Pharmacokinetic Factors Associated With Early Meropenem Target Attainment in Pediatric Severe Sepsis.

Objectives: To determine the frequency of early meropenem concentration target attainment (TA) in critically ill children with severe sepsis; to explore clinical, therapeutic, and pharmacokinetic factors associated with TA; and to assess how fluid resuscitation and volume status relate to early TA.

Design: Retrospective analysis of prospective observational cohort study.

Setting: PICU in a single academic quaternary care children's hospital.

Acute kidney injury is associated with abnormal cefepime exposure among critically ill children and young adults.

Background: Elevated cefepime blood concentrations can cause neurotoxicity in adults. The consequences of elevated cefepime concentrations among pediatric patients are unknown. Future exploration of such effects requires first identifying patients at risk for elevated cefepime exposure.

Diagnostic Validation of the Updated Pediatric Sepsis Biomarker Risk II for Acute Kidney Injury Prediction Model in Pediatric Septic Shock.

Objectives: We previously derived the updated Pediatric Sepsis Biomarker Risk for Acute Kidney Injury (PERSEVERE-II AKI) prediction model, which had robust diagnostic test characteristics for severe AKI on day 3 (D3 severe AKI) of septic shock. We now sought to validate this model in an independent cohort of children to the one in which the model was developed.

Design: A secondary analysis of a multicenter, prospective, observational study carried out from January 2019 to December 2022.

Identifying optimal dosing strategies for meropenem in the paediatric intensive care unit through modelling and simulation.

Background: Meropenem, a β-lactam antibiotic commonly prescribed for severe infections, poses dosing challenges in critically ill patients due to highly variable pharmacokinetics.

Objectives: We sought to develop a population pharmacokinetic model of meropenem for critically ill paediatric and young adult patients.

Patients And Methods: Paediatric intensive care unit patients receiving meropenem 20-40 mg/kg every 8 h as a 30 min infusion were prospectively followed for clinical data collection and scavenged opportunistic plasma sampling.

Curbing the Obesity Epidemic: Should GLP-1 Receptor Agonists Be the Standard of Care for Obesity?

Purpose Of Review: This article summarizes the medical management of obesity with an emphasis on incretin-based therapeutics that target the neuro-hormonal basis of obesity.

Recent Findings: Medications that mimic the effect of incretins, a group of peptide hormones released in response to nutrient intake that regulate appetite, result in potent and durable weight loss. Glucagon-like peptide 1 (GLP-1) agonists and glucose-dependent insulinotropic polypeptide (GIP) agonists such as semaglutide and tirzepatide are approved by the United States Food and Drug Administration (FDA) for the management of obesity.

Humanism Rounds: A Multifaceted "Back to Bedside" Initiative to Improve Meaning at Work for Internal Medicine Residents.

Introduction: Burnout is an increasingly prevalent problem among resident physicians. To address this problem, the Accreditation Council on Graduate Medical Education (ACGME) created the Back to Bedside initiative, supporting resident-driven projects focused on increasing direct interactions with patients. In 2017, Baylor College of Medicine (BCM) Internal Medicine Residency received a Back to Bedside grant to develop and implement "Humanism Rounds," a multifaceted program which sought to promote personal connections between residents and patients and foster reflection about patients' non-clinical stories, with the hopes of reducing burnout and increasing residents' sense of meaning at work.

Treatment preferences in diverticulitis are common and rarely change after a clinic visit.

With the increasing prevalence of diverticulitis, professional guidelines encourage the individualization of treatment. However, the frequency of treatment preferences of both surgeons, and patients, and the resultant impact of that preference on diverticulitis management is underexplored. We reviewed 27 consecutive patient visits of 3 colorectal surgeons at our institution to evaluate factors that drove their treatment, as well as their equipoise for patient randomization into medical or surgical treatments.

Ceftriaxone Pharmacokinetics and Pharmacodynamic Target Attainment for Three Pediatric Patients Receiving Continuous Kidney Replacement Therapy.

Ceftriaxone is used commonly for sepsis, including in children requiring continuous kidney replacement therapy (CKRT). No reports exist of pharmacokinetic (PK) parameters for children receiving ceftriaxone on CKRT. We enrolled children admitted to our pediatric intensive care unit (PICU) who received CKRT for >24 hours and received >1 dose of ceftriaxone while on and off CKRT.

Cystatin C Outperforms Creatinine in Predicting Cefepime Clearance in Pediatric Stem Cell Transplant Recipients.

Pediatric hematopoietic stem cell transplant (HSCT) patients are at risk of developing both sepsis and altered kidney function. Cefepime is used for empiric coverage post-HSCT and requires dose adjustment based on kidney function. Since cefepime's antimicrobial efficacy is determined by the time free concentrations exceed bacterial minimum inhibitory concentration (MIC), it is important to assess kidney function accurately to ensure adequate concentrations.

Piperacillin pharmacokinetics and pharmacodynamics in paediatric patients who received high frequency intra-operative piperacillin/tazobactam dosing.

Piperacillin/tazobactam (PTZ) is a broad-spectrum antibiotic, typically dosed every six hours (q6h). Guidelines recommend dosing PTZ every 2 hours (q2h) intra-operatively for complex abdominal surgery, including liver transplant. The data supporting the guidelines for intra-operative dosing are sparse and the pharmacokinetics/pharmacodynamics (PK/PD) of q2h dosing has not been studied by simulation or in humans.

Derivation, validation, and transcriptomic assessment of pediatric septic shock phenotypes identified through latent profile analyses: Results from a prospective multi-center observational cohort.

Background: Sepsis poses a grave threat, especially among children, but treatments are limited due to clinical and biological heterogeneity among patients. Thus, there is an urgent need for precise subclassification of patients to guide therapeutic interventions.

Methods: We used clinical, laboratory, and biomarker data from a prospective multi-center pediatric septic shock cohort to derive phenotypes using latent profile analyses.

External validation of the modified sepsis renal angina index for prediction of severe acute kidney injury in children with septic shock.

Background: Acute kidney injury (AKI) occurs commonly in pediatric septic shock and increases morbidity and mortality. Early identification of high-risk patients can facilitate targeted intervention to improve outcomes. We previously modified the renal angina index (RAI), a validated AKI prediction tool, to improve specificity in this population (sRAI).

The Impact of Prolonged Operative Time Associated With Minimally Invasive Colorectal Surgery: A Report From the Surgical Care Outcomes Assessment Program.

Background: Increased operative time in colorectal surgery is associated with worse surgical outcomes. Laparoscopic and robotic operations have improved outcomes, despite longer operative times. Furthermore, the definition of "prolonged" operative time has not been consistently defined.

Obesity Alters cytokine signaling and gut microbiome in septic mice.

Sepsis is a leading cause of mortality. Plasma cytokine levels may identify those at increased risk of mortality from sepsis. Our aim was to understand how obesity alters cytokine levels during early sepsis and its correlation with survival.

Ceftriaxone Pharmacokinetics and Pharmacodynamics in 2 Pediatric Patients on Extracorporeal Membrane Oxygenation Therapy.

Background: Critically ill patients with cardiac or respiratory failure may require extracorporeal membrane oxygenation (ECMO). Antibiotics are frequently administered when the suspected cause of organ failure is an infection. Ceftriaxone, a β-lactam antibiotic, is commonly used in patients who are critically ill.

Characterizing Regionalization of Inflammatory Bowel Disease Hospitalizations and Operations in Washington State.

Background: Hospitalizations for inflammatory bowel disease (IBD) are a major contributor of healthcare utilization. We assessed IBD hospitalizations and surgical operations in Washington State to characterize regionalization patterns.

Methods: We identified a cohort of hospitalizations for Crohn's disease (CD) or ulcerative colitis (UC) from 2008 to 2019 using Washington State's Comprehensive Hospital Abstract Reporting System (CHARS).

Cefepime pharmacokinetics in critically ill children and young adults undergoing continuous kidney replacement therapy.

Objectives: Cefepime is an antibiotic commonly used to treat sepsis and is cleared by renal excretion. Cefepime dosing requires adjustment in patients with decreased kidney function and in those receiving continuous kidney replacement therapy (CKRT). We aimed to characterize cefepime PK in a diverse cohort of critically ill paediatric patients on CKRT.

Diverticulitis is a population health problem: Lessons and gaps in strategies to implement and improve contemporary care.

The disease burden of diverticulitis is high across inpatient and outpatient settings, and the prevalence of diverticulitis has increased. Historically, patients with acute diverticulitis were admitted routinely for intravenous antibiotics and many had urgent surgery with colostomy or elective surgery after only a few episodes. Several recent studies have challenged the standards of how acute and recurrent diverticulitis are managed, and many clinical practice guidelines (CPGs) have pivoted to recommend outpatient management and individualized decisions about surgery.

Implementation of a structured robotic colorectal curriculum for general surgery residents.

There is increasing demand for colorectal robotic training for general surgery residents. We implemented a robotic colorectal surgery curriculum expecting that it would increase resident exposure to the robotic platform and would increase the number of graduating general surgery residents obtaining a robotic equivalency certificate. The aim of this study is to describe the components of the curriculum and characterize the immediate impact of the implementation or residents.

Understanding the Geographic Distribution of Diverticulitis Hospitalizations in Washington State.

Background: The incidence of diverticulitis in the United States is increasing, and hospitalization remains a surrogate for disease severity. State-level characterization of diverticulitis hospitalization is necessary to better understand the distribution of disease burden and target interventions.

Methods: A retrospective cohort of diverticulitis hospitalizations from 2008 through 2019 was created using Washington State's Comprehensive Hospital Abstract Reporting System.

Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure.

Obesity is caused by a prolonged positive energy balance. Whether reduced energy expenditure stemming from reduced activity levels contributes is debated. Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time.

SEX-DEPENDENT EFFECTS OF ADIPOCYTE STAT3 INHIBITION ON THE INFLAMMATORY RESPONSE DURING SEVERE SEPSIS.

Introduction: Sepsis is a dysregulated host response to infection that can lead to life-threatening organ dysfunction. Clinical and animal studies consistently demonstrate that female subjects are less susceptible to the adverse effects of sepsis, demonstrating the importance of understanding how sex influences sepsis outcomes. The signal transducer and activator of transcription 3 (STAT3) pathway are a major signaling pathway that facilitates inflammation during sepsis.