Diverse NKT cells regulate early inflammation and neurological outcomes after cardiac arrest and resuscitation.

Neurological injury drives most deaths and morbidity among patients hospitalized for out-of-hospital cardiac arrest (OHCA). Despite its clinical importance, there are no effective pharmacological therapies targeting post-cardiac arrest (CA) neurological injury. Here, we analyzed circulating immune cells from a large cohort of patients with OHCA, finding that lymphopenia independently associated with poor neurological outcomes.

Adherence to Lung Protective Ventilation in ARDS: A Mixed Methods Study Using Real-Time Continuously Monitored Ventilation Data.

Background: Lung-protective ventilation is a standard intervention for mitigating ventilator-induced lung injury in patients with ARDS. Despite its efficacy, adherence to contemporary evidence-based guidelines remains suboptimal. We aimed to identify factors that affect the adherence of staff to applying lung-protective ventilation guidelines by analyzing real-time, continuously monitored ventilation data over a 5-year longitudinal period.

Utilization of Remote Patient Monitoring for Neurological Disorders: A Nationwide Analysis of Administrative Claims Data.

: The use of remote patient monitoring (RPM) services for neurological disorders remains understudied, particularly in the context of newer billing codes introduced before the COVID-19 pandemic. : This retrospective cohort study utilized data from commercial and Medicare employer-sponsored administrative claims between January 1, 2019, to December 31, 2021. The study population included all patients with at least one qualifying RPM-related Current Procedural Terminology (CPT) code for a neurological disorder, separated into first-generation (CPT 99091) codes and second-generation (CPT 99453, 99454, 99457, 99458) code cohorts.

A metabolomics pipeline highlights microbial metabolism in bloodstream infections.

The growth of antimicrobial resistance (AMR) highlights an urgent need to identify bacterial pathogenic functions that may be targets for clinical intervention. Although severe infections profoundly alter host metabolism, prior studies have largely ignored microbial metabolism in this context. Here, we describe an iterative, comparative metabolomics pipeline to uncover microbial metabolic features in the complex setting of a host and apply it to investigate gram-negative bloodstream infection (BSI) in patients.

Lactate transport inhibition therapeutically reprograms fibroblast metabolism in experimental pulmonary fibrosis.

Myofibroblast differentiation, essential for driving extracellular matrix synthesis in pulmonary fibrosis, requires increased glycolysis. While glycolytic cells must export lactate, the contributions of lactate transporters to myofibroblast differentiation are unknown. In this study, we investigated how MCT1 and MCT4, key lactate transporters, influence myofibroblast differentiation and experimental pulmonary fibrosis.

Plasma renin as a novel prognostic biomarker of sepsis-associated acute respiratory distress syndrome.

Sepsis-associated acute respiratory distress syndrome (ARDS) is a life-threatening condition in critical care medicine for which there is a substantial need for early prognostic biomarkers of outcome. The present study seeks to link plasma renin levels and 30-day mortality in sepsis-associated ARDS patients treated at our institution. The Registry of Critical Illness (RoCI) prospectively enrolled patients from the intensive care units (ICU) within a single academic medical center, and a convenience sample of patients with sepsis-associated ARDS was analyzed from this cohort.

Investigating the Association Between Dynamic Driving Pressure and Mortality in COVID-19-Related Acute Respiratory Distress Syndrome: A Joint Modeling Approach Using Real-Time Continuously-Monitored Ventilation Data.

Importance And Objectives: COVID-19-related acute respiratory distress syndrome (ARDS) is associated with high mortality and often necessitates invasive mechanical ventilation (IMV). Previous studies on non-COVID-19 ARDS have shown driving pressure to be robustly associated with ICU mortality; however, those studies relied on "static" driving pressure measured periodically and manually. As "continuous" automatically monitored driving pressure is becoming increasingly available and reliable with more advanced mechanical ventilators, we aimed to examine the effect of this "dynamic" driving pressure in COVID-19 ARDS throughout the entire ventilation period.

Circulating N-lactoyl-amino acids and N-formyl-methionine reflect mitochondrial dysfunction and predict mortality in septic shock.

Introduction: Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging.

Objective: To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality.

Identification and targeting of microbial putrescine acetylation in bloodstream infections.

