RESUMO
OBJECTIVE: To characterize industry nonresearch payments made to general and fellowship-trained surgeons between 2016 and 2020. BACKGROUND: The Centers for Medicare & Medicaid Services Open Payments Data (OPD) reports industry payments made to physicians related to drugs and medical devices. General payments are those not associated with research. METHODS: OPD data were queried for general and fellowship-trained surgeons who received general payments from 2016 to 2020. Payments' nature, amount, company, covered product, and location were collected. Surgeons' demographics, subspecialty, and leadership roles in hospitals, societies, and editorial boards were evaluated. RESULTS: From 2016 to 2020, 44,700 general and fellowship-trained surgeons were paid $535,425,543 in 1,440,850 general payments. The median payment was $29.18. The most frequent payments were for food and beverage (76.6%) and travel and lodging (15.6%); however, the highest dollar payments were for consulting fees ($93,128,401; 17.4%), education ($88,404,531; 16.5%), royalty or license ($87,471,238; 16.3%), and travel and lodging ($66,333,149; 12.4%). Five companies made half of all payments ($265,654,522; 49.6%): Intuitive Surgical ($128,517,411; 24%), Boston Scientific ($48,094,570; 9%), Edwards Lifesciences ($41,835,544, 7.8%), Medtronic Vascular ($33,607,136; 6.3%), and W. L. Gore & Associates ($16,626,371; 3.1%). Medical devices comprised 74.7% of payments ($399,897,217), followed by drugs and biologicals ($33,945,300; 6.3%). Texas, California, Florida, New York, and Pennsylvania received the most payments; however, the top dollar payments were in California ($65,702,579; 12.3%), Michigan ($52,990,904, 9.9%), Texas ($39,362,131; 7.4%), Maryland ($37,611,959; 7%), and Florida ($33,417,093, 6.2%). General surgery received the highest total payments ($245,031,174; 45.8%), followed by thoracic surgery ($167,806,514; 31.3%) and vascular surgery ($60,781,266; 11.4%). A total of 10,361 surgeons were paid >$5000, of which 1614 were women (15.6%); in this group, men received higher payments than women (means, $53,446 vs $22,571; P <0.001) and thoracic surgeons received highest payments (mean, $76,381; NS, P =0.14). A total of 120 surgeons were paid >$500,000 ($203,011,672; 38%)-5 non-Hispanic White (NHW) women (4.2%) and 82 NHW (68.3%), 24 Asian (20%), 7 Hispanic (5.8%), and 2 Black (1.7%) men; in this group, men received higher payments than women (means, $1,735,570 vs $684,224), and NHW men received payments double those of other men (means, $2,049,554 vs $955,368; NS, P =0.087). Among these 120 highly paid surgeons (>$500,000), 55 held hospital and departmental leadership roles, 30 were leaders in surgical societies, 27 authored clinical guidelines, and 16 served on journal editorial boards. During COVID-19, 2020 experienced half the number of payments than the preceding 3 years. CONCLUSIONS: General and fellowship-trained surgeons received substantial industry nonresearch payments. The highest-paid recipients were men. Further work is warranted in assessing how race, gender, and leadership roles influence the nature of industry payments and surgical practice. A significant decline in payments was observed early during the COVID-19 pandemic.
Assuntos
COVID-19 , Cirurgiões , Idoso , Masculino , Humanos , Feminino , Estados Unidos , Bolsas de Estudo , Pandemias , COVID-19/epidemiologia , Medicare , Conflito de Interesses , Bases de Dados FactuaisRESUMO
BACKGROUND: Much is still unknown about the actual incidence of anesthesia-related cardiac arrest in the United States. METHODS: The authors identified all of the cases of cardiac arrest from their quality improvement database from 1999 to 2009 and submitted them for review by an independent study commission to give them the best estimate of anesthesia-related cardiac arrest at their institution. One hundred sixty perioperative cardiac arrests within 24 h of surgery were identified from an anesthesia database of 217,365 anesthetics. An independent study commission reviewed all case abstracts to determine which cardiac arrests were anesthesia-attributable or anesthesia-contributory. Anesthesia-attributable cardiac arrests were those cases in which anesthesia was determined to be the primary cause of cardiac arrest. Anesthesia-contributory cardiac arrests were those cases where anesthesia was determined to have contributed to the cardiac arrest. RESULTS: Fourteen cardiac arrests were anesthesia-attributable, resulting in an incidence of 0.6 per 10,000 anesthetics (95% CI, 0.4 to 1.1). Twenty-three cardiac arrests were found to be anesthesia-contributory resulting in an incidence of 1.1 per 10,000 anesthetics (95% CI, 0.7 to 1.6). Sixty-four percent of anesthesia-attributable cardiac arrests were caused by airway complications that occurred primarily with induction, emergence, or in the postanesthesia care unit, and mortality was 29%. Anesthesia-contributory cardiac arrest occurred during all phases of the anesthesia, and mortality was 70%. CONCLUSION: As judged by an independent study commission, anesthesia-related cardiac arrest occurred in 37 of 160 cardiac arrests within the 24-h perioperative period.
