Regulation of human neutrophil IL-1ß secretion induced by Escherichia coli O157:H7 responsible for hemolytic uremic syndrome.

Shiga-toxin producing Escherichia coli (STEC) infections can cause from bloody diarrhea to Hemolytic Uremic Syndrome. The STEC intestinal infection triggers an inflammatory response that can facilitate the development of a systemic disease. We report here that neutrophils might contribute to this inflammatory response by secreting Interleukin 1 beta (IL-1ß). STEC stimulated neutrophils to release elevated levels of IL-1ß through a mechanism that involved the activation of caspase-1 driven by the NLRP3-inflammasome and neutrophil serine proteases (NSPs). Noteworthy, IL-1ß secretion was higher at lower multiplicities of infection. This secretory profile modulated by the bacteria:neutrophil ratio, was the consequence of a regulatory mechanism that reduced IL-1ß secretion the higher were the levels of activation of both caspase-1 and NSPs, and the production of NADPH oxidase-dependent reactive oxygen species. Finally, we also found that inhibition of NSPs significantly reduced STEC-triggered IL-1ß secretion without modulating the ability of neutrophils to kill the bacteria, suggesting NSPs might represent pharmacological targets to be evaluated to limit the STEC-induced intestinal inflammation.

Epidemiology, patterns of care and prognosis of acute kidney injury in critically ill patients: A multicenter study in Argentina (The EPIRA study).

BACKGROUND: Acute kidney injury (AKI) is associated with high morbidity and mortality rates in the intensive care unit (ICU). In low- and middle-income countries (LMICs), epidemiological information about this condition is still scarce. Our main objective was to characterize its epidemiology, prognosis, and its treatment. METHODS: This multicenter prospective cohort study included 1466 patients from 35 ICUs during 6 months in Argentina in 2018. Risk factors and outcomes in patients with and without AKI, and between AKI on admission (AKIadm) and that developed during hospitalization (AKIhosp) were analyzed. RESULTS: AKI occurred in 61.3% of patients (900/1466); 72.6% were AKIadm and 27.3% AKIhosp. Risk factors were age, BMI, arterial hypertension, cardiovascular diseases, diabetes, SOFA, APACHE II, dehydration, sepsis, vasopressor use, radiocontrast, diuresis/h and mechanical ventilation. Independent predictors for AKI were sepsis, diabetes, dehydration, vasopressors on admission, APACHE II and radiocontrast use. Renal replacement therapies (RRT) requirement in AKI patients was 14.8%. Hospital mortality in AKI vs. non-AKI was 38.7% and 23.3% (p < 0.001); and in AKIadm vs. AKIhosp, 41.2% and 37.8% (p = 0.53). CONCLUSIONS: ICU-acquired AKI has high incidence, complications and mortality. Risk factors for AKI and RRT utilization were similar to those described in other epidemiological studies. AKIadm was more frequent than AKIhosp, but had equal prognosis.

[Structural capacity, technological human resources and mechanical ventilation requirements in 58 intensive care units in Argentina during the SARS-CoV-2 pandemic. A SATICOVID-19 Study]. / Capacidad estructural, recursos humanos tecnológicos y requerimientos de ventilación mecánica en 58 unidades de cuidados intensivos en Argentina durante la pandemia por SARS-CoV-2. Estudio SATICOVID-19.

During the SARS-CoV-2 pandemic, there was a marked requirement for critical care beds, supplies and trained professionals to assist patients with severe respiratory failure. The Argentine Society of Intensive Care (SATI) designed a study to characterize these aspects in intensive care units (ICUs). Multicenter, prospective cohort study; the participating ICUs completed a form at the end of the study (31/10/2020) on hospital characteristics, number of beds in pre- and intra-pandemic critical areas, incorporation of professionals, technological resources, and workload. Fifty-eight ICUs participated; 28(48%) were located in Buenos Aires Province, 22(38%) in Buenos Aires Autonomous City and 10 (17%) in other provinces; 31 (53%) of UCIs belonged to the public sector; 23 (47%) to the private-social security. In 35/58 (60%) of the hospitals critical care beds increased from 902 to 1575 (75%), 37% in ICU and 63% mainly in Coronary Care Unit and Emergency-shock room. In 41/55 (75%) UCIs, staff were incorporated: 27(49%) physicians (70% intensivists), 36 (65%) nurses, 28 (51%) respiratory therapists, 20(36%) cleaning staff, and 1(2%) others. A 96% of the ICUS reported having sufficient ventilators and 95% enough supplies and PPE. Of all patients on invasive mechanical ventilation, 55% [43-64] had COVID-19. Oxygen therapy was required as noninvasive support in 14% [8-24] of COVID-19 admissions. There was a significant expansion of critical operational areas, secondary to the increase in beds, staff, and adequate availability of ventilators and essential supplies. The burden of critical illness from COVID-19 was intense, with more than half of patients on mechanical ventilation.

