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2.
J Surg Res ; 259: 493-499, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33070996

RESUMO

BACKGROUND: Limited exposure to surgical subspecialties during medical school may be responsible for decreasing medical student interest in surgery. Although most medical schools have surgery interest groups to increase exposure, our aim was to evaluate the impact of a focused surgical subspecialty roundtable on preclerkship students' perceptions of surgical careers. METHODS: Faculty members from each surgical subspecialty shared their experiences and led roundtable discussions with five to seven first- and second-year medical students at a time (total n = 59). Pre-event and post-event surveys were administered to assess students' interest in surgery, knowledge of training paths, values related to specialty selection, and perception of surgeons. RESULTS: Forty students completed pre-event and post-event surveys. The number of students who were extremely or very interested in surgery increased after this event (65% versus 72.5%, P < 0.001). The greatest number of students indicated an interest in orthopedic surgery, and the fewest indicated an interest in neurosurgery. After the event, thirteen (32.5%) students changed their preferences for the subspecialty in which they were most interested. Students demonstrated improved knowledge of training length and integrated residencies (83.8% versus 96.3%, P = 0.003). The perceived importance of intellectual challenge, research opportunities, and training length decreased, whereas the importance of compensation, work/life balance, long-term patient follow-up, and the job market increased. Students' perceptions of surgeons' work/life balance (10% versus 25%, P < 0.001) and ability to be team players (82.5% versus 85%, P = 0.01) improved significantly after the roundtable. CONCLUSIONS: The surgical specialty roundtable increased students' interest in surgery, improved knowledge of training paths, and altered perceptions related to career decision-making.


Assuntos
Escolha da Profissão , Educação de Graduação em Medicina/estatística & dados numéricos , Especialidades Cirúrgicas/educação , Estudantes de Medicina/psicologia , Adulto , Feminino , Humanos , Internato e Residência/estatística & dados numéricos , Masculino , Pennsylvania , Percepção , Especialidades Cirúrgicas/estatística & dados numéricos , Estudantes de Medicina/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Equilíbrio Trabalho-Vida , Adulto Jovem
3.
J Trauma Acute Care Surg ; 82(2): 280-286, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27893639

RESUMO

BACKGROUND: The evolving field of acute care surgery (ACS) traditionally includes trauma, emergency general surgery, and critical care. However, the critical role of ACS in the rescue of patients with a surgical complication has not been explored. We here describe the role of "surgical rescue" in the practice of ACS. METHODS: A prospective, electronic medical record-based ACS registry spanning January 2013 to May 2014 at a large urban academic medical center was screened by ICD-9 codes for acute surgical complications of an operative or interventional procedure. Long-term outcomes were derived from the Social Security Death Index. RESULTS: Of 2,410 ACS patients, 320 (13%) required "surgical rescue": most commonly, from wound complications (32%), uncontrolled sepsis (19%), and acute obstruction (15%). The majority of complications (85%) were related to an operation; 15% were related to interventional procedures. The most common rescue interventions required were bowel resection (23%), wound debridement (18%), and source control of infection (17%); 63% of patients required operative intervention, and 22% required surgical critical care. Thirty-six percent of complications occurred in ACS primary patients ("local"), whereas 38% were referred from another surgical service ("institutional") and 26% referred from another institution ("regional"). Hospital length of stay was longer, and in-hospital and 1-year mortalities were higher in rescue patients compared with those without a complication. Outcomes were equivalent between "local" and "institutional" patients, but hospital length of stay and discharge to home were significantly worse in "institutional" referrals. CONCLUSION: We here describe the distinct role of the acute care surgeon in the surgical management of complications; this is an additional pillar of ACS. In this vital role, the acute care surgeon provides crucial support to other providers as well as direct patient care in the "surgical rescue" of surgical and procedural complications. LEVEL OF EVIDENCE: Epidemiological study, level III; therapeutic/care management study, level IV.


