Effects of Glucagon-Like Peptide-1 Receptor Agonists on Gastric Mucosal Visibility and Retained Gastric Contents During Esophagogastroduodenoscopy.

BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are increasingly utilized in diabetes and obesity management. GLP-1RAs delay gastric emptying; however, their impact on visibility during esophagogastroduodenoscopy (EGD) remains uncertain. METHODS: A 1:1 matched case-control study was conducted. Individuals undergoing EGD on GLP-1RAs were matched to non-users based on demographics and diabetes status. A validated scale (POLPREP) was used to determine gastric mucosal visibility scores. RESULTS: A total of 84 pairs (n=168) were included. GLP-1RA users showed significantly lower visibility scores, with a 2.54 times higher likelihood of lower scores compared to non-users. Additionally, GLP-1RA users had a higher incidence of retained gastric contents (13.1% vs. 4.8%, aOR:4.62, p=0.025) and aborted procedures due to this issue. No anesthesia-related adverse events were observed. CONCLUSIONS: GLP-1RA use at the time of endoscopy exhibited higher odds of lower gastric mucosal visibility scores, retained contents and aborted procedures. Further research is warranted.

Society for Ambulatory Anesthesia Updated Consensus Statement on Perioperative Blood Glucose Management in Adult Patients With Diabetes Mellitus Undergoing Ambulatory Surgery.

WHAT OTHER GUIDELINES ARE AVAILABLE ON THIS TOPIC: Since the publication of the SAMBA Consensus Statement for perioperative blood glucose management in the ambulatory setting in 2010, several recent guidelines have been issued by the American Diabetes Association (ADA), the American Association of Clinical Endocrinologists (AACE), the Endocrine Society, the Centre for Perioperative Care (CPOC), and the Association of Anaesthetists of Great Britain and Ireland (AAGBI) on DM care in hospitalized patients; however, none are specific to ambulatory surgery. HOW DOES THIS GUIDELINE DIFFER FROM THE PREVIOUS GUIDELINES: Previously posed clinical questions that were outdated were revised to reflect current clinical practice. Additional questions were developed relating to the perioperative management of patients with DM to include the newer therapeutic interventions.

Using Bibliometric Data to Define and Understand Publishing Network Equity in Anesthesiology.

BACKGROUND: Anesthesiology departments and professional organizations increasingly recognize the need to embrace diverse membership to effectively care for patients, to educate our trainees, and to contribute to innovative research. 1 Bibliometric analysis uses citation data to determine the patterns of interrelatedness within a scientific community. Social network analysis examines these patterns to elucidate the network's functional properties. Using these methodologies, an analysis of contemporary scholarly work was undertaken to outline network structure and function, with particular focus on the equity of node and graph-level connectivity patterns. METHODS: Using the Web of Science, this study examines bibliographic data from 6 anesthesiology-specific journals between January 1, 2017, and August 26, 2022. The final data represent 4453 articles, 19,916 independent authors, and 4436 institutions. Analysis of coauthorship was performed using R libraries software. Collaboration patterns were assessed at the node and graph level to analyze patterns of coauthorship. Influential authors and institutions were identified using centrality metrics; author influence was also cataloged by the number of publications and highly cited papers. Independent assessors reviewed influential author photographs to classify race and gender. The Gini coefficient was applied to examine dispersion of influence across nodes. Pearson correlations were used to investigate the relationship between centrality metrics, number of publications, and National Institutes of Health (NIH) funding. RESULTS: The modularity of the author network is significantly higher than would be predicted by chance (0.886 vs random network mean 0.340, P < .01), signifying strong community formation. The Gini coefficient indicates inequity across both author and institution centrality metrics, representing moderate to high disparity in node influence. Identifying the top 30 authors by centrality metrics, number of published and highly cited papers, 79.0% were categorized as male; 68.1% of authors were classified as White (non-Latino) and 24.6% Asian. CONCLUSIONS: The highly modular network structure indicates dense author communities. Extracommunity cooperation is limited, previously demonstrated to negatively impact novel scientific work. 2 , 3 Inequitable node influence is seen at both author and institution level, notably an imbalance of information transfer and disparity in connectivity patterns. There is an association between network influence, article publication (authors), and NIH funding (institutions). Female and minority authors are inequitably represented among the most influential authors. This baseline bibliometric analysis provides an opportunity to direct future network connections to more inclusively share information and integrate diverse perspectives, properties associated with increased academic productivity. 3 , 4.

A Call to Action: A Specialty-Specific Course to Support the Next Generation of Clinician Scientists in Anesthesiology.