Assuntos
Anestesia/efeitos adversos , Anestesia/estatística & dados numéricos , Parada Cardíaca/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Causalidade , Criança , Pré-Escolar , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Parada Cardíaca/etiologia , Mortalidade Hospitalar , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Distribuição por Sexo , Inquéritos e Questionários , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Farm machinery is a major source of injury. The objective of this study is to characterize the incidence, injury characteristics, and outcomes of patients admitted with farm machinery injuries (FMIs) to an urban joint trauma system in a rural state. A retrospective 15-year review of the trauma registries of the two trauma centers that function as a single state-designated Level I joint trauma center system was conducted. There were 65 admissions for FMIs at hospital A and 41 at hospital B; this represents under 0.4% of total trauma admissions. The patients ranged in age from 2 to 87 years. At hospital A, 89% of admitted patients sustained extremity injuries, 16% sustained torso trauma, 92% required surgical intervention, and the mortality rate was 0%. At hospital B, 60% of admitted patients sustained extremity injuries, 36.6% of patients sustained torso trauma, 63% required surgical intervention, and the mortality rate was 14.6%. Tractor-related injuries were responsible for 17% of admissions at hospital A and 69% at hospital B. Of the six fatalities, five were tractor related. The data demonstrate that FMIs affect people in nearly all decades of life. FMIs at the two hospitals had differing injury characteristics and outcomes, in large part secondary to the differing frequency of tractor-related injuries. FMIs frequently required surgical intervention.
Assuntos
Acidentes de Trabalho/estatística & dados numéricos , Agricultura/instrumentação , Acidentes de Trabalho/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Agricultura/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Nebraska/epidemiologia , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , População Rural , Centros de Traumatologia , Adulto JovemRESUMO
INTRODUCTION: Trauma patients who develop multi-organ dysfunction have increased systemic levels of chemotactic cytokines. Ischemia-reperfusion (IR) injury to the gut may play a role. The purpose of this study was to examine chemokine production in a mouse model of mesenteric IR injury. Given the pre-eminent role of the neutrophil, there has been much investigation of the CXC chemokines, but very limited research on the CC and XC chemokines. We hypothesized that intestinal IR injury would induce remote organ injury and enhance serum CC and XC chemokine levels. METHODS: Fasted female C57BL6 mice were anesthetized prior to laparotomy. In IR animals, the superior mesenteric artery (SMA) was occluded for 30, 45, or 75 min, while controls underwent sham laparotomy, n = 5-7 per group. After the indicated time point, the incision was closed and the mouse was allowed to recover for six hours. Following euthanasia, serum levels of 15 chemokines (10 CC, 4 CXC, and 1 XC) were assessed and histopathologic analyses performed. RESULTS: Seventy-five minutes of SMA occlusion was the key time frame for significant serum cytokine level up-regulation, intestinal and remote organ injury, and neutrophil influx into tissues. With 75 min of intestinal ischemia, significantly elevated serum levels, as compared to shams, were noted for seven CC chemokines: MCP-1, MCP-3, MIP-1ß, MIP-3ß, eotaxin, MDC, and RANTES. Levels of the XC chemokine lymphotactin also increased. Levels of MIP-2, IP-10, and KC/GRO (CXC chemokines) rose significantly. MIP-1α levels were only significantly increased at 45 min IR. We did not find any significant IR injury-induced changes in levels of MCP-5, MIP-1γ, or GCP-2, at any ischemia time frame. Serum levels of IL-6 correspondingly increased significantly with longer ischemia times. CONCLUSIONS: The novel finding of this study is the demonstration of significant systemic increases in the CC chemokines eotaxin, MCP-3, MDC, MIP-3ß in a time-dependent manner, along with tissue injury. The data suggest a complex response to IR injury whereby chemokines that are active on a variety of leukocytes may play a role in inducing local and remote tissue injury.
