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1.
Anesth Analg ; 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38517760

RESUMEN

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 HOW DOES THIS GUIDELINE DIFFER FROM THE PREVIOUS GUIDELINES: Previously posed clinical questions that were outdated were revised to reflect current clinical practice.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.

2.
J Diabetes Sci Technol ; : 19322968241231565, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38465586

RESUMEN

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.

3.
Proc (Bayl Univ Med Cent) ; 36(5): 651-656, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37614867

RESUMEN

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.

4.
J Educ Perioper Med ; 24(3): E689, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36274996

RESUMEN

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 and 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.

5.
Anesth Analg ; 135(4): 728-731, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-36108188

RESUMEN

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.


Asunto(s)
Anestesiología , Médicos , Anestesiólogos , Anestesiología/educación , Eficiencia , Humanos , National Institutes of Health (U.S.) , Estados Unidos
6.
Anesthesiol Clin ; 40(2): 399-413, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35659410

RESUMEN

Physician engagement is often discussed in the medical literature; yet health care research examining this construct has been disjointed and plagued by conceptual ambiguities. Examining validated organizational evidence, we offer 3 key antecedents of work engagement that show promise as resources for medical professionals and health care organizations: psychological safety, organizational justice, and job crafting. In addition, we outline the nomological network of related, yet distinct, concepts, to demonstrate the relationship between engagement, burnout, and job satisfaction. As health care organizations facilitate engagement, they provide an additional avenue to decrease physician burnout, while also positively impacting provider and organizational outcomes.


Asunto(s)
Agotamiento Profesional , Cultura Organizacional , Agotamiento Profesional/prevención & control , Agotamiento Profesional/psicología , Humanos , Satisfacción en el Trabajo , Justicia Social , Encuestas y Cuestionarios
7.
Front Digit Health ; 4: 872675, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35547090

RESUMEN

As implementation of artificial intelligence grows more prevalent in perioperative medicine, a clinician's ability to distinguish differentiating aspects of these algorithms is critical. There are currently numerous marketing and technical terms to describe these algorithms with little standardization. Additionally, the need to communicate with algorithm developers is paramount to actualize effective and practical implementation. Of particular interest in these discussions is the extent to which the output or predictions of algorithms and tools are understandable by medical practitioners. This work proposes a simple nomenclature that is intelligible to both clinicians and developers for quickly describing the interpretability of model results. There are three high-level categories: transparent, translucent, and opaque. To demonstrate the applicability and utility of this terminology, these terms were applied to the artificial intelligence and machine-learning-based products that have gained Food and Drug Administration approval. During this review and categorization process, 22 algorithms were found with perioperative utility (in a database of 70 total algorithms), and 12 of these had publicly available citations. The primary aim of this work is to establish a common nomenclature that will expedite and simplify descriptions of algorithm requirements from clinicians to developers and explanations of appropriate model use and limitations from developers to clinicians.

8.
Microorganisms ; 10(3)2022 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-35336127

RESUMEN

Peptidoglycan (PGN), a polymeric glycan macromolecule, is a major constituent of the bacterial cell wall and a conserved pathogen-associated molecular pattern (PAMP) that triggers immune responses through cytosolic sensors. Immune cells encounter both PGN polymers and hydrolyzed muropeptides during infections, and primary human innate immune cells respond better to polymeric PGN than the minimal bioactive subunit muramyl dipeptide (MDP). While MDP is internalized through macropinocytosis and/or clathrin-mediated endocytosis, the internalization of particulate polymeric PGN is unresolved. We show here that PGN macromolecules isolated from Bacillus anthracis display a broad range of sizes, making them amenable for multiple internalization pathways. Pharmacologic inhibition indicates that PGN primarily, but not exclusively, is internalized by actin-dependent endocytosis. An alternate clathrin-independent but dynamin dependent pathway supports 20-30% of PGN uptake. In primary monocytes, this alternate pathway does not require activities of RhoA, Cdc42 or Arf6 small GTPases. Selective inhibition of PGN uptake shows that phagolysosomal trafficking, processing and downstream immune responses are drastically affected by actin depolymerization, while dynamin inhibition has a smaller effect. Overall, we show that polymeric PGN internalization occurs through two endocytic pathways with distinct potentials to trigger immune responses.

9.
Curr Diab Rep ; 21(12): 50, 2021 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-34902056

RESUMEN

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.


Asunto(s)
Sistemas de Apoyo a Decisiones Clínicas , Diabetes Mellitus , Aplicaciones Móviles , Diabetes Mellitus/tratamiento farmacológico , Registros Electrónicos de Salud , Humanos , Pacientes Ambulatorios
12.
Curr Diab Rep ; 19(11): 134, 2019 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-31749027

RESUMEN

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.


Asunto(s)
Diabetes Mellitus , Hiperglucemia , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Cuidados Intraoperatorios , Adulto , Glucemia , Diabetes Mellitus/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quirófanos , Procedimientos Quirúrgicos Operativos
13.
A A Pract ; 13(7): 278-280, 2019 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-31361662

RESUMEN

A 44-year-old man, American Society of Anesthesiologists physical status class IV, presented for fulguration of anal condyloma and diverting colostomy. The patient's medical history includes World Health Organization (WHO) class I pulmonary hypertension (PH), right heart failure, and bilateral lower extremity paralysis due to Pott's disease. The patient was not a candidate for neuraxial anesthesia due to sacral decubitus ulcers, and alternative options to general anesthesia (GA) were considered to avoid the high risk of right ventricular (RV) failure and ensuing complications. The case was successfully performed under sedation with dexmedetomidine infusion and bilateral rectus sheath blocks for surgical anesthesia.


