RESUMO
BACKGROUND: Sacral nerve stimulation is a treatment option for severe, medically refractory fecal incontinence, although its use in patients with anatomic abnormalities remains controversial. OBJECTIVE: This study aimed to determine whether patients with rectoanal intussusception achieve similar benefits from device implantation to patients without rectoanal intussusception. DESIGN: Retrospective review of a prospectively maintained database. Demographics and clinical data were collected for each patient, including preoperative pelvic floor testing. Defecographies were reanalyzed in a blinded manner. Preoperative rectoanal intussusception was determined on the basis of the Oxford system (grade III-IV vs not; grade V excluded). SETTINGS: Academic-affiliated pelvic health center. PATIENTS: All patients undergoing sacral nerve stimulation for fecal incontinence between July 2011 and July 2019. MAIN OUTCOME MEASURES: Cleveland Clinic Florida Incontinence/Wexner Scores, Fecal Incontinence Severity Indices, and Fecal Incontinence Quality of Life Indices at 1 year. RESULTS: One hundred sixty-nine patients underwent sacral nerve stimulation for fecal incontinence during the study period. The average age was 60.3 years and 91% were female. Forty-six patients (27.2%) had concomitant rectoanal intussusception (38 patients [22.5%] grade III and 8 patients [4.7%] grade IV). Before surgery, patients reported an average of 10.8 accidents per week and a Wexner score of 15.7, with no difference between patients with and without rectoanal intussusception ( p = 0.22 and 0.95). At 1 year after surgery, the average Wexner score was 9.5. There was no difference in postoperative Wexner scores (10.4 vs 9.2, p = 0.23) or improvement over time between patients with and without rectoanal intussusception (-6.7 vs -5.7, p = 0.40). Similarly, there was no difference in quality of life or frequency of incontinence to liquid or solid stool. LIMITATIONS: Single-institution, moderate sample size, incomplete survey response. CONCLUSIONS: Concomitant rectoanal intussusception does not appear to affect clinical outcomes or quality of life after sacral nerve stimulation for fecal incontinence. Appropriate patients with fecal incontinence and rectoanal intussusception can be considered for sacral nerve stimulation placement. See Video Abstract at http://links.lww.com/DCR/C192 . LA INTUSUSCEPCIN RECTOANAL LIMITA LAS MEJORAS EN EL RESULTADO CLNICO Y LA CALIDAD DE VIDA DESPUS DE LA NEUROESTIMULACION SACRA PARA LA INCONTINENCIA FECAL: ANTECEDENTES:La neuroestimulación sacra es una opción de tratamiento para la incontinencia fecal grave refractaria al tratamiento médico, aunque su uso en pacientes con anomalías anatómicas sigue siendo controvertido.OBJETIVO:Determinar si los pacientes con intususcepción rectoanal logran beneficios similares de la implantación del dispositivo a los pacientes sin intususcepción rectoanal.DISEÑO:Revisión retrospectiva de una base de datos mantenida prospectivamente. Se recopilaron datos demográficos y clínicos de cada paciente, incluidas las pruebas preoperatorias del piso pélvico. Las defecografías se volvieron a analizar de forma ciega. La intususcepción rectoanal preoperatoria se determinó según el sistema de Oxford (grado III-IV vs. no; grado V excluido).ESCENARIO:Centro académico de salud pélvica.PACIENTES:Todos los pacientes sometidos a neuroestimulación sacra por incontinencia fecal entre julio de 2011 y julio de 2019.PRINCIPALES MEDIDAS DE RESULTADO:Cleveland Clinic Florida Incontinence/Wexner Scores, Índices de gravedad de la incontinencia fecal, Índices de calidad de vida de la incontinencia fecal al año.RESULTADOS:169 pacientes se sometieron a neuroestimulación sacra por incontinencia fecal durante el período de estudio. La edad promedio fue de 60.3 años y el 91% eran mujeres. Cuarenta y seis pacientes (27.2%) tenían intususcepción rectoanal concomitante (38 [22.5%] grado III y 8 [4.7%] grado IV). Antes de la cirugía, los pacientes informaron un promedio de 10.8 accidentes por semana y una puntuación de Wexner de 15.7 sin diferencia entre pacientes con y sin intususcepción rectoanal (p = 0.22 y 0.95). Un año después de la cirugía, la puntuación promedio de Wexner fue de 9.5. No hubo diferencia en las puntuaciones de Wexner posoperatorias (10.4 frente a 9.2, p = 0.23) o mejoría con el tiempo entre los pacientes con y sin intususcepción rectoanal (-6.7 frente a -5.7, p = 0.40). De manera similar, no hubo diferencia en la calidad de vida o la frecuencia de incontinencia de heces líquidas o sólidas.LIMITACIONES:Institución única, tamaño de muestra moderado, respuesta de encuesta incompleta.CONCLUSIÓN:La intususcepción rectoanal concomitante no parece afectar los resultados clínicos o la calidad de vida después de la neuroestimulación sacra para la incontinencia fecal. Los pacientes apropiados con incontinencia fecal e intususcepción rectoanal pueden ser considerados para la neuroestimulación sacra. Consulte Video Resumen en http://links.lww.com/DCR/C192(Traducción-Dr. Jorge Silva Velazco ).
