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.

A Prodrug Strategy to Reposition Atovaquone as a Long-Acting Injectable for Malaria Chemoprotection.

Recent malaria drug discovery approaches have been extensively focused on the development of oral, smallmolecule inhibitors for disease treatment whereas parenteral routes of administration have been avoided due to limitations in deploying a shelf-stable injectable even though it could be dosed less frequently. However, an updated target candidate profile from Medicines for Malaria Venture (MMV) and stakeholders have advocated for long-acting injectable chemopreventive agents as an important interventive tool to improve malaria prevention. Here, we present strategies for the development of a long-acting, intramuscular, injectable atovaquone prophylactic therapy.

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.

Comorbidities Matter as Distressed Communities Index Fails to Predict Mortality in Necrotizing Soft Tissue Infection.

Necrotizing soft tissue infections (NSTIs) are life-threatening infections requiring prompt intervention. The Distressed Communities Index (DCI) is a comprehensive ranking of socioeconomic well-being based on zip code. We sought to identify the role of DCI in predicting mortality in NSTI, because it remains unknown.

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.

Characterization of Necrotizing Soft Tissue Infections in Obese and Non-Obese Patients.

The impact of obesity on the pathogenesis and prognosis of necrotizing soft tissue infections (NSTIs) is unclear. The goal of this study was to characterize differences in NSTI presentation and outcomes by obesity status. A retrospective analysis of institutional data for patients diagnosed with NSTIs were identified (n = 619; 2011-2020).

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.

Outcomes of Patients with Necrotizing Soft Tissue Infections: A Propensity-Matched Analysis Using the National Inpatient Sample.

Necrotizing soft tissue infections (NSTIs) are severe, rapidly spreading infections with high morbidity and mortality. Attempts to identify risk factors for mortality and morbidity have produced variable results. We hope to determine which factors across the NSTI population impact mortality, morbidities, and discharge disposition.

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).

Phosphatidylinositol 3-Kinase δ-Specific Inhibitor-Induced Changes in the Ovary and Testis in the Sprague Dawley Rat and Cynomolgus Monkey.

Phosphatidylinositol 3-kinase (PI3K) δ is a lipid kinase primarily found in leukocytes, which regulates important cell functions. AMG2519493 was a PI3K δ-specific inhibitor in development for treatment of various inflammatory diseases. AMG2519493-related changes in the male and/or female reproductive organs were observed in the 1- and 3-month oral repeat dose toxicology studies in the rat and cynomolgus monkey.

Phosphatidylinositol 3-Kinase δ Inhibitor-Induced Immunomodulation and Secondary Opportunistic Infection in the Cynomolgus Monkey ().

Phosphatidylinositol 3-kinases (PI3Ks) regulate intracellular signaling events for multiple cell surface receptors. Phosphatidylinositol 3-kinase δ, 1 of 4 class I PI3K isoforms, is primarily found in leukocytes and regulates immune cell functions. Here, we report changes in the immune and digestive systems that were associated with AMG2519493, a highly selective small-molecule PI3Kδ inhibitor.

The Need for Accurate Risk Assessment in a High-Risk Patient Population: A NSQIP Study Evaluating Outcomes of Cholecystectomy in the Patient With Cancer.

Background: Cholecystectomy is considered a low-risk procedure with proven safety in many high-risk patient populations. However, the risk of cholecystectomy in patients with active cancer has not been established.

Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was queried to identify all patients with disseminated cancer who underwent cholecystectomy from 2005 to 2016.

Leaving Against Medical Advice After Emergency General Surgery: Avoiding a Two-Hit Effect.

Background: Emergency general surgery has higher adverse outcomes than elective surgery. Patients leaving the hospital against medical advice (AMA) have a greater risk for readmission and complications. We sought to identify clinical and demographic characteristics along with hospital factors associated with leaving AMA after EGS operations.

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.