Durante la pandemia por SARS-CoV-2 hubo un marcado requerimiento de camas de cuidados críticos, insumos y profesionales entrenados para asistir a pacientes con insuficiencia respiratoria grave. La Sociedad Argentina de Terapia Intensiva (SATI) diseñó un estudio para caracterizar estos aspectos en las Unidades de Cuidados Intensivos (UCIs). Estudio multicéntrico, de cohorte prospectiva; las UCIs participantes completaron un formulario al final del estudio (31/10/2020) sobre características hospitalarias, número de camas de áreas críticas pre- e intra-pandemia, incorporación de profesionales, insumos y recursos tecnológicos, y carga de trabajo. Participaron 58 UCIs; 28(48%) de Provincia de Buenos Aires, 22(38%) de Ciudad Autónoma de Buenos Aires, 10(17%) de otras; 31(53%) UCIs pertenecían al sector público; 23(47%) al privado-seguridad social. En 35/58(60%) hospitales las camas de cuidados críticos aumentaron de 902 a 1575(75%); 37% en UCI y 63% principalmente en Unidad Coronaria y Emergencias-shock room. En 41/55(75%) UCIs se incorporó personal: 27(49%) médicos/as (70% intensivistas), 36(65%) enfermeros/as, 28(51%) kinesiólogos/as, 20(36%) personal de limpieza, y 1(2%) otros/as; 96% de las UCIS reportaron disponer de respiradores suficientes, y 95%, insumos y EPP suficientes. De todos los pacientes en ventilación mecánica invasiva, 55% [43-64] presentaron COVID-19. Se requirió oxigenoterapia como soporte no invasivo en 14% [8-24] de los ingresos por COVID-19. Se registró una importante expansión de las áreas críticas operativas, secundariamente al aumento de camas, personal, y adecuada disponibilidad de respiradores e insumos esenciales. La carga de la enfermedad crítica por COVID-19 fue intensa, constituyendo más de la mitad de los pacientes en ventilación mecánica.

Effects of short-term hyperoxia on sytemic hemodynamics, oxygen transport, and microcirculation: An observational study in patients with septic shock and healthy volunteers.

PURPOSE: To characterize the microvascular effects of a brief period of hyperoxia, in patients with septic shock and in healthy volunteers. MATERIALS AND METHODS: In 20 patients with septic shock, we assessed systemic hemodynamics, sublingual microcirculation by SDF-videomicroscopy, and skin perfusion by capillary refill time (CRT), central-peripheral temperature (ΔT°), and perfusion index. Measurements were performed at baseline and after 5 min of inspired oxygen fraction of 1.00. Additionally, we studied 8 healthy volunteers, in whom hyperoxia was prolonged to 30 min. RESULTS: In septic patients, hyperoxia increased mean arterial pressure and systemic vascular resistance, but cardiac output remained unchanged. The only significant change in sublingual microcirculation was a decreased heterogeneity flow index (1.03 [1.01-1.07] vs 1.01 [0.34-1.05], P = .002). Perfused vascular density (13.1 [12.0-15.0] vs 14.0 [12.2-14.8] mm/mm2, P = .21) and the other sublingual microvascular variables were unmodified. CRT and ΔT° did not change but perfusion index slightly decreased. In healthy volunteers, sublingual microcirculation and skin perfusion were stable. CONCLUSIONS: Short-term hyperoxia induced systemic cardiovascular changes but was not associated with noticeable derangement in sublingual microcirculation and skin perfusion. Nevertheless, longer exposures to hyperoxia might have produced different results.

Relationship of at Admission Lactate, Unmeasured Anions, and Chloride to the Outcome of Critically Ill Patients.

OBJECTIVES: To investigate the association between the concentration of the causative anions responsible for the main types of metabolic acidosis and the outcome. DESIGN: Prospective observational study. SETTING: Teaching ICU. PATIENTS: All patients admitted from January 2006 to December 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four thousand nine hundred one patients were admitted throughout the study period; 1,609 met criteria for metabolic acidosis and 145 had normal acid-base values. The association between at admission lactate, unmeasured anions, and chloride concentration with outcome was assessed by multivariate analysis in the whole cohort and in patients with metabolic acidosis. We also compared the mortality of patients with lactic, unmeasured anions, and hyperchloremic metabolic acidosis with that of patients without acid-base disorders. In the whole population, increased lactate and unmeasured anions were independently associated with increased mortality, even after adjusting for potential confounders (odds ratio [95% CI], 1.14 (1.08-1.20); p < 0.0001 and 1.04 (1.02-1.06); p < 0.0001, respectively). In patients with metabolic acidosis, the results were similar. Patients with lactic and unmeasured anions acidosis, but not those with hyperchloremic acidosis, had an increased mortality compared to patients without alterations (17.7%, 12.7%, 4.9%, and 5.8%, respectively; p < 0.05). CONCLUSIONS: In this large cohort of critically ill patients, increased concentrations of lactate and unmeasured anions, but not chloride, were associated with increased mortality. In addition, increased unmeasured anions were the leading cause of metabolic acidosis.

Higher Fluid Balance Increases the Risk of Death From Sepsis: Results From a Large International Audit.

OBJECTIVES: Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis. DESIGN: Observational cohort study. SETTING: Seven hundred and thirty ICUs in 84 countries. PATIENTS: All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission. MEASUREMENTS AND MAIN RESULTS: ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (-90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (-951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher fluid output in these patients. Fluid balances became negative after the third ICU day in survivors but remained positive in nonsurvivors. After adjustment for possible confounders in multivariable analysis, the 24-hour cumulative fluid balance was not associated with an increased hazard of 28-day in-hospital death. However, there was a stepwise increase in the hazard of death with higher quartiles of 3-day cumulative fluid balance in the whole population and after stratification according to the presence of septic shock. CONCLUSIONS: In this large cohort of patients with sepsis, higher cumulative fluid balance at day 3 but not in the first 24 hours after ICU admission was independently associated with an increase in the hazard of death.