Assuntos
Terapia por Estimulação Elétrica , Incontinência Fecal , Intussuscepção , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Incontinência Fecal/etiologia , Qualidade de Vida , Intussuscepção/etiologia , Resultado do Tratamento , Canal Anal/cirurgia , Plexo Lombossacral , Diafragma da PelveRESUMO
OBJECTIVE: We aimed to identify the role of the enzyme acid sphingomyelinase in the aging of stored units of packed red blood cells (pRBCs) and subsequent lung inflammation after transfusion. SUMMARY BACKGROUND DATA: Large volume pRBC transfusions are associated with multiple adverse clinical sequelae, including lung inflammation. Microparticles are formed in stored pRBCs over time and have been shown to contribute to lung inflammation after transfusion. METHODS: Human and murine pRBCs were stored with or without amitriptyline, a functional inhibitor of acid sphingomyelinase, or obtained from acid sphingomyelinase-deficient mice, and lung inflammation was studied in mice receiving transfusions of pRBCs and microparticles isolated from these units. RESULTS: Acid sphingomyelinase activity in pRBCs was associated with the formation of ceramide and the release of microparticles. Treatment of pRBCs with amitriptyline inhibited acid sphingomyelinase activity, ceramide accumulation, and microparticle production during pRBC storage. Transfusion of aged pRBCs or microparticles isolated from aged blood into mice caused lung inflammation. This was attenuated after transfusion of pRBCs treated with amitriptyline or from acid sphingomyelinase-deficient mice. CONCLUSIONS: Acid sphingomyelinase inhibition in stored pRBCs offers a novel mechanism for improving the quality of stored blood.
Assuntos
Amitriptilina/farmacologia , Preservação de Sangue/métodos , Inibidores Enzimáticos/farmacologia , Transfusão de Eritrócitos/efeitos adversos , Eritrócitos/efeitos dos fármacos , Pneumonia/etiologia , Esfingomielina Fosfodiesterase/antagonistas & inibidores , Animais , Biomarcadores/metabolismo , Preservação de Sangue/efeitos adversos , Micropartículas Derivadas de Células/metabolismo , Eritrócitos/enzimologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/metabolismo , Pneumonia/patologia , Pneumonia/prevenção & controle , Esfingomielina Fosfodiesterase/deficiênciaRESUMO
Although advances in medical care have significantly improved sepsis survival, sepsis remains the leading cause of death in the ICU. This is likely due to a lack of complete understanding of the pathophysiologic mechanisms that lead to dysfunctional immunity. Neutrophil derived microparticles (NDMPs) have been shown to be the predominant microparticle present at infectious and inflamed foci in human models, however their effect on the immune response to inflammation and infection is sepsis has not been fully elucidated. As NDMPs may be a potential diagnostic and therapeutic target, we sought to determine the impact NDMPs on the immune response to a murine polymicrobial sepsis. We found that peritoneal neutrophil numbers, bacterial loads, and NDMPs were increased in our abdominal sepsis model. When NDMPs were injected into septic mice, we observed increased bacterial load, decreased neutrophil recruitment, increased expression of IL-10 and worsened mortality. Furthermore, the NDMPs express phosphatidylserine and are ingested by F4/80 macrophages via a Tim-4 and MFG-E8 dependent mechanism. Finally, upon treatment, NDMPs decrease macrophage activation, increase IL-10 release and decrease macrophage numbers. Altogether, these data suggest that NDMPs enhance immune dysfunction in sepsis by blunting the function of neutrophils and macrophages, two key cell populations involved in the early immune response to infection. This article is part of a Special Issue entitled: Immune and Metabolic Alterations in Trauma and Sepsis edited by Dr. Raghavan Raju.
Assuntos
Micropartículas Derivadas de Células/imunologia , Neutrófilos/imunologia , Sepse/imunologia , Animais , Carga Bacteriana , Micropartículas Derivadas de Células/patologia , Micropartículas Derivadas de Células/transplante , Modelos Animais de Doenças , Humanos , Interleucina-10/imunologia , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Proteínas de Membrana/imunologia , Camundongos , Neutrófilos/patologia , Fosfatidilserinas/imunologia , Sepse/microbiologia , Sepse/patologiaRESUMO
Following burn injury, a key factor for patients susceptible to opportunistic infections is immune suppression. Butyrate levels are important in maintaining a functional immune system and these levels can be altered after injury. The acid sphingomyelinase (Asm) lipid signaling system has been implicated in a T cell actions with some evidence of being influenced by butyrate. Here, we hypothesized that burn-injury changes in butyrate levels would mediate Asm activity and, consequently, T cell homeostasis. We demonstrate that burn injury temporally decreases butyrate levels. We further determined that T cell Asm activity is increased by butyrate and decreased after burn injury. We additionally observed decreased T cell numbers in Asm-deficient, burn-injured, and microbiota-depleted mice. Finally, we demonstrate that butyrate reduced T cell death in an Asm-dependent manner. These data suggest that restoration of butyrate after burn injury may ameliorate the T cell lost observed in burn-injured patients by Asm regulation.
Assuntos
Queimaduras/imunologia , Esfingomielina Fosfodiesterase/metabolismo , Linfócitos T/imunologia , Animais , Apoptose , Butiratos/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Homeostase , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Transdução de Sinais , Esfingomielina Fosfodiesterase/genéticaRESUMO
BACKGROUND: Neoadjuvant chemoradiation reduces local recurrence in locally advanced rectal cancer, and adherence to national and societal recommendations remains unknown. OBJECTIVE: To determine variability in guideline adherence in rectal cancer treatment and investigate whether hospital volume correlated with variability seen. DESIGN: We performed a retrospective analysis using the National Cancer Database rectal cancer participant user files from 2005 to 2010. Stage-specific predictors of neoadjuvant chemotherapy and radiation use were determined, and variation in use across hospitals analyzed. Hospitals were ranked based on likelihood of preoperative therapy use by stage, and observed-to-expected ratios for neoadjuvant therapy use calculated. Hospital outliers were identified, and their center characteristics compared. RESULTS: A total of 23,488 patients were identified at 1183 hospitals. There was substantial variability in the use of neoadjuvant chemoradiation across hospitals. Patients managed outside clinical guidelines for both stage 1 and stage 3 disease tended to receive treatment at lower-volume, community cancer centers. CONCLUSIONS: There is substantial variability in adherence to national guidelines in the use of neoadjuvant chemoradiation for rectal cancer across all stages. Both hospital volume and center type are associated with over-treatment of early-stage tumors and under-treatment of more invasive tumors. These findings identify a clear need for national quality improvement efforts in the treatment of rectal cancer.
Assuntos
Institutos de Câncer/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Terapia Neoadjuvante/estatística & dados numéricos , Neoplasias Retais/terapia , Idoso , Institutos de Câncer/normas , Bases de Dados Factuais , Feminino , Hospitais com Alto Volume de Atendimentos/normas , Hospitais com Baixo Volume de Atendimentos/normas , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/normas , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do Tratamento , Estados UnidosRESUMO
Genetic ablation or pharmacologic inhibition of matrix metalloproteinase-8 (MMP8) improves survival in an adult murine sepsis model. Because developmental age influences the host inflammatory response, we hypothesized that developmental age influences the role of MMP8 in sepsis. First, we compared sepsis survival between wild type (WT, C57BL/6) and MMP8 null juvenile-aged mice (12-14 days) after intraperitoneal injection of a standardized cecal slurry. Second, peritoneal lavages collected at 6 and 18 hours after cecal slurry injection were analyzed for bacterial burden, leukocyte subsets, and inflammatory cytokines. Third, juvenile WT mice were pretreated with an MMP8 inhibitor prior to cecal slurry injection; analysis of their bacterial burden was compared to vehicle-injected animals. Fourth, the phagocytic capacity of WT and MMP8 null peritoneal macrophages was compared. Finally, peritoneal neutrophil extracellular traps (NETs) were compared using immunofluorescent imaging and quantitative image analysis. We found that juvenile MMP8 null mice had greater mortality and higher bacterial burden than WT mice. Leukocyte counts and cytokine concentrations in the peritoneal fluid were increased in the MMP8 null mice, relative to the wild type mice. Peritoneal macrophages from MMP8 null mice had reduced phagocytic capacity compared to WT macrophages. There was no quantitative difference in NET formation, but fewer bacteria were adherent to NETs from MMP8 null animals. In conclusion, in contrast to septic adult mice, genetic ablation of MMP8 increased mortality following bacterial peritonitis in juvenile mice. The increase in mortality in MMP8 null juvenile mice was associated with reduced bacterial clearance and reduced NET efficiency. We conclude that developmental age influences the role of MMP8 in sepsis.
RESUMO
The morbidity and mortality from sepsis continues to remain high despite extensive research into understanding this complex immunologic process. Further, while source control and antibiotic therapy have improved patient outcomes, many immunologically based therapies have fallen short. Microparticles (MPs) are intact vesicles that serve as mediators of intercellular communication as well as markers of inflammation in various disease processes. We have previously demonstrated that MPs can be produced at the infected foci during sepsis, are predominantly of neutrophil derivation (NDMPs) and can modulate immune cells. In this study, we sought to elucidate the molecular mechanisms underlying NDMP generation. Using thioglycolate (TGA) to recruit and activate neutrophils, we first determined that intra-peritoneal TGA increase NDMP accumulation. We next utilized TGA-elicited neutrophils in vitro to investigate signaling intermediates involved in NDMP production, including the intrinsic and extrinsic caspase pathways, cAMP dependent PKA and Epac activation as well as the role myosin light chain kinase (MLCK) as a final mediator of NDMP release. We observed that NDMP generation was dependent on the extrinsic caspase apoptotic pathway (caspase 3 and caspase 8), cAMP activation of PKA but not of Epac, and on activation of MLCK. Altogether, these data contribute to an overall framework depicting the molecular mechanisms that regulate NDMP generation.
Assuntos
Caspase 8/imunologia , Micropartículas Derivadas de Células/imunologia , Proteínas Quinases Dependentes de AMP Cíclico/imunologia , Quinase de Cadeia Leve de Miosina/imunologia , Ativação de Neutrófilo/imunologia , Neutrófilos/imunologia , Animais , Células Cultivadas , Regulação da Expressão Gênica/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/citologiaRESUMO
BACKGROUND: We hypothesized that after controlling for case-mix differences, the rates of positive resection margin after rectal cancer surgery vary substantially in the United States and that high-volume hospitals have lower margin positivity rates. MATERIALS AND METHODS: Patients treated with oncologic resection for stage I-III rectal cancer were selected from the 1998-2010 National Cancer Data Base. Hierarchical regression models were used to calculate risk- and reliability-adjusted positive margin rates and hospital level variability in positive margin rates using Empirical Bayes techniques. RESULTS: A total of 113,113 patients were treated at 1446 hospitals. The mean overall risk- and reliability-adjusted positive margin rate was 7.3%. High-volume hospitals did not have a lower rate of adjusted margin positivity (7.4%, P = 0.75). When both case mix and hospital volume differences were factored into the model, variability in margin positivity rates increased by 9.8%, implying that referral to high-volume hospitals alone would not improve margin positivity rates. CONCLUSIONS: Rectal cancer margin positivity rates vary substantially in the United States, despite adjusting for differences in case mix. These results support standardization of surgical technique and pathologic assessment as part of a broader initiative that identifies and refers patients to higher performing hospitals rather than simply to higher volume hospitals.
Assuntos
Hospitais com Alto Volume de Atendimentos/normas , Hospitais com Baixo Volume de Atendimentos/normas , Margens de Excisão , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Neoplasias Retais/cirurgia , Reto/cirurgia , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Reto/patologia , Risco Ajustado , Estados UnidosRESUMO
BACKGROUND: Laparoscopic colectomy has been associated with improved postoperative pain control, earlier return to work, and shorter hospital stays compared to open colectomy. However, there are varied technical approaches to laparoscopic resections. We therefore sought to determine whether the straight laparoscopic approach was associated with shorter length of stay compared to hand-assisted and laparoscopic-assisted techniques for sigmoid colectomies. METHODS: A retrospective review of laparoscopic sigmoid colectomies performed by five colorectal surgeons from 2010 to 2014 was performed. Approaches were defined as: (1) straight laparoscopic if colon mobilization, inferior mesenteric artery transection and intra-corporeal anastomosis were performed laparoscopically, (2) hand assisted if a hand port was utilized to assist with mobilization and vessel transection, and (3) laparoscopic assisted if only the colon mobilization was performed intra-corporeally. Poisson regression was performed to determine the impact of surgical technique on LOS while controlling for differences in patient factors. RESULTS: A total of 191 patients were identified with 71 straight laparoscopic, 57 hand-assisted, and 63 laparoscopic-assisted cases. Substantial variability in choice of surgical technique was seen across surgeons. Patient populations were similar, with the exception of hand-assisted procedures being more often used in obese patients. Unadjusted average postoperative days to discharge were 3.6 days for straight laparoscopic and 4.1 and 4.0 days for hand-assisted and laparoscopic-assisted approaches, respectively. While controlling for factors associated with longer hospital stay, the straight laparoscopic approach was associated with a 14 % shorter stay compared to laparoscopic-assisted colectomy and a 15 % shorter stay compared to hand-assisted colectomy. The straight laparoscopic approach was also associated with earlier return of bowel function compared to other approaches. CONCLUSIONS: The straight laparoscopic approach to sigmoid colectomy is associated with substantially shorter postoperative stay and earlier return of bowel function when compared to hand-assisted and laparoscopic-assisted techniques. When technically feasible, the straight laparoscopic approach is preferred.
Assuntos
Colectomia/métodos , Colo Sigmoide/cirurgia , Laparoscopia/métodos , Adulto , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Previous research has identified a number of patient and operative factors associated with anastomotic leak after colectomy; however, a study that examines these factors on a national level with direct coding for anastomotic leak is lacking. OBJECTIVE: The purpose of this work was to identify risk factors associated with anastomotic leak on a national level and quantify the additional morbidity and mortality experienced by these patients. DESIGN: We performed a retrospective analysis of patients who underwent segmental colectomy with anastomosis from the 2012 American College of Surgeons National Surgical Quality Improvement Program colectomy procedure-targeted database. Anastomotic leak was defined as minor leak requiring percutaneous intervention or major leak requiring laparotomy. Multivariate logistic regression was used to determine predictors of anastomotic leak and its impact on postoperative outcomes. SETTINGS: This study was conducted at a tertiary university department. PATIENTS: This study includes 13,684 patients who underwent segmental colectomy with anastomosis at American College of Surgeons National Surgical Quality Improvement Program-affiliated hospitals in 2012. MAIN OUTCOME MEASURES: The primary outcome studied was anastomotic leak. RESULTS: The overall leak rate was 3.8%. Male sex, steroid use, smoking, open approach, operative time, and preoperative chemotherapy were associated with increased anastomotic leaks and diverting ileostomy with decreased incidence of leaks on multivariate analysis. Increased length of stay (13 vs 5 days; p < 0.001) and increased 30-day mortality (6.8% vs 1.6%; p < 0.001) were also seen in patients who experienced leaks. These patients also experienced increased readmission rates (43.5% vs 8.3%; p < 0.001) and were 37 times more likely to require reoperation as a complication of their primary procedure (p < 0.001). LIMITATIONS: The main limitations of this study include its retrospective nature and the limited 30-day outcomes recorded in the American College of Surgeons National Surgical Quality Improvement Program database. CONCLUSIONS: This study identified patient and operative risk factors for anastomotic leak on a national scale. It also demonstrates that these patients have increased morbidity and 30-day mortality rates, experience multiple readmissions to the hospital, and have a higher likelihood of requiring further operative intervention.
Assuntos
Anastomose Cirúrgica , Fístula Anastomótica , Colectomia , Doenças do Colo/cirurgia , Readmissão do Paciente/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/mortalidade , Fístula Anastomótica/fisiopatologia , Fístula Anastomótica/terapia , Colectomia/efeitos adversos , Colectomia/métodos , Tratamento Farmacológico/métodos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Duração da Cirurgia , Avaliação de Resultados em Cuidados de Saúde , Cuidados Pré-Operatórios/métodos , Melhoria de Qualidade , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fumar/efeitos adversos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Cecal ligation and puncture (CLP) is considered the gold standard for inducing abdominal sepsis in mice. However, the model lacks source control, a component of sepsis management in humans. Using a CLP-excision model, we characterized peritoneal cytokines and cells and hypothesized these analyses would allow us to predict survival. METHODS: Fifty-eight mice were first subjected to CLP. Twenty hours later, the necrotic cecums were debrided, abdominal cavity lavaged, and intraperitoneal antibiotics administered. Peritoneal cytokines and leukocytes collected from the peritoneal lavage were analyzed. These immune parameters were used to generate receiver operator characteristic curves. In separate experiments, the accuracy of the model was verified with a survival cohort. Finally, we collected the peritoneal lavage and analyzed both serum and peritoneal cytokines, bacterial load, and leukocyte functionality. RESULTS: Peritoneal interleukin (IL)-6 levels and neutrophil CD11b intensity were observed to be significantly different in mice that lived versus those who died. In separate experiments, mice predicted to live (P-LIVE) had decreased bacterial loads, systemic IL-10, and neutrophil oxidative burst and increased peritoneal inflammatory monocyte numbers and phagocytosis. CONCLUSIONS: This study couples a clinically relevant sepsis model with methodology to limit pathogen spread. Using surgical waste, stratification of the mice into groups P-LIVE and predicted to die was possible with a high degree of accuracy and specificity. In mice P-LIVE, increased inflammatory monocyte recruitment and phagocytosis were associated with decreased systemic IL-10 and bacterial loads.
Assuntos
Líquido Ascítico , Lavagem Peritoneal , Sepse/mortalidade , Animais , Líquido Ascítico/imunologia , Líquido Ascítico/metabolismo , Líquido Ascítico/microbiologia , Carga Bacteriana , Biomarcadores/metabolismo , Ceco/cirurgia , Citocinas/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Leucócitos/metabolismo , Ligadura , Masculino , Camundongos , Prognóstico , Punções , Curva ROC , Sepse/diagnóstico , Sepse/metabolismo , Sepse/microbiologiaRESUMO
BACKGROUND: The pathophysiology that drives the subacute hypercoagulable state commonly seen after traumatic brain injury (TBI) is not well understood. Alterations caused by TBI in platelet and microparticle (MP) numbers and function have been suggested as possible causes; however, the contributions of platelets and MPs are currently unknown. MATERIALS AND METHODS: A weight-drop technique of TBI using a murine model of moderate head injury was used. Blood was collected at intervals after injury. MP enumeration and characterization were performed using Nanoparticle Tracking Analysis, and platelet counts and coagulation parameters were determined using thromboelastometry. A MP procoagulant assay was used to compare activity between injured and sham mice. RESULTS: At 24 h after injury, there were no changes in circulating platelet numbers. However, there was a decrease in platelet contribution to clot formation. In contrast, there was a decline in circulating total MP numbers. When MPs from sham mice were added to the blood from head-injured animals, there was a normalization of platelet contribution to clot formation. Conversely, when MPs from TBI mice were added to sham blood, there was a significant decrease in platelet contribution to clot formation. Notably, there was an increase in MP procoagulant activity in head-injured mice. CONCLUSIONS: MPs generated after TBI likely contribute to altered coagulation after head injury and may play a key role in the development of a posttraumatic hypercoagulable state in TBI patients.
Assuntos
Coagulação Sanguínea/fisiologia , Plaquetas/metabolismo , Lesões Encefálicas/sangue , Micropartículas Derivadas de Células/metabolismo , Animais , Biomarcadores/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Contagem de Plaquetas , TromboelastografiaRESUMO
A complete evaluation of living donor liver transplantation (LDLT) in the United States has been difficult because of the persistent low volume and the lack of adequate comparisons with deceased donor liver transplantation (DDLT). Recent reports have suggested outcomes equivalent to those for DDLT, but these studies did not adjust for differences in recipient selection. From a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified 14,282 patients at 62 centers who underwent DDLT from 2007 to 2012 and 715 patients at 35 centers who underwent LDLT during the same period. Then, we performed 1:1 propensity score matching for 708 LDLT recipients based on age, Model for End-Stage Liver Disease (MELD) score, and pretransplant patient status. The median follow-up was 2 years. Compared with DDLT recipients, LDLT recipients were more likely to be white (84.5% versus 72.2%) and female (41.1% versus 31.7%), to have lower MELD scores (15 versus 19), and to be classified preoperatively as independent (65.3% versus 46.7%) and not hospitalized (91.3% versus 78.4%). The posttransplant length of stay (LOS), in-hospital mortality, costs, and survival were similar between the groups, but LDLT recipients were more likely to be readmitted within 30 days (44.9% versus 37.1%, P = 0.001). After matching, the difference in 30-day readmission rates persisted (45.1% versus 33.8%, P = 0.001), but there were no differences in the LOS, costs, patient survival, or graft survival. This national report shows that LDLT is associated with higher readmission rates in comparison with DDLT, but the results are comparable for other key patient metrics.
Assuntos
Transplante de Fígado/mortalidade , Doadores Vivos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Complete obstruction of the distal colon or rectum often presents as a surgical emergency. This study evaluated the efficacy of blowhole colostomy versus transverse loop colostomy for the emergent management of distal large intestinal obstruction. METHODS: Retrospective chart review of all colostomy procedures (CPT 44320) performed for complete distal large bowel obstruction during the past 6 y in a university hospital practice was undertaken. Blowhole was compared with loop colostomy with a primary endpoint of successful colonic decompression. RESULTS: One hundred forty-one patients underwent colostomy creation during the study period. Of these, 61 were completed for acute obstruction of the distal colon or rectum (19 blowhole versus 42 loop colostomy). No differences between study groups were seen in age, gender, body mass index, malnutrition, American Society of Anesthesiology class, time to liquid or regular diet, 30-d or inhospital mortality, or rates of complications. Patients undergoing blowhole colostomy had significantly higher cecal diameters at diagnosis (9.14 versus 7.31 cm, P = 0.0035). Operative time was shorter in blowhole procedures (43 versus 51 min, P = 0.017). Postoperative length of stay was significantly shorter for blowhole colostomy (6 versus 8 d, P = 0.014). The primary endpoint of successful colonic decompression was met in all colostomy patients. CONCLUSIONS: Diverting blowhole colostomy is a safe, quick, and effective procedure for the urgent management of distal colonic obstruction associated with obstipation and massive distention.
Assuntos
Doenças do Colo/cirurgia , Colostomia/métodos , Obstrução Intestinal/cirurgia , Adulto , Idoso , Doenças do Colo/etiologia , Serviços Médicos de Emergência , Feminino , Humanos , Obstrução Intestinal/etiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Sepsis and subsequent multiorgan system failure is associated with high rates of mortality and morbidity. Thymic stromal lymphopoietin (TSLP) is a cytokine that can be produced by keratinocytes and epithelial cells. Primarily, TSLP has been shown to promote counter-inflammatory processes. However, its potential expression or role in the pathogenesis of sepsis is largely unexplored. We hypothesized that TSLP is expressed during sepsis and TSLP blockade would alter the immune response and mortality. MATERIALS AND METHODS: Mice underwent cecal ligation and puncture (CLP) to produce a physiologically relevant murine model for sepsis. Cohorts were either treated with neutralizing TSLP antibodies or isotype controls before the CLP to determine changes in survival, bacterial loads, cytokine levels, and neutrophil function. RESULTS: It was observed that TSLP levels peaked at 6 h and remained detectable up to 48 h after CLP. Mice pretreated with neutralizing TSLP showed decreased mortality and bacterial load after CLP. Additionally, we determined that septic mice pretreated with the anti-TSLP antibody had increased tumor necrosis factor alpha and oxidative burst as well as increased interleukin 17 and neutrophil numbers compared with mice pretreated with isotype controls. CONCLUSIONS: TSLP levels peak early but are sustained during the first 48 h of sepsis. We speculate that TSLP blunts the neutrophil response resulting in increased bacterial load and mortality.
Assuntos
Citocinas/imunologia , Citocinas/metabolismo , Sepse/imunologia , Sepse/mortalidade , Animais , Anticorpos Monoclonais/farmacologia , Bacteriemia/imunologia , Bacteriemia/metabolismo , Bacteriemia/mortalidade , Ceco/lesões , Citocinas/antagonistas & inibidores , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/metabolismo , Insuficiência de Múltiplos Órgãos/mortalidade , Neutrófilos/imunologia , Explosão Respiratória/efeitos dos fármacos , Explosão Respiratória/imunologia , Sepse/metabolismo , Taxa de Sobrevida , Linfopoietina do Estroma do TimoRESUMO
BACKGROUND: Unintentional injury or trauma remains the leading cause of death among young adults. About one fifth of these trauma patients require care in an intensive care unit (ICU) because of severity of injuries and comorbidities. Patients hospitalized in an ICU are at increased risk for nosocomial infections, such as urinary tract infections, pneumonia, bacteremia, and wound infections. Many of these patients will develop sepsis or septic shock, and some will progress to multiple organ failure and death. The balance between the proinflammatory and counterinflammatory immune response appears to be a driving factor in this progression. At present, there is no proposed method for the timely detection of the immune status in trauma patients, making rational decisions to use immune-altering therapies difficult. OBJECTIVE: We demonstrate that flow cytometry, with its capabilities to characterize and/or enumerate (a) leukocyte subtypes, (b) leukocyte activation markers, (c) leukocyte-derived cytokines and microvesicles, and (d) leukocyte function is well suited to monitor the immune status of critically ill trauma patients. METHODS: Information for the review was obtained from the extant literature. DISCUSSION: We suggest that flow cytometry is a research method that might aid nurse scientists in investigating the immune status of critically ill patients, the recovery status of conditions such as hemorrhagic shock and tissue injury and the relationship between cancer disease progression and symptoms. Therefore, flow cytometry has the potential to broaden nursing research priority areas so that a comprehensive approach to understanding the cellular response is attained.
Assuntos
Imunidade Adaptativa/fisiologia , Estado Terminal , Citometria de Fluxo , Imunidade Inata/fisiologia , Contagem de Células Sanguíneas , Proteína C-Reativa/análise , Micropartículas Derivadas de Células/fisiologia , Quimiocinas/sangue , Citocinas/sangue , Humanos , Células Matadoras Naturais/fisiologia , Linfócitos/fisiologia , Espécies Reativas de Oxigênio/sangue , Sepse/imunologiaRESUMO
BACKGROUND: Before elective colectomy, many advocate mechanical bowel preparation with oral antibiotics, whereas enhanced recovery pathways avoid mechanical bowel preparations. The optimal preparation for right versus left colectomy is also unclear. We sought to determine which strategy for bowel preparation decreases surgical site infection (SSI) and anastomotic leak (AL). METHODS: Elective colectomies from the National Surgical Quality Improvement Program colectomy database (2012-2015) were divided by (1) type of bowel preparation: no preparation (NP), mechanical preparation (MP), oral antibiotics (PO), or mechanical and oral antibiotics (PO/MP); and (2) type of colonic resection: right, left, or segmental colectomy. Univariate and multivariate analyses identified predictors of SSI and AL, and their risk-adjusted incidence was determined by logistic regression. RESULTS: When analyzed as the odds ratio compared with NP, the PO and PO/MP groups were associated with a decrease in SSI (PO = 0.70 [0.55-0.88] and PO/MP = 0.47 [0.42-0.53]; P < .01). Use of PO/MP was associated with a decrease in SSI across all types of resections (right colectomy = 0.40 [0.33-0.50], left colectomy = 0.57 [0.47-0.68], and segmental colectomy = 0.43 (0.34-0.54); P < .01). Similarly, use of PO/MP was associated with a decrease in AL in left colectomy = 0.50 ([0.37-0.69]; P < .01) and segmental colectomy = 0.53 ([0.36-0.80]; P < .01). CONCLUSION: Mechanical bowel preparation with oral antibiotics is the preferred preoperative preparation strategy in elective colectomy because of decreased incidence of SSI and AL.
Assuntos
Fístula Anastomótica/prevenção & controle , Antibioticoprofilaxia , Catárticos/uso terapêutico , Colectomia/efeitos adversos , Cuidados Pré-Operatórios , Infecção da Ferida Cirúrgica/prevenção & controle , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fístula Anastomótica/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Estados Unidos , Adulto JovemRESUMO
The gut microbiome is a community of commensal organisms that are known to play a role in nutrient production as well as gut homeostasis. The composition of the gut flora can be affected by many factors; however, the impact of burn injury on the microbiome is not fully known. Here, we hypothesized that burn-induced changes to the microbiome would impact overall colon health. After scald-burn injury, cecal samples were analyzed for aerobic and anaerobic colony forming units, bacterial community, and butyrate levels. In addition, colon and total intestinal permeabilities were determined. These parameters were further determined in a germ-reduced murine model. Following both burn injury and germ reduction, we observed decreases in aerobic and anaerobic bacteria, increased colon permeability and no change to small intestinal permeability. After burn injury, we further observed a significant decrease in the butyrate producing bacteria R. Gnavus, C. Eutactus, and Roseburia species as well as decreases in colonic butyrate. Finally, in mice that underwent burn followed by fecal microbiota transplant, bacteria levels and mucosal integrity were restored. Altogether our data demonstrate that burn injury can alter the microbiome leading to decreased butyrate levels and increased colon permeability. Of interest, fecal microbiota transplant treatment was able to ameliorate the burn-induced changes in colon permeability. Thus, fecal transplantation may represent a novel therapy in restoring colon health after burn injury.
Assuntos
Queimaduras/microbiologia , Colo/microbiologia , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Animais , Queimaduras/patologia , Queimaduras/terapia , Modelos Animais de Doenças , Transplante de Microbiota Fecal/métodos , Intestinos/microbiologia , Camundongos , Microbiota , PermeabilidadeRESUMO
An acute burn induced coagulopathy develops after scald injury, which evolves into a subacute, hypercoagulable state. Microparticles, specifically platelet-derived MPs (PMPs), have been suggested as possible contributors. We first developed a model of burn-induced coagulopathy and then sought to investigate the role of platelets and PMPs in coagulation after burn. We hypothesized that changes in circulating platelet and PMP populations after injury would contribute to the post-burn, hypercoagulable state. A murine scald model with 28% TBSA full thickness burn injury was utilized and blood samples were collected at intervals after injury. Circulating MP populations, platelet counts, overall coagulation, and platelet function were determined. Burn injury led to hypercoagulability on post-burn day one (PBD1), which persisted 6 days after injury (PBD6). On PBD1, there was a significant decrease in platelet numbers and a decline in platelet contribution to clot formation with a concomitant increase in circulating procoagulant PMPs. On PBD6, there was a significant increase in platelet numbers and in platelet activation with no change in PMPs compared with sham. Further, on PBD1 decreased ADP-induced platelet activation was observed with a contrasting increase in ADP-induced platelet activation on PBD6. We therefore concluded that there was a temporal change in the mechanisms leading to a hypercoagulable state after scald injury, that PMPs are responsible for changes seen on PBD1, and finally that ADP-induced platelet activation was key to the augmented clotting mechanisms 6 days after burn.
Assuntos
Plaquetas/fisiologia , Queimaduras/complicações , Micropartículas Derivadas de Células/fisiologia , Trombofilia/etiologia , Animais , Coagulação Sanguínea/fisiologia , Queimaduras/sangue , Fibrinogênio/metabolismo , Masculino , Camundongos , Contagem de Plaquetas , Tromboelastografia/métodos , Trombofilia/sangue , Fator de von Willebrand/metabolismoRESUMO
INTRODUCTION: It is well established that obesity-related hormones can have modulatory effects associated with the immune response. Ghrelin, a hormone mainly derived from endocrine cells of the gastric mucosa, regulates appetite, energy expenditure and body weight counteracting leptin, a hormone mainly derived from adipocytes. Additionally, receptors of both have been detected on immune cells and demonstrated an immune regulatory function during sepsis. METHODS: In the present study, the effect of peripheral ghrelin administration on early immune response and survival was investigated with lean mice and mice with diet-induced obesity using cecal ligation and puncture to induce sepsis. RESULTS: In the obese group, we found that ghrelin treatment improved survival, ameliorated hypothermia, and increased hyperleptinemia as compared to the lean controls. We also observed that ghrelin treatment divergently regulated serum IL-1ß and TNF-α concentrations in both lean and obese septic mice. Ghrelin treatment initially decreased but later resulted in increased bacteriaemia in lean mice while having no impact upon obese mice. Similarly, ghrelin treatment increased early neutrophil oxidative burst while causing a decrease 48 hours after sepsis inducement. CONCLUSION: In conclusion, as the immune response to sepsis temporally changes, ghrelin treatment differentially mediates this response. Specifically, we observed that ghrelin conferred protective effects during the early phase of sepsis, but during the later phase deteriorated immune response and outcome. These adverse effects were more pronounced upon lean mice as compared to obese mice.