RESUMEN
INTRODUCTION: Uninsured pediatric trauma patients are at increased risk of poor outcomes. The impact of the Patient Protection and Affordable Care Act (ACA) on pediatric trauma patients has not been studied. We hypothesized that the expansion of Medicaid coverage under the ACA was associated with increased insurance coverage and improved outcomes. METHODS: Retrospective review of patients <18 y old presenting to a level 1 pediatric trauma center 2009-2019. An interrupted time series analysis was performed to assess the impact of Medicaid expansion under the ACA in January 2014. The primary outcome was rate of insurance coverage. Secondary outcomes included in-hospital mortality, disposition, 30-day readmission, length of stay (LOS), and intensive care unit (ICU) LOS. RESULTS: A total of 5645 patients were evaluated, (pre-ACA n = 2,243, post-ACA n = 3402). Expansion of Medicaid was associated with minimal changes on insurance coverage. There a decrease in mortality (RR = 0.96, P = 0.0355) and a slight increase in disposition to a rehabilitation facility (RR = 1.02, P = 0.0341). There was no association with 30-day readmission (RR = 1.02, P = 0.3498). Similarly, expansion of Medicaid was not associated with change in LOS (estimate = -0.00, P = 0.8893). There was a slight decrease in ICU LOS (estimate = -0.03, P < 0.0001). CONCLUSIONS: Medicaid expansion was associated with marginal changes in insurance coverage among pediatric trauma patients. We did not identify significant impacts on patient outcomes.
Asunto(s)
Medicaid , Patient Protection and Affordable Care Act , Niño , Humanos , Cobertura del Seguro , Seguro de Salud , Pacientes no Asegurados , Centros Traumatológicos , Estados UnidosRESUMEN
INTRODUCTION: The Management of Myelomeningocele Study demonstrated that in utero repair of myelomeningocele improved motor outcomes compared with postnatal repair. However, even after in utero repair, many children were still unable to walk. We have previously demonstrated that augmentation of in utero repair with early-gestation placental mesenchymal stromal cells (PMSCs) improves motor outcomes in lambs compared with standard in utero repair. The neuroprotective potential of PMSCs of all gestational ages has not been evaluated previously. METHODS: PMSCs were isolated from discarded first trimester (n = 3), second trimester (n = 3), and term (n = 3) placentas by explant culture. Cytokine array analysis was performed. Secretion of two neurotrophic factors, brain-derived neurotrophic factor and hepatocyte growth factor, was evaluated by enzyme-linked immunosorbent assay. An in vitro neuroprotective assay demonstrated to be associated with in vivo function was performed. RESULTS: All cell lines secreted immunomodulatory and neuroprotective cytokines and secreted the neurotrophic factors evaluated. Increased neuroprotective capabilities relative to no PMSCs were demonstrated in two of the three first trimester cell lines (5.61, 4.96-6.85, P < 0.0001 and 2.67, 1.67-4.12, P = 0.0046), two of the three second trimester cell lines (2.82, 2.45-3.43, P = 0.0004 and 3.25, 2.62-3.93, P < 0.0001), and two of the three term cell lines (2.72, 2.32-2.92, P = 0.0033 and 2.57, 1.41-4.42, P = 0.0055). CONCLUSIONS: We demonstrated variation in neuroprotective function between cell lines and found that some cell lines from each trimester had neuroprotective properties. This potentially expands the donor pool of PMSCs for clinical use. Further in-depth studies are needed to understand potential subtle differences in cell function at different gestational ages.
