Enrolling High-Acuity Emergency General Surgery Patients in a Prospective Longitudinal Cohort Study.

Over three million patients are admitted to hospitals annually with high-acuity conditions mandating emergency abdominal or skin/soft-tissue operation. Patients with these high-acuity emergency general surgery (HA-EGS) diseases experience significant morbidity/mortality, yet the quality of life (QOL) impact on survivors is not well studied. Acuity, transfer patterns, and adverse social determinants of health (SDOH) documented in epidemiologic studies are cited reasons for inability to measure patient-reported outcomes (PROs) among HA-EGS survivors.

The calcineurin-NFATc pathway modulates the lipid mediators in BAL fluid extracellular vesicles, thereby regulating microvascular endothelial cell barrier function.

Extracellular vesicles mediate intercellular communication by transporting biologically active macromolecules. Our prior studies have demonstrated that the nuclear factor of activated T cell cytoplasmic member 3 (NFATc3) is activated in mouse pulmonary macrophages in response to lipopolysaccharide (LPS). Inhibition of NFATc3 activation by a novel cell-permeable calcineurin peptide inhibitor CNI103 mitigated the development of acute lung injury (ALI) in LPS-treated mice.

Obesity is associated with improved early survival but increased late mortality in surgical patients with Sepsis: A propensity matched analysis.

Background: While obesity is a risk factor for postoperative complications, its impact following sepsis is unclear. The primary objective of this study was to evaluate the association between obesity and mortality following admission to the surgical intensive care unit (SICU) with sepsis.

Methods: We conducted a single center retrospective review of SICU patients grouped into obese (n = 766, body mass index ≥30 kg/m 2 ) and nonobese (n = 574; body mass index, 18-29.

Area Deprivation Index Predicts Mortality for Critically Ill Surgical Patients With Sepsis.

The impact of socioeconomic status on outcomes after sepsis has been challenging to define, and no polysocial metric has been shown to predict mortality in sepsis. The primary objective of this study was to evaluate the association between the Area Deprivation Index (ADI) and mortality in patients admitted to the surgical intensive care unit (SICU) with sepsis. All patients admitted to the SICU with sepsis (Sequential Organ Failure Assessment [SOFA] score ≥2) were retrospectively reviewed.

Characterization of Mortality by Sepsis Source in Patients Admitted to the Surgical Intensive Care Unit.

Introduction: The impact of infectious source on sepsis outcomes for surgical patients is unclear. The objective of this study was to evaluate the association between sepsis sources and cumulative 90-d mortality in patients admitted to the surgical intensive care unit (SICU) with sepsis.

Methods: All patients admitted to the SICU at an academic institution who met sepsis criteria (2014-2019, n = 1296) were retrospectively reviewed.

Distressed Communities Index Is Not Associated with Mortality for Critically Ill Surgical Patients with Sepsis.

The impact of socioeconomic metrics on outcomes after sepsis is unclear. The Distressed Communities Index (DCI) is a composite score quantifying socioeconomic well-being by zip code. The primary objective of this study was to evaluate the association between DCI and mortality in patients with sepsis admitted to the surgical intensive care unit (SICU).

Microvesicle-Mediated Transfer of DNA Methyltransferase Proteins Results in Recipient Cell Immunosuppression.

Introduction: Patients with sepsis exhibit significant, persistent immunologic dysfunction. Evidence supports the hypothesis that epigenetic regulation of key cytokines plays an important role in this dysfunction. In sepsis, circulating microvesicles (MVs) containing elevated levels of DNA methyltransferase (DNMT) mRNA cause gene methylation and silencing in recipient cells.

Exosomal Transfer of DNA Methyl-Transferase mRNA Induces an Immunosuppressive Phenotype in Human Monocytes.

Introduction: Survivors of sepsis exhibit persistent immunosuppression. Epigenetic events may be responsible for some of these immunosuppressive changes. During sepsis circulating exosomes contain large quantities of DNA methyltransferase (DNMT) mRNAs.

Self-selection vs Randomized Assignment of Treatment for Appendicitis.

Importance: For adults with appendicitis, several randomized clinical trials have demonstrated that antibiotics are an effective alternative to appendectomy. However, it remains unknown how the characteristics of patients in such trials compare with those of patients who select their treatment and whether outcomes differ.

Objective: To compare participants in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) randomized clinical trial (RCT) with a parallel cohort study of participants who declined randomization and self-selected treatment.

Lipidomic Profiling of Bronchoalveolar Lavage Fluid Extracellular Vesicles Indicates Their Involvement in Lipopolysaccharide-Induced Acute Lung Injury.

Emerging data support the pivotal role of extracellular vesicles (EVs) in normal cellular physiology and disease conditions. However, despite their abundance, there is much less information about the lipid mediators carried in EVs, especially in the context of acute lung injury (ALI). Our data demonstrate that C57BL/6 mice subjected to intranasal Escherichia coli lipopolysaccharide (LPS)-induced ALI release, a higher number of EVs into the alveolar space, compared to saline-treated controls.

Patient Factors Associated With Appendectomy Within 30 Days of Initiating Antibiotic Treatment for Appendicitis.

Importance: Use of antibiotics for the treatment of appendicitis is safe and has been found to be noninferior to appendectomy based on self-reported health status at 30 days. Identifying patient characteristics associated with a greater likelihood of appendectomy within 30 days in those who initiate antibiotics could support more individualized decision-making.

Objective: To assess patient factors associated with undergoing appendectomy within 30 days of initiating antibiotics for appendicitis.

Transfer Status and 90-Day Mortality in Intensive Care Unit Patients With Sepsis: A Propensity Matched Analysis.

Background: Timely identification and management of sepsis in surgical patients is crucial, and transfer status may delay optimal treatment of these patients. The objective of this study was to compare in-house and 90-day mortality between patients primarily admitted or transferred into the surgical ICU (SICU) at a tertiary referral center.

Material And Methods: All patients admitted to the SICU with a diagnosis of sepsis (Sepsis III) were reviewed at a single institution between 2014 to 2019 (n = 1489).

Analyzing Outcomes Among Older Adults With Necrotizing Soft-Tissue Infections in the United States.

Background: Necrotizing soft-tissue infections (NSTIs) encompass a group of severe, life-threatening diseases with high morbidity and mortality. Evidence suggests advanced age is associated with worse outcomes. To date, no large data sets exist describing outcomes in older individuals, and risk factor identification is lacking.

Computed Tomography-Measured Psoas Muscle Density as a Predictive Factor for Hypophosphatemia Associated With Refeeding.

Background: Initiation of parenteral nutrition (PN) after a period of starvation can be complicated by refeeding syndrome (RFS). RFS is associated with electrolyte abnormalities including hypomagnesemia, hyponatremia, and hypophosphatemia. Risk factors include recent weight loss, low body mass index, and electrolyte deficiencies; however, these associations are not strong.

Circulating extracellular vesicle content reveals DNA methyltransferase expression as a molecular method to predict septic shock.

Extracellular vesicles (EVs) are mRNA-containing cell fragments shed into circulation during pathophysiological events. DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) regulate gene expression by modifying DNA methylation and altering transcription. Sepsis is a systemic insult resulting in vascular dysfunction, which can lead to shock and death.

Proteomic Pathway Analysis of Monocyte-Derived Exosomes during Surgical Sepsis Identifies Immunoregulatory Functions.

Patients with sepsis exhibit significant long-term immunosuppressive sequelae. Monocyte dysfunction is a hallmark of this damage. Circulating exosomes are an important mediator of the systemic signaling events that occur during the septic response; thus, we sought to characterize the contribution of circulating exosomes to the inflammatory process induced during sepsis Monocyte-derived exosomes were isolated from cultured monocytes from healthy adult donors via stimulation with lipopolysaccharide (LPS) or phosphate-buffered saline (PBS).

Methodological challenges in utilizing miRNAs as circulating biomarkers.

MicroRNAs (miRNAs) have emerged as important regulators in the post-transcriptional control of gene expression. The discovery of their presence not only in tissues but also in extratissular fluids, including blood, urine and cerebro-spinal fluid, together with their changes in expression in various pathological conditions, has implicated these extracellular miRNAs as informative biomarkers of disease. However, exploiting miRNAs in this capacity requires methodological rigour.

Analyzing the circulating microRNAs in exosomes/extracellular vesicles from serum or plasma by qRT-PCR.

Small extracellular vesicles are released from both healthy and disease cells to facilitate cellular communication. They have a wide variety of names including exosomes, microvesicles and microparticles. Depending on their size, very small extracellular vesicles originating from the endocytic pathway have been called exosomes and in some cases nanovesicles.

The relationship between acute and chronic hyperglycemia and outcomes in burn injury.

A significant proportion of patients with burn injury have diabetes. Although hyperglycemia during critical illness has been associated with poor outcomes, patients with chronic hyperglycemia based on elevated hemoglobin A1c (HbA1c) measurements at admission have been shown to tolerate higher glucose levels during hospitalization. This relationship has not been evaluated in the burn population.

Macrophage microvesicles induce macrophage differentiation and miR-223 transfer.

Microvesicles are small membrane-bound particles comprised of exosomes and various-sized extracellular vesicles. These are released by several cell types. Microvesicles have a variety of cellular functions from communication to mediating growth and differentiation.

Challenges and opportunities in implementing pharmacogenomics testing in the clinics.

The field of pharmacogenomics aims to incorporate individual patient genomic information into treatment selection. This is a rapidly evolving field with significant clinical promise. Implementation into clinical practice has several challenges that must be overcome.

The effect of left ventricular size on right ventricular hemodynamics in pediatric survivors with hypoplastic left heart syndrome.

Background: Outcome status in patients with hypoplastic left heart syndrome (HLHS) is partially dependent on right ventricular (RV) systolic function. In other disease states, ventricular function is impacted by anatomy and physiology of the contralateral ventricle. In HLHS, it is suggested that a relatively larger left ventricular (LV) size may negatively impact RV function because it becomes a "passenger" without providing any systolic or diastolic physiologic benefit.