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1.
J Trauma Acute Care Surg ; 95(3): 419-425, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37158803

RESUMO

BACKGROUND: Significant increases in firearm-related mortality in the US pediatric population drive an urgent need to study these injuries to drive prevention policies. The purpose of this study was (1) to characterize those with and without readmissions, (2) to identify risk factors for 90-day unplanned readmission, and (3) to examine reasons for hospital readmission. METHODS: The 2016-2019 Nationwide Readmission Database of the Healthcare Cost and Utilization Project was used to identify hospital admissions with unintentional firearm injury in patients younger than 18 years. Ninety-day unplanned readmission characteristics were assessed and detailed. Multivariable regression analysis was used to assess factors associated with unplanned 90-day readmission. RESULTS: Over 4 years, 1,264 unintentional firearm injury admissions resulted in 113 subsequent readmissions (8.9%). There were no significant differences in age or payor, but more women (14.7% vs. 23%) and older children (13-17 years [80.5%]) had readmissions. The mortality rate during primary hospitalization was 5.1%. Survivors of initial firearm injury were more frequently readmitted if they had a mental health diagnosis (22.1% vs. 13.8%; p = 0.017). Readmission diagnosis included complications (15%), mental health or drug/alcohol (9.7%), trauma (33.6%), a combination of the prior three (28.3%), and chronic disease (13.3%). More than a third (38.9%) of the trauma readmissions were for new traumatic injury. Female children, those with longer lengths of stay, and those with more severe injuries were more likely to have unplanned 90-day readmissions. Mental health and drug/alcohol abuse diagnoses were not an independent predictor for readmission. CONCLUSION: This study provides insight into the characteristics of and risk factors for unplanned readmission in the pediatric unintentional firearm injury population. In addition to using prevention strategies, the utilization of trauma-informed care must be integrated into all aspects of care for this population to help minimize the long-term psychological impact of surviving firearm injury. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.


Assuntos
Lesões Acidentais , Armas de Fogo , Ferimentos por Arma de Fogo , Criança , Humanos , Feminino , Estados Unidos/epidemiologia , Adolescente , Readmissão do Paciente , Ferimentos por Arma de Fogo/epidemiologia , Ferimentos por Arma de Fogo/diagnóstico , Estudos Retrospectivos , Hospitalização , Fatores de Risco , Bases de Dados Factuais
2.
Nat Commun ; 14(1): 1187, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36864031

RESUMO

Ferroptosis is mediated by lipid peroxidation of phospholipids containing polyunsaturated fatty acyl moieties. Glutathione, the key cellular antioxidant capable of inhibiting lipid peroxidation via the activity of the enzyme glutathione peroxidase 4 (GPX-4), is generated directly from the sulfur-containing amino acid cysteine, and indirectly from methionine via the transsulfuration pathway. Herein we show that cysteine and methionine deprivation (CMD) can synergize with the GPX4 inhibitor RSL3 to increase ferroptotic cell death and lipid peroxidation in both murine and human glioma cell lines and in ex vivo organotypic slice cultures. We also show that a cysteine-depleted, methionine-restricted diet can improve therapeutic response to RSL3 and prolong survival in a syngeneic orthotopic murine glioma model. Finally, this CMD diet leads to profound in vivo metabolomic, proteomic and lipidomic alterations, highlighting the potential for improving the efficacy of ferroptotic therapies in glioma treatment with a non-invasive dietary modification.


Assuntos
Ferroptose , Glioma , Humanos , Animais , Camundongos , Metionina , Cisteína , Proteômica , Racemetionina , Glioma/tratamento farmacológico
3.
J Trauma Acute Care Surg ; 95(3): 313-318, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36787433