Asunto(s)
Meningomielocele , Células Madre Mesenquimatosas , Animales , Citocinas/metabolismo , Femenino , Edad Gestacional , Células Madre Mesenquimatosas/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Placenta , Embarazo , OvinosRESUMEN
BACKGROUND: Two weeks' isolation is widely recommended for people commencing treatment for pulmonary tuberculosis (TB). The evidence that this corresponds to clearance of potentially infectious tuberculous mycobacteria in sputum is not well established. This World Health Organization-commissioned review investigated sputum sterilisation dynamics during TB treatment. METHODS AND FINDINGS: For the main analysis, 2 systematic literature searches of OvidSP MEDLINE, Embase, and Global Health, and EBSCO CINAHL Plus were conducted to identify studies with data on TB infectiousness (all studies to search date, 1 December 2017) and all randomised controlled trials (RCTs) for drug-susceptible TB (from 1 January 1990 to search date, 20 February 2018). Included articles reported on patients receiving effective treatment for culture-confirmed drug-susceptible pulmonary TB. The outcome of interest was sputum bacteriological conversion: the proportion of patients having converted by a defined time point or a summary measure of time to conversion, assessed by smear or culture. Any study design with 10 or more particpants was considered. Record sifting and data extraction were performed in duplicate. Random effects meta-analyses were performed. A narrative summary additionally describes the results of a systematic search for data evaluating infectiousness from humans to experimental animals (PubMed, all studies to 27 March 2018). Other evidence on duration of infectiousness-including studies reporting on cough dynamics, human tuberculin skin test conversion, or early bactericidal activity of TB treatments-was outside the scope of this review. The literature search was repeated on 22 November 2020, at the request of the editors, to identify studies published after the previous censor date. Four small studies reporting 3 different outcome measures were identified, which included no data that would alter the findings of the review; they are not included in the meta-analyses. Of 5,290 identified records, 44 were included. Twenty-seven (61%) were RCTs and 17 (39%) were cohort studies. Thirteen studies (30%) reported data from Africa, 12 (27%) from Asia, 6 (14%) from South America, 5 (11%) from North America, and 4 (9%) from Europe. Four studies reported data from multiple continents. Summary estimates suggested smear conversion in 9% of patients at 2 weeks (95% CI 3%-24%, 1 single study [N = 1]), and 82% of patients at 2 months of treatment (95% CI 78%-86%, N = 10). Among baseline smear-positive patients, solid culture conversion occurred by 2 weeks in 5% (95% CI 0%-14%, N = 2), increasing to 88% at 2 months (95% CI 84%-92%, N = 20). At equivalent time points, liquid culture conversion was achieved in 3% (95% CI 1%-16%, N = 1) and 59% (95% CI 47%-70%, N = 8). Significant heterogeneity was observed. Further interrogation of the data to explain this heterogeneity was limited by the lack of disaggregation of results, including by factors such as HIV status, baseline smear status, and the presence or absence of lung cavitation. CONCLUSIONS: This systematic review found that most patients remained culture positive at 2 weeks of TB treatment, challenging the view that individuals are not infectious after this interval. Culture positivity is, however, only 1 component of infectiousness, with reduced cough frequency and aerosol generation after TB treatment initiation likely to also be important. Studies that integrate our findings with data on cough dynamics could provide a more complete perspective on potential transmission of Mycobacterium tuberculosis by individuals on treatment. TRIAL REGISTRATION: Systematic review registration: PROSPERO 85226.
Asunto(s)
Mycobacterium tuberculosis/fisiología , Esputo/microbiología , Tuberculosis Pulmonar/terapia , HumanosRESUMEN
BACKGROUND: Limited English proficiency (LEP) is associated with decreased access to healthcare. We hypothesized that LEP children with appendicitis would experience more delays in care than EP children. METHODS: Retrospective review of patients <18 y presenting to a tertiary pediatric hospital July 2014-July 2019 with appendicitis. LEP patients were compared to EP patients. The primary outcome was appendiceal perforation. Secondary outcomes included prior pediatrician or emergency department (ED) visits without definitive management, duration of symptoms, length of stay (LOS), initial operative or non-operative management, time from presentation to operation and return to the ED within 30 d. Multivariable regression was performed to evaluate LEP as a predictor of study outcomes. RESULTS: A total of 893 patients with appendicitis were identified, 15.6% (n = 140) had LEP. On multivariate regression LEP was not a significant predictor of appendiceal perforation (AOR 1.20, 95% CI 0.79, 1.80, P = 0.390). LEP was a significant predictor of a prior ED or pediatrician visit without definitive management (AOR 2.05, 95 % CI 1.05, 3.98, P= 0.034) and longer LOS (Coefficient 1.01, 95% CI 0.41, 1.61, P= 0.001). LEP was associated with a minimal increase in duration of pain prior to presentation that was not clinically significant and was not associated with initial operative or non-operative management or a significantly longer time between presentation and operation. CONCLUSIONS: LEP children did not experience higher rates of appendiceal perforation at our institution, but were more frequently initially evaluated by a pediatrician or at an ED and discharged without definitive management and had longer LOS.