Assuntos
Cuidados Críticos , Complicações Pós-Operatórias/cirurgia , Radiografia Intervencionista/efeitos adversos , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pennsylvania/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Sistema de Registros , Centros de Traumatologia
5.
J Trauma Acute Care Surg ; 75(1): 44-9; discussion 49, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23778437

RESUMO

BACKGROUND: Single-center experience has shown that American College of Surgeons (ACS) trauma verification can improve outcomes. The current objective was to compare mortality between ACS-verified and state-designated centers in a national sample. METHODS: Subjects 16 years or older from ACS-verified or state-designated Level I and II centers were identified in the National Trauma Databank 2007 to 2008. A predictive mortality model was constructed using Trauma Quality Improvement Project methodology. Imputation was used for missing data. Probability of mortality in the model determined expected deaths. Observed-to-expected (O/E) mortality ratios with 90% confidence interval (CI) and outliers (90% CI more than or less than 1.0) were compared across ACS and state Level I and II centers. The mortality model was repeated with ACS versus state included. RESULTS: There were 900,274 subjects. The model had an area under the curve of 0.92 to predict death. Level I ACS centers had a lower median O/E ratio compared with state centers (0.95 [interquartile range, 0.82-1.05] vs. 1.02 [interquartile range, 0.87-1.15]; p < 0.01), with no difference in Level II centers. Level II state centers had more high O/E outliers. ACS verification was an independent predictor of survival in Level II centers (odds ratio, 1.26; 95% CI, 1.20-1.32; p < 0.01) but not in Level I centers (p = 0.84). CONCLUSION: Level II centers have a disproportionate number of high mortality outliers, and ACS verification is a predictor of survival. Level I ACS centers have lower O/E ratios overall, but no difference in outliers. ACS verification seems beneficial. These data suggest that Level II centers benefit most, and promoting Level II ACS verification may be an opportunity for improved outcomes. LEVEL OF EVIDENCE: Prognostic study, level III.


Assuntos
Mortalidade Hospitalar/tendências , Avaliação de Resultados em Cuidados de Saúde , Centros de Traumatologia/normas , Ferimentos e Lesões/mortalidade , Adolescente , Adulto , Causas de Morte , Intervalos de Confiança , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Medição de Risco , Sociedades Médicas/normas , Estados Unidos , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/terapia , Adulto Jovem
6.
J Trauma Nurs ; 20(1): 37-43, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23459431

RESUMO

Although, historically, shock associated with traumatic injury has been evaluated through knowledge of the 4 recognized shock patterns--cardiogenic, obstructive, distributive, and hypovolemic--many trauma practitioners view traumatic shock as a unique fifth shock pattern. Although secondary to a systemic inflammatory response syndrome triggered by endogenous danger signals, traumatic shock represents a unique pathological condition that begins with multiple, usually blunt, trauma and may conclude with multiple organ dysfunction syndrome and death. While varying mechanisms of injury may lead to different presentations of shock and cardiovascular decompensation, a unifying theme of traumatic shock is an overwhelming inflammatory response driven by proinflammatory cytokines, and the downstream results of this cytokine storm including, but not limited to, acute respiratory distress syndrome, coagulopathy, sepsis, and multiple organ dysfunction syndrome. Treatment is primarily supportive; however, research into novel therapeutics for traumatic shock is ongoing and promises some direction for future care.


Assuntos
Acidentes de Trânsito , Serviços Médicos de Emergência/métodos , Enfermagem em Emergência/métodos , Insuficiência de Múltiplos Órgãos , Choque Traumático , Adolescente , Evolução Fatal , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/enfermagem , Insuficiência de Múltiplos Órgãos/fisiopatologia , Insuficiência de Múltiplos Órgãos/terapia , Veículos Off-Road , Choque Traumático/enfermagem , Choque Traumático/fisiopatologia , Choque Traumático/terapia
7.
J Trauma ; 70(6): 1381-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21817975