RESUMO

INTRODUCTION: The role of calcium is ubiquitous in human physiology. Emerging evidence suggests that the lethal triad be revised to include hypocalcemia (hypoCa) and thus be known as the lethal diamond . There are data showing that traumatic injury may result in hypoCa independent from the mechanism of calcium chelation by citrate-based blood preservatives. Minimal literature exists analyzing the role of hypoCa in pediatric trauma patients. We hypothesize that there is an independent association of hypoCa with increased blood product requirements and mortality. METHODS: A retrospective cohort study of severely injured pediatric trauma patients was conducted. Trauma registry data were collected from January 2016 to August 2021. Ionized calcium (iCa) levels were obtained from arrival blood draws. Subjects were categorized into two groups by a threshold iCa level of 1.00 mmol/L and compared. Shock Index Pediatric Adjusted scores were used to adjust for age-specific differences in vital signs. RESULTS: A total of 142 patients were compared, of which 46.5% were hypocalcemic (iCa <1.00 mmol/L). Patients were well matched in terms of demographics and injury severity. The hypocalcemic group had lower systolic blood pressure and a higher percentage of Shock Index Pediatric Adjusted-positive patients. Weight-adjusted transfusion volumes were significantly higher in the hypocalcemic group at both the 4-hour and 24-hour time points without a difference in prehospital transfusion requirements. There was no observed difference in early or in-hospital mortality. CONCLUSION: This study contributes to the body of literature regarding the association between hypoCa and traumatic injury in the pediatric population. Hypocalcemia was associated with increased blood product requirements without a difference in prehospital transfusion requirements, suggesting a possible independent association. Further prospective studies are needed to better understand this relationship. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.


Assuntos
Hipocalcemia , Ferimentos e Lesões , Humanos , Criança , Cálcio , Estudos Retrospectivos , Transfusão de Sangue , Mortalidade Hospitalar , Escala de Gravidade do Ferimento , Ferimentos e Lesões/complicações , Ferimentos e Lesões/terapia
4.
Obstet Gynecol ; 141(2): 371-374, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36649332

RESUMO

We used a claims database to identify patients with uterine leiomyomas who underwent hysterectomy between 2011 and 2019. Use of conservative medical and surgical interventions in the 24-month period before hysterectomy was explored. Overall, 59.7% of patients did not receive any conservative intervention before hysterectomy. Individuals who underwent hysterectomy in more recent years and those with endometriosis, abnormal bleeding, greater comorbidity, or prior venous thromboembolism were more likely to receive conservative interventions.


Assuntos
Endometriose , Leiomioma , Neoplasias Uterinas , Feminino , Humanos , Neoplasias Uterinas/cirurgia , Tratamento Conservador , Leiomioma/cirurgia , Histerectomia , Endometriose/cirurgia
5.
J Trauma Acute Care Surg ; 93(6): e182-e184, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36044513

RESUMO

INTRODUCTION: Firearm-related deaths have become the leading cause of death in adolescents and children. Since the Sutherland Springs, TX mass casualty incident (MCI), the Southwest Texas Regional Advisory Council for trauma instituted a prehospital whole blood (WB) program and blood deployment program for MCIs. METHODS: The program was adopted statewide by the Texas Emergency Medical Task Force, of which Southwest Texas Regional Advisory Council is the lead for Emergency Medical Task Force 8. The recent active shooter MCI in Uvalde, TX was the first time the MCI blood deployment program had been used. To our knowledge, no other similar programs exist in this or any other country. RESULTS: On May 24, 2022, 19 children and 2 adults were killed at an MCI in Uvalde, TX. The MCI WB deployment protocol was initiated, and South Texas Blood and Tissue Center prepared 15 U of low-titer O-positive whole blood and 10 U of leukoreduced O packed cells. The deployed blood arrived at Uvalde Memorial Hospital within 67 minutes. One of the pediatric patients sustained multiple gunshots to the chest and extremities. The child was hypotensive and received 2 U of leukoreduced O packed cells, one at the initial hospital and another during transport. On arrival, the patient required 2 U of low-titer O-positive whole blood and underwent a successful hemorrhage control operation. The remaining blood was returned to South Texas Blood and Tissue Center for distribution. CONCLUSION: Multiple studies have shown the association of early blood product resuscitation and improved mortality, with WB being the ideal resuscitative product for many. The ongoing efforts in South Texas serve as a model for development of similar programs throughout the country to reduce preventable deaths. This event represents the first ever successful deployment of WB to the site of an MCI related to a school shooting in the modern era. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level V.


Assuntos
Incidentes com Feridos em Massa , Ferimentos por Arma de Fogo , Adulto , Adolescente , Humanos , Criança , Texas , Ressuscitação/métodos , Ferimentos por Arma de Fogo/terapia , Hemorragia
6.
Obstet Gynecol ; 140(1): 55-64, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35849456

RESUMO

OBJECTIVE: To examine temporal trends in cervical cancer screening practices and associated downstream abnormalities and procedures. METHODS: Women aged 18-64 years with commercial insurance or Medicaid insurance from 2008 to 2019 were identified using the IBM MarketScan databases. The annual rates of screening overall and by type of test (cytology, co-testing, or primary human papillomavirus testing) were examined. Downstream abnormal cytologic and histologic test results, colposcopies, and excisional procedures were examined, and rates were reported for the population of eligible patients with continuous insurance and for those who underwent screening. Changes over time in testing and outcomes were compared using χ2 tests and Spearman's correlation. RESULTS: From 2008 to 2019, the annual screening prevalence decreased from 42.6% to 29.4% in women with commercial insurance (P<.001) and from 27.9% to 12.4% among women with Medicaid insurance (P<.001). In the cohort of women with commercial insurance, cytology usage decreased from 79.4% to 38.9% and co-testing increased from 20.1% to 59.6% (P<.001). Per 1,000 women screened, the rate of abnormal histologic and cytologic test results rose from 96 to 119 (P<.001) and colposcopies rose from 33 to 42 (P<.001); excisional procedures remained relatively constant. Per 1,000 eligible women, the rate of abnormal histologic and cytologic test results decreased from 41 to 35 (P<.001), colposcopies declined from 14 to 12, and excisional procedures decreased from 3 to 2. CONCLUSION: Human papillomavirus testing has been rapidly incorporated into cervical cancer screening and is associated with an increasing trend of downstream abnormalities and procedures among screened women but a declining trend at the population level.


Assuntos
Seguro , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Colposcopia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Programas de Rastreamento/métodos , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Gravidez , Estados Unidos , Neoplasias do Colo do Útero/patologia
7.
J Matern Fetal Neonatal Med ; 35(25): 6489-6497, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33910462

RESUMO

OBJECTIVE: It is possible that in the setting of increasing patient comorbidity and obesity, risk for surgical injury and need for reoperation is increasing. It is also possible that with differential uptake of evidence-based recommendations and increasing prevalence of risk factors such as obesity, risk for surgical site complications is increasing. The objective of this study was to evaluate trends in, risk factors for, and racial disparities related to cesarean complications. METHODS: This repeated cross-sectional study evaluated cesarean deliveries in the 2002-2014 National Inpatient Sample for women age 15-54. The primary outcome was a cesarean surgical complication composite including (i) surgical injuries, (ii) reoperation, and (iii) surgical site complications. Surgical injuries, reoperation, and surgical site complications were additionally evaluated individually as outcomes. Univariable and multivariable log linear regression models including demographic, clinical, and hospital factors were performed to assess risk for outcomes with unadjusted and adjusted risk ratios (aRR) with 95% confidence intervals (CI) as measures of association. Temporal trends were estimated using average annual percentage change from a joinpoint regression model. A stratified analysis was performed restricted to non-Hispanic black women. Data was weighted to provide national estimates. RESULTS: A total of 16.2 million estimated cesarean deliveries (3.2 million unweighted cesarean deliveries) from 2002 to 2014 were included in this analysis. The prevalence of the cesarean surgical complication composite was 1.14%, surgical site complications occurred in 0.60%, surgical injuries in 0.49%, and reoperations in 0.10%. Comparing the end of the study (2012-2014) to the beginning of the study (2002-2003), adjusted risk for the composite was similar (aRR 0.93, 95% CI 0.92, 0.95). In comparison, surgical site complication risk was lower at the end of the study (aRR 0.77, 95% CI 0.75, 0.79) while risks for surgical injury (aRR 1.18, 95% CI 1.15, 1.22) and reoperation (1.18, 95% CI 1.10, 1.26) were higher. Non-Hispanic black women were at increased risk for surgical site complications (aRR 1.83, 95% CI 1.80, 1.87) and reoperation (aRR 1.44, 95% CI 1.37, 1.51), but not surgical injury (aRR 0.99, 95% CI 0.97, 1.02). In analyses stratified for non-Hispanic black women, there was a reduction in risk for surgical site complications at the end of the study period compared to the beginning similar to the primary analysis (aRR 0.76, 95% 0.72, 0.81) with a modest decrease in overall risk for the composite outcome (aRR 0.85, 95% CI 0.81, 0.89). CONCLUSION: A decrease in risk for surgical site complications was offset by slightly increased risk for surgical injury and reoperation in adjusted analyses. Among non-Hispanic black women, surgical site complication risk decreased proportionately with this group still at significantly higher overall risk.


Assuntos
Cesárea , Complicações Intraoperatórias , Gravidez , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Cesárea/efeitos adversos , Complicações Intraoperatórias/epidemiologia , Grupos Raciais , Fatores de Risco , Obesidade/etiologia
8.
J Trauma Acute Care Surg ; 91(4): 579-583, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33990534

RESUMO

BACKGROUND: While massive transfusion protocols (MTPs) are associated with decreased mortality in adult trauma patients, there is limited research on the impact of MTP on pediatric trauma patients. The purpose of this study was to compare pediatric trauma patients requiring massive transfusion with all other pediatric trauma patients to identify triggers for MTP activation in injured children. METHODS: Using our level I trauma center's registry, we retrospectively identified all pediatric trauma patients from January 2015 to January 2018. Massive transfusion (MT) was defined as infusion of 40 mL/kg of blood products in the first 24 hours of admission. Patients missing prehospital vital sign data were excluded from the study. We retrospectively collected data including demographics, blood utilization, variable outcome data, prehospital vital signs, prehospital transport times, and Injury Severity Scores. Statistical significance was determined using Mann-Whitney U test and χ2 test. p Values of less than 0.05 were considered significant. RESULTS: Thirty-nine (1.9%) of the 2,035 pediatric patients met the criteria for MT. All-cause mortality in MT patients was 49% (19 of 39 patients) versus 0.01% (20 of 1996 patients) in non-MT patients. The two groups significantly differed in Injury Severity Score, prehospital vital signs, and outcome data.Both systolic blood pressure (SBP) of <100 mm Hg and shock index (SI) of >1.4 were found to be highly specific for MT with specificities of 86% and 92%, respectively. The combination of SBP of <100 mm Hg and SI of >1.4 had a specificity of 94%. The positive and negative predictive values of SBP of <100 mm Hg and SI of >1.4 in predicting MT were 18% and 98%, respectively. Based on positive likelihood ratios, patients with both SBP of <100 mm Hg and SI of >1.4 were 7.2 times more likely to require MT than patients who did not meet both of these vital sign criteria. CONCLUSION: Pediatric trauma patients requiring early blood transfusion present with lower blood pressures and higher heart rates, as well as higher SIs and lower pulse pressures. We found that SI and SBP are highly specific tools with promising likelihood ratios that could be used to identify patients requiring early transfusion. LEVEL OF EVIDENCE: Therapeutic/care management, level V.


Assuntos
Pressão Sanguínea , Transfusão de Sangue/estatística & dados numéricos , Frequência Cardíaca , Choque Hemorrágico/diagnóstico , Ferimentos e Lesões/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Valor Preditivo dos Testes , Curva ROC , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Choque Hemorrágico/etiologia , Choque Hemorrágico/terapia , Centros de Traumatologia/estatística & dados numéricos , Ferimentos e Lesões/complicações , Ferimentos e Lesões/terapia
9.
BMC Health Serv Res ; 20(1): 678, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32698825

RESUMO

BACKGROUND: Patient satisfaction is increasingly being used to assess, and financially reward, provider performance. Previous studies suggest that race/ethnicity (R/E) may impact satisfaction, yet few practices adjust for patient R/E. The objective of this study is to examine R/E differences in patient satisfaction ratings and how these differences impact provider rankings. METHODS: Patient satisfaction survey data linked to electronic health records from two large outpatient centers in northern California - a non-profit organization of community-based clinics (Site A) and an academic medical center (Site B) - was collected and analyzed. Participants consisted of adult patients who received outpatient care at Site A from December 2010 to November 2014 and Site B from March 2013 to August 2014, and completed Press-Ganey Medical Practice Survey questionnaires (N = 216,392 (Site A) and 30,690 (Site B)). Self-reported non-Hispanic white (NHW), Black, Latino, and Asian patients were studied. For six questions each representing a survey subdomain, favorable ratings were defined as top-box ("very good") compared to all other categories ("very poor," "poor," "fair," and "good"). Using multivariable logistic regression with provider random effects, we assessed whether the likelihood of giving favorable ratings differed by patient R/E, adjusting for patient age and sex. RESULTS: Asian, younger and female patients provided less favorable ratings than other R/E, older and male patients. After adjustment, Asian patients were less likely than NHW patients to provide top-box ratings to the overall assessment question "likelihood of recommending this practice to others" (Site A: Asian predicted probability (PP) 0.680, 95% confidence interval (CI): 0.675-0.685 compared to NHW PP 0.820, 95% CI: 0.818-0.822; Site B: Asian PP 0.734, 95% CI: 0.733-0.736 compared to NHW PP 0.859, 95% CI: 0.859-0.859). The effect sizes for Asian R/E were greater than the effect sizes for older age and female sex. An absolute 3% decrease in mean composite score between providers serving different percentages of Asian patients translated to an absolute 40% drop in national ranking. CONCLUSIONS: Patient satisfaction scores may need to be adjusted for patient R/E, particularly for providers caring for high panel percentages of Asian patients.


Assuntos
Povo Asiático/psicologia , Satisfação do Paciente/etnologia , Centros Médicos Acadêmicos , Adolescente , Adulto , Idoso , Assistência Ambulatorial , Povo Asiático/estatística & dados numéricos , California , Centros Comunitários de Saúde , Etnicidade/psicologia , Etnicidade/estatística & dados numéricos , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Grupos Raciais/psicologia , Grupos Raciais/estatística & dados numéricos , Adulto Jovem
10.
J Clin Neurosci ; 70: 118-122, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31421993

RESUMO

OBJECT: Guidelines for the management of pediatric epidural hematoma (PEDH) remain poorly defined. Here we seek to characterize the disease course of PEDH in patients with presenting Glasgow Coma Scale (GCS) of 14+, and suggest high-risk characteristics for progression to surgery. METHODS: A prospectively maintained, single-institution, level-1 trauma hospital admission database was queried to identify patients ages 6 months to 18 years presenting with PEDH between 2006 and 2016. Selected charts were reviewed for clinical information and treatment. Head imaging was reviewed for hematoma size, location, fractures, and midline shift. RESULTS: Of 210 cases reviewed, 117 presented with a GCS of 14+. Of these, 24 required surgery while 93 were managed conservatively. Factors leading to surgery included decline in GCS (40%), size alone (21%), localizing neurological deficit (20%), progression on repeat imaging (12%), and other (7%). Hematomas involving the temporal lobe plus an adjacent lobe were more likely to proceed to surgery than those involving the temporal lobe alone (OR: 24.8, 95% CI (4.74, 129.26)). Hematomas in proximity to the superior sagittal and transverse sinuses proceeded to surgery in 33.3% and 37.5% of cases, respectively. Of the 93 patients with a thickness:biparietal skull diameter ratio of ≤0.15, 89 (95.7%) were managed conservatively. CONCLUSION: In this single-institution experience, 21% of pediatric patients presenting with a GCS of 14+ proceeded to surgery. High-risk features include large hematoma thickness, proximity to the transverse sinus, and multilobar location. A thickness:biparietal skull diameter ratio less than 0.15 was highly unlikely to proceed to surgery.


Assuntos
Hematoma Epidural Craniano/patologia , Hematoma Epidural Craniano/terapia , Adolescente , Criança , Progressão da Doença , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Masculino , Fatores de Risco
11.
Childs Nerv Syst ; 35(11): 2195-2203, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31177323

RESUMO

INTRODUCTION: Management of pediatric epidural hematoma (PEDH) ranges from observation to emergent craniotomy. Guidelines for management remain poorly defined. More so, serial CT imaging in the pediatric population is often an area of controversy given the concern for excessive radiation as well as increased costs. This work aims to further elucidate the need for serial imaging to surgical decision-making. METHODS: A prospectively maintained single-institution trauma database was reviewed at a level-1 trauma center to identify patients 18 years old and younger presenting with PEDH over a 10-year period. Selected charts were reviewed for demographic information, mechanisms of injury, neurologic exam, radiographic findings, and treatment course. Surgical decisions were at the discretion of the neurosurgeon on call, often in discussion with a pediatric neurosurgeon. RESULTS: Two hundred and ten records with traumatic epidural hematomas were reviewed. Seventy-three (35%) were taken emergently for hematoma evacuation. Of these, 18 (25%) underwent repeat imaging prior to surgery. One hundred and thirty-seven (65%) were admitted for observation. Seventy-two patients (53%) did not undergo repeat imaging. Sixty-five (47%) admitted for conservative management had at least one repeat scan during their hospitalization. Indications for follow-up imaging during conservative management included routine follow-up (74%), initial scan in our system following transfer (17%), neurological decline (8%), and unknown (1%). Thirteen patients (9%) were taken for surgery in a delayed fashion following admission. Twelve patients who went to surgery in a delayed fashion demonstrated progression on follow-up imaging; however, increase in hematoma size on repeat imaging was the sole surgical indication in only four patients (3%). There were no deaths related to the epidural hemorrhage or postoperatively, regardless of management, and all patients recovered to their pre-trauma baseline. CONCLUSION: Given that isolated hematoma expansion accounted for an exceptionally small proportion of operative indications, this data suggests changes seen on CT should not be solely relied upon to dictate surgical management. The benefit of obtaining follow-up imaging must be strongly considered and weighed against the known deleterious effects of excessive radiation in pediatric patients, let alone its clinical utility.


Assuntos
Tratamento Conservador , Craniotomia , Hematoma Epidural Craniano/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Acidentes por Quedas , Acidentes de Trânsito , Adolescente , Traumatismos em Atletas , Criança , Pré-Escolar , Tomada de Decisão Clínica , Estudos de Coortes , Progressão da Doença , Feminino , Hematoma Epidural Craniano/terapia , Humanos , Hemorragia Intracraniana Traumática/diagnóstico por imagem , Hemorragia Intracraniana Traumática/cirurgia , Masculino , Estudos Retrospectivos , Centros de Traumatologia
12.
Cell ; 175(7): 1972-1988.e16, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30550791

RESUMO

In vitro cancer cultures, including three-dimensional organoids, typically contain exclusively neoplastic epithelium but require artificial reconstitution to recapitulate the tumor microenvironment (TME). The co-culture of primary tumor epithelia with endogenous, syngeneic tumor-infiltrating lymphocytes (TILs) as a cohesive unit has been particularly elusive. Here, an air-liquid interface (ALI) method propagated patient-derived organoids (PDOs) from >100 human biopsies or mouse tumors in syngeneic immunocompetent hosts as tumor epithelia with native embedded immune cells (T, B, NK, macrophages). Robust droplet-based, single-cell simultaneous determination of gene expression and immune repertoire indicated that PDO TILs accurately preserved the original tumor T cell receptor (TCR) spectrum. Crucially, human and murine PDOs successfully modeled immune checkpoint blockade (ICB) with anti-PD-1- and/or anti-PD-L1 expanding and activating tumor antigen-specific TILs and eliciting tumor cytotoxicity. Organoid-based propagation of primary tumor epithelium en bloc with endogenous immune stroma should enable immuno-oncology investigations within the TME and facilitate personalized immunotherapy testing.