Asunto(s)
Apendicitis , Dominio Limitado del Inglés , Apendicitis/diagnóstico , Apendicitis/cirugía , Niño , Barreras de Comunicación , Servicio de Urgencia en Hospital , Hospitales Pediátricos , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: The July Phenomenon describes concerns that patients presenting early in the academic year experience worse outcomes. Given the standardized approach to pediatric trauma patients, we hypothesized that the July Phenomenon would not impact morbidity or mortality. METHODS: A retrospective review of patients ≤16 Y presenting to a level I pediatric trauma center between March 2009 and March2019 was performed. Pediatric patients admitted during the study period were compared for differences in outcome by month of presentation. The primary outcome was mortality. Secondary outcomes were complications, and length of emergency department, hospital and Intensive Care Unit stay. Multivariable regression was used to evaluate the effect of month of admission on outcomes. RESULTS: A total of 6,135 patients were evaluated, with 605 patients presenting in July. Univariate analysis failed to demonstrate consistently increased mortality, complications, or length of emergency department, hospital or Intensive Care Unit stay in July compared to months later in the academic year. On multivariate analysis, admission in July was not an independent predictor of worse outcomes. CONCLUSIONS: In this level I pediatric trauma center, pediatric trauma patients presenting earlier in the academic year have similar outcomes to those presenting later, and there is no evidence of a July Phenomenon in this population.
Asunto(s)
Hospitalización , Centros Traumatológicos , Niño , Servicio de Urgencia en Hospital , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Análisis Multivariante , Estudios RetrospectivosRESUMEN
BACKGROUND: Traumatic abdominal wall hernia (TAWH) in children is an uncommon injury and most commonly occurs after blunt abdominal trauma. There is no consensus on the management of these rare cases. We performed a systematic review of the literature to describe injuries, management, and outcomes. MATERIALS AND METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines, a systematic literature search of PubMed, Web of Science, Embase, and Google Scholar was performed to identify English-language publications of blunt TAWH in patients <18 y old. Conflicts were resolved by consensus. Data were collected on demographics, associated injuries, management, and outcomes. RESULTS: A total of 71 articles were reviewed with 100 cases of TAWH. A total of 82.5% of patients were male, and the median age was 9 y old (range 2-15). Injury by bicycle handlebars was most common (72%) followed by motor vehicle collision (14%). Forty patients had intraabdominal injuries, most commonly bowel (70%) or mesentery (37.5%). Rate of intraabdominal injury was significantly higher in patients with injuries due to nonbicycle handlebar injuries when compared with bicycle handlebar injuries (60.7% versus 33.3%, P = 0.02). Most patients were managed operatively (85%), most commonly via laparotomy (68/85, 80%), with six laparoscopic repairs and five laparoscopic converted to open repairs. There were three reported complications and no recurrences over a median of follow-up of 5 mo in patients who underwent repair. CONCLUSIONS: Pediatric TAWH is a rare injury with a high rate of intraabdominal injuries, particularly when due to high-impact mechanisms such as motor vehicle collision. Although open repair is more commonly performed, laparoscopic repair has been described with success. Recurrence rates appear low, but follow-up has been short term.
Asunto(s)
Traumatismos Abdominales/cirugía , Hernia Abdominal/cirugía , Traumatismos Abdominales/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Hernia Abdominal/diagnóstico , Humanos , Laparoscopía , Masculino , Complicaciones Posoperatorias/epidemiología , RecurrenciaRESUMEN
BACKGROUND: Myelomeningocele (MMC) is the congenital failure of neural tube closure in utero, for which the standard of care is prenatal surgical repair. We developed clinical-grade placental mesenchymal stromal cells seeded on a dural extracellular matrix (PMSC-ECM), which have been shown to improve motor outcomes in preclinical ovine models. To evaluate the long-term safety of this product prior to use in a clinical trial, we conducted safety testing in a murine model. METHODS: Clinical grade PMSCs obtained from donor human placentas were seeded onto a 6 mm diameter ECM at a density of 3 × 105 cells/cm2. Immunodeficient mice were randomized to receive either an ECM only or PMSC-ECM administered into a subcutaneous pocket. Mice were monitored for tumor formation until two study endpoints: 4 wk and 6 mo. Pathology and histology on all tissues was performed to evaluate for tumors. Quantitative polymerase chain reaction (qPCR) was performed to evaluate for the presence of human DNA, which would indicate persistence of PMSCs. RESULTS: Fifty-four mice were included; 13 received ECM only and 14 received PMSC-ECM in both the 4-wk and 6-mo groups. No mice had gross or microscopic evidence of tumor development. A nodular focus of mature fibrous connective tissue was identified at the subcutaneous implantation pocket in the majority of mice with no significant difference between ECM only and PMSC-ECM groups (P = 0.32 at 4 wk, P > 0.99 at 6 mo). Additionally, no human DNA was detected by qPCR in any mice at either time point. CONCLUSIONS: Subcutaneous implantation of the PMSC-ECM product did not result in tumor formation and we found no evidence that PMSCs persisted. These results support the safety of the PMSC-ECM product for use in a Phase 1/2a human clinical trial evaluating fetal MMC repair augmented with PMSC-ECM.
Asunto(s)
Meningomielocele , Células Madre Mesenquimatosas , Animales , Matriz Extracelular/patología , Femenino , Feto/cirugía , Meningomielocele/cirugía , Ratones , Placenta , EmbarazoRESUMEN
BACKGROUND: Surgeons frequently care for children who have sustained gunshot wounds (GSWs). However, firearm safety education is not a focus in general surgery training. We hypothesised that firearm safety discussions do not routinely take place when children present to a trauma centre with a GSW. METHOD: A retrospective review of patients <18 years presenting with GSWs to a level 1 paediatric trauma centre from 2009 to 2019 was performed. The primary outcome was discussion of firearm safety with the patient or family. The secondary outcome was notification of child protective services (CPS). RESULTS: A total of 226 patients with GSWs were identified, 22% were unintentional and 63% were assault. Firearm safety discussions took place in 10 cases (4.4%). Firearm safety discussions were more likely to occur after unintentional injuries compared with other mechanisms (16.0% vs 1.3%, p<0.001). CPS was contacted in 29 cases (13%). CPS notification was more likely for unintentional injuries compared with other mechanisms (40% vs 3.9%, p<0.001) and for younger patients (7 years vs 15 years, p<0.001). CONCLUSION: At a paediatric trauma centre, firearm safety discussions occurred in 4.4% of cases of children presenting with a GSW. There is a significant room for improvement in providing safety education interventions.
Asunto(s)
Lesiones Accidentales , Armas de Fuego , Heridas por Arma de Fuego , Niño , Humanos , Estudios Retrospectivos , Centros Traumatológicos , Heridas por Arma de Fuego/epidemiología , Heridas por Arma de Fuego/prevención & controlRESUMEN
BACKGROUND: Recent work has demonstrated that an accelerated pathway for pediatric patients with blunt solid organ injuries is safe; however, this is not well-studied in a dual trauma center. We hypothesized that implementation of an accelerated pathway would decrease length of stay (LOS) and hospitalization cost without increased mortality. METHODS: Retrospective review of patients < 15 years presenting to a dual level 1 trauma center between 2015 and 2020 with traumatic blunt liver and splenic injuries. Patients presenting pre- and post-protocol implementation were compared. The primary outcome was total hospital LOS. Secondary outcomes were number of lab draws, intensive care unit (ICU) LOS, cost of hospitalization, readmissions within 30 days, and mortality. RESULTS: 103 patients were evaluated, 67 pre-protocol and 63 post-protocol. LOS was significantly shorter post-protocol (2 days vs. 4 days, p < 0.001). The ICU LOS was unchanged. There was a decrease in direct hospitalization cost per patient from $6,246 pre-protocol to $4,294 post-protocol (p = 0.001). There was one readmission post-protocol and none pre-protocol. There were no deaths. CONCLUSION: Implementation of an accelerated pathway for management of blunt solid organ injury at a dual trauma center was associated with decreased LOS and decreased costs with no increased morbidity or mortality.
Asunto(s)
Traumatismos Abdominales/terapia , Tiempo de Internación/tendencias , Centros Traumatológicos/estadística & datos numéricos , Heridas no Penetrantes/terapia , Traumatismos Abdominales/epidemiología , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios Retrospectivos , Estados Unidos/epidemiología , Heridas no Penetrantes/epidemiologíaRESUMEN
BACKGROUND: The inherent morbidity associated with fetal ovine models of myelomeningocele (MMC) has created challenges for long-term survival of lambs. We aimed to develop a fetal ovine surgical spinal exposure model which could be used to evaluate long-term safety after direct spinal cord application of novel therapeutics for augmentation of in utero MMC repair. METHODS: At gestational age (GA) 100-106, fetal lambs underwent surgical intervention. Laminectomy of L5-L6 was performed, dura was removed, and an experimental product was directly applied to the spinal cord. Paraspinal muscles and skin were closed and the fetus was returned to the uterus. Lambs were delivered via cesarean section at GA 140-142. Lambs were survived for 3 months with regular evaluation of motor function by the sheep locomotor rating scale. Spinal angulation was evaluated by magnetic resonance imaging at 2 weeks and 3 months. RESULTS: Five fetal surgical intervention lambs and 6 control lambs who did not undergo surgical intervention were included. All lambs survived to the study endpoint of 3 months. No lambs had motor function abnormalities or increased spinal angulation. CONCLUSION: This model allows for long-term survival after fetal spinal cord exposure with product application directly onto the spinal cord.