Assuntos
Quimiocinas CC/sangue , Quimiocinas CXC/sangue , Intestinos/patologia , Artéria Mesentérica Superior/patologia , Traumatismo por Reperfusão/patologia , Animais , Feminino , Intestinos/irrigação sanguínea , Mesentério/irrigação sanguínea , Mesentério/patologia , Camundongos , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos , Neutrófilos , Regulação para CimaRESUMO
The provision of critical care in any environment is resource intensive. However, the provision of critical care in an austere environment/mass disaster zone is particularly challenging. While providers are well trained for care in a modern intensive care unit, they may be under-prepared for resource-poor environments where there are limited or unfamiliar equipment and fewer support personnel. Based primarily on our experiences at a field hospital in Haiti, we created a short guide to critical care in a mass disaster in an austere environment. This guide will be useful to the team of physicians, nurses, respiratory care, logistics, and other support personnel who volunteer in future critical care relief efforts in limited resource settings.
Assuntos
Cuidados Críticos/organização & administração , Planejamento em Desastres/organização & administração , Equipamentos e Provisões Hospitalares , Unidades de Terapia Intensiva/organização & administração , Área Carente de Assistência Médica , Cuidados Críticos/métodos , Planejamento em Desastres/métodos , Serviços Médicos de Emergência/organização & administração , Haiti , Humanos , Garantia da Qualidade dos Cuidados de Saúde , Ressuscitação/métodos , Capacidade de Resposta ante Emergências/organização & administraçãoRESUMO
Clostridium difficile-associated infection (CDI) can have varying severity from asymptomatic carriage to fulminant colitis. Its incidence and virulence in North America are increasing. The increase in virulence is associated with emergence of the highly toxigenic North American pulsed field gel electrophoresis-1 strain. The major risk factor for CDI is exposure to antibiotics. Another major risk factor is hospitalization. The spectrum of CDI ranges from asymptomatic carriers to fulminant disease. Although asymptomatic carriers require no treatment, fulminant disease carries a substantial mortality regardless of management strategy.
Assuntos
Clostridioides difficile , Infecções por Clostridium , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Infecções Assintomáticas , Clostridioides difficile/patogenicidade , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/etiologia , Infecções por Clostridium/terapia , Colectomia , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/etiologia , Infecções Comunitárias Adquiridas/terapia , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/etiologia , Infecção Hospitalar/terapia , Diarreia/microbiologia , Enterocolite Pseudomembranosa/diagnóstico , Enterocolite Pseudomembranosa/epidemiologia , Enterocolite Pseudomembranosa/etiologia , Enterocolite Pseudomembranosa/terapia , Humanos , Incidência , Recidiva , Fatores de Risco , Índice de Gravidade de Doença , Estados Unidos/epidemiologia , VirulênciaRESUMO
BACKGROUND: Trauma centers are closing at an alarming rate, but the need for trauma care persists. This article shows the sustainability and feasibility of a joint trauma system whereby 2 university-affiliated hospitals function as a single trauma center system in a moderate-sized city. METHODS: Since 1994, 3 days per week, trauma patients are transported by emergency medical services (EMS) to hospital A. The other 4 days they are transported to hospital B. Trauma registry data from 1994 to 2008 were analyzed. Cost data were also examined. RESULTS: The joint system admitted 28,338 trauma patients. On each center's nontrauma days, trauma team activation was required infrequently. The 2 centers share costs; they perform joint outreach, educational training, and quality control. The joint trauma system has been sustained since 1994. CONCLUSIONS: Two hospitals functioning as a single trauma center system is a viable model of care for injured patients in a moderate-sized city with mostly blunt trauma.
