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BACKGROUND: iNKT-cells are innate regulatory lymphocytes capable of directing immune and inflammatory responses to sepsis. Repeat stimulation of iNKT-cells leads to the induction of anergy with the emergence of a hyporesponsive CD3low iNKT-cell subpopulation. METHODS: iNKT-cells were isolated from critical ill surgical patients with sepsis and phenotyped for CD3 expression. This was correlated with degree of severity of illness, as denoted by APACHE-II score. RESULTS: Comparing healthy volunteers to critically ill septic patients, it was noted that increasing severity of sepsis was associated with increasing frequency of circulating CD3low-iNKT-cell populations. CONCLUSION: The emergence of CD3low -iNKT-cells may serve as a clinically translatable marker of degree of sepsis-induced immune dysfunction.
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Enfermedad Crítica , Sepsis , Humanos , LinfocitosRESUMEN
INTRODUCTION: A dysregulated immune system is a major driver of the mortality and long-term morbidity from sepsis. With respect to macrophages, it has been shown that phenotypic changes are critical to effector function in response to acute infections, including intra-abdominal sepsis. Invariant natural killer T cells (iNKT cells) have emerged as potential central regulators of the immune response to a variety of infectious insults. Specifically, various iNKT cell:macrophage interactions have been noted across a spectrum of diseases, including acute events such as sepsis. However, the potential for iNKT cells to affect peritoneal macrophages during an abdominal septic event is as yet unknown. METHODS: Cecal ligation and puncture (CLP) was performed in both wild type (WT) and invariant natural killer T cell knockout (iNKT-/-) mice. 24 h following CLP or sham operation, peritoneal macrophages were collected for analysis. Analysis of macrophage phenotype and function was undertaken to include analysis of bactericidal activity and cytokine or superoxide production. RESULTS: Within iNKT-/- mice, a greater degree of intraperitoneal macrophages in response to the sepsis was noted. Compared to WT mice, within iNKT-/- mice, CLP did induce an increase in CD86+ and CD206+, but no difference in CD11b+. Unlike WT mice, intra-abdominal sepsis within iNKT-/- mice induced an increase in Ly6C-int (5.2% versus 14.9%; P < 0.05) and a decrease in Ly6C-high on peritoneal macrophages. Unlike phagocytosis, iNKT cells did not affect macrophage bactericidal activity. Although iNKT cells did not affect interleukin-6 production, iNKT cells did affect IL-10 production and both nitrite and superoxide production from peritoneal macrophages. CONCLUSIONS: The observations indicate that iNKT cells affect specific phenotypic and functional aspects of peritoneal macrophages during polymicrobial sepsis. Given that pharmacologic agents that affect iNKT cell functioning are currently in clinical trial, these findings may have the potential for translation to critically ill surgical patients with abdominal sepsis.
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Macrófagos Peritoneales , Ratones Endogámicos C57BL , Ratones Noqueados , Células T Asesinas Naturales , Sepsis , Animales , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Sepsis/inmunología , Sepsis/microbiología , Células T Asesinas Naturales/inmunología , Ratones , Masculino , Superóxidos/metabolismo , Citocinas/metabolismo , Modelos Animales de EnfermedadRESUMEN
INTRODUCTION: Currently, there is no mandatory standard for reporting race and ethnicity in medical journals, presenting significant barriers to studying disparities in medical outcomes. We seek to investigate whether greater recent awareness of diversity and inclusion reflects in reporting of race and ethnicity by peer-reviewed cardiothoracic articles. METHODS: Pubmed was queried for clinical outcomes articles published from January 2017 to June 2023 in the Journal of Thoracic and Cardiovascular Surgery, Annals of Thoracic Surgery, Journal of Heart and Lung Transplantation, and CHEST Journal. Basic science, translational studies, and international studies were excluded. SAS Studio was used for statistical analysis. RESULTS: 817 papers were reviewed, 378 reported race/ethnicity with 354 (93%) reporting White, 267 (71%) reporting Black, 128 (34%) reporting Hispanic, and 119 (31%) reporting Asian. Over 8-y, there were no statistically significant changes in percent of articles that included White (odds ratio 0.808 95% confidence interval [0.624-1.047], P = 0.1068), Black (1.125 [0.984-1.288], P = 0.0857), or Asian (1.096 [0.960-1.250], P = 0.1751) groups. Hispanics were more likely to be reported in recent years (1.147 [1.006-1.307], P = 0.0397). Subset analysis was performed on cardiac (n = 157) and thoracic articles (n = 157) with no significant trends for race reporting in these subsets. CONCLUSIONS: Minorities remain underrepresented in reported patient populations in peer-reviewed cardiothoracic journals. Future efforts should prioritize accurately representing these populations in the literature. Inaccurate data and exclusion of minority populations can contribute to disparities observed in overall outcomes.
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BACKGROUND: Herpes virus entry mediator (HVEM) is a coinhibitory molecule which can both stimulate and inhibit host immune responses. Altered expression of HVEM and its ligands is associated with increased nosocomial infections in septic patients. We hypothesize critically ill trauma patients will display increased lymphocyte HVEM expression and that such alteration is predictive of infectious events. MATERIALS AND METHODS: Trauma patients prospectively enrolled from the ICU were compared with healthy controls. Leukocytes were isolated from whole blood, stained for CD3 (lymphocytes) and HVEM, and evaluated by flow cytometry. Charts were reviewed for injuries sustained, APACHE II score, hospital course, and secondary infections. RESULTS: Trauma patients (n = 31) were older (46.7 ± 2.4 versus 36.8 ± 2.1 y; P = 0.03) than healthy controls (n = 10), but matched for male sex (74% versus 60%; P = 0.4). Trauma patients had higher presenting WBC (13.9 ± 1.3 versus 5.6 ± 0.5 × 106/mL; P = 0.002), lower percentage of CD3+ lymphocytes (7.5% ± 0.8 versus 22.5% ± 0.9; P < 0.001), but significantly greater expression of HVEM+/CD3+ lymphocytes (89.6% ± 1.46 versus 67.3% ± 1.7; P < 0.001). Among trauma patients, secondary infection during the hospitalization was associated with higher APACHE II scores (20.6 ± 1.6 versus 13.6 ± 1.4; P = 0.03) and markedly lower CD3+ lymphocyte HVEM expression (75% ± 2.6 versus 93% ± 0.7; P < 0.01). CONCLUSIONS: HVEM expression on CD3+ cells increases after trauma. Patients developing secondary infections have less circulating HVEM+CD3+. This implies HVEM signaling in lymphocytes plays a role in maintaining host defense to infection in after trauma. HVEM expression may represent a marker of infectious risk as well as a potential therapeutic target, modulating immune responses to trauma.
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Tolerancia Inmunológica , Infecciones/inmunología , Linfocitos/inmunología , Miembro 14 de Receptores del Factor de Necrosis Tumoral/metabolismo , Heridas y Lesiones/inmunología , APACHE , Adulto , Biomarcadores/metabolismo , Complejo CD3/metabolismo , Estudios de Casos y Controles , Femenino , Voluntarios Sanos , Humanos , Infecciones/sangre , Infecciones/diagnóstico , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Miembro 14 de Receptores del Factor de Necrosis Tumoral/inmunología , Heridas y Lesiones/sangre , Heridas y Lesiones/complicacionesRESUMEN
Sepsis remains a major public health concern, characterized by marked immune dysfunction. Innate lymphoid cells develop from a common lymphoid precursor but have a role in orchestrating inflammation during innate response to infection. Here, we investigate the pathologic contribution of the group 2 innate lymphoid cells (ILC2s) in a murine model of acute septic shock (cecal ligation and puncture). Flow cytometric data revealed that ILC2s increase in number and percentage in the small intestine and in the peritoneal cells and inversely decline in the liver at 24 hours after septic insult. Sepsis also resulted in changes in ILC2 effector cytokine (IL-13) and activating cytokine (IL-33) in the plasma of mice and human patients in septic shock. Of interest, the sepsis-induced changes in cytokines were abrogated in mice deficient in functionally invariant natural killer T cells. Mice deficient in IL-13-producing cells, including ILC2s, had a survival advantage after sepsis along with decreased morphologic evidence of tissue injury and reduced IL-10 levels in the peritoneal fluid. Administration of a suppressor of tumorigenicity 2 (IL-33R) receptor-blocking antibody led to a transient survival advantage. Taken together, these findings suggest that ILC2s may play an unappreciated role in mediating the inflammatory response in both mice and humans; further, modulating ILC2 response in vivo may allow development of immunomodulatory strategies directed against sepsis.
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Modelos Animales de Enfermedad , Inmunidad Innata/inmunología , Inflamación/inmunología , Hígado/inmunología , Linfocitos/inmunología , Sepsis/complicaciones , Animales , Estudios de Casos y Controles , Células Cultivadas , Citocinas/metabolismo , Humanos , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología , Interleucina-33/inmunología , Masculino , Ratones , Células T Asesinas Naturales/inmunología , Sepsis/microbiologíaRESUMEN
BACKGROUND: Critically ill patients with sepsis and acute respiratory distress syndrome have severely altered physiology and immune system modifications. RNA splicing is a basic molecular mechanism influenced by physiologic alterations. Immune checkpoint inhibitors, such as B and T Lymphocyte Attenuator (BTLA) have previously been shown to influence outcomes in critical illness. We hypothesize altered physiology in critical illness results in alternative RNA splicing of the immune checkpoint protein, BTLA, resulting in a soluble form with biologic and clinical significance. METHODS: Samples were collected from critically ill humans and mice. Levels soluble BTLA (sBTLA) were measured. Ex vivo experiments assessing for cellular proliferation and cytokine production were done using splenocytes from critically ill mice cultured with sBTLA. Deep RNA sequencing was done to look for alternative splicing of BTLA. sBTLA levels were fitted to models to predict sepsis diagnosis. RESULTS: sBTLA is increased in the blood of critically ill humans and mice and can predict a sepsis diagnosis on hospital day 0 in humans. Alternative RNA splicing results in a premature stop codon that results in the soluble form. sBTLA has a clinically relevant impact as splenocytes from mice with critical illness cultured with soluble BTLA have increased cellular proliferation. CONCLUSION: sBTLA is produced as a result of alternative RNA splicing. This isoform of BTLA has biological significance through changes in cellular proliferation and can predict the diagnosis of sepsis.
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Empalme Alternativo , Enfermedad Crítica , Receptores Inmunológicos/sangre , Animales , Humanos , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Sepsis/diagnóstico , Bazo/citologíaRESUMEN
BACKGROUND: A proportion of trauma patients present for evaluation in a delayed fashion after injury, likely due to a variety of medical and nonmedical reasons. There has been little investigation into the characteristics and outcomes of trauma patients who present delayed. We hypothesize that trauma patients who present in a delayed fashion are a unique population at risk of increased trauma-related complications. MATERIALS AND METHODS: This was a retrospective review from 2010-2015 at a Level I trauma center. Patients were termed delayed if they presented >24 hours after injury. Patients admitted within 24 hours of their injury were the comparison group. Charts were reviewed for demographics, mechanism, comorbidities, complications and outcomes. A subgroup analysis was done on patients who suffered falls. RESULTS: During the 5-y period, 11,705 patients were admitted. A total of 588 patients (5%) presented >24 h after their injury. Patients in the delayed group were older (65 versus 55 y, P < 0.001) and more likely to have psychiatric comorbidities (33% vs. 24%, P = 0.0001) than the control group. They were also more likely to suffer substance withdrawal (8.9% vs. 4.1%, P < 0.001) but had toxicology testing for drugs and alcohol done at significantly lower rates. Patients that presented delayed after falls were similar in age and injury severity score (ISS) but more likely to suffer substance withdrawal when compared to those with falls that presented within 24 hours. Patients with falls that presented delayed had toxicology testing at significantly lower rates than the comparison group. CONCLUSIONS: Trauma patients that present to the hospital in a delayed fashion have unique characteristics and are more likely to suffer negative outcomes including substance withdrawal. Future goals will include exploring strategies for early intervention, such as automatic withdrawal monitoring and social work referral for all patients who present in a delayed fashion.
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Diagnóstico Tardío , Heridas y Lesiones/epidemiología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rhode Island/epidemiología , Factores de TiempoRESUMEN
BACKGROUND: Despite advances in perioperative care, the rate of cardiac events in vascular patients remains high. We have previously shown that infections in trauma patients are associated with higher rates of subsequent cardiac complications, likely due to the additive effect of a second hit of an infection following the trauma. The aim of this study was to investigate whether there is an association between postoperative infections and subsequent cardiac events in vascular patients. METHODS: A 5-year retrospective review of demographics, comorbidities, operative interventions, infectious, and cardiac events in all vascular patients who underwent an operative intervention at a single tertiary referral center was performed. In patients with clinical suspicion of myocardial injury, myocardial damage was defined as troponin >0.15 ng/mL and myocardial infarction (MI) as troponin >1 ng/mL. Pneumonia was diagnosed using bronchoalveolar lavage (BAL) and considered positive if BAL fluid culture contained >10,000 colony-forming units (cfu). Urinary tract infection (UTI) was diagnosed if the urine culture contained >100,000 cfu. All other infections were diagnosed by culture data. Regression analysis was performed to assess risk of cardiac events as a function of infections adjusting for age, gender, and comorbidities. RESULTS: We analyzed 1,835 vascular operative interventions with the mean age of the cohort 65.5 years (65.9% male). The overall infection rate was 13.2%, with UTI being the most common (60.3%). The overall rate of myocardial damage was 8.1% and the rate of MI 3.8%. Rates of both myocardial damage (15.5 vs. 7.7%; P = 0.0015) and MI (7.1 vs. 3.4%; P = 0.018) were significantly higher in patients with infections, compared to those without infections. Adjusting for age, gender, medical comorbidities, open versus endovascular cases as well as statin and steroid use, patients with UTI were more likely to subsequently develop either myocardial damage (odds ratio [OR] = 3.57 [95% confidence interval = 1.51-8.45]) or MI (OR = 4.20 [1.23-14.3]). A similar association was noted between any infections and either myocardial damage (OR = 2.97 [1.32-6.65]) or MI (OR = 4.31 [1.44-12.94]). CONCLUSIONS: We herein describe an association between postoperative infections, most commonly UTI, and subsequent cardiac events. Efforts should be made to minimize the risk of developing infections to ensure cardioprotection in vascular patients during perioperative period.
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Infecciones Bacterianas/microbiología , Cardiopatías/epidemiología , Procedimientos Quirúrgicos Vasculares/efectos adversos , Anciano , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/epidemiología , Distribución de Chi-Cuadrado , Comorbilidad , Femenino , Cardiopatías/diagnóstico , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Oportunidad Relativa , Neumonía Bacteriana/epidemiología , Neumonía Bacteriana/microbiología , Estudios Retrospectivos , Rhode Island/epidemiología , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Infecciones Urinarias/epidemiología , Infecciones Urinarias/microbiologíaRESUMEN
BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a common organ dysfunction in the critically ill patient. Mechanisms for its development have focused on immune mediated causes, aspects of our understanding are not complete, and we lack biomarkers. DESIGN, SETTING, AND SUBJECTS: Blood and bronchial alveolar lavage fluid (BAL) from humans (n = 10-13) with ARDS and controls (n = 5-10) as well as a murine model of ARDS (n = 5-6) with controls (n = 6-7) were studied. METHODS: ARDS was induced in mice by hemorrhagic shock (day 1) followed by poly-microbial sepsis (day 2). Samples were then collected on the third day after the animals were euthanized. Ex vivo experiments used splenocytes from animals with ARDS cultured with and without soluble programmed death receptor-1 (sPD-1). RESULTS: Levels of sPD-1 are increased in both the serum (11,429.3 pg/mL(SD 2133.3) vs. 8061.4(SD 4187.8), p = 0.036) and bronchial alveolar lavage (BAL) fluid (6,311.1 pg/mL(SD 3758.0) vs. 90.7 pg/mL(SD 202.8), p = 0.002) of humans with ARDS. Similar results are seen in the serum (9396.1 pg/mL(SD 1546.0) vs. 3464.5 pg/mL(SD 2511.8), p = 0.001) and BAL fluid (2891.7 pg/mL(SD 868.1) vs. 1385.9 pg/mL(SD 927.8), p = 0.012) of mice. sPD-1 levels in murine blood (AUC = 1(1-1), p = 0.006), murine BAL fluid (AUC = 0.905(0.717-1.093), p = 0.015), and human BAL (AUC = 1(1-1), p = 0.001) fluid predicted ARDS. To assess the importance of sPD-1 in ARDS, ex vivo experiments were undertaken. BAL fluid from mice with ARDS dampens the TNF-α production compared to cells cultured with BAL lacking sPD-1 (2.7 pg/mL(SD 3.8) vs. 52.38 pg/mL(SD 25.1), p = 0.002). CONCLUSIONS: This suggests sPD-1 is elevated in critical illness and may represent a potential biomarker for ARDS. In addition, sPD-1 has an anti-inflammatory mechanism in conditions of marked stress and aids in the resolution of severe inflammation. sPD-1 could be used to not only diagnose ARDS, but may be a potential therapy.
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Antiinflamatorios/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Síndrome de Dificultad Respiratoria/metabolismo , Animales , Biomarcadores/metabolismo , Líquido del Lavado Bronquioalveolar , Complejo CD3/metabolismo , Células Cultivadas , Demografía , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Síndrome de Dificultad Respiratoria/patología , Solubilidad , Linfocitos T/metabolismoRESUMEN
OBJECTIVES: Recent studies have shown that the occurrence rate of bloodstream infections associated with arterial catheters is 0.9-3.4/1,000 catheter-days, which is comparable to that of central venous catheters. In 2011, the Centers for Disease Control and Prevention published new guidelines recommending the use of limited barrier precautions during arterial catheter insertion, consisting of sterile gloves, a surgical cap, a surgical mask, and a small sterile drape. The goal of this study was to assess the attitudes and current infection prevention practices used by clinicians during insertion of arterial catheters in ICUs in the United States. DESIGN: An anonymous, 22-question web-based survey of infection prevention practices during arterial catheter insertion. SETTING: Clinician members of the Society of Critical Care Medicine. SUBJECTS: Eleven thousand three hundred sixty-one physicians, nurse practitioners, physician assistants, respiratory therapists, and registered nurses who elect to receive e-mails from the Society of Critical Care Medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 1,265 responses (11% response rate), with 1,029 eligible participants after exclusions were applied. Only 44% of participants reported using the Centers for Disease Control and Prevention-recommended barrier precautions during arterial catheter insertion, and only 15% reported using full barrier precautions. The mean and median estimates of the incidence density of bloodstream infections associated with arterial catheters were 0.3/1,000 catheter-days and 0.1/1,000 catheter-days, respectively. Thirty-nine percent of participants reported that they would support mandatory use of full barrier precautions during arterial catheter insertion. CONCLUSIONS: Barrier precautions are used inconsistently by critical care clinicians during arterial catheter insertion in the ICU setting. Less than half of clinicians surveyed were in compliance with current Centers for Disease Control and Prevention guidelines. Clinicians significantly underestimated the infectious risk posed by arterial catheters, and support for mandatory use of full barrier precautions was low. Further studies are warranted to determine the optimal preventive strategies for reducing bloodstream infections associated with arterial catheters.
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Antiinfecciosos Locales/uso terapéutico , Cateterismo Periférico/efectos adversos , Catéteres de Permanencia/microbiología , Infección Hospitalaria/prevención & control , Unidades de Cuidados Intensivos , Prevención Primaria/normas , Patógenos Transmitidos por la Sangre/aislamiento & purificación , Cateterismo Periférico/métodos , Catéteres de Permanencia/efectos adversos , Centers for Disease Control and Prevention, U.S./normas , Cuidados Críticos/métodos , Infección Hospitalaria/epidemiología , Contaminación de Equipos/prevención & control , Femenino , Adhesión a Directriz , Encuestas de Atención de la Salud , Humanos , Control de Infecciones/normas , Modelos Logísticos , Masculino , Guías de Práctica Clínica como Asunto , Medición de Riesgo , Sociedades Médicas , Encuestas y Cuestionarios , Estados UnidosRESUMEN
BACKGROUND AND OBJECTIVES: Optimal surgical decision-making and informed consent for palliative procedures is limited by a lack of appropriate outcomes data. Elevated C-reactive protein (CRP) may help guide patient selection for palliative surgery. METHODS: Procedures to palliate symptoms of advanced cancer were identified from a prospective palliative surgery database. Patients with a recorded preoperative serum CRP were identified and observed for at least 180 days or until death. RESULTS: Fifty patients were identified who underwent an elective palliative procedure from July 2006 to June 2012. Presenting symptoms included gastrointestinal obstruction (40%), tumor-related pain (38%) or bleeding (12%), and other (10%). Symptom improvement was documented for 37 patients (74%). Palliative procedures were associated with 30-day postoperative morbidity (42%) and mortality (10%). CRP (range 1-144 mg/L, median 9.7 mg/L) was elevated in 27 patients (54%) and was independently associated with developing a major complication (P = 0.005) and decreased overall survival (166 vs. 659 days, P < 0.0001). CONCLUSIONS: Patients with advanced cancer can be afforded symptom improvement and the opportunity for improved quality of life following palliative procedures. Elevated preoperative CRP may help identify patients who are less likely to realize the benefits of palliative operations.
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Biomarcadores de Tumor/sangre , Proteína C-Reactiva/análisis , Neoplasias/mortalidad , Neoplasias/cirugía , Cuidados Paliativos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hemorragia/etiología , Hemorragia/cirugía , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias/sangre , Neoplasias/complicaciones , Dolor/etiología , Dolor/cirugía , Complicaciones Posoperatorias , Estudios Retrospectivos , Adulto JovenRESUMEN
ABSTRACT: Background: The recruitment of neutrophils to sites of localized injury or infection is initiated by changes on the surface of endothelial cells located in proximity to tissue damage. Inflammatory mediators, such as TNF-α, increase surface expression of adhesive ligands and receptors on the endothelial surface to which neutrophils tether and adhere. Neutrophils then transit through the activated endothelium to reach sites of tissue injury with little lasting vascular injury. However, in cases of sepsis, the interaction of endothelial cells with highly activated neutrophils can cause damage vascular damage. The identification of molecules that are essential for neutrophil diapedesis may reveal targets of therapeutic opportunity for preservation of endothelial function in the presence of critical illness. We tested the hypothesis that inhibition of neutrophil ß1 integrin very late antigen-3 (VLA-3; α3ß1) and/or inhibition of the tetraspanin (TM4) family member CD151 would protect against neutrophil-mediated loss of endothelial function. Methods: Blood was obtained from septic patients or healthy donors. Neutrophils were purified, and aliquots were treated with/without proinflammatory molecules. Confluent human umbilical vascular endothelial cells were activated with TNF-α. Electric cell impedance sensing was used to determine monolayer resistance over time after the addition of neutrophils that were treated with blocking antibodies against VLA-3 and/or CD151 or isotype controls. Groups (depending on relevancy) were analyzed by Mann-Whitney U test, Wilcoxon test, or repeated-measures one-way ANOVA. Results: Neutrophils from septic patients and neutrophils activated ex vivo reduced endothelial monolayer resistance to a greater extent than neutrophils from healthy donors. Antibody blockade of VLA-3 and/or CD151 significantly reduced activation-associated endothelial damage. Similar findings were demonstrated on fibronectin, collagen I, collagen IV, and laminin, suggesting that neutrophil surface VLA-3 and CD151 are responsible for endothelial damage regardless of substrata and are likely to be operative in all bodily tissues. Conclusion: This report identifies VLA-3 and CD151 on the activated human neutrophil, which are responsible for damage to endothelial function. Targeting these molecules in vivo may demonstrate preservation of organ function during critical illness.
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Integrina alfa3beta1 , Neutrófilos , Sepsis , Tetraspanina 24 , Humanos , Neutrófilos/metabolismo , Tetraspanina 24/metabolismo , Sepsis/metabolismo , Integrina alfa3beta1/metabolismo , Masculino , Femenino , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Persona de Mediana Edad , Células Endoteliales/metabolismo , Endotelio Vascular/metabolismoRESUMEN
Background: The Surgical Infection Society (SIS) published evidence-based guidelines for the management of intra-abdominal infection (IAI) in 1992, 2002, 2010, and 2017. Here, we present the most recent guideline update based on a systematic review of current literature. Methods: The writing group, including current and former members of the SIS Therapeutics and Guidelines Committee and other individuals with content or guideline expertise within the SIS, working with a professional librarian, performed a systematic review using PubMed/Medline, the Cochrane Library, Embase, and Web of Science from 2016 until February 2024. Keyword descriptors combined "surgical site infections" or "intra-abdominal infections" in adults limited to randomized controlled trials, systematic reviews, and meta-analyses. Additional relevant publications not in the initial search but identified during literature review were included. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system was utilized to evaluate the evidence. The strength of each recommendation was rated strong (1) or weak (2). The quality of the evidence was rated high (A), moderate (B), or weak (C). The guideline contains new recommendations and updates to recommendations from previous IAI guideline versions. Final recommendations were developed by an iterative process. All writing group members voted to accept or reject each recommendation. Results: This updated evidence-based guideline contains recommendations from the SIS for the treatment of adult patients with IAI. Evidence-based recommendations were developed for antimicrobial agent selection, timing, route of administration, duration, and de-escalation; timing of source control; treatment of specific pathogens; treatment of specific intra-abdominal disease processes; and implementation of hospital-based antimicrobial agent stewardship programs. Summary: This document contains the most up-to-date recommendations from the SIS on the prevention and management of IAI in adult patients.
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Infecciones Intraabdominales , Humanos , Infecciones Intraabdominales/tratamiento farmacológico , Infecciones Intraabdominales/terapia , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/terapia , Infección de la Herida Quirúrgica/tratamiento farmacológico , Antibacterianos/uso terapéutico , Guías de Práctica Clínica como AsuntoRESUMEN
INTRODUCTION: Ventilator-associated pneumonia (VAP) occurs in up to 25% of mechanically ventilated patients, with an associated mortality up to 50%. Early diagnosis and appropriate empiric antibiotic coverage of VAP are crucial. Given the multitude of noninfectious clinical and radiographic anomalies within trauma patients, microbiology from bronchioalveolar lavage (BAL) is often needed. Empiric antibiotics are administered while awaiting BAL culture data. Little is known about the effects of these empiric antibiotics on patients with negative BAL microbiology if a subsequent VAP occurs during the same hospital course. METHODS: This is a retrospective chart review of intubated trauma patients undergoing BAL for suspected pneumonia over a 3-y period at a Level 1 trauma center. All patients with suspected VAP undergoing a BAL receive empiric antibiotics. If microbiology data are negative at 72 h, all antibiotics are stopped; however, if the BAL returns with ≥10(5) colony-forming units per milliliter, the diagnosis of VAP is confirmed. We divided patients into three groups. Group 1 consisted of patients in whom the initial BAL was positive for VAP. Group 2 consisted of patients with an initial negative BAL, who subsequently developed VAP at a later point in the hospital course. Group 3 consisted of patients with negative BAL who did not develop a subsequent VAP. RESULTS: We obtained 499 BAL specimens in 185 patients over the 3-y period. A total of 14 patients with 23 BAL specimens initially negative for VAP subsequently developed VAP later during the same hospital stay. These patients did not have an increase in the hospital length of stay, intensive care unit days, ventilator days, or mortality compared with those who had a positive culture on the first suspicion of VAP. There was a significant increase in the percentage of Enterobacter (21% versus 8%) and Morganella (8% versus 0%) as the causative organism in these 14 patients when the VAP occurred. Furthermore, the profile of the top two organisms in each group changed. Enterobacter (21%) and Pseudomonas (17%) were the principal organisms in the initial BAL-negative group, whereas the two predominant strains in the initial positive BAL group were methicillin-sensitive Staphylococcus aureus (21%) and Haemophilus influenza (11%). Interestingly, methicillin-resistant S. aureus remained the third most common organism in both groups. Empiric antibiotics also did not seem to induce the growth of multidrug-resistant organisms, and there was no increased rate of secondary infections such as Clostridium difficile. CONCLUSIONS: Ventilator-associated pneumonia remains a significant cause of morbidity and mortality in mechanically ventilated trauma patients. The diagnosis and treatment of VAP continue to be challenging. Once clinically suspected, empiric coverage decreases morbidity and mortality. Our data demonstrate that patients who receive empiric coverage exhibit a significantly different microbiologic profile compared with those who had an initial positive BAL culture. Initial empiric antibiotics in BAL-negative patients were not associated with an increase in multidrug-resistant organisms, hospital, or intensive care unit length of stay, ventilator days, and mortality or secondary infections.
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Antibacterianos/uso terapéutico , Líquido del Lavado Bronquioalveolar/microbiología , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Bacterias Grampositivas/efectos de los fármacos , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Neumonía Asociada al Ventilador/tratamiento farmacológico , Acetamidas/farmacología , Acetamidas/uso terapéutico , Antibacterianos/farmacología , Lavado Broncoalveolar , Cefepima , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , Farmacorresistencia Bacteriana/efectos de los fármacos , Quimioterapia Combinada , Femenino , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/mortalidad , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/mortalidad , Humanos , Linezolid , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Oxazolidinonas/farmacología , Oxazolidinonas/uso terapéutico , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/farmacología , Ácido Penicilánico/uso terapéutico , Piperacilina/farmacología , Piperacilina/uso terapéutico , Neumonía Asociada al Ventilador/diagnóstico , Neumonía Asociada al Ventilador/microbiología , Neumonía Asociada al Ventilador/mortalidad , Estudios Retrospectivos , Tazobactam , Resultado del Tratamiento , Vancomicina/farmacología , Vancomicina/uso terapéutico , Heridas y Lesiones/terapiaRESUMEN
INTRODUCTION: Sepsis is characterized by systemic immune activation and neutrophil-mediated endothelial barrier integrity compromise, contributing to end-organ dysfunction. Studies evaluating endothelial barrier dysfunction induced by neutrophils from septic patients are lacking, despite its clinical significance. We hypothesized that septic neutrophils would cause characteristic patterns of endothelial barrier dysfunction, distinct from experimental stimulation of normal neutrophils, and that treatment with the immunomodulatory drug ß-glucan would attenuate this effect. METHODS: Blood was obtained from critically ill septic patients. Patients were either general surgery patients (Primary Sepsis (PS)) or those with sepsis following trauma (Secondary Sepsis (SS)). Those with acute respiratory distress syndrome (ARDS) were identified. Healthy volunteers served as controls. Neutrophils were purified and aliquots were untreated, or treated with fMLP or ß-glucan. Endothelial cells were grown to confluence and activated with tissue necrosis factor (TNF)-α . Electric Cell-substrate Impedance Sensing (ECIS) was used to determine monolayer resistance after neutrophils were added. Groups were analyzed by two-way analysis of variance (ANOVA). RESULTS: Neutrophils from all septic patients, as well as fMLP-normal neutrophils, reduced endothelial barrier integrity to a greater extent than untreated normal neutrophils (normalized resistance of cells from septic patients at 30 mins = 0.90 ± 0.04; at 60 mins = 0.73 ± 0.6 and at 180 mins = 0.56 ± 0.05; p < 0.05 vs normal). Compared to untreated PS neutrophils, fMLP-treated PS neutrophils caused further loss of barrier function at all time points; no additive effect was noted in stimulation of SS neutrophils beyond 30 min. Neutrophils from ARDS patients caused greater loss of barrier integrity than those from non-ARDS patients, despite similarities in age, sex, septic source, and neutrophil count. Neutrophils obtained after resolution of sepsis caused less barrier dysfunction at all time points. ß-glucan treatment of septic patients' neutrophils attenuated barrier compromise, rendering the effect similar to that induced by neutrophils obtained once sepsis had resolved. CONCLUSIONS: Neutrophils from septic patients exert dramatic compromise of endothelial barrier integrity. This pattern is mimicked by experimental activation of healthy neutrophils. The effect of septic neutrophils on the endothelium depends upon the initial inflammatory event, correlates with organ dysfunction and resolution of sepsis, and is ameliorated by ß-glucan.
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Enfermedad Crítica , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Sepsis/tratamiento farmacológico , Sepsis/inmunología , beta-Glucanos/uso terapéutico , Adulto , Técnicas de Cultivo de Célula , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
INTRODUCTION: Sepsis is a deadly inflammatory condition that often leads to an immune suppressed state; however, the events leading to this state remain poorly understood. B and T lymphocyte attenuator (BTLA) is an immune-regulatory receptor shown to effectively inhibit CD4+ T-cell function. Therefore, our objectives were to determine: 1) if lymphocyte BTLA expression was altered in critically ill patients and experimentally induced septic mice, 2) whether augmented CD4+ T-cell BTLA expression was associated with poor septic patient outcomes, and 3) if BTLA expression affected the CD4+ T-cell apoptotic cell loss observed in the lymphoid organs of septic mice. METHODS: Changes in CD4+ lymphocyte BTLA expression were compared with morbid event development in critically ill ICU patients (11 septic and 28 systemic inflammatory response syndrome subjects). Wild type and BTLA gene deficient mice were utilized to evaluate the expression and role of BTLA in septic lymphocyte apoptotic cell loss. RESULTS: The observed septic ICU patients had a significantly higher percentage of peripheral blood BTLA+ CD4+ lymphocytes compared with critically ill non-septic individuals. Moreover, the non-septic patients with CD4+ T-cells that were greater than 80% BTLA+ were more susceptible to developing nosocomial infections. Additionally, in general, critically ill patients with CD4+ T-cells that were greater than 80% BTLA+ had longer hospital stays. Comparatively, circulating CD4+ T-cell and B-cell BTLA expression increased in septic mice, which associated with the increased septic loss of these cells. Finally, the loss of these cells and cellular apoptosis induction in primary and secondary lymphoid organs were reversed in BTLA deficient mice. CONCLUSIONS: An increased BTLA+ CD4+ lymphocyte frequency in the observed critically ill non-septic patients was associated with a subsequent infection; therefore, BTLA may act as a biomarker to help determine nosocomial infection development. Additionally, BTLA expression contributed to primary and secondary lymphoid organ apoptotic cell loss in experimentally septic mice; thus, BTLA-induced apoptotic lymphocyte loss may be a mechanism for increased nosocomial infection risk in critically ill patients. This study had a relatively small human subject cohort; therefore, we feel these findings warrant future studies evaluating the use of BTLA as a critically ill patient nosocomial infection biomarker.
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Linfocitos T CD4-Positivos/metabolismo , Infección Hospitalaria/inmunología , Receptores Inmunológicos/sangre , Sepsis/inmunología , Animales , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Ratones Endogámicos C57BL , PronósticoRESUMEN
Small bowel obstructions are common surgical presentations that are most often caused by adhesions following abdominopelvic surgeries. However, in patients with no history of abdominal surgical interventions, assessment of the cause of a small bowel obstruction is more complex, and such patients frequently require operative intervention. We present a case of a 65-year-old man who presented with a small bowel obstruction caused by an inadvertent ingestion of a bread tag that was not identified on preoperative imaging. The sharp end of the bread tag had eroded through the small bowel leading to a walled-off perforation of the small bowel. Surgical resection was required.
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Cuerpos Extraños , Obstrucción Intestinal , Perforación Intestinal , Masculino , Humanos , Anciano , Perforación Intestinal/diagnóstico por imagen , Perforación Intestinal/etiología , Perforación Intestinal/cirugía , Cuerpos Extraños/complicaciones , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/cirugía , Intestino Delgado/diagnóstico por imagen , Intestino Delgado/cirugía , Obstrucción Intestinal/diagnóstico por imagen , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Tomografía Computarizada por Rayos XRESUMEN
ABSTRACT: Background: Sepsis is marked by a dysregulated immune response to an infection. Invariant natural killer T cells ( i NKT cells) are a pluripotent lymphocyte subpopulation capable of affecting and coordinating the immune response to sepsis. The spleen is an important site of immune interactions in response to an infection. Splenic i NKT cells have emerged as important potential frontline mediators of chronic immune response. There are few data addressing the role splenic of i NKT cells in response to intra-abdominal polymicrobial sepsis. Methods: The cecal ligation and puncture model was used to create intra-abdominal sepsis in 8- to 12-week-old wild-type, i NKT -/- , or programmed cell death receptor-1 (PD-1) -/- mice. Twenty-four hours later, spleens were harvested. Flow cytometry was used for phenotyping using monoclonal antibodies. Cell sort was used to isolate i NKT cells. A macrophage cell line was used to assess i NKT cell-phagocyte interactions. Enzyme-linked immunosorbent assay was used for cytokine analysis. Results: Splenic i NKT-cell populations rapidly declined following induction of sepsis. Within i NKT-cell -/- mice, a distinct baseline hyperinflammatory environment was noted. Within wild type, sepsis induced an increase in splenic IL-6 and IL-10, whereas in i NKT -/- mice, there was no change in elevated IL-6 levels and a noted decrease in IL-10 expression. Further, following sepsis, PD-1 expression was increased upon spleen i NKT cells. With respect to PD-1 ligands upon phagocytes, PD-1 ligand expression was unaffected, whereas PD-L2 expression was significantly affected by the presence of PD-1. Conclusions: Invariant natural killer T cells play a distinct role in the spleen response to sepsis, an effect mediated by the checkpoint protein PD-1. Given that modulators are available in clinical trials, this offers a potential therapeutic target in the setting of sepsis-induced immune dysfunction.
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Células T Asesinas Naturales , Sepsis , Animales , Ratones , Receptor de Muerte Celular Programada 1 , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Bazo , Sepsis/metabolismoRESUMEN
BACKGROUND: Acute Appendicitis (AA), one of the most common surgical emergencies, is usually managed operatively. There is a paucity of data addressing how HIV/AIDS affects management of acute uncomplicated appendicitis. METHODS: A retrospective review of HIV/AIDS positive (HPos) versus negative (HNeg) patients with acute, uncomplicated appendicitis over a 19-year period. The primary outcome was undergoing appendectomy. RESULTS: Among 912,779 AA patients, 4,291 patients were HPos. HIV rates increased from 3.8/1,000 in 2000 to 6.3 per 1,000 appendicitis cases in 2019 (p<0.001). HPos patients were older, less likely to have private insurance, and more likely to have psychiatric illnesses, hypertension, and a history of prior malignancy. HPos AA patients underwent operative intervention less often than HNeg AA patients (90.7% versus 97.7%;p<0.001). Overall, comparing HPos to HNeg patients, there was no difference in post-operative infections or mortality. CONCLUSION: HIV-positive status should not deter surgeons from offering definitive care for acute uncomplicated appendicitis.
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Síndrome de Inmunodeficiencia Adquirida , Apendicitis , Laparoscopía , Humanos , Apendicitis/epidemiología , Apendicitis/cirugía , Apendicitis/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/cirugía , Apendicectomía , Complicaciones Posoperatorias , Enfermedad Aguda , Estudios Retrospectivos , Resultado del Tratamiento , Antibacterianos/uso terapéuticoRESUMEN
Introduction: The co-regulatory molecule, HVEM, can stimulate or inhibit immune function, but when co-expressed with BTLA, forms an inert complex preventing signaling. Altered HVEM or BTLA expression, separately have been associated with increased nosocomial infections in critical illness. Given that severe injury induces immunosuppression, we hypothesized that varying severity of shock and sepsis in murine models and critically ill patients would induce variable increases in HVEM/BTLA leukocyte co-expression. Methods: In this study, varying severities of murine models of critical illness were utilized to explore HVEM+BTLA+ co-expression in the thymic and splenic immune compartments, while circulating blood lymphocytes from critically ill patients were also assessed for HVEM+BTLA+ co-expression. Results: Higher severity murine models resulted in minimal change in HVEM+BTLA+ co-expression, while the lower severity model demonstrated increased HVEM+BTLA+ co-expression on thymic and splenic CD4+ lymphocytes and splenic B220+ lymphocytes at the 48-hour time point. Patients demonstrated increased co-expression of HVEM+BTLA+ on CD3+ lymphocytes compared to controls, as well as CD3+Ki67- lymphocytes. Both L-CLP 48hr mice and critically ill patients demonstrated significant increases in TNF-α. Discussion: While HVEM increased on leukocytes after critical illness in mice and patients, changes in co-expression did not relate to degree of injury severity of murine model. Rather, co-expression increases were seen at later time points in lower severity models, suggesting this mechanism evolves temporally. Increased co-expression on CD3+ lymphocytes in patients on non-proliferating cells, and associated TNF-α level increases, suggest post-critical illness co-expression does associate with developing immune suppression.