Background In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary. Methods In 31 emergency departments in the United States, we randomly assigned patients with septic shock to one of three groups for 6 hours of resuscitation: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or usual care. The primary end point was 60-day in-hospital mortality. We tested sequentially whether protocol-based care (EGDT and standard-therapy groups combined) was superior to usual care and whether protocol-based EGDT was superior to protocol-based standard therapy. Secondary outcomes included longer-term mortality and the need for organ support. Results We enrolled 1341 patients, of whom 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care. Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths in the protocol-based EGDT group (21.0%), 81 in the protocol-based standard-therapy group (18.2%), and 86 in the usual-care group (18.9%) (relative risk with protocol-based therapy vs. usual care, 1.04; 95% confidence interval [CI], 0.82 to 1.31; P = 0.83; relative risk with protocol-based EGDT vs. protocol-based standard therapy, 1.15; 95% CI, 0.88 to 1.51; P = 0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support. Conclusions In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes. (Funded by the National Institute of General Medical Sciences; ProCESS ClinicalTrials.gov number, NCT00510835.)

Among critically ill patients and their surrogates, a family-support intervention delivered by the interprofessional ICU team did not significantly affect the surrogates' burden of psychological symptoms, but the surrogates' ratings of the quality of communication and the patient- and family-centeredness of care were better and the length of stay in the ICU was shorter with the intervention than with usual care. (Funded by the UPMC Health System and the Greenwall Foundation; PARTNER ClinicalTrials.gov number, NCT01844492 .).

The provision of procalcitonin assay results, along with instructions on their interpretation, to emergency department and hospital-based clinicians did not result in less use of antibiotics than did usual care among patients with suspected lower respiratory tract infection. (Funded by the National Institute of General Medical Sciences; ProACT ClinicalTrials.gov number, NCT02130986 .).

EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

In patients with septic shock, AKI is common and associated with adverse outcomes, but it is not influenced by protocolized resuscitation compared with usual care.

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Background and Aims The effects of diet quality (DQ), physical activity (PA), and socioeconomic status (SES) on the risk of NAFLD are unclear. We examined the association among DQ, PA, SES, and NAFLD risk. Approach and Results This is a cross‐sectional analysis of the National Health and Nutrition Examination Surveys, 2017–2018, which included 3589 participants with reliable information on vibration‐controlled transient elastography (VCTE) measurements, 24‐h dietary recalls, PA, and SES. DQ was assessed by the Healthy Eating Index (HEI)‐2015. PA was determined by the Global Physical Activity Questionnaire. SES was assessed by the educational attainment and family poverty income ratio (PIR). Risk of NAFLD was considered by means of a composite outcome using VCTE measurements: non‐NAFLD versus NAFLD without clinically significant fibrosis (CSF) versus NAFLD with CSF. The NAFLD risk was lower in physically active (≥600 metabolic equivalent of task [MET] min/week) versus inactive participants (<600 MET min/week) (OR: 0.71, p = 0.043). A high‐quality diet (HQD) (HEI > 56.64) was associated with a lower risk of NAFLD (OR: 0.58, p < 0.01) compared with a non‐HQD. The lowest NAFLD risk was observed in those physically active with HQD (OR: 0.43, p < 0.01). Body mass index and waist circumference significantly mediated the effect of DQ and PA on NAFLD risk. Education (college or above) (OR: 0.65, p = 0.034), but not PIR, was associated with a reduced NAFLD risk. HQD and increased PA partially mediated the effect of education on NAFLD risk. The total effect of education on NAFLD risk mediated by DQ was 29% and by PA was 8%. Conclusions HQD, increased physical activity, and college education were associated with lower NAFLD risk in the US population.

Elevated plasma concentrations of inflammatory and apoptosis biomarkers are associated with RRT dependence and death. Our data suggest that future interventions should investigate broad-spectrum immune-modulation to improve outcomes.