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INTRODUCTION: Necrotizing soft tissue infections (NSTIs) are surgical emergencies associated with high morbidity and mortality. Identifying risk factors for poor outcome is a critical part of preoperative decision-making and counseling. Sarcopenia, the loss of lean muscle mass, has been associated with an increased risk of mortality and can be measured using cross-sectional imaging. Our aim was to determine the impact of sarcopenia on mortality in patients with NSTI. We hypothesized that sarcopenia would be associated with an increased risk of mortality in patients with NSTI. METHODS: This is a retrospective cohort study of NSTI patients admitted from 1995 to 2015 to two academic institutions. Operative and pathology reports were reviewed to confirm the diagnosis in all cases. Average bilateral psoas muscle cross-sectional area at L4, normalized for height (Total Psoas Index [TPI]), was calculated using computed tomography (CT). Sarcopenia was defined as TPI in the lowest sex-specific quartile. Primary outcome was in-hospital mortality. Multivariate logistic regression was performed to assess the association between sarcopenia and in-hospital mortality. RESULTS: There were 115 patients with preoperative imaging, 61% male and a median age of 57 y interquartile range (IQR 46.6-67.0). Overall in-hospital mortality was 12.1%. There was no significant difference in sex, body mass index (BMI), comorbidities and American Society of Anesthesiologists classification (Table 1). After multivariate analysis, sarcopenia was independently associated with increased in-hospital mortality (Odds ratio, 3.5; 95% Confidence Interval [CI], 1.05-11.8). CONCLUSIONS: Sarcopenia is associated with increased risk of in-hospital mortality in patients with NSTIs. Sarcopenia identifies patients with higher likelihood of poor outcomes, which can possibly help surgeons in counseling their patients and families.
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Sarcopenia , Infecciones de los Tejidos Blandos , Femenino , Humanos , Masculino , Músculos Psoas/diagnóstico por imagen , Músculos Psoas/patología , Estudios Retrospectivos , Factores de Riesgo , Sarcopenia/complicaciones , Sarcopenia/diagnóstico por imagen , Infecciones de los Tejidos Blandos/complicaciones , Infecciones de los Tejidos Blandos/patologíaRESUMEN
OBJECTIVE: Assess the prevalence of anxiety, depression, and posttraumatic stress disorder (PTSD) after injury and their association with long-term functional outcomes. BACKGROUND: Mental health disorders (MHD) after injury have been associated with worse long-term outcomes. However, prior studies almost exclusively focused on PTSD. METHODS: Trauma patients with an injury severity score ≥9 treated at 3 Level-I trauma centers were contacted 6-12 months post-injury to screen for anxiety (generalized anxiety disorder-7), depression (patient health questionnaire-8), PTSD (8Q-PCL-5), pain, and functional outcomes (trauma quality of life instrument, and short-form health survey)). Associations between mental and physical outcomes were established using adjusted multivariable logistic regression models. RESULTS: Of the 531 patients followed, 108 (20%) screened positive for any MHD: of those who screened positive for PTSD (7.9%, N = 42), all had co-morbid depression and/or anxiety. In contrast, 66 patients (12.4%) screened negative for PTSD but positive for depression and/or anxiety. Compared to patients with no MHD, patients who screened positive for PTSD were more likely to have chronic pain {odds ratio (OR): 8.79 [95% confidence interval (CI): 3.21, 24.08]}, functional limitations [OR: 7.99 (95% CI: 3.50, 18.25)] and reduced physical health [ß: -9.3 (95% CI: -13.2, -5.3)]. Similarly, patients who screened positive for depression/anxiety (without PTSD) were more likely to have chronic pain [OR: 5.06 (95% CI: 2.49, 10.46)], functional limitations [OR: 2.20 (95% CI: 1.12, 4.32)] and reduced physical health [ß: -5.1 (95% CI: -8.2, -2.0)] compared to those with no MHD. CONCLUSIONS: The mental health burden after injury is significant and not limited to PTSD. Distinguishing among MHD and identifying symptom-clusters that overlap among these diagnoses, may help stratify risk of poor outcomes, and provide opportunities for more focused screening and treatment interventions.
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Trastornos de Ansiedad/epidemiología , Trastorno Depresivo/epidemiología , Calidad de Vida , Trastornos por Estrés Postraumático/epidemiología , Heridas y Lesiones/psicología , Heridas y Lesiones/terapia , Boston/epidemiología , Dolor Crónico/epidemiología , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Prevalencia , Escalas de Valoración Psiquiátrica , Recuperación de la Función , Reinserción al Trabajo/estadística & datos numéricos , Centros TraumatológicosRESUMEN
BACKGROUND: Traumatic brain injury (TBI) is common, and significant institutional variation exists with regards to structure and processes of care. Affected patients may be admitted to one of several different services, and this may drive differential care and outcomes. We sought to evaluate differential care and outcomes for patients with isolated mild-to-moderate traumatic brain injury based on admission service. MATERIALS AND METHODS: This is a single-institution retrospective study of all adult (≥18 y old) patients admitted with isolated TBI (AIS ≤1 in all other body regions) over a 3-year period (6/2015-6/2018). Patients who underwent neurosurgical intervention (craniectomy/craniotomy) and those with a head AIS ≥4 were excluded. Patients were assigned to one of three groups based upon admission service: Trauma Surgery, Neurology/Medicine or Neurosurgery. Outcomes evaluated included in-hospital mortality and markers of differential care. We performed multivariate analyses adjusting for patient demographics and clinical characteristics. RESULTS: A total of 401 isolated mild-to-moderate TBI patients were identified. Overall mortality was 1.7%. Adjusted multivariate logistic regression analysis demonstrated no difference in mortality. Patients admitted to Neurosurgery underwent more repeat head CTs and were more likely to receive antiseizure medication in the absence of seizure activity, and those admitted to Neurology/Medicine were less likely to receive venous thromboembolism chemoprophylaxis compared to those admitted to Trauma Surgery. CONCLUSIONS: We identify several important metrics of variation in care received by patients with an isolated mild-to-moderate TBI based upon admission service. These findings deserve further study, and this study may lay the foundation for future efforts at protocolizing care in an evidence-based fashion for this patient cohort.
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Lesiones Traumáticas del Encéfalo/terapia , Anciano , Anciano de 80 o más Años , Lesiones Traumáticas del Encéfalo/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Admisión del Paciente , Estudios Retrospectivos , Convulsiones/prevención & control , Tromboembolia Venosa/prevención & controlRESUMEN
OBJECTIVES: The aims of this study were to assess for changes in uninsured rates among trauma patients at age 64 versus 65 years and whether there are associated changes in post-discharge rehabilitation; determine whether changes are driven by rehabilitation provided at home, skilled nursing facilities (SNFs), or acute inpatient facilities; and determine whether changes vary among stratified subgroups of trauma-related "best-practice" factors. SUMMARY BACKGROUND DATA: Rehabilitation is an important component of high-quality trauma systems with access heavily influenced by insurance status. In the wake of policy changes affecting insurance coverage, it remains unknown the extent to which insurance changes associate with variations in rehabilitation access/use among otherwise similar patients. METHODS: Regression discontinuity models were used to assess for changes in insurance status and rehabilitation at age 64 versus 65 years among adults ages 54 to 75 years (±10 years age-related Medicare eligibility). Data were extracted from the 2007-2012 National Trauma Data Bank. RESULTS: A total of 305,198 patients were included; 40.1% were discharged to rehabilitation. Medicare eligibility was associated with an abrupt 6.4 (95% confidence interval: 5.8-7.0) percentage-point decline in uninsured and a 9.6 (95% confidence interval: 6.5-12.6) percentage-point increase in rehabilitation at age 64 versus 65 years, enabling an additional 1-in-10 patients to access rehabilitation. Differences were driven by SNF use and were greatest among patients with less-severe clinical presentations. Restriction based on Medicare-payment eligibility to patients with length of stay ≥3days (SNF requirement) and ≥1 "presumptive diagnosis codes" (inpatient facilities' 60% rule) demonstrated abrupt gains in both SNF and inpatient care. CONCLUSIONS: The results reveal the magnitude of changes in access to rehabilitation associated with changes in insurance coverage at age 65 years. Use of quasiexperimental models enabled meaningful consideration of health-policy change.
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Determinación de la Elegibilidad , Costos de la Atención en Salud , Medicare/economía , Centros de Rehabilitación/economía , Heridas y Lesiones/rehabilitación , Adulto , Factores de Edad , Anciano , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Puntaje de Gravedad del Traumatismo , Cobertura del Seguro/economía , Cobertura del Seguro/estadística & datos numéricos , Masculino , Medicare/estadística & datos numéricos , Persona de Mediana Edad , Evaluación de Necesidades , Evaluación de Resultado en la Atención de Salud , Alta del Paciente/economía , Alta del Paciente/estadística & datos numéricos , Cuidados Posoperatorios/economía , Cuidados Posoperatorios/estadística & datos numéricos , Centros de Rehabilitación/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo , Estados Unidos , Heridas y Lesiones/cirugíaRESUMEN
We describe the radiological and intraoperative correlation of large bowel obstruction due to sigmoid volvulus in a 52-year-old female. The purpose of this article is to emphasize the importance of recognizing sigmoid volvulus as a cause of bowel obstruction in patients presenting with abdominal pain, since it can lead to bowel ischemia and necrosis.
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Obstrucción Intestinal/diagnóstico por imagen , Obstrucción Intestinal/etiología , Vólvulo Intestinal/complicaciones , Vólvulo Intestinal/diagnóstico por imagen , Tomografía Computarizada Multidetector , Enfermedades del Sigmoide/complicaciones , Enfermedades del Sigmoide/diagnóstico por imagen , Medios de Contraste , Diagnóstico Diferencial , Femenino , Humanos , Obstrucción Intestinal/cirugía , Vólvulo Intestinal/cirugía , Persona de Mediana Edad , Enfermedades del Sigmoide/cirugíaRESUMEN
BACKGROUND: Surgical risk prediction models traditionally use patient attributes and measures of physiology to generate predictions about postoperative outcomes. However, the surgeon's assessment of the patient may be a valuable predictor, given the surgeon's ability to detect and incorporate factors that existing models cannot capture. We compare the predictive utility of surgeon intuition and a risk calculator derived from the American College of Surgeons (ACS) NSQIP. STUDY DESIGN: From January 10, 2021 to January 9, 2022, surgeons were surveyed immediately before performing surgery to assess their perception of a patient's risk of developing any postoperative complication. Clinical data were abstracted from ACS NSQIP. Both sources of data were independently used to build models to predict the likelihood of a patient experiencing any 30-day postoperative complication as defined by ACS NSQIP. RESULTS: Preoperative surgeon assessment was obtained for 216 patients. NSQIP data were available for 9,182 patients who underwent general surgery (January 1, 2017 to January 9, 2022). A binomial regression model trained on clinical data alone had an area under the receiver operating characteristic curve (AUC) of 0.83 (95% CI 0.80 to 0.85) in predicting any complication. A model trained on only preoperative surgeon intuition had an AUC of 0.70 (95% CI 0.63 to 0.78). A model trained on surgeon intuition and a subset of clinical predictors had an AUC of 0.83 (95% CI 0.77 to 0.89). CONCLUSIONS: Preoperative surgeon intuition alone is an independent predictor of patient outcomes; however, a risk calculator derived from ACS NSQIP is a more robust predictor of postoperative complication. Combining intuition and clinical data did not strengthen prediction.
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Intuición , Cirujanos , Humanos , Estados Unidos , Pronóstico , Medición de Riesgo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Factores de Riesgo , Estudios Retrospectivos , Mejoramiento de la CalidadRESUMEN
Venous thromboembolism (VTE) is a potential sequela of injury, surgery, and critical illness. Patients in the Trauma Intensive Care Unit are at risk for this condition, prompting daily discussions during patient care rounds and routine use of mechanical and/or pharmacologic prophylaxis measures. While VTE rightfully garners much attention in clinical patient care and in the medical literature, optimal strategies for VTE prevention are still evolving. Furthermore, trauma and surgical patients often have real or perceived contraindications to prophylaxis that affect the timing of preventive measures and the consistency with which they can be applied. In this Clinical Consensus Document, the American Association for the Surgery of Trauma Critical Care Committee addresses several practical clinical questions pertaining to specific or unique aspects of VTE prophylaxis in critically ill and injured patients.
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CD4+ regulatory T cells (Tregs) are acutely activated by traumatic injury, which suggests that they may react to injury with similar kinetics as memory T cells. Here, we used a mouse burn trauma model to screen for memory-like T cell responses to injury by transferring T cells from sham or burn CD45.1 mice into CD45.2 mice and performing secondary injuries in recipient mice. Among all T cell subsets that were measured, only Tregs expanded in response to secondary injury. The expanded Tregs were a CD44high /CD62Llow subpopulation, markers indicative of memory T cells. CyTOF (cytometry by time-of-flight) mass cytometry was used to demonstrate that injury-expanded Tregs expressed higher levels of CD44, CTLA-4, ICOS, GITR, and Helios than Tregs from noninjured mice. Next, we tested whether a similar population of Tregs might react acutely to burn trauma. We observed that Tregs with a phenotype that matched the injury-expanded Tregs were activated by 6 h after injury. To test if Treg activation by trauma requires functional MHC class II, we measured trauma-induced Treg activation in MHC class II gene deficient (MHCII-/- ) mice or in mice that were given Fab fragment of anti-MHC class II antibody to block TCR activation. Injury-induced Treg activation occurred in normal mice but only partial activation was detected in MHCII-/- mice or in mice that were given Fab anti-MHCII antibody. These findings demonstrate that trauma activates a memory-like Treg subpopulation and that Treg activation by injury is partially dependent on TCR signaling by an MHC class II dependent mechanism.
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Memoria Inmunológica , Activación de Linfocitos/inmunología , Linfocitos T Reguladores/inmunología , Heridas y Lesiones/inmunología , Animales , Biomarcadores/metabolismo , Quemaduras/inmunología , Quemaduras/patología , Proliferación Celular , Antígenos de Histocompatibilidad Clase II/metabolismo , Ganglios Linfáticos/patología , Ratones Endogámicos C57BL , Bazo/patología , Heridas y Lesiones/patologíaRESUMEN
BACKGROUND: Racial disparities in trauma outcomes have been documented, but little is known about racial differences in post-discharge healthcare utilization. This study compares the utilization of post-discharge healthcare services by African-American and Caucasian trauma patients. METHODS: Trauma patients with an Injury Severity Score (ISS)≥9 from three Level-I trauma centers were contacted between 6 and 12 months post-injury. Utilization of trauma-related healthcare services was asked. Coarsened exact matching (CEM) was used to match African-American and Caucasian patients. Conditional logistic regression then compared matched patients in terms of post-discharge healthcare utilization. RESULTS: 182 African-American and 1,117 Caucasian patients were followed. Of these, 141 African-Americans were matched to 628 Caucasians. After CEM, we found that African-American patients were less likely to use rehabilitation services [OR:0.64 (95% CI:0.43-0.95)] and had fewer injury-related outpatient visits [OR:0.59 (95% CI:0.40-0.86)] after discharge. CONCLUSIONS: This study shows the existence of racial disparities in post-discharge healthcare utilization after trauma for otherwise similarly injured, matched patients.
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Negro o Afroamericano , Utilización de Instalaciones y Servicios/estadística & datos numéricos , Disparidades en Atención de Salud/etnología , Aceptación de la Atención de Salud/etnología , Alta del Paciente , Población Blanca , Heridas y Lesiones/terapia , Adulto , Anciano , Boston/epidemiología , Femenino , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Humanos , Puntaje de Gravedad del Traumatismo , Modelos Logísticos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud/estadística & datos numéricos , Centros Traumatológicos , Heridas y Lesiones/etnologíaRESUMEN
BACKGROUND: Lower socioeconomic status (SES) is known to be associated with higher morbidity and mortality following injury. However, the impact of individual SES on long-term outcomes after trauma is unknown. The objective of this study was to determine the impact of educational level and income on long-term outcomes after injury. METHODS: Trauma patients with moderate to severe injuries admitted to three Level-I trauma centers were contacted 6 months to 12 months after injury to evaluate functional status, return to work/school, chronic pain, and posttraumatic stress disorder (PTSD). Lower SES status was determined by educational level and income. Adjusted logistic regression models were built to determine the association between educational level and income (lowest vs. highest quartile determined by census-tract area) on each of the long-term outcomes. A sensitivity analysis was performed using the national median household income ($57,617) as threshold for defining low versus high income. RESULTS: A total of 1,516 patients were followed during a 36-month period. Forty-nine percent had a low educational level, and 26% were categorized in the low-income group. Mean (SD) age and injury severity score were 60 (21.5) and 14.3 (7.3), respectively, with most patients (94%) having blunt injuries. After adjusting for confounders, low educational level was associated with poor long-term outcomes: functional limitation [odds ratio (OR), 1.78 (95% confidence interval (CI), 1.41-2.26)], has not yet returned to work/school [OR, 2.48 (95% CI, 1.70-3.62)], chronic pain [OR, 1.63 (95% CI, 1.27-2.10)], and PTSD [OR, 2.23 (95% CI, 1.60-3.11)]. Similarly, low-income level was associated with not yet return to work/school [OR, 1.97 (95% CI, 1.09-3.56)], chronic pain [OR,1.70 (95% CI, 1.14-2.53)], and PTSD [OR, 2.20 (95% CI, 1.21-3.98)]. In sensitivity analyses, there were no significant differences in long-term outcomes between income levels. CONCLUSION: Low educational level is strongly associated with worse long-term outcomes after injury. However, although household income is associated with long-term outcomes, it matters where the threshold is. The impact of different socioeconomic measures on long-term outcomes after trauma cannot be assumed to be interchangeable. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.
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Escolaridad , Renta , Heridas y Lesiones/terapia , Actividades Cotidianas , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Renta/estadística & datos numéricos , Puntaje de Gravedad del Traumatismo , Modelos Logísticos , Masculino , Persona de Mediana Edad , Reinserción al Trabajo/estadística & datos numéricos , Resultado del Tratamiento , Heridas y Lesiones/complicacionesRESUMEN
INTRODUCTION: Red cell distribution width (RDW) is associated with mortality and bloodstream infection risk in critically ill patients. We hypothesized that an increase in RDW at hospital discharge in critically ill patients who received emergency general surgery (EGS) would be associated with increased mortality after hospital discharge. METHODS: We performed a two-center observational study of patients treated in medical and surgical intensive care units. We studied 1567 patients, who received critical care between 1998 and 2012 who underwent EGS and survived hospitalization. The exposure of interest was RDW within 24 hours of hospital discharge and categorized a priori in quintiles as ≤13.3%, 13.3% to 14.0%, 14.0% to 14.7%, 14.7% to 15.8%, 15.8% to 17.0% and >17.0%. The primary outcome was 90-day all-cause mortality. Adjusted ORs were estimated by multivariable logistic regression models with inclusion of covariate terms for age, race, gender, Deyo-Charlson Index, sepsis and number of organs with acute failure. RESULTS: The cohort patients were 51.4% male and 23.2% non-white. 23.9% had sepsis and the mean age was 58 years. 90-day postdischarge mortality was 6.8%. Patients with a discharge RDW 15.8% to 17.0% or RDW >17.0% have an adjusted OR of 90-day postdischarge mortality of 3.64 (95% CI 1.04 to 12.68; p=0.043) or 4.58 (95% CI 1.32 to 15.93; p=0.02), respectively, relative to patients with a discharge RDW ≤13.3%. Further, patients with a discharge RDW ≥15.8 have an adjusted OR of 30-day hospital readmission of 2.12 (95% CI 1.17 to 3.83; p=0.013) relative to patients with a discharge RDW ≤13.3%. CONCLUSIONS: In EGS patients requiring critical care who survive hospitalization, an elevated RDW at the time of discharge is a robust predictor of all-cause patient mortality and hospital readmission after discharge. LEVEL OF EVIDENCE: Level II, prognostic retrospective study.
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BACKGROUND: Emergency general surgery (EGS) patients are at an increased risk for morbidity and mortality compared with non-EGS patients. Limited information exists regarding the contribution of malnutrition to the outcome of critically ill patients who undergo EGS. We hypothesized that malnutrition would be associated with increased risk of 90-day all-cause mortality following intensive care unit (ICU) admission in EGS patients. MATERIALS AND METHODS: We performed an observational study of patients treated in medical and surgical ICUs at a single institution in Boston. We included patients who underwent an EGS procedure and received critical care between 2005 and 2011. The exposure of interest, malnutrition, was determined by a registered dietitian's formal assessment within 48 hours of ICU admission. The primary outcome was all-cause 90-day mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. RESULTS: The cohort consisted of 1361 patients. Sixty percent had nonspecific malnutrition, 8% had protein-energy malnutrition, and 32% were without malnutrition. The 30-day readmission rate was 18.9%. Mortality in-hospital and at 90 days was 10.1% and 17.9%, respectively. Patients with nonspecific malnutrition had a 1.5-fold increased odds of 90-day mortality (adjusted odds ratio [OR], 1.51; 95% confidence interval [CI], 1.09-5.04; P = .009) and patients with protein-energy malnutrition had a 3.1-fold increased odds of 90-day mortality (adjusted OR, 3.06; 95% CI, 1.89-4.92; P < .001) compared with patients without malnutrition. CONCLUSION: In critically ill patients who undergo EGS, malnutrition at ICU admission is predictive of adverse outcomes. In survivors of hospitalization, malnutrition at ICU admission is associated with increases in readmission and mortality.
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Hospitalización , Unidades de Cuidados Intensivos , Desnutrición/epidemiología , Procedimientos Quirúrgicos Operativos/mortalidad , Anciano , Boston/epidemiología , Estudios de Cohortes , Cuidados Críticos , Urgencias Médicas , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Desnutrición/diagnóstico , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Factores de RiesgoRESUMEN
The use of risk stratification tools (RST) aids in clinical triage, decision making and quality assessment in a wide variety of medical fields. Although emergency general surgery (EGS) is characterized by a comorbid, physiologically acute patient population with disparately high rates of perioperative morbidity and mortality, few RST have been explicitly examined in this setting. We examined the available RST with the intent of identifying a tool that comprehensively reflects an EGS patients perioperative risk for death or complication. The ideal tool would combine individualized assessment with relative ease of use. Trauma Scoring Systems, Critical Care Scoring Systems, Surgical Scoring Systems and Track and Trigger Models are reviewed here, with the conclusion that Emergency Surgery Acuity Score and the American College of Surgeons National Surgical Quality Improvement Programme Universal Surgical Risk Calculator are the most applicable and appropriate for EGS.
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BACKGROUND: Traumatic injury is strongly associated with long-term mental health disorders, but the risk factors for developing these disorders are poorly understood. We report on a multi-institutional collaboration to collect long-term patient-centered outcomes after trauma, including screening for post-traumatic stress disorder. The objective of this study is to determine the prevalence of and risk factors for the development of post-traumatic stress disorder after traumatic injury. METHODS: Adult trauma patients (aged 18-64) with moderate to severe injuries (Injury Severity Score ≥ 9) admitted to 3 level I trauma centers were screened between 6 and 12 months after injury for post-traumatic stress disorder. Patients were divided by mechanism: fall, road traffic injury, and intentional injury. Multiple logistic regression models were used to determine the association between baseline patient and injury-related characteristics and the development of post-traumatic stress disorder for the overall cohort and by mechanism of injury. RESULTS: A total of 450 patients completed the screen. Overall 32% screened positive for post-traumatic stress disorder, but this differed significantly by mechanism, with the lowest being after a fall (25%) and highest after intentional injury (60%). Injury severity was not associated with post-traumatic stress disorder for any group, but lower educational level was associated with post-traumatic stress disorder within all the groups. Only 21% of patients who screened positive for post-traumatic stress disorder were receiving treatment at the time of the survey. CONCLUSION: Post-traumatic stress disorder is common after traumatic injury, and the prevalence varies significantly by injury mechanism but is not associated with injury severity. Only a small proportion of patients who screen positive for post-traumatic stress disorder are currently receiving treatment.
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Trastornos por Estrés Postraumático/etiología , Heridas y Lesiones/complicaciones , Adulto , Boston/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Trastornos por Estrés Postraumático/epidemiología , Heridas y Lesiones/psicologíaAsunto(s)
Dolor Abdominal/etiología , Colon/anomalías , Estreñimiento/etiología , Adulto , Femenino , Humanos , LaparoscopíaRESUMEN
Synaptic spines are dynamic structures that regulate neuronal responsiveness and plasticity. We examined the role of the schizophrenia risk factor DISC1 in the maintenance of spine morphology and function. We found that DISC1 anchored Kalirin-7 (Kal-7), regulating access of Kal-7 to Rac1 and controlling the duration and intensity of Rac1 activation in response to NMDA receptor activation in both cortical cultures and rat brain in vivo. These results explain why Rac1 and its activator (Kal-7) serve as important mediators of spine enlargement and why constitutive Rac1 activation decreases spine size. This mechanism likely underlies disturbances in glutamatergic neurotransmission that have been frequently reported in schizophrenia that can lead to alteration of dendritic spines with consequential major pathological changes in brain function. Furthermore, the concept of a signalosome involving disease-associated factors, such as DISC1 and glutamate, may well contribute to the multifactorial and polygenetic characteristics of schizophrenia.
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Espinas Dendríticas/fisiología , Ácido Glutámico/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Sinapsis/fisiología , Proteína de Unión al GTP rac1/metabolismo , Animales , Células Cultivadas , Corteza Cerebral/citología , Corteza Cerebral/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Técnicas de Silenciamiento del Gen , Proteínas del Tejido Nervioso/genética , Neuronas/citología , Neuronas/fisiología , Interferencia de ARN , Ratas , Ratas Sprague-Dawley , Receptores AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transducción de Señal , Factores de Tiempo , Técnicas de Cultivo de TejidosRESUMEN
Schizophrenia (SZ) is a highly polygenic disease with strong genetic predisposition. Although genetic susceptibility factors for SZ are likely to have an influence in some brain regions and related neural circuits during neurodevelopment, direct proof for spatiotemporal causality in the development of SZ, and the alteration of what gene function at what brain region during what developmental stage, remains to be elucidated. Gene manipulation by viral vector stereotaxically injected into a specific brain region is now becoming available for psychiatric research. This technique has several advantages, e.g., the exceptional spatiotemporal control, simultaneous manipulation of multiple genes, and its simple protocol. These properties can make this technique one of the most valuable approaches for research in SZ, which is a complex brain disorder with multifactorial, genetic, and developmental features. This review summarizes the benefits and actual use of this technique together with discussion of spatiotemporal aspect for SZ.