Clinical production pressure is a significant problem for faculty of anesthesiology departments who seek to remain involved in research. Lack of protected time to dedicate to research and insufficient external funding add to this long-standing issue. Recent trends in funding to the departments of anesthesiology and their academic output validate these concerns. A 2022 study examining National Institutes of Health (NIH) grant recipients associated with anesthesiology departments across 10 years (2011-2020) outlines total awarded funds at $1,676,482,440, with most of the funds awarded to only 10 departments in the United States. Of note, the total 1-year NIH funding in 2021 for academic internal medicine departments was 3 times higher than the 10-year funding of anesthesiology departments. Additionally, American Board of Anesthesiology (ABA) diplomats represent a minority (37%) of the anesthesiology researchers obtaining grant funding, with a small number of faculty members receiving a prevalence of monies. Overall, the number of publications per academic anesthesiologist across the United States remains modest as does the impact of the scholarly work. Improving environments in which academic anesthesiologists thrive may be paramount to successful academic productivity. In fact, adding to the lack of academic time is the limited bandwidth of senior academic physicians to mentor and support aspiring physician scientists. Given then the challenges for individual departments and notable successes of specialty-specific collaborative efforts (eg, Foundation for Anesthesia Education and Research [FAER]), additional pooled-resource approaches may be necessary to successfully support and develop clinician scientists. It is in this spirit that the leadership of Anesthesia & Analgesia and The Journal of Education in Perioperative Medicine, unified with the Association of University Anesthesiologists, aim to sponsor the Introduction to Clinical Research for Academic Anesthesiologists (ICRAA) Course. Directed toward early career academic anesthesiologists who wish to gain competency specifically in the fundamentals of clinical research and receive mentorship to develop an investigative project, the yearlong course will provide participants with the skills necessary to design research initiatives, ethically direct research teams, successfully communicate ideas with data analysts, and write and submit scientific articles. Additionally, the course, articulated in a series of interactive lectures, mentored activities, and workshops, will teach participants to review articles submitted for publication to medical journals and to critically appraise evidence in published research. It is our hope that this initiative will be of interest to junior faculty of academic anesthesiology departments nationally and internationally.

Implementation of App-Based Diabetes Medication Management: Outpatient and Perioperative Clinical Decision Support.

PURPOSE OF REVIEW: Outpatient and perioperative therapeutic decision making for patients with diabetes involves increasingly complex medical-decision making due to rapid advances in knowledge and treatment modalities. We sought to review mobile decision support tools available to clinicians for this essential and increasingly difficult task, and to highlight the development and implementation of novel mobile applications for these purposes. RECENT FINDINGS: We found 211 mobile applications related to diabetes from the search, but only five were found to provide clinical decision support for outpatient diabetes management and none for perioperative decision support. We found a dearth of tools for clinicians to navigate these tasks. We highlight key aspects for effective development of future diabetes decision support. These include just-in-time availability, respect for the five rights of clinical decision support, and integration with clinical workflows including the electronic medical record.

Poor glycemic control is a strong predictor of postoperative morbidity and mortality in patients undergoing vascular surgery.

OBJECTIVE: Hyperglycemia is a common occurrence in patients undergoing cardiovascular surgery. It has been identified in several surgical cohorts that improved perioperative glycemic control reduced postoperative morbidity and mortality. A significant portion of the population with peripheral arterial disease suffers from the sequelae of diabetes or metabolic syndrome. A paucity of data exists regarding the relationship between perioperative glycemic control and postoperative outcomes in vascular surgery patients. The objective of this study was to better understand this relationship and to determine which negative perioperative outcomes could be abated with improved glycemic control. METHODS: This is a retrospective review of a vascular patient database at a large academic center from 2009 to 2013. Eligible procedures included carotid endarterectomy and stenting, endovascular and open aortic aneurysm repair, and all open bypass revascularization procedures. Data collected included standard demographics, outcome parameters, and glucose levels in the perioperative period. Perioperative hyperglycemia was defined as at least one glucose value >180 mg/dL within 72 hours of surgery. The primary outcome was 30-day mortality, with secondary outcomes of complications, need to return to the operating room, and readmission. RESULTS: Of the total 1051 patients reviewed, 366 (34.8%) were found to have perioperative hyperglycemia. Hyperglycemic patients had a higher 30-day mortality (5.7% vs 0.7%; P < .01) and increased rates of acute renal failure (4.9% vs 0.9%; P < .01), postoperative stroke (3.0% vs 0.7%; P < .01), and surgical site infections (5.7% vs 2.6%; P = .01). In addition, these patients were also more likely to undergo readmission (12.3% vs 7.9%; P = .02) and reoperation (6.3% vs 1.8%; P < .01). Furthermore, multivariable logistic regression demonstrated that perioperative hyperglycemia had a strong association with increased 30-day mortality and multiple negative postoperative outcomes, including myocardial infarction, stroke, renal failure, and wound complications. CONCLUSIONS: This study demonstrates a strong association between perioperative glucose control and 30-day mortality in addition to multiple other postoperative outcomes after vascular surgery.