Assuntos
Redução de Custos , Mortalidade Hospitalar/tendências , Hospitais Universitários/organização & administração , Avaliação de Resultados em Cuidados de Saúde , Centros de Traumatologia/organização & administração , Centros Médicos Acadêmicos/organização & administração , Adolescente , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/diagnóstico , Traumatismo Múltiplo/mortalidade , Traumatismo Múltiplo/terapia , Inovação Organizacional , Sistema de Registros , Medição de Risco , Taxa de Sobrevida , Estados Unidos , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/mortalidade , Ferimentos e Lesões/terapia , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/mortalidade , Ferimentos não Penetrantes/terapia , Adulto JovemRESUMO
MOTIVATION: Although trauma is the leading cause of death for those below 45years of age, there is a dearth of information about the temporal behavior of the underlying biological mechanisms in those who survive the initial trauma only to later suffer from syndromes such as multiple organ failure. Levels of serum cytokines potentially affect the clinical outcomes of trauma; understanding how cytokine levels modulate intra-cellular signaling pathways can yield insights into molecular mechanisms of disease progression and help to identify targeted therapies. However, developing such analyses is challenging since it necessitates the integration and interpretation of large amounts of heterogeneous, quantitative and qualitative data. Here we present the Pathway Semantics Algorithm (PSA), an algebraic process of node and edge analyses of evoked biological pathways over time for in silico discovery of biomedical hypotheses, using data from a prospective controlled clinical study of the role of cytokines in multiple organ failure (MOF) at a major US trauma center. A matrix algebra approach was used in both the PSA node and PSA edge analyses with different matrix configurations and computations based on the biomedical questions to be examined. In the edge analysis, a percentage measure of crosstalk called XTALK was also developed to assess cross-pathway interference. RESULTS: In the node/molecular analysis of the first 24h from trauma, PSA uncovered seven molecules evoked computationally that differentiated outcomes of MOF or non-MOF (NMOF), of which three molecules had not been previously associated with any shock/trauma syndrome. In the edge/molecular interaction analysis, PSA examined four categories of functional molecular interaction relationships--activation, expression, inhibition, and transcription--and found that the interaction patterns and crosstalk changed over time and outcome. The PSA edge analysis suggests that a diagnosis, prognosis or therapy based on molecular interaction mechanisms may be most effective within a certain time period and for a specific functional relationship.
Assuntos
Algoritmos , Progressão da Doença , Insuficiência de Múltiplos Órgãos/metabolismo , Insuficiência de Múltiplos Órgãos/patologia , Choque Traumático/patologia , Transdução de Sinais , Humanos , SemânticaRESUMO
BACKGROUND: The aim of this study was to analyze national trends in minimally invasive and open cases of all graduating residents in general surgery. METHODS: A retrospective analysis was performed on data obtained from Accreditation Council for Graduate Medical Education logs (1999-2008) of graduating residents from all US general surgery residency programs. Data were analyzed using Mantel-Haenszel χ(2) tests and the Bonferroni adjustment to detect trends in the number of minimally invasive and open cases. RESULTS: Minimally invasive procedures accounted for an increasing proportion of cases performed (3.7% to 11.1%, P < .0001), with a proportional decrease in open cases. An increase in minimally invasive procedures with a proportional decrease in open procedures was noted in subcategories such as alimentary tract, abdominal, vascular, thoracic, and pediatric surgery (P < .0001). CONCLUSIONS: The results of this study demonstrate that general surgery residents in the United States are performing a greater number of minimally invasive and fewer open procedures for common surgical conditions.
Assuntos
Competência Clínica , Currículo/normas , Educação de Pós-Graduação em Medicina/tendências , Cirurgia Geral/educação , Internato e Residência/normas , Procedimentos Cirúrgicos Minimamente Invasivos/tendências , Procedimentos Cirúrgicos Operatórios/tendências , Escolha da Profissão , Avaliação Educacional , Cirurgia Geral/tendências , Pesquisas sobre Atenção à Saúde , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/educação , Estudos Retrospectivos , Procedimentos Cirúrgicos Operatórios/educação , Estados UnidosRESUMO
BACKGROUND: Endotoxemia from lipopolysaccharide (LPS) induces systemic cytokine production, whereas traumatic brain injury (TBI) increases intracerebral cytokine production. In anesthetic doses, ketamine has potent anti-inflammatory properties. However, its anti-inflammatory effects at subanesthetic doses and its effects on TBI-induced inflammation have not been fully investigated. We hypothesized that ketamine would attenuate both LPS- and TBI-induced inflammatory responses. METHODS: Male rats received intraperitoneal (i.p.) ketamine (70 mg/kg, 7 mg/kg, or 1 mg/kg) or saline 1 hour before LPS (20 mg/kg i.p.) or saline. Five hours after LPS, rats were killed. Serum was collected for cytokine analysis. In other experiments, male rats were given ketamine (7 mg/kg i.p.) or saline 1 hour before induction of TBI with controlled cortical impact (or sham). One hour and 6 hours after injury, brain was extracted for analysis of cerebral edema and cytokine production. RESULTS: LPS increased the serum concentrations of interleukin (IL)-1α, IL-1ß, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ. Ketamine dose dependently attenuated these changes. TBI caused cerebral edema and increased concentrations of cerebral IL-1α, IL-1ß, IL-6, IL-10, and tumor necrosis factor-α. However, ketamine had minimal effect on TBI-induced inflammation. CONCLUSIONS: Although ketamine did not seem to exert any beneficial effects against TBI in the rat, it did not exacerbate cytokine production or enhance cerebral edema as some studies have suggested.
Assuntos
Edema Encefálico/tratamento farmacológico , Lesões Encefálicas/tratamento farmacológico , Citocinas/sangue , Endotoxemia/tratamento farmacológico , Ketamina/farmacologia , Análise de Variância , Animais , Endotoxemia/metabolismo , Endotoxinas/farmacologia , Lipopolissacarídeos/farmacologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Today, there is an ever-increasing amount of biological and clinical data available that could be used to enhance a systems-based understanding of disease progression through innovative computational analysis. In this article, we review a selection of published research regarding computational methods, primarily from systems biology, which support translational research from the molecular level to the bedside, with a focus on applications in trauma and critical care. Trauma is the leading cause of mortality in Americans younger than 45 years, and its rapid progression offers both opportunities and challenges for computational analysis of trends in molecular patterns associated with outcomes and therapeutic interventions.This review presents methods and domain-specific examples that may inspire the development of new algorithms and computational methods that use both molecular and clinical data for diagnosis, prognosis, and therapy in disease progression.
Assuntos
Biologia Computacional/métodos , Pesquisa Translacional Biomédica/métodos , Adulto , Algoritmos , Teorema de Bayes , Pesquisa Biomédica , Simulação por Computador , Progressão da Doença , Humanos , Pessoa de Meia-Idade , Modelos Estatísticos , Prognóstico , Biologia de Sistemas , Teoria de Sistemas , Resultado do Tratamento , Estados Unidos , Ferimentos e LesõesRESUMO
BACKGROUND: Although ketamine has many beneficial effects in a rat model of noninfectious inflammation with lipopolysaccharide (LPS), its effects on gut ileus are unknown. We hypothesized that ketamine would improve LPS-induced ileus and therefore examined its effects on gastric emptying and intestinal transit as well as duodenogastric bile reflux and associated gastric bleeding. METHODS: Male rats received saline or ketamine (7 mg/kg ip) 1 hour before saline or LPS (20 mg/kg ip) for 5 hours. Thirty minutes before killing, rats received orogastric rhodamine B isothiocyanate-labeled dextran and 5 minutes later fluorescein isothiocyanate-labeled dextran via a duodenal catheter. GI contents were collected for dye, bile acid, and hemoglobin (index of bleeding) determinations. RESULTS: LPS significantly impaired intestinal transit and increased duodenogastric bile reflux and gastric luminal hemoglobin content. Ketamine improved intestinal transit, prevented LPS-induced bile reflux, and diminished gastric bleeding. In mechanistic studies, ketamine also attenuated LPS-induced upregulation of the proinflammatory genes inducible nitric oxide synthase and cyclo-oxygenase-2 in the stomach but preserved expression of the anti-inflammatory gene heme-oxygenase-1 (Western blot). CONCLUSIONS: These data suggest that ketamine may prevent LPS-induced gastric bleeding by decreasing bile reflux through improved intestinal transit or by local changes in nitric oxide, prostaglandin, and carbon monoxide metabolism.
Assuntos
Refluxo Duodenogástrico/fisiopatologia , Hemorragia Gastrointestinal/fisiopatologia , Ketamina/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , Refluxo Duodenogástrico/induzido quimicamente , Escherichia coli , Esvaziamento Gástrico/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Conteúdo Gastrointestinal/química , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/tratamento farmacológico , Trânsito Gastrointestinal/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Hemoglobinas/análise , Hipnóticos e Sedativos/farmacologia , Lipopolissacarídeos , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Lipopolysaccharide (LPS) increases systemic inflammation and causes duodenogastric reflux of bile and gastric bleeding. Laparotomy prevents gastric injury from the luminal irritant bile, but its effects on LPS-induced gastric injury are unknown. We hypothesized that laparotomy would diminish inflammation and attenuate gastric bleeding caused by LPS. In the rat, laparotomy, done either before or after administration of LPS, attenuated LPS-induced bile reflux, gastric bleeding, and cyclooxygenase-2, but not inducible nitric oxide synthase, expression when compared to controls given LPS. Laparotomy also blunted LPS-induced changes in serum cytokine production. These data suggest that laparotomy has gastroprotective effects by preventing LPS-induced bile reflux and gastric bleeding and by a mechanism mediated, at least in part by cyclooxygenase-2.
Assuntos
Refluxo Biliar/complicações , Escherichia coli , Hemorragia Gastrointestinal/prevenção & controle , Laparotomia , Lipopolissacarídeos/toxicidade , Animais , Refluxo Biliar/induzido quimicamente , Refluxo Biliar/fisiopatologia , Ciclo-Oxigenase 2/fisiologia , Citocinas/sangue , Refluxo Duodenogástrico/induzido quimicamente , Refluxo Duodenogástrico/fisiopatologia , Refluxo Duodenogástrico/prevenção & controle , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/fisiopatologia , Masculino , Óxido Nítrico Sintase Tipo II/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Shock is a prime inciting event for postinjury multiple organ failure (MOF), believed to induce a state of injurious systemic inflammation. In animal models of hemorrhagic shock, early (< 24 hours) changes in cytokine production are an index of the systemic inflammatory response syndrome. However, their predictive value in trauma patients remains to be fully elucidated. STUDY DESIGN: In a prospective observational pilot study of > 1 year at an urban Level I trauma center, serial (every 4 hours) serum cytokine levels were determined during a 24-hour period using multiplex suspension immunoassay in patients with major torso trauma (excluding severe brain injury) who met criteria for standardized shock resuscitation. Temporal cytokine expression was assessed during shock resuscitation in severe trauma patients to predict risk for MOF. MOF was assessed with the Denver score. RESULTS: Of 48 study patients (mean age 39 +/- 3 years, 67% men, 88% blunt mechanism, mean Injury Severity Score 25 +/- 2), MOF developed in 11 (23%). MOF patients had a considerably higher mortality (64% versus 3%) and fewer ICU-free days (3.5 +/- 2 versus 17.8 +/- 1.3 days) compared with non-MOF patients. Traditional predictors of MOF, including age (45 +/- 7 versus 38 +/- 3 years; p=0.21), Injury Severity Score (26 +/- 3 versus 25 +/- 2; p=0.67), admission hemoglobin (11.4 +/- 0.9 versus 12.1 +/- 0.5 g/dL; p=0.22), international normalized ratio (1.6 +/- 0.2 versus 1.4 +/- 0.06; p=0.17), and base deficit (9.0 +/- 2 versus 7.1 +/- 0.8; p=0.19), were not significantly different between MOF and non-MOF patients. Statistical analysis identified six candidate predictors of MOF: inducible protein 10, macrophage inflammatory protein-1beta, interleukin-10, interleukin-6, interleukin-1Ra, and eotaxin. CONCLUSIONS: These data provide insight into cytokine expression during traumatic shock that can enable earlier identification of patients at risk for development of MOF.
Assuntos
Citocinas/sangue , Insuficiência de Múltiplos Órgãos/classificação , Choque/sangue , Adulto , Teorema de Bayes , Feminino , Humanos , Imunoensaio/métodos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de RiscoRESUMO
Lipopolysaccharide (LPS) causes hepatic injury that is mediated, in part, by upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Ketamine has been shown to prevent these effects. Because upregulation of heme oxygenase-1 (HO-1) has hepatoprotective effects, as does carbon monoxide (CO), an end product of the HO-1 catalytic reaction, we examined the effects of HO-1 inhibition on ketamine-induced hepatoprotection and assessed whether CO could attenuate LPS-induced hepatic injury. One group of rats received ketamine (70 mg/kg ip) or saline concurrently with either the HO-1 inhibitor tin protoporphyrin IX (50 micromol/kg ip) or saline. Another group of rats received inhalational CO (250 ppm over 1 h) or room air. All rats were given LPS (20 mg/kg ip) or saline 1 h later and euthanized 5 h after LPS or saline. Liver was collected for iNOS, COX-2, and HO-1 (Western blot), NF-kappaB and PPAR-gamma analysis (EMSA), and iNOS and COX-2 mRNA analysis (RT-PCR). Serum was collected to measure alanine aminotransferase as an index of hepatocellular injury. HO-1 inhibition attenuated ketamine-induced hepatoprotection and downregulation of iNOS and COX-2 protein. CO prevented LPS-induced hepatic injury and upregulation of iNOS and COX-2 proteins. Although CO abolished the ability of LPS to diminish PPAR-gamma activity, it enhanced NF-kappaB activity. These data suggest that the hepatoprotective effects of ketamine are mediated primarily by HO-1 and its end product CO.
Assuntos
Heme Oxigenase (Desciclizante)/fisiologia , Ketamina/farmacologia , Hepatopatias/prevenção & controle , Alanina Transaminase/sangue , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Monóxido de Carbono/farmacologia , Doença Hepática Induzida por Substâncias e Drogas , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Inibidores Enzimáticos/farmacologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Heme Oxigenase (Desciclizante)/antagonistas & inibidores , Ketamina/uso terapêutico , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias/sangue , Hepatopatias/metabolismo , Masculino , Metaloporfirinas/farmacologia , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , PPAR gama/metabolismo , Protoporfirinas/farmacologia , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
BACKGROUND: Alpha-melanocyte stimulating hormone (alpha-MSH) is a neuropeptide which modulates inflammation. Prior studies have documented decreased alpha-MSH concentrations in patients with acute traumatic brain injury and subarachnoid hemorrhage. We hypothesized that alpha-MSH levels would be decreased in critically injured patients and that this would correlate with poor outcome. METHODS: We performed a retrospective review of prospectively collected data more than 12 months ending December 2005. alpha-MSH concentrations were measured in major torso trauma patients (excluding severe head injuries) who underwent standardized shock resuscitation. alpha-MSH concentrations were measured every 4 hours for the first 24 hours of intensive care unit admission and daily thereafter for hospital days 2 to 5. Controls were similarly aged, healthy volunteers. Outcomes measured included lengths of stay, infectious morbidity, and the incidence of multiple organ failure (MOF) and mortality. RESULTS: Fifty-one trauma patients were studied with a median age of 33 (22-54) years. Seventy-five percent were male and 82% sustained blunt trauma. The median Injury Severity Score was 25 (16-34). Eighteen percent of the patients developed MOF, 18% died, and 24% developed MOF and died. The mean initial (first value on the first day) alpha-MSH concentration was significantly lower than in controls (15.9 pg/mL +/- 7.6 pg/mL vs. 26.1 pg/mL +/- 7.4 pg/mL, p = 0.0008) and did not change significantly during the 5-day study period. On univariate and adjusted multivariate analyses, initial alpha-MSH concentrations did not predict either MOF or mortality. CONCLUSIONS: The current study is the first to document significantly decreased alpha-MSH concentrations in critically injured trauma patients as compared with controls. Furthermore, alpha-MSH concentrations remained so throughout the study period.
Assuntos
Estado Terminal , Traumatismo Múltiplo/sangue , alfa-MSH/sangue , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Humanos , Incidência , Escala de Gravidade do Ferimento , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/mortalidade , Traumatismo Múltiplo/mortalidade , Análise de Regressão , Estudos RetrospectivosRESUMO
INTRODUCTION: Enteral nutrition improves clinical outcomes. The effects of feeding on LPS induced liver injury are unknown. We hypothesized that feeding would attenuate liver injury from LPS. METHODS: Fasted or fed rats were given LPS (20 mg/kg i.p.) or saline for 5 h and sacrificed. Serum aminotransferases and cytokines (immunoassay) were measured. Oxidative stress protein (iNOS, COX2, and HO1) assessments (Western immunoblot) were also obtained. RESULTS: In fasted rats, LPS significantly increased serum aminotransferase levels, enhanced hepatic COX2, iNOS, and HO1 immunoreactivity, and increased serum cytokine levels when compared to controls. While feeding diminished liver enzymes, attenuated expression of COX2 and iNOS, and blunted production of pro-inflammatory cytokines, it did not modulate LPS-induced expression of the anti-inflammatory markers HO1 and IL-10. CONCLUSION: These data suggest that feeding decreases liver injury by attenuating expression of pro-inflammatory mediators while maintaining expression of anti-inflammatory mediators, both systemically and locally.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Ciclo-Oxigenase 2/metabolismo , Ingestão de Alimentos/fisiologia , Jejum/fisiologia , Heme Oxigenase-1/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Animais , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Citocinas/sangue , Nutrição Enteral , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Masculino , Ratos , Ratos Sprague-Dawley , Regulação para CimaRESUMO
BACKGROUND: Although cellular therapy has shown promise in the management of traumatic brain injury (TBI), microenvironment interactions between the intracerebral milieu and therapeutic stem cells are poorly understood. We sought to characterize the acute, regional inflammatory response after TBI. METHODS: Rats underwent a controlled cortical impact (CCI) injury or sham injury, were killed at 6, 12, 24, 48, and 72 hours, and intracerebral fluid (IF) was isolated from the direct injury, penumbral, ipsilateral frontal, and contralateral regions. Cortical and hippocampal areas were also isolated. Regional cytokine levels were measured. Polymorphonuclear cell (PMN) oxidative burst and marker expression were assessed after incubation with the IF. Immunohistochemistry was used to identify intracerebral CD68(+) cells (microglia/macrophages). RESULTS: The proinflammatory cytokines interleukin (IL)-1alpha, IL-1beta, IL-6, and tumor necrosis factor-alpha were significantly elevated after CCI in the injury and penumbral regions. Increases in the same cytokines were localized to the cortex and the hippocampus. Increased PMN expression of CD11b and L-selectin was identified after incubation with injury or penumbral area IF, without change in PMN oxidative burst. CD68(+) cells were noted in the direct injury and penumbral areas. CONCLUSION: The local cerebral milieu in the first 48 hours after TBI is highly proinflammatory. This response is most pronounced in areas at or proximal to the direct injury. The local, acute proinflammatory response after TBI may serve as a therapeutic target of early cell therapy or, conversely, may create an unfavorable local milieu, limiting the efficacy of early cellular therapy.