Asunto(s)
Condiloma Acuminado/cirugía , Dexmedetomidina/administración & dosificación , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Adulto , Anestesia General , Colostomía , Humanos , Masculino , Bloqueo Nervioso , Resultado del Tratamiento
14.
J Vasc Surg ; 69(4): 1219-1226, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30459015

RESUMEN

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.


Asunto(s)
Glucemia/metabolismo , Hiperglucemia/etiología , Procedimientos Quirúrgicos Vasculares/efectos adversos , Anciano , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Bases de Datos Factuales , Femenino , Humanos , Hiperglucemia/sangre , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/mortalidad , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Reoperación , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/mortalidad
15.
Mediators Inflamm ; 2018: 6808934, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30532653

RESUMEN

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.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteína 58 DEAD Box/metabolismo , Virus de la Influenza A/patogenicidad , Infecciones por Orthomyxoviridae/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Lavado Broncoalveolar , Proteína 58 DEAD Box/genética , Humanos , Inmunoensayo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Noqueados , Proteína Adaptadora de Señalización NOD2/genética , Proteína Adaptadora de Señalización NOD2/metabolismo , Infecciones por Orthomyxoviridae/genética , Infecciones por Orthomyxoviridae/inmunología , Transducción de Señal/fisiología , Receptor Toll-Like 3/genética , Receptor Toll-Like 3/metabolismo , Receptor Toll-Like 7/genética , Receptor Toll-Like 7/metabolismo
16.
J Diabetes Complications ; 32(12): 1091-1096, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30253968

RESUMEN

AIM: We investigated if a dipeptidyl peptidase-4 inhibitor, sitagliptin, can prevent perioperative stress hyperglycemia in patients without prior history of diabetes mellitus undergoing general surgery. METHODS: This double-blind pilot trial randomized general surgery patients to receive sitagliptin (n = 44) or placebo (n = 36) once daily, starting one day prior to surgery and continued during the hospital stay. The primary outcome was occurrence of stress hyperglycemia, defined by blood glucose (BG) >140 mg/dL and >180 mg/dL after surgery. Secondary outcomes included: length-of-stay, ICU transfers, hypoglycemia, and hospital complications. RESULTS: BG >140 mg/dL was present in 44 (55%) of subjects following surgery. There were no differences in hyperglycemia between placebo and sitagliptin (56% vs. 55%, p = 0.93). BG >180 mg/dL was observed in 19% and 11% of patients treated with placebo and sitagliptin, respectively, p = 0.36. Both treatment groups had resulted in similar postoperative BG (148.9 ±â€¯29.4 mg/dL vs. 146.9 ±â€¯35.2 mg/dL, p = 0.73). There were no differences in length-of-stay (4 vs. 3 days, p = 0.84), ICU transfer (3% vs. 5%, p = 1.00), hypoglycemia <70 mg/dL (6% vs. 11%, p = 0.45), and complications (14% vs. 18%, p = 0.76). CONCLUSION: Preoperative treatment with sitagliptin did not prevent stress hyperglycemia or complications in individuals without diabetes undergoing surgery.


Asunto(s)
Hiperglucemia/prevención & control , Cuidados Preoperatorios/métodos , Fosfato de Sitagliptina/uso terapéutico , Estrés Psicológico/tratamiento farmacológico , Procedimientos Quirúrgicos Operativos/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Método Doble Ciego , Estudios de Factibilidad , Femenino , Hospitalización , Humanos , Hiperglucemia/etiología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estrés Psicológico/sangre , Estrés Psicológico/complicaciones , Procedimientos Quirúrgicos Operativos/efectos adversos , Adulto Joven
17.
Microb Pathog ; 121: 9-21, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29704667

RESUMEN

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.


Asunto(s)
Células Epiteliales Alveolares/microbiología , Bacillus anthracis/patogenicidad , Quimiocinas/metabolismo , Perfilación de la Expresión Génica , Esporas Bacterianas/patogenicidad , Carbunco/genética , Carbunco/metabolismo , Quimiocina CCL20/genética , Quimiocina CCL20/metabolismo , Quimiocina CXCL5/genética , Quimiocina CXCL5/metabolismo , Quimiocinas/genética , Humanos , Interleucina-8/genética , Interleucina-8/metabolismo , Monocitos/metabolismo , Monocitos/microbiología , Neutrófilos/metabolismo , Neutrófilos/microbiología , Factor Plaquetario 4/genética , Factor Plaquetario 4/metabolismo , Infecciones del Sistema Respiratorio/genética , Infecciones del Sistema Respiratorio/metabolismo , Regulación hacia Arriba
19.
Anesthesiology ; 127(5): 900-901, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-29040104
20.
Respir Res ; 18(1): 166, 2017 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-28865477

RESUMEN

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.


Asunto(s)
Proteína 58 DEAD Box/biosíntesis , Subtipo H1N1 del Virus de la Influenza A , Infecciones por Orthomyxoviridae/metabolismo , Infecciones por Orthomyxoviridae/mortalidad , Fumar/metabolismo , Fumar/mortalidad , Animales , Proteína 58 DEAD Box/genética , Perros , Expresión Génica , Humanos , Exposición por Inhalación/efectos adversos , Células de Riñón Canino Madin Darby , Ratones , Ratones Transgénicos , Mortalidad/tendencias , Fumar/efectos adversos , Contaminación por Humo de Tabaco/efectos adversos
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