Glycemic Management in the Operating Room: Screening, Monitoring, Oral Hypoglycemics, and Insulin Therapy.

PURPOSE OF REVIEW: This review provides a literature update and practical outline for the management of diabetes and stress hyperglycemia for adult surgical patients in the pre- and intraoperative settings. RECENT FINDINGS: Hyperglycemia in surgical patients has been associated with increased risk of complication in both diabetic and non-diabetic patients in the perioperative setting. While current recommended perioperative blood glucose target is < 180 mg/dL (10 mmol/L), optimal outcomes may require different treatment targets for diabetic versus non-diabetic patients. Hemoglobin A1C level is associated with elevated risk of hyperglycemia and adverse outcomes, but there is insufficient evidence to recommend routine preoperative testing or optimal values in elective surgical patients. Day of surgery blood glucose testing and treatment are recommended in the perioperative period, and anesthetic management includes appropriate patient selection for use of subcutaneous insulin, intravenous insulin infusions, and insulin pumps. Additionally, administration of both intravenous and perineural dexamethasone is associated with increased blood glucose levels and clinicians should consider the risk benefit ratio in surgical patients. For enhanced recovery after surgery protocols, further evidence is needed to support routine use of carbohydrate loading in diabetic patients. Optimal perioperative care includes screening at-risk patients, use of preoperative oral hypoglycemics and home insulin, anesthetic type and medication selection, blood glucose testing, and treatment for hyperglycemia in the operating room. Partnerships with surgery and endocrinology teams aid optimal postoperative management and discharge planning.

Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets.

The respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cells that work together to maintain steady-state respiration. Owing to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systematically identify these subsets in human airways by developing a schema of isolating large numbers of cells by whole-lung bronchoalveolar lavage. Six subsets of phagocytic APC (HLA-DR+) were consistently observed. Aside from alveolar macrophages, subsets of Langerin+, BDCA1-CD14+, BDCA1+CD14+, BDCA1+CD14-, and BDCA1-CD14- cells were identified. These subsets varied in their ability to internalize Escherichia coli, Staphylococcus aureus, and Bacillus anthracis particles. All subsets were more efficient at internalizing S. aureus and B. anthracis compared with E. coli Alveolar macrophages and CD14+ cells were overall more efficient at particle internalization compared with the four other populations. Subsets were further separated into two groups based on their inherent capacities to upregulate surface CD83, CD86, and CCR7 expression levels. Whole-genome transcriptional profiling revealed a clade of "true dendritic cells" consisting of Langerin+, BDCA1+CD14+, and BDCA1+CD14- cells. The dendritic cell clade was distinct from a macrophage/monocyte clade, as supported by higher mRNA expression levels of several dendritic cell-associated genes, including CD1, FLT3, CX3CR1, and CCR6 Each clade, and each member of both clades, was discerned by specific upregulated genes, which can serve as markers for future studies in healthy and diseased states.

Gene expression profiling of primary human type I alveolar epithelial cells exposed to Bacillus anthracis spores reveals induction of neutrophil and monocyte chemokines.

The lung is the entry site for Bacillus anthracis in inhalation anthrax, the most deadly form of the disease. Spores must escape through the alveolar epithelial cell (AEC) barrier and migrate to regional lymph nodes, germinate and enter the circulatory system to cause disease. Several mechanisms to explain alveolar escape have been postulated, and all these tacitly involve the AEC barrier. In this study, we incorporate our primary human type I AEC model, microarray and gene enrichment analysis, qRT-PCR, multiplex ELISA, and neutrophil and monocyte chemotaxis assays to study the response of AEC to B. anthracis, (Sterne) spores at 4 and 24 h post-exposure. Spore exposure altered gene expression in AEC after 4 and 24 h and differentially expressed genes (±1.3 fold, p ≤ 0.05) included CCL4/MIP-1ß (4 h), CXCL8/IL-8 (4 and 24 h) and CXCL5/ENA-78 (24 h). Gene enrichment analysis revealed that pathways involving cytokine or chemokine activity, receptor binding, and innate immune responses to infection were prominent. Microarray results were confirmed by qRT-PCR and multiplex ELISA assays. Chemotaxis assays demonstrated that spores induced the release of biologically active neutrophil and monocyte chemokines, and that CXCL8/IL-8 was the major neutrophil chemokine. The small or sub-chemotactic doses of CXCL5/ENA-78, CXCL2/GROß and CCL20/MIP-3α may contribute to chemotaxis by priming effects. These data provide the first whole transcriptomic description of the human type I AEC initial response to B. anthracis spore exposure. Taken together, our findings contribute to an increased understanding of the role of AEC in the pathogenesis of inhalational anthrax.

