Lung Ultrasound Score at Hospital Discharge as a Predictor of Emergency Department Visit and Hospital Readmission in Patients With Acute Heart Failure.

Purpose The number of B-lines on lung ultrasound at hospital discharge in patients admitted with acute heart failure (AHF) is associated with poor outcomes. Assessing B-lines can be challenging to execute and replicate, depending on the clinical context. This study aims to determine whether the lung ultrasound score (LUS) at discharge predicts hospital readmission or emergency department (ED) visits in the 30 days after an AHF hospital admission. Methods  We conducted an observational study at the medical ward of the emergency unit of the Clinics Hospital of the Ribeirao Preto Medical School, University of Sao Paulo, a tertiary university hospital in Ribeirao Preto, Sao Paulo, Brazil, where consecutive adults admitted with AHF were included. On the day of hospital discharge, we measured the LUS and tracked these patients for up to 30 days to monitor emergency department visits, hospital readmission, and the number of days free from hospital stay. Results  A total of 46 patients were included in the study. A composite outcome of ED visits or hospital readmission in the 30 days after hospital discharge was achieved for 22 (47.8%) patients. The LUS at hospital discharge had a receiver operating characteristic (ROC) area of 0.93 (95% CI, 0.82-0.99) to predict the composite outcome, against 0.67 (95% CI, 0.52-0.81) for the clinical congestion score (CCS). A LUS ≥ 7 at discharge had a sensitivity of 95.5% and a specificity of 87.5% to predict the composite outcome. The average exam duration was 176±65 (sd) seconds. Conclusions The LUS at hospital discharge following admission for AHF proves to be an accurate tool for predicting the likelihood of return to the ED and/or hospital readmission within 30 days post discharge.

Early Neuromuscular Electrical Stimulation in Addition to Early Mobilization Improves Functional Status and Decreases Hospitalization Days of Critically Ill Patients.

OBJECTIVES: To evaluate the impact of the additional use of early neuromuscular electrical stimulation (NMES) on an early mobilization (EM) protocol. DESIGN: Randomized controlled trial. SETTING: ICU of the Clinical Hospital of Ribeirão Preto, University of São Paulo, Brazil. PATIENTS: One hundred and thirty-nine consecutive mechanically ventilated patients were included in the first 48 hours of ICU admission. INTERVENTIONS: The patients were divided into two groups: EM and EM+NMES. Both groups received EM daily. In the EM+NMES group, patients additionally received NMES 5 days a week, for 60 minutes, starting in the first 48 hours of ICU admission until ICU discharge. MEASUREMENTS AND MAIN RESULTS: Functional status, muscle strength, ICU and hospital length of stay (LOS), frequency of delirium, days on mechanical ventilation, mortality, and quality of life were assessed. Patients in the EM+NMES group presented a significant higher score of functional status measured by the Functional Status Score for the ICU scale when compared with the EM group in the first day awake: 22 (15-26) versus 12 (8-22) (p = 0.019); at ICU discharge: 28 (21-33) versus 18 (11-26) (p = 0.004); and hospital discharge: 33 (27-35) versus 25 (17-33) (p = 0.014), respectively. They also had better functional status measured by the Physical Function Test in the ICU scale, took less days to stand up during the ICU stay, and had a significant shorter hospital LOS, lower frequency of ICU-acquired weakness, and better global muscle strength. CONCLUSIONS: The additional application of early NMES promoted better functional status outcomes on the first day awake and at ICU and hospital discharge. The patients in the EM+NMES group also took fewer days to stand up and had shorter hospital LOS, lower frequency of ICU-acquired weakness, and better muscle strength. Future studies are still necessary to clarify the effects of therapies associated with EM, especially to assess long-term outcomes.

Sepsis expands a CD39+ plasmablast population that promotes immunosuppression via adenosine-mediated inhibition of macrophage antimicrobial activity.

Sepsis results in elevated adenosine in circulation. Extracellular adenosine triggers immunosuppressive signaling via the A2a receptor (A2aR). Sepsis survivors develop persistent immunosuppression with increased risk of recurrent infections. We utilized the cecal ligation and puncture (CLP) model of sepsis and subsequent infection to assess the role of adenosine in post-sepsis immune suppression. A2aR-deficient mice showed improved resistance to post-sepsis infections. Sepsis expanded a subset of CD39hi B cells and elevated extracellular adenosine, which was absent in mice lacking CD39-expressing B cells. Sepsis-surviving B cell-deficient mice were more resistant to secondary infections. Mechanistically, metabolic reprogramming of septic B cells increased production of ATP, which was converted into adenosine by CD39 on plasmablasts. Adenosine signaling via A2aR impaired macrophage bactericidal activity and enhanced interleukin-10 production. Septic individuals exhibited expanded CD39hi plasmablasts and adenosine accumulation. Our study reveals CD39hi plasmablasts and adenosine as important drivers of sepsis-induced immunosuppression with relevance in human disease.

Gasdermin D inhibition prevents multiple organ dysfunction during sepsis by blocking NET formation.

Multiple organ dysfunction is the most severe outcome of sepsis progression and is highly correlated with a worse prognosis. Excessive neutrophil extracellular traps (NETs) are critical players in the development of organ failure during sepsis. Therefore, interventions targeting NET release would likely effectively prevent NET-based organ injury associated with this disease. Herein, we demonstrate that the pore-forming protein gasdermin D (GSDMD) is active in neutrophils from septic humans and mice and plays a crucial role in NET release. Inhibition of GSDMD with disulfiram or genic deletion abrogated NET formation, reducing multiple organ dysfunction and sepsis lethality. Mechanistically, we demonstrate that during sepsis, activation of the caspase-11/GSDMD pathway controls NET release by neutrophils during sepsis. In summary, our findings uncover a novel therapeutic use for disulfiram and suggest that GSDMD is a therapeutic target to improve sepsis treatment.