RESUMO

BACKGROUND: Venous thromboembolism is a major cause of morbidity and mortality after injury. Prophylactic anticoagulation is often delayed as a result of injuries or required procedures. Those patients at highest risk in this early vulnerable window postinjury are not well characterized. We sought to determine those patients at highest risk for an early pulmonary embolism (PE) after injury. METHODS: A retrospective analysis using data derived from a large state wide trauma registry (1997-2007) was performed. Patients with a documented PE and time of occurrence were selected (n = 712). Patients with fat emboli and lower extremity vascular injuries were excluded. Patients with a PE within the first 72 hours of admission (EARLY, n = 122) were compared with those with DELAYED presentation. Kaplan-Meier survival analysis was used to characterize the timing of death between the two groups. Backward stepwise logistic regression was used to determine independent risk factors for EARLY PE relative to those with DELAYED PE. RESULTS: EARLY and DELAYED groups were similar in age, gender, Glasgow Coma Scale, emergency department systolic blood pressure, and injury mechanism. The EARLY PE group had a lower Injury Severity Score but injuries more commonly included femur fracture. Kaplan-Meier analysis revealed that EARLY PE patients have a significantly higher risk of early mortality relative to DELAYED PE patients (p = 0.012). Regression analysis revealed that the only independent risk factor for EARLY PE was lower extremity/pelvic orthopedic fixation (<48 hours from injury). The risk of EARLY PE was more than threefold higher (odds ratios, 3.85; 95% CI, 1.9-7.6; p < 0.001) for those who underwent early lower extremity orthopedic fixation versus those who did not. CONCLUSION: Early lower extremity/pelvis orthopedic fixation is the single independent predictor of EARLY PE in this patient cohort. Venous thromboembolism/PE prevention strategies should be made a priority in this group of patients, including early preoperative institution of anticoagulation prophylaxis. These results suggest that those with contraindications to early anticoagulation may benefit from insertion of retrievable inferior vena cava filters preoperatively.


Assuntos
Fraturas Ósseas/terapia , Extremidade Inferior/lesões , Embolia Pulmonar/prevenção & controle , Filtros de Veia Cava , Trombose Venosa/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Humanos , Escala de Gravidade do Ferimento , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pennsylvania/epidemiologia , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Sistema de Registros , Estudos Retrospectivos , Risco , Fatores Sexuais , Estatísticas não Paramétricas , Análise de Sobrevida , Fatores de Tempo
8.
J Surg Educ ; 68(4): 266-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21708362

RESUMO

BACKGROUND: There is poor interrater reliability in the assessment of a medical student's ability to generate a differential diagnosis list using Likert-based scales in the surgical clerkship. This important clinical skill is tested on the United States Medical Licensing Examination Step 2 Clinical Skills Examination. OBJECTIVE: We hypothesize that third-year medical students in the surgical clerkship will be able to accurately diagnose adult patients with acute abdominal pain after performing a focused history and physical examination in a 3-station Objective Structured Clinical Examination (OSCE). Second, we want to test our hypothesis that service assessments of a student's ability to analyze data will not correspond with OSCE performance. METHODS: In this retrospective study, third-year medical student differential diagnosis lists from a 3-station OSCE and medical student clerkship assessments were collected from the 2009-2010 academic year. Differential diagnosis lists were scored for accuracy. Differences between groups were compared with nonparametric statistics, using an α = 0.05. RESULTS: Seventy-eight third-year medical students (56.4% female) were evaluated. For 2 stations, more than half of the medical students had the correct diagnosis on the differential diagnosis list (p < 0.0001). For 1 station, less than half of the medical students had the correct diagnosis on the differential diagnosis list (p = 0.0001). There were no differences in the service evaluation scores and the number of correct differential diagnosis lists for the students (p = 0.91). CONCLUSIONS: Third-year medical students are generally accurate with the ability to diagnosis adult patients with acute abdominal pain after performing a history and physical examination. Additionally, surgical service faculty and resident assessments of a student's ability to analyze data do not correspond with OSCE performance. We recommend some changes that might lead to improved grading for third-year medical students in the surgical clerkship.


Assuntos
Dor Abdominal/diagnóstico , Estágio Clínico/organização & administração , Competência Clínica , Educação de Graduação em Medicina/métodos , Exame Físico/normas , Abdome Agudo/diagnóstico , Doença Aguda , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Anamnese , Avaliação das Necessidades , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Faculdades de Medicina , Estudantes de Medicina , Adulto Jovem
9.
Neoplasia ; 13(3): 198-205, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21390183

RESUMO

INTRODUCTION: The CD95/CD95L pathway plays a critical role in tissue homeostasis and immune system regulation; however, the function of this pathway in malignancy remains poorly understood. We hypothesized that CD95L expression in esophageal adenocarcinoma confers advantages to the neoplasm other than immune privilege. METHODS: CD95L expression was characterized in immortalized squamous esophagus (HET-1A) and Barrett esophagus (BAR-T) cells; adenocarcinoma cell lines FLO-1, SEG-1, and BIC-1, and MDA468 (- control); and KFL cells (+ control). Analyses included reverse transcription-polymerase chain reaction, immunoblots of whole cell and secretory vesicle lysates, FACScan analysis, laser scanning confocal microscopy of native proteins and fluorescent constructs, and assessment of apoptosis and ERK1/2 pathways. RESULTS: Cleaved, soluble CD95L is expressed at both the RNA and protein levels in these cell lines derived from esophageal adenocarcinoma and other human tissues. CD95L was neither trafficked to the cell membrane nor secreted into the media or within vesicles, rather the protein seems to be sequestered in the cytoplasm. CD95 and CD95L colocalize by immunofluorescence, but an interaction was not proven by immunoprecipitation. Overexpression of CD95L in the adenocarcinoma cell lines induced robust apoptosis and, under conditions of pan-caspase inhibition, resulted in activation of ERK signaling. CONCLUSIONS: CD95L localization in EA cells is inconsistent with the conference of immune privilege and is more consistent with a function that promotes tumor growth through alternative CD95 signaling. Reduced cell surface expression of CD95 affects cell sensitivity to extracellular apoptotic signals more significantly than alterations in downstream modulators of apoptosis.


Assuntos
Apoptose , Citoplasma/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Proteína Ligante Fas/metabolismo , Receptor fas/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Western Blotting , Proliferação de Células , Neoplasias Esofágicas/tratamento farmacológico , Proteína Ligante Fas/genética , Humanos , Técnicas Imunoenzimáticas , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Células Tumorais Cultivadas , Receptor fas/genética
10.
Surgery ; 148(4): 618-24, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20705305

RESUMO

BACKGROUND: With liberal use of computed tomography in the diagnostic management of trauma patients, incidental findings are common and represent a major patient-care and medical-legal concern. Consequently, we began an initiative to capture, notify, and documentadequately incidental finding events with a dedicated incidental finding coordinator. We hypothesized a dedicated incidental finding coordinator would increase incidental finding capture and promote notification, follow-up, and documentation of incidental finding events. METHODS: A quality-improvement project to record and follow-up incidental findings postinjury was initiated at our level I trauma center (April 2007-March 2008, prededicated incidental finding). Because of concerns for inadequate documentation of identified incidental finding events, we implemented a dedicated incidental finding coordinator (April 2008-March 2009, postdedicated incidental finding). The dedicated incidental finding coordinator documented incidental findings daily from trauma admission radiology final reads. Incidental findings were divided into 3 groups; category 1: attention prior to discharge; category 2: follow-up with primary doctor within 2 weeks; category 3: no specific follow-up. For category 1 incidental findings, in-hospital consultation of the appropriate service was verified. On discharge, patient notification, follow-up, and documentation of events were confirmed. Certified mail or telephone contact was used to notify either the patient or the primary doctor in those who lacked appropriate notification or documentation. RESULTS: Admission rates and incidental finding categories were similar across the 2 time periods. Implementation of a dedicated incidental finding coordinator resulted in more than a 165% increase in incidental finding capture (n = 802 vs n = 302; P < .001). Patient notification was attempted, and appropriate documentation of events was confirmed in 99.8% of patients. Patient notification was verified, and follow-up was initiated in 95.8% of cases. CONCLUSION: The implementation of a dedicated incidental finding coordinator resulted in more than a 2.5-fold higher capture of incidental findings. Dedicated attention to incidental findings resulted in a near complete initiation of patient notification, follow-up, and hospital record documentation of incidental finding events. Inadequate patient notification and follow-up would delay appropriate care and potentially would result in morbidity or even mortality. A dedicated incidental finding coordinator represents a potential solution to this patient-care and medical-legal dilemma.


Assuntos
Achados Incidentais , Ferimentos e Lesões/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Revelação , Documentação , Feminino , Seguimentos , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Estudos Prospectivos , Garantia da Qualidade dos Cuidados de Saúde , Radiografia , Centros de Traumatologia/normas , Adulto Jovem
11.
Crit Care ; 14(2): 305, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20377922
12.
J Trauma ; 67(2): 221-7; discussion 228-30, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19667872