RIG-I Signaling via MAVS Is Dispensable for Survival in Lethal Influenza Infection In Vivo.

Retinoic acid-inducible gene I (RIG-I) is an important regulator of virus-induced antiviral interferons (IFNs) and proinflammatory cytokines. It requires interaction with an adaptor molecule, mitochondrial antiviral-signaling protein (MAVS), to activate downstream signaling pathways. To elucidate the mechanism(s) by which RIG-I-dependent recognition of IAV infection in vivo triggers innate immune responses, we infected mutant mice lacking RIG-I or MAVS with influenza A virus (IAV) and measured their innate immune responses. As has previously been demonstrated with isolated deletion of the virus recognition receptors TLR3, TLR7, and NOD2, RIG-I or MAVS knockout (KO) did not result in higher mortality and did not reduce IAV-induced cytokine responses in mice. Infected RIG-I KO animals displayed similar lung inflammation profiles as did WT mice, in terms of the protein concentration, total cell count, and inflammatory cell composition in the bronchoalveolar lavage fluid. RNA-Seq results demonstrated that all types of mice exhibited equivalent antiviral and inflammatory gene responses following IAV infection. Together, the results indicated that although RIG-I is important in innate cytokine responses in vitro, individual deletion of the genes encoding RIG-I or MAVS did not change survival or innate responses in vivo after IAV infection in mice.

RIG-I overexpression decreases mortality of cigarette smoke exposed mice during influenza A virus infection.

BACKGROUND: Retinoic acid-inducible gene I (RIG-I) is an important regulator of virus-induced antiviral interferons (IFNs) and proinflammatory cytokines which participate in clearing viral infections. Cigarette smoke (CS) exposure increases the frequency and severity of respiratory tract infections. METHODS: We generated a RIG-I transgenic (TG) mouse strain that expresses the RIG-I gene product under the control of the human lung specific surfactant protein C promoter. We compared the mortality and host immune responses of RIG-I TG mice and their litter-matched wild type (WT) mice following challenge with influenza A virus (IAV). RESULTS: RIG-I overexpression increased survival of IAV-infected mice. CS exposure increased mortality in WT mice infected with IAV. Remarkably, the effect of RIG-I overexpression on survival during IAV infection was enhanced in CS-exposed animals. CS-exposed IAV-infected WT mice had a suppressed innate response profile in the lung compared to sham-exposed IAV-infected WT mice in terms of the protein concentration, total cell count and inflammatory cell composition in the bronchoalveolar lavage fluid. RIG-I overexpression restored the innate immune response in CS-exposed mice to that seen in sham-exposed WT mice during IAV infection, and is likely responsible for enhanced survival in RIG-I TG mice as restoration preceded death of the animals. CONCLUSIONS: Our results demonstrate that RIG-I overexpression in mice is protective for CS enhanced susceptibility of smokers to influenza infection, and that CS mediated RIG-I suppression may be partially responsible for the increased morbidity and mortality of the mice exposed to IAV. Thus, optimizing the RIG-I response may be an important treatment strategy for CS-enhanced lung infections, particularly those due to IAV.

The Emory University Perioperative Algorithm for the Management of Hyperglycemia and Diabetes in Non-cardiac Surgery Patients.