The growth of antimicrobial resistance (AMR) has highlighted an urgent need to identify bacterial pathogenic functions that may be targets for clinical intervention. Although severe bacterial infections profoundly alter host metabolism, prior studies have largely ignored alterations in microbial metabolism in this context. Performing metabolomics on patient and mouse plasma samples, we identify elevated levels of bacterially-derived -acetylputrescine during gram-negative bloodstream infections (BSI), with higher levels associated with worse clinical outcomes.

Timing of invasive mechanical ventilation and death in critically ill adults with COVID-19: A multicenter cohort study.

Purpose: To investigate if the timing of initiation of invasive mechanical ventilation (IMV) for critically ill patients with COVID-19 is associated with mortality.

Materials And Methods: The data for this study were derived from a multicenter cohort study of critically ill adults with COVID-19 admitted to ICUs at 68 hospitals across the US from March 1 to July 1, 2020. We examined the association between early (ICU days 1-2) versus late (ICU days 3-7) initiation of IMV and time-to-death.

The upper and lower respiratory tract microbiome in severe aspiration pneumonia.

Uncertainty persists whether anaerobic bacteria represent important pathogens in aspiration pneumonia. In a nested case-control study of mechanically ventilated patients classified as macro-aspiration pneumonia (MAsP, n = 56), non-macro-aspiration pneumonia (NonMAsP, n = 91), and uninfected controls (n = 11), we profiled upper (URT) and lower respiratory tract (LRT) microbiota with bacterial 16S rRNA gene sequencing, measured plasma host-response biomarkers, analyzed bacterial communities by diversity and oxygen requirements, and performed unsupervised clustering with Dirichlet Multinomial Models (DMM). MAsP and NonMAsP patients had indistinguishable microbiota profiles by alpha diversity and oxygen requirements with similar host-response profiles and 60-day survival.

Effect of total cholesterol and statin therapy on mortality in ARDS patients: a secondary analysis of the SAILS and HARP-2 trials.

Background: Two acute respiratory distress syndrome (ARDS) trials showed no benefit for statin therapy, though secondary analyses suggest inflammatory subphenotypes may have a differential response to simvastatin. Statin medications decrease cholesterol levels, and low cholesterol has been associated with increased mortality in critical illness. We hypothesized that patients with ARDS and sepsis with low cholesterol could be harmed by statins.

Novel Grading Scales for Static and Flexion-Extension Magnetic Resonance Imaging in Patients with Cervical Spondylotic Myelopathy.

Background: Flexion-extension magnetic resonance imaging (MRI) has potential to identify cervical pathology not detectable on conventional static MRI. Our study evaluated standard quantitative and novel subjective grading scales for assessing the severity of cervical spondylotic myelopathy in dynamic sagittal MRI as well as in static axial and sagittal images.

Methods: Forty-five patients underwent both conventional and flexion-extension MRI prior to anterior cervical discectomy and fusion from C4 through C7.

Circulating N-formylmethionine and metabolic shift in critical illness: a multicohort metabolomics study.

Background: Cell stress promotes degradation of mitochondria which release danger-associated molecular patterns that are catabolized to N-formylmethionine. We hypothesized that in critically ill adults, the response to N-formylmethionine is associated with increases in metabolomic shift-related metabolites and increases in 28-day mortality.

Methods: We performed metabolomics analyses on plasma from the 428-subject Correction of Vitamin D Deficiency in Critically Ill Patients trial (VITdAL-ICU) cohort and the 90-subject Brigham and Women's Hospital Registry of Critical Illness (RoCI) cohort.

Thrombosis-Related Loss of Arterial Lines in the First Wave of COVID-19 and Non-COVID-19 Intensive Care Unit Patients.

Background: Patients with coronavirus disease 2019 (COVID-19) can present with severe respiratory distress requiring intensive care unit (ICU)-level care. Such care often requires placement of an arterial line for monitoring of pulmonary disease progression, hemodynamics, and laboratory tests. During the first wave of the COVID-19 pandemic in March 2020, experienced physicians anecdotally reported multiple attempts, decreased insertion durations, and greater need for replacement of arterial lines in patients with COVID-19 due to persistent thrombosis.

Redefining critical illness.

Research and practice in critical care medicine have long been defined by syndromes, which, despite being clinically recognizable entities, are, in fact, loose amalgams of heterogeneous states that may respond differently to therapy. Mounting translational evidence-supported by research on respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-suggests that the current syndrome-based framework of critical illness should be reconsidered. Here we discuss recent findings from basic science and clinical research in critical care and explore how these might inform a new conceptual model of critical illness.