Assuntos
Modelos Imunológicos , Neoplasias Experimentais/imunologia , Organoides/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Microambiente Tumoral/imunologia , Animais , Antígeno B7-H1/imunologia , Técnicas de Cocultura , Feminino , Humanos , Imunoterapia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Neoplasias/imunologia , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , Organoides/patologia
14.
Clin Plast Surg ; 44(3): 603-610, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28576249

RESUMO

Severe pediatric burns require a multidisciplinary team approach at a specialized pediatric burn center. Special attention must be paid to estimations of total body surface area, fluid resuscitation and metabolic demands, and adequate analgesia and sedation. Long-term effects involve scar management and psychosocial support to the child and their family. Compassionate comprehensive burn care is accomplished by a multidisciplinary team offering healing in the acute setting and preparing the child and family for long-term treatment and care.


Assuntos
Queimaduras/terapia , Adolescente , Fatores Etários , Unidades de Queimados , Queimaduras/complicações , Queimaduras/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Cicatrização
15.
Am Surg ; 82(5): 412-5, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27215721

RESUMO

Increasing reports on the incidental ingestion of metallic bristles from barbeque grill cleaning brushes have been reported. We sought to describe the clinical presentation and grilling habits of patients presenting after ingesting metallic bristles in an attempt to identify risk factors. We performed a chart review of six patients with documented enteric injury from metallic bristles. Subjects were contacted and administered a survey focused on the events surrounding the bristle ingestion. We arranged for in-home visits to inspect the grill and grill brush whenever possible. Of the six subjects identified, three (50%) were male, five (83%) were white, and they ranged in age from 18 to 65 years (mean 42.5). All complained of abdominal pain. All bristles were identified by CT scan. Three patients underwent laparoscopic enterorrhaphy, and two underwent laparotomy. The remaining patients did not require intervention. None had replaced their grill brush in at least two years. Surgeon's awareness of this unusual injury is important to identify and manage this problem. Alternative methods to clean the grill should be sought and grill brushes should be replaced at least every two years.


Assuntos
Corpos Estranhos/epidemiologia , Perfuração Intestinal/etiologia , Intestino Delgado/lesões , Metais/efeitos adversos , Adulto , Distribuição por Idade , Estudos de Coortes , Utensílios de Alimentação e Culinária , Feminino , Corpos Estranhos/prevenção & controle , Corpos Estranhos/cirurgia , Humanos , Incidência , Perfuração Intestinal/epidemiologia , Perfuração Intestinal/cirurgia , Masculino , Pessoa de Meia-Idade , Prevenção Primária , Estudos Retrospectivos , Medição de Risco , Distribuição por Sexo , Texas
16.
Artigo em Inglês | MEDLINE | ID: mdl-26333898
17.
J Trauma Acute Care Surg ; 77(1): 166-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24977773

RESUMO

BACKGROUND: Head injury is the most common cause of neurologic disability and mortality in children. Previous studies have demonstrated that depressed skull fractures (SFs) represent approximately one quarter of all SFs in children and approximately 10% percent of hospital admissions after head injury. We hypothesized that nondepressed SFs (NDSFs) in children are not associated with adverse neurologic outcomes. METHODS: Medical records were reviewed for all children 5 years or younger with SFs who presented to our Level I trauma center during a 4-year period. Data collected included patient demographics, Glasgow Coma Scale (GCS) score at admission, level of consciousness at the time of injury, type of SF (depressed SF vs. NDSF), magnitude of the SF depression, evidence of neurologic deficit, and the requirement for neurosurgical intervention. RESULTS: We evaluated 1,546 injured young children during the study period. From this cohort, 563 had isolated head injury, and 223 of them had SF. Of the SF group, 163 (73%) had NDSFs, of whom 128 (78%) presented with a GCS score of 15. None of the NDSF patients with a GCS score of 15 required neurosurgical intervention or developed any neurologic deficit. Of the remaining 35 patients with NDSF and GCS score less than 15, 7 (20%) had a temporary neurologic deficit that resolved before discharge, 4 (11%) developed a persistent neurologic deficit, and 2 died (6%). CONCLUSION: Children 5 years or younger with NDSFs and a normal neurologic examination result at admission do not develop neurologic deterioration. LEVEL OF EVIDENCE: Epidemiological study, level III.


Assuntos
Fraturas Cranianas/complicações , Fraturas Cranianas/diagnóstico , Criança , Pré-Escolar , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Exame Neurológico , Fraturas Cranianas/terapia
18.
Am J Surg ; 206(6): 1016-22; discussion 1022-3, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24124658

RESUMO

BACKGROUND: Multiple studies have documented a significant decrease in the general surgery workforce in the United States, both rural and urban, for the past 3 decades. This 11-year study evaluates the Texas general surgery workforce at both the state and local level in 2002 and 2012. METHODS: Data were obtained from the Texas Medical Board, the United States Census Bureau/Texas State Library and Archives Commission, and the Texas Department of State Health Services for 2002 and 2012. A benchmark target of 7 general surgeons per 100,000 population was used. RESULTS: During the study period, the Texas population increased 21%, and actively practicing physicians increased 44%. All surgical specialists increased by 26%. General surgeons increased 4%; however, the number of general surgeons per 100,000 population decreased 14% (from 6.7 to 5.8/10(5)). Using the total Texas population for 2012, an additional 329 general surgeons are needed by benchmark standards. However, when analyzed by individual county population, 449 additional general surgeons are needed in the individual counties. These effects were greater in the nonmetropolitan areas of Texas where per capita general surgeons decreased by 21%. CONCLUSIONS: The absolute increase in Texas general surgeons over the past decade has not kept pace with an increase in the Texas population. The general surgery workforce deficit based on the Texas state population underestimates the local workforce shortage, particularly in the nonmetropolitan areas of Texas.


Assuntos
Cirurgia Geral , Mão de Obra em Saúde/estatística & dados numéricos , Médicos/provisão & distribuição , População Rural , Humanos , Texas
19.
Bioorg Med Chem Lett ; 18(18): 5118-22, 2008 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-18722118

RESUMO

Clinical candidate AMG 517 (1) is a potent antagonist toward multiple modes of activation of TRPV1; however, it suffers from poor solubility. Analogs with various substituents at the R region of 3 were prepared to improve the solubility while maintaining the potent TRPV1 activity of 1. Compounds were identified that maintained potency, had good pharmacokinetic properties, and improved solubility relative to 1.


Assuntos
Benzotiazóis/farmacologia , Pirimidinas/farmacologia , Canais de Cátion TRPV/antagonistas & inibidores , Animais , Benzotiazóis/farmacocinética , Técnicas de Química Combinatória , Estrutura Molecular , Pirimidinas/síntese química , Pirimidinas/farmacocinética , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
20.
Am J Surg ; 190(6): 923-6, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16307947

RESUMO

BACKGROUND: A retrospective review of our experience with percutaneous tracheostomy was performed to determine our complication rate and pattern of use since this modality was introduced at our institution. METHODS: A retrospective chart review captured all patients in whom tracheostomy was performed or supervised by a trauma/critical care faculty member. Dates of hospital admission, ICU admission, intubation, discontinuation of mechanical ventilation, type and location of procedure, procedural complications, Injury Severity Score, charges, and patient demographics were collected. Percutaneous tracheostomy (PT) and open tracheostomy (OT) experiences were compared. RESULTS: Three hundred sixty-eight tracheostomies were performed (190 OT and 178 PT). The average time to tracheostomy (TTT) for PT patients decreased from 12.7 to 7.4 days. The average TTT for OT patients remained stable at 14.0 days. The complication rate was 3.5%, with 4 complications (1.5%) associated with OT and 9 complications (5.1%) associated with PT. All complications in the PT group occurred before using a single dilator system. The 9 complications in the PT group occurred among 5 surgeons, all before their 11th attempt. PT saves 444 dollars in charges per procedure. CONCLUSION: OT continues to be a safe method of performing tracheostomies. PT has a steep learning curve but can be mastered quickly. Benefits include a shorter time to tracheostomy, elimination of patient transport, and saving in charges. Initial PT attempts should be supervised by an experienced surgeon.


Assuntos
Traqueostomia/métodos , Feminino , Seguimentos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
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