RESUMO

BACKGROUND: Blood transfusion is known to be an independent risk factor for mortality, multiple organ failure (MOF), acute respiratory distress syndrome (ARDS), and nosocomial infection after injury. Less is known about the independent risks associated with plasma-rich transfusion components including fresh frozen plasma (FFP), platelets (PLTS), and cryoprecipitate (CRYO) after injury. We hypothesized that plasma-rich transfusion components would be independently associated with a lower risk of mortality but result in a greater risk of morbid complications. METHODS: Data were obtained from a multicenter prospective cohort study evaluating clinical outcomes in bluntly injured adults with hemorrhagic shock. All patients required blood transfusion for enrollment. Patients with isolated traumatic brain injury and those not surviving beyond 48 hours were excluded. Cox proportional hazard regression models were used to estimate the outcome risks (per unit) associated with plasma-rich transfusion requirements during the initial 24 hours after injury after controlling for important confounders. RESULTS: For the entire study population (n = 1,175), 65%, 41%, and 28% of patients received FFP, PLTS and CRYO, respectively. There was no association with plasma-rich transfusion components and mortality or nosocomial infection. For every unit given, FFP was independently associated with a 2.1% and 2.5% increased risk of MOF and ARDS, respectively. CRYO was associated with a 4.4% decreased risk of MOF (per unit), and PLTS were not associated with any of the outcomes examined. When early deaths (within 48 hours) were included in the model, FFP was associated with a 2.9% decreased risk of mortality per unit transfused. CONCLUSIONS: In patients who survive their initial injury, FFP was independently associated with a greater risk of developing MOF and ARDS, whereas CRYO was associated with a lower risk of MOF. Further investigation into the mechanisms by which these plasma-rich component transfusions are associated with these effects are required.


Assuntos
Transfusão de Componentes Sanguíneos/efeitos adversos , Insuficiência de Múltiplos Órgãos/etiologia , Plasma , Síndrome do Desconforto Respiratório/etiologia , Choque Hemorrágico/terapia , Adulto , Fator VIII , Feminino , Fibrinogênio , Humanos , Masculino , Pessoa de Meia-Idade , Transfusão de Plaquetas , Estudos Prospectivos , Fatores de Risco , Choque Hemorrágico/complicações , Ferimentos não Penetrantes/complicações , Adulto Jovem
13.
J Trauma ; 63(1): 44-9, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17622867

RESUMO

BACKGROUND: Splenic artery arteriography with possible therapeutic embolization (SAE) has been postulated to improve the success rate of nonoperative management of blunt splenic injuries and increase splenic salvage. Previous reports, however, have compared SAE with historical controls. We compared nonoperative success with SAE with a contemporaneous group treated nonoperatively without SAE. METHODS: Patients who suffered blunt splenic trauma from 2000 to 2004 were identified. Demographic and outcome data were abstracted. Data on the performance of SAE, type of vessel embolized, and success or failure of nonoperative management were collected. Analysis of variance, chi, and regression analysis were used to evaluate the impact of SAE on outcome. RESULTS: There were 570 patients who suffered blunt splenic trauma and 221 (39%) were treated operatively. There were 349 patients who were treated nonoperatively and 46 (13.2%) underwent SAE. SAE was more frequently used for patients with spleen Abbreviated Injury Score (AIS) > or =3 (31%) than AIS = 2 (6.7%). For patients with spleen AIS > or =3, there was no difference in age, gender, Injury Severity Score, or admission blood pressure between those who did or did not undergo SAE. The nonoperative success rate was similar for patients who did (79.3%) and those that did not (78.8%) undergo SAE. CONCLUSIONS: Patients who underwent splenic arteriography did not have improved nonoperative splenic salvage rates compared with a contemporaneous control group of similarly injured patients. Subsets of patients with blunt trauma may benefit from SAE but further study will be required to define these patients.


Assuntos
Baço/lesões , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/terapia , Adulto , Angiografia , Embolização Terapêutica , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Seleção de Pacientes , Análise de Regressão , Estudos Retrospectivos , Baço/diagnóstico por imagem , Baço/cirurgia , Artéria Esplênica/diagnóstico por imagem , Falha de Tratamento , Resultado do Tratamento , Ferimentos não Penetrantes/cirurgia
14.
Am Surg ; 73(6): 585-9; discussion 590, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17658096

RESUMO

Nonoperative management (NOM) of blunt splenic injury has become more frequent in the past several decades. Criteria that predict successful NOM remain poorly defined, and one factor that has been studied previously has been patient age. Previous studies have defined older patients as those greater than 55 years of age, but no studies have compared younger patients (55-75 years) with older patients (75+ years) within this age group. A total of 1008 patients > or =55 years of age who sustained blunt splenic injury between 1993 and 2001 were analyzed from the Pennsylvania Trauma Systems Foundation database. Statistical analysis was performed using regression analysis. Data was expressed as mean +/- SD, and a P value of < or = 0.05 was considered significant. Patients were classified as operative management (OM; 39.9%) or NOM (60.1%) according to their initial plan of treatment. Of the patients in the NOM group, 75.3 per cent were successfully managed nonoperatively (SNOM), whereas 24.7 per cent eventually required surgery. The Injury Severity Score of the OM group was highest (34) compared with the SNOM group (22) and failed NOM (FNOM; 27) groups. The mean splenic injury grade for OM, SNOM, and FNOM was 3.5, 2.4, and 3.3, respectively. The number of pre-existing conditions did not differ among the three groups. An upward trend in the failure rate of NOM was observed with increasing age (19.0%, 27.1%, and 28.3%, respectively) for three age groups, 55-64, 65-74, and 75+, but this trend was not statistically significant. Mortality rate was highest in the OM group (35.6%) compared with the successful (16.7%) and failed NOM (17.9%). Hospital length of stay (LOS) and intensive care unit (ICU) LOS were highest among patients who failed NOM (mean hospital LOS = 20.7 days, mean ICU LOS = 13.2 days) compared with OM (17.2 and 10.4, respectively) and successful NOM (12.4 and 6.9, respectively). The majority of patients > or = 55 years with blunt splenic injuries can be managed nonoperatively when carefully selected. In the subset of patients older than 55 years of age, increasing age is associated with a trend toward higher failure rates. Mortality was high regardless of management, and failure of NOM in older patients is associated with significantly longer hospital and ICU LOS.


Assuntos
Baço/lesões , Ferimentos não Penetrantes/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Cuidados Críticos/estatística & dados numéricos , Doença , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Estudos Retrospectivos , Fatores de Risco , Baço/cirurgia , Esplenectomia , Taxa de Sobrevida , Resultado do Tratamento , Ferimentos não Penetrantes/classificação , Ferimentos não Penetrantes/cirurgia
15.
Neoplasia ; 8(11): 949-55, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17132227

RESUMO

The hepatocyte growth factor (HGF) receptor c-Met is a tyrosine kinase receptor with established oncogenic properties. We have previously shown that c-Met is usually overexpressed in esophageal adenocarcinoma (EA), yet the implications of c-Met inhibition in EA remain unknown. Three c-Met-overexpressing EA cell lines (Seg-1, Bic-1, and Flo-1) were used to examine the effects of a c-Met-specific small molecule inhibitor (PHA665752) on cell viability, apoptosis, motility, invasion, and downstream signaling pathways. PHA665752 demonstrated dose-dependent inhibition of constitutive and/or HGF-induced phosphorylation of c-Met, which correlated with reduced cell viability and inhibition of extracellular regulated kinase 1/2 phosphorylation in all three EA cell lines. In contrast, PHA665752 induced apoptosis and reduced motility and invasion in only one EA cell line, Flo-1. Interestingly, Flo-1 was the only cell line in which phosphatidylinositol 3-kinase (PI3K)/Akt was induced following HGF stimulation. The PI3K inhibitor LY294002 produced effects equivalent to those of PHA665752 in these cells. We conclude that inhibition of c-Met may be a useful therapeutic strategy for EA. Factors other than receptor overexpression, such as c-Met-dependent PI3K/Akt signaling, may be predictive of an individual tumor's response to c-Met inhibition.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Receptores de Fatores de Crescimento/antagonistas & inibidores , Apoptose , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Immunoblotting , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-met , Transdução de Sinais , Cicatrização
16.
J Trauma ; 61(5): 1113-8; discussion 1118-9, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17099516

RESUMO

BACKGROUND: Most minor splenic injuries are readily treated nonoperatively but controversy exists regarding the role of nonoperative management for higher-grade injuries. The infrequency of these injuries has made evaluation of factors critical to their management difficult. METHODS: Through the National Trauma Data Bank, 3,085 adults sustaining severe (Abbreviated Injury Scale score > or = 4) blunt splenic injury from 1997 to 2003 were retrospectively reviewed. Patient management, demographic information, physiologic data, procedures performed, and outcomes were analyzed. RESULTS: Nonoperative management was attempted in 40.5% of patients but ultimately failed in 54.6% of those. Failure of nonoperative management was associated with increased age, low admission systolic blood pressure, higher injury severity score, and increased hospital and intensive care unit length of stay. Mortality associated with failure of nonoperative management (12.3%) and successful observation (13.8%) was similar. CONCLUSIONS: Nonoperative management of higher-grade splenic injuries is associated with a high rate of failure and prolonged hospital stay. Careful judgment must be exercised in applying nonoperative management to patients with severe splenic injuries.


Assuntos
Baço/lesões , Ferimentos não Penetrantes/terapia , Adulto , Pressão Sanguínea/fisiologia , Bases de Dados como Assunto , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índices de Gravidade do Trauma , Falha de Tratamento , Ferimentos não Penetrantes/classificação , Ferimentos não Penetrantes/mortalidade
17.
Am J Physiol Regul Integr Comp Physiol ; 291(4): R970-6, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16675630

RESUMO

Extensive soft tissue injury and bone fracture are significant contributors to the initial systemic inflammatory response in multiply injured patients. Systemic inflammation can lead to organ dysfunction remote from the site of traumatic injury. The mechanisms underlying the recognition of peripheral injury and the subsequent activation of the immune response are unknown. Toll-like receptors (TLRs) recognize microbial products but also may recognize danger signals released from damaged tissues. Here we report that peripheral tissue trauma initiates systemic inflammation and remote organ dysfunction. Moreover, this systemic response to a sterile local injury requires toll-like receptor 4 (TLR4). Compared with wild-type (C3H/HeOuJ) mice, TLR4 mutant (C3H/HeJ) mice demonstrated reduced systemic and hepatic inflammatory responses to bilateral femur fracture. Trauma-induced nuclear factor (NF)-kappaB activation in the liver required functional TLR4 signaling. CD14-/- mice failed to demonstrate protection from fracture-induced systemic inflammation and hepatocellular injury. Therefore, our results also argue against a contribution of intestine-derived LPS to this process. These findings identify a critical role for TLR4 in the rapid recognition and response pathway to severe traumatic injury. Application of these findings in an evolutionary context suggests that multicellular organisms have evolved to use the same pattern recognition receptor for surviving traumatic and infectious challenges.


Assuntos
Fraturas do Fêmur/imunologia , Hepatite/imunologia , Inflamação/imunologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Alanina Transaminase/sangue , Animais , Fraturas do Fêmur/complicações , Hepatite/etiologia , Inflamação/etiologia , Interleucina-10/sangue , Interleucina-10/genética , Interleucina-6/sangue , Interleucina-6/genética , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Mutantes , RNA Mensageiro/análise , Transdução de Sinais/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
18.
Neoplasia ; 8(1): 31-7, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16533423

RESUMO

The nuclear transcription factor interferon regulatory factor-1 (IRF-1) is a putative tumor suppressor, but the expression and function of IRF-1 in esophageal adenocarcinoma (EA) remain unknown. We hypothesized that IRF-1 expression was reduced or lost in EA and that restoration of IRF-1 would result in the apoptosis of EA cells in vitro and the inhibition of tumor growth in vivo. Three EA cell lines were used to examine IRF-1 expression, IFN-gamma responsiveness, and the effects of IRF-1 overexpression using a recombinant adenoviral vector (Ad-IRF-1). All three EA cell lines produced IRF-1 protein following IFN-gamma stimulation, although IFN-gamma did not induce cell death. In contrast, Ad-IRF-1 infection resulted in high levels of IRF-1 protein and triggered apoptosis in all three EA cell lines. Potential mechanisms for the differential response to IFN-gamma versus Ad-IRF-1--such as modulation of c-Met or extracellular regulated kinase signaling, or altered expression of IRF-2, Fas, or survivin--were investigated, but none of these mechanisms can account for this observation. In vivo administration of IRF-1 in a murine model of EA modestly inhibited tumor growth, but did not lead to tumor regression. Strategies aimed at increasing or restoring IRF-1 expression may have therapeutic benefits in EA.


Assuntos
Adenocarcinoma/genética , Adenoviridae/genética , Apoptose , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , Fator Regulador 1 de Interferon/genética , Animais , Linhagem Celular Tumoral , Separação Celular , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Interferon gama/metabolismo , Masculino , Camundongos , Camundongos Nus , Neoplasias/metabolismo
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