Hyperglycemia is a frequent manifestation of critical and surgical illness, resulting from the acute metabolic and hormonal changes associated with the response to injury and stress (Umpierrez and Kitabchi, Curr Opin Endocrinol. 11:75-81, 2004; McCowen et al., Crit Care Clin. 17(1):107-24, 2001). The exact prevalence of hospital hyperglycemia is not known, but observational studies have reported a prevalence of hyperglycemia ranging from 32 to 60 % in community hospitals (Umpierrez et al., J Clin Endocrinol Metab. 87(3):978-82, 2002; Cook et al., J Hosp Med. 4(9):E7-14, 2009; Farrokhi et al., Best Pract Res Clin Endocrinol Metab. 25(5):813-24, 2011), and 80 % of patients after cardiac surgery (Schmeltz et al., Diabetes Care 30(4):823-8, 2007; van den Berghe et al., N Engl J Med. 345(19):1359-67, 2001). Retrospective and randomized controlled trials in surgical populations have reported that hyperglycemia and diabetes are associated with increased length of stay, hospital complications, resource utilization, and mortality (Frisch et al., Diabetes Care 33(8):1783-8, 2010; Kwon et al., Ann Surg. 257(1):8-14, 2013; Bower et al., Surgery 147(5):670-5, 2010; Noordzij et al., Eur J Endocrinol. 156(1):137-42, 2007; Mraovic et al., J Arthroplasty 25(1):64-70, 2010). Substantial evidence indicates that correction of hyperglycemia reduces complications in critically ill, as well as in general surgery patients (Umpierrez et al., J Clin Endocrinol Metab. 87(3):978-82, 2002; Clement et al., Diabetes Care 27(2):553-97, 2004; Pomposelli et al., JPEN J Parented Enteral Nutr. 22(2):77-81, 1998). This manuscript reviews the pathophysiology of stress hyperglycemia during anesthesia and the perioperative period. We provide a practical outline for the diagnosis and management of preoperative, intraoperative, and postoperative care of patients with diabetes and hyperglycemia.

Cigarette smoke attenuates the RIG-I-initiated innate antiviral response to influenza infection in two murine models.

Cigarette smoke (CS) exposure increases the frequency and severity of respiratory tract infections. Despite this association, the mechanisms underlying the increased susceptibility to respiratory virus infection are poorly understood. Retinoic acid-inducible gene I (RIG-I) is an important regulator of influenza virus-induced expression of antiviral cytokines, mainly interferons (IFNs), which are necessary to clear viral infections. In this study, we compared the innate cytokine responses of two mouse CS exposure models following a challenge with influenza A virus (IAV): 1) exposure of the mice to cigarette smoke extract (CSE) intratracheally and 2) exposure of the mice to CS in a whole body exposure chamber. Both intratracheal CSE treatment and whole body CS exposure caused antiviral immunosuppression in these mice, and both CS exposure methods inhibited RIG-I induction. CS attenuated influenza-induced antiviral IFNs and IP-10 expression in vivo. However, we did not find that CS inhibited induction of the proinflammatory cytokines IL-6 and TNF-α, whose expression was induced by IAV. Interestingly, IAV infection also increased Toll-like receptor 3 (TLR3) expression in mouse lung, but CS exposure did not impact TLR3 induction in these mice. Together, the results support our previous finding in a human lung organ culture model that the suppression of RIG-I induction and antiviral cytokine responses by CS are likely important in the enhanced susceptibility of smokers to influenza infection in the lung.

Should We Stop Glucagon-Like Peptide-1 Receptor Agonists Before Surgical or Endoscopic Procedures? Balancing Limited Evidence With Clinical Judgment.

The American Society of Anesthesiologists (ASA) Task Force recently recommended discontinuing glucagon-like peptide-1 receptor agonist (GLP-1 RA) agents before surgery because of the potential risk of pulmonary aspiration. However, there is limited scientific evidence to support this recommendation, and holding GLP-1 RA treatment may worsen glycemic control in patients with diabetes. As we await further safety data to manage GLP-1 RA in the perioperative period, we suggest an alternative multidisciplinary approach to manage patients undergoing elective surgery. Well-conducted observational and prospective studies are needed to determine the risk of pulmonary aspiration in persons receiving GLP-1 RA for the treatment of diabetes and obesity, as well as the short-term impact of discontinuing GLP-1 RA on glycemic control before elective procedures in persons with diabetes.

Sixth Annual Enhanced Recovery After Surgery Symposium highlights: work in progress or standard care?

Enhanced Recovery After Surgery (ERAS) protocols have demonstrated effectiveness in accelerating patient recovery and improving outcomes. Since the systemwide implementation of ERAS protocols at Baylor Scott & White Health, an annual multidisciplinary conference has provided a review of outcomes and advancements in the ERAS program. This meeting, coined the ERAS symposium, allows providers who utilize recovery protocols to collaborate with national and international leaders in the field to improve the clinical care of patients. The sixth annual ERAS symposium was held on February 10, 2023, and provided key presentations that discussed the latest results from ERAS efforts across multiple surgical specialties along with updates in anesthesia, nursing, and nutrition. A summary of those presentations, which included perioperative glycemic control, misconceptions in pain management, and emerging ERAS protocols in different surgical specialties, is provided to document the system progress.

Bacillus anthracis lethal toxin reduces human alveolar epithelial barrier function.

The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness.