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.

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.

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.

OBESE MICE WITH PNEUMONIA HAVE HYPERLEPTINEMIA AND INCREASED PULMONARY SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3 ACTIVATION.

Obesity is an ongoing epidemic that influences pathobiology in numerous disease states. Obesity is associated with increased plasma leptin levels, a hormone that activates the signal transducer and activator of transcription 3 (STAT3) pathway. Pneumonia is a significant cause of morbidity and mortality.

A Comparison of US Medicare Expenditures for Hemodialysis and Peritoneal Dialysis.

Background: Observations that peritoneal dialysis (PD) may be an effective, lower-cost alternative to hemodialysis for the treatment of ESKD have led to policies encouraging PD and subsequent increases in its use in the United States.

Methods: In a retrospective cohort analysis of Medicare beneficiaries who started dialysis between 2008 and 2015, we ascertained average annual expenditures (for up to 3 years after initiation of dialysis) for patients ≥67 years receiving in-center hemodialysis or PD. We also determined whether differences in Medicare expenditures across dialysis modalities persisted as more patients were placed on PD.

Demonstrating Feasibility of an Opportunistic Sampling Approach for Pharmacokinetic Studies of β-Lactam Antibiotics in Critically Ill Children.

There has been increasing interest in incorporating β-lactam precision dosing into routine clinical care, but robust population pharmacokinetic models in critically ill children are needed for these purposes. The objective of this study was to demonstrate the feasibility of an opportunistic sampling approach that utilizes scavenged residual blood for future pharmacokinetic studies of cefepime, meropenem, and piperacillin. We aimed to show that opportunistic samples would cover the full concentration-versus-time profiles and to evaluate stability of the antibiotics in whole blood and plasma to optimize future use of the opportunistic sampling approach.

Weight as a Risk Factor for Mortality in Critically Ill Patients.

Objectives: To explore the hypothesis that obesity is associated with increased mortality and worse outcomes in children who are critically ill.

Methods: Secondary analysis of the Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology study, a prospective, multinational observational study. Patients between 3 months and 25 years across Asia, Australia, Europe, and North America were recruited for 3 consecutive months.

Route of Oseltamivir Administration Affects Metabolite Concentrations in Critically Ill Children.

We performed a prospective cohort study to investigate oseltamivir administration in critically ill children. We found that enteric tube administration of oseltamivir resulted in lower concentrations of its active metabolite compared with oral delivery. These findings could have significant clinical implications, and more studies are required to better understand the effects of administration route on potential lower systemic metabolite exposure.

A Case of Methotrexate Neurotoxicity Presented as Status Epilepticus, Encephalopathy, and High Fever.

High-dose methotrexate is used to treat a range of adult and childhood cancers including osteosarcoma. Significant neurotoxicity is reported in 1% to 4.5% of patients treated with high-dose methotrexate and can present in a wide variety of symptoms.

Sepsis Induces Adipose Tissue Browning in Nonobese Mice But Not in Obese Mice.

Severe sepsis and septic shock are the biggest cause of mortality in critically ill patients. Obesity today is one of the world's greatest health challenges. Little is known about the extent of involvement of the white adipose tissue (WAT) in sepsis and how it is being modified by obesity.

High fat diet-induced obesity increases myocardial injury and alters cardiac STAT3 signaling in mice after polymicrobial sepsis.

Little is known about how obesity affects the heart during sepsis and we sought to investigate the obesity-induced cardiac effects that occur during polymicrobial sepsis. Six-week old C57BL/6 mice were randomized to a high fat (HFD) (60% kcal fat) or normal diet (ND) (16% kcal fat). After 6weeks of feeding, mice were anesthetized with isoflurane and polymicrobial sepsis was induced by cecal ligation and puncture (CLP).

Obesity enhances sepsis-induced liver inflammation and injury in mice.

Objective: How obesity affects the response to sepsis was not completely understood. It was hypothesized that obesity alters adipose and hepatic tissue inflammation through signal transducer and activator of transcription (STAT3) activation.

Methods: Male C57BL/6 mice at 6 weeks of age were randomized to a high-fat diet (60% kcal fat) or normal diet (16% kcal fat) for 6 to 7 weeks.

A Case of Salicylate Intoxication Complicated by Coagulopathy, Pulmonary Edema, and Pancreatitis.

The large availability of salicylic acid products makes them an often encountered source of poisoning in the emergency department. Even though in most cases the prognosis is good, with a low incidence of long-term morbidity and mortality, complications do occur, and some of those can be life threatening. We present an unusual case of salicylate intoxication in an adolescent in which several uncommon complications (severe coagulopathy, pulmonary edema, and pancreatitis) conjoined together.

Higher-volume hypertonic saline and increased thrombotic risk in pediatric traumatic brain injury.

Purpose: Hyperosmolar therapy is a mainstay in the acute medical management of traumatic brain injury (TBI). Emerging literature suggests that a hyperosmolar state may lead to thrombotic complications. The primary objective of this study was to investigate associations between hypertonic saline (HTS) and the outcome of deep venous thrombosis (DVT) in pediatric patients with severe TBI.

Short-term high fat feeding increases organ injury and mortality after polymicrobial sepsis.

The purpose of this study was to examine the effect of short-term high fat feeding on the inflammatory response in polymicrobial sepsis. Male C57BL/6 mice at 6 weeks of age were randomized to a high-fat diet (HFD) (60% kcal fat) or control diet (CD) (16% kcal fat) for 3 weeks. After 3 weeks of feeding, sepsis was induced by cecal ligation and puncture (CLP) and animals were monitored for survival.

Validation of a gene expression-based subclassification strategy for pediatric septic shock.

Objective: Septic shock heterogeneity has important implications for clinical trial implementation and patient management. We previously addressed this heterogeneity by identifying three putative subclasses of children with septic shock based exclusively on a 100-gene expression signature. Here we attempted to prospectively validate the existence of these gene expression-based subclasses in a validation cohort.

Phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 Is associated with the downregulation of peroxisome proliferator-activated receptor (PPAR)-γ during polymicrobial sepsis.

Peroxisome proliferator-activated receptor (PPAR)-γ is a ligand-activated transcription factor and regulates inflammation. Posttranslational modifications regulate the function of PPARγ, potentially affecting inflammation. PPARγ contains a mitogen-activated protein kinase (MAPK) site, and phosphorylation by extracellular signal-regulated kinase (ERK)-1/2 leads to inhibition of PPARγ.

Toward a clinically feasible gene expression-based subclassification strategy for septic shock: proof of concept.

Objective: To develop a clinically feasible stratification strategy for pediatric septic shock, using gene expression mosaics and a 100-gene signature representing the first 24 hrs of admission to the pediatric intensive care unit.

Design: Prospective, observational study involving microarray-based bioinformatics.

Setting: Multiple pediatric intensive care units in the United States.