprometidos não HIV (p = 0,015), mas não houve diferença na sobrevida entre esses dois últimos grupos (p = 0,848). Entre os pacientes imunocomprometidos não HIV, o único fator estatisticamente associado à mortalidade foi a necessidade de ventilação mecânica. Entre os maiores de 60 anos, dispneia e presença de fibrose/atelectasias na radiografia de tórax foram mais comuns, enquanto febre e consolidações foram menos frequentes nesse grupo. A febre também foi um sintoma encontrado menos comumente nos pacientes com neoplasias. O tempo até o início do tratamento foi significativamente maior nos pacientes maiores de 60 anos, nos diabéticos e nos pacientes renais crônicos. Nos pacientes diabéticos e naqueles usuários de corticosteroides, o emagrecimento foi um sintoma menos frequentemente relatado. CONCLUSÕES: A menor prevalência de sintomas clássicos, a ocorrência de tuberculose extrapulmonar, o atraso no início do tratamento e a alta taxa de mortalidade refletem o desafio diagnóstico e terapêutico da tuberculose em pacientes imunocomprometidos não HIV.

OBJECTIVE: To investigate the characteristics of and risk factors for mortality among non-HIV-infected immunocompromised patients with an in-hospital diagnosis of tuberculosis. METHODS: This was a two-year, retrospective cohort study of patients with an in-hospital diagnosis of tuberculosis. The predictive factors for mortality were evaluated. RESULTS: During the study period, 337 hospitalized patients were diagnosed with tuberculosis, and 61 of those patients presented with immunosuppression that was unrelated to HIV infection. Extrapulmonary tuberculosis was found in 47.5 percent of cases. In the latter group, the in-hospital mortality rate was 21.3 percent, and the mortality rate after discharge was 18.8 percent. One-year survival was significantly higher among the immunocompetent patients than among the HIV patients (p = 0.008) and the non-HIV-infected immunocompromised patients (p = 0.015), although there was no such difference between the two latter groups (p = 0.848). Among the non-HIV-infected immunocompromised patients, the only factor statistically associated with mortality was the need for mechanical ventilation. Among the patients over 60 years of age, fibrosis/atelectasis on chest X-rays and dyspnea were more common, whereas fever and consolidations were less common. Fever was also less common among the patients with neoplasms. The time from admission to the initiation of treatment was significant longer in patients over 60 years of age, as well as in those with diabetes and those with end-stage renal disease. Weight loss was least common in patients with diabetes and in those using corticosteroids. CONCLUSIONS: The lower prevalence of classic symptoms, the occurrence of extrapulmonary tuberculosis, the delayed initiation of treatment, and the high mortality rate reflect the diagnostic and therapeutic challenges of tuberculosis in non-HIV-infected immunocompromised patients.

Factors associated with mortality in hospitalized patients with newly diagnosed tuberculosis.

The purpose of this study was to identify clinical and epidemiological factors associated with death in patients with an in-hospital diagnosis of tuberculosis (TB), in a city with a high prevalence of TB and human immunodeficiency virus (HIV) infection. The study was a retrospective, cohort study conducted at a general, tertiary-care, university-affiliated hospital. Patients who began treatment for TB after hospitalization were included. Predictors of mortality were assessed. The primary outcomes were the in-hospital mortality and the mortality after discharge. We evaluated the medical records of 311 patients with TB. The overall mortality rate of all study participants was 99/311 (31.8%). The mortality rates during hospitalization and after discharge were 50/311 (16.1%) and 49/261 (18.8%), respectively. Mechanical ventilation, consolidation in chest X-ray, and negative sputum smear were predictors of in-hospital death in multivariate analysis. Independent predictors of mortality after discharge in multivariate analysis included total duration of hospitalization and being a current smoker. We found a high overall mortality rate for patients hospitalized with TB in a region with a high prevalence of TB and HIV. The risk of mortality once patients with TB are hospitalized is unlikely to be explained only by the HIV epidemic.