Assuntos
Reação de Fase Aguda/etiologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Reação de Fase Aguda/metabolismo , Reação de Fase Aguda/terapia , Animais , Lesões Encefálicas/terapia , Antígeno CD11b/metabolismo , Citocinas/metabolismo , Selectina L/metabolismo , Ratos , Explosão Respiratória/fisiologia , Superóxidos/metabolismo , Fatores de TempoRESUMO
BACKGROUND: Poloxamer 188 (P188), a nonionic block copolymer chemical surfactant known to have cytoprotective, rheologic, anti-inflammatory, and anti-thrombotic activity, has shown promise in the management of selected trauma patients. We studied human PMN oxidative burst and adhesion molecule expression when exposed to P188. METHODS: After RBC lysis of whole blood samples, white blood cell components were primed with phosphotidylcholine, primed and activated with fMLP, primed and activated with PMA, or left unstimulated. Each group was treated with vehicle or P188 (0.005-15 mg/ml concentrations). Flow cytometry quantified: (1) PMN superoxide anion production and (2) PMN marker expression of CD11b and L-selectin. RESULTS: Among non-PMA activated PMNs, P188 increased superoxide anion production. PMA-activated PMNs decreased superoxide anion production, proportional to P188 dose. Among fMLP-activated PMNs, the highest P188 dose increased the expression of CD11b. Among PMA-activated PMNs, decreased CD11b expression was seen for the mid-range doses. CONCLUSIONS: PMNs altered their oxidative burst and marker expression after exposure to P188. When used at lower doses, P188 may increase the oxidative burst response and, when used at very high doses, increase CD11b expression. However, if PMNs are in a maximally activated state, a higher dose of P188 may decrease the oxidative burst response and decrease CD11b expression.
Assuntos
Neutrófilos/efeitos dos fármacos , Poloxâmero/farmacologia , Tensoativos/farmacologia , Antígeno CD11b/metabolismo , Humanos , Técnicas In Vitro , Selectina L/metabolismo , Neutrófilos/metabolismo , Explosão Respiratória/efeitos dos fármacos , Superóxidos/metabolismoRESUMO
BACKGROUND: Matrix metalloproteinases (MMPs) are a group of endopeptidases induced under inflammatory conditions in the intestine which possess the capacity to degrade components of the extracellular matrix. We have previously demonstrated that MMP-2 expression correlates with increased inducible nitric oxide synthase (iNOS) production in the stomach and that iNOS is upregulated in the postischemic gut by the luminal nutrient arginine and repressed by luminal glutamine. We therefore hypothesized that arginine would enhance expression of MMP-2 in the postischemic gut. METHODS: Jejunal sacs were created in rats at laparotomy and filled with either 60 mM glutamine, arginine, or magnesium sulfate (osmotic control) followed by 60 minutes of superior mesenteric artery occlusion (SMAO) and 6 hours of reperfusion and compared with shams. Jejunum was harvested, and membrane type-1 matrix metalloproteinase (MT1-MMP), MMP-2, and iNOS protein expression was determined by Western analysis and MMP-9 production by gelatin zymography. RESULTS: MMP-2, MT1-MMP, MMP-9, and iNOS were all increased after SMAO compared with shams. Arginine maintained while glutamine inhibited the increase in iNOS, MT1-MMP, and MMP-2 expression in the postischemic gut. Pretreatment of the arginine group with a selective iNOS inhibitor blunted the induction of MMP-2 in the postischemic gut. There was no differential modulation of MMP-9 by the luminal nutrients. CONCLUSIONS: The arginine-induced upregulation of iNOS may contribute to increased activity of MT1-MMP and MMP-2. The mechanism for this differential regulation by arginine warrants further investigation.