Asunto(s)
Cesárea , Meningomielocele , Animales , Modelos Animales de Enfermedad , Femenino , Feto , Meningomielocele/diagnóstico por imagen , Meningomielocele/cirugía , Embarazo , Ovinos , Médula Espinal/diagnóstico por imagenRESUMEN
Microenvironments play a significant part in understanding the post-mortem interval in forensic taphonomy. Recently, the value of weathering factors in relation to obtaining a PMI has been investigated further. In this study, observations were made to calculate the length of time it takes for three different bone elements (femur, rib, and scapula) to bleach in a UK summer and winter. This research also investigated whether there were any physicochemical modifications to the bone caused by bleaching. Porcine femora, scapulae, and ribs were placed into open and shaded areas of an outdoor research facility located in Oxfordshire, UK, during summer (July-Sep) and winter months (Dec-Mar). The specimens were monitored at 3-week intervals using photography, and an observational scoring method was developed to quantify the extent of bleaching. As temperatures are typically much lower in the UK compared with warmer climates, a controlled indoor-simulated desert experiment was also undertaken to be used as a control. This allowed sun bleaching and changes to the bone chemistry to be monitored in a controlled, high-UV environment for comparison with the UK outdoor experiments. Fourier transform infrared spectroscopy (FTIR) was employed to analyze physicochemical modifications to both the mineral and organic components of the bone. The FTIR was used to calculate crystallinity index (CI), mineral to organic ratio, and the relative amount of carbonate concentrations. Weather data was collected and a positive correlation was found between both ultraviolet (UV) levels and accumulated degree days (ADD) when compared with observational bleaching scores. Bleaching (whitening) of the bone samples occurred in both seasons but at different rates, with the bleaching process occurring at a slower rate in winter. During summer, the initial bleaching process was evident at 6 weeks, and by 9 weeks, the bones were an off-white colour. During the winter period, whitening of the bone started at 9 weeks; however, only the scapula and rib samples displayed a similar off-white colour. This colouration was observed at 13 weeks rather than at 9 weeks. The desert simulation samples started bleaching in a similar pattern to the outdoor samples after 1 week but the bones did not fully bleach. The bone chemistry, based on physicochemical properties obtained from the FTIR, showed a significant statistical difference between the simulated desert and winter season when compared against a control sample. For the winter samples, the mineral to organic ratio was significantly higher than that in the control, suggesting a reduction in the proportion of organic. For the samples in the simulated desert environment, the crystallinity index was significantly higher than that in the control samples, suggesting an increase in crystallinity. The results of this experiment support the fact that it is possible to achieve bleaching in a UK environment and that the minimal time frame for this to occur differs in seasons.
Asunto(s)
Huesos/química , Fotoblanqueo , Estaciones del Año , Luz Solar , Temperatura , Animales , Clima Desértico , Fémur/química , Modelos Animales , Cambios Post Mortem , Costillas/química , Escápula/química , Espectroscopía Infrarroja por Transformada de Fourier , Porcinos , Rayos Ultravioleta , Reino UnidoRESUMEN
BACKGROUND: Fetal repair of myelomeningocele (MMC) with placental mesenchymal stromal cells (PMSCs) rescues ambulation in the ovine model up to 48 h postnatally. Outcomes past 48 h are unknown as MMC lambs have not been survived past this timepoint. OBJECTIVE: We aimed to survive lambs for 6 months following the fetal repair of MMC with PMSCs. METHODS: Fetal MMC lambs were repaired with PMSCs. Lambs received either no additional treatment or postnatal bracing and physical therapy (B/PT). Motor function was assessed with the sheep locomotor rating (SLR). Lambs with an SLR of 15 at birth were survived for 6 months or until a decline in SLR less than 15, whichever came first. All lambs underwent a perimortem MRI. RESULTS: The lambs with no postnatal treatment (n = 2) had SLR declines to 7 and 13 at 29 and 65 days, respectively, and were euthanized. These lambs had a spinal angulation of 57° and 47°, respectively. The B/PT lamb (n = 1) survived for 6 months with a sustained SLR of 15 and a lumbar angulation of 42°. CONCLUSION: Postnatal physical therapy and bracing counteracted the inherent morbidity of the absent paraspinal muscles in the ovine MMC model allowing for survival and maintenance of rescued motor function of the prenatally treated lamb up to 6 months.
Asunto(s)
Meningomielocele , Células Madre Mesenquimatosas , Animales , Femenino , Feto , Meningomielocele/cirugía , Proyectos Piloto , Placenta/diagnóstico por imagen , Embarazo , OvinosRESUMEN
In order to characterize the oxidation of metallic surfaces, the reactions of O2 with a number of Al(x)(-) and, for the first time, Ga(x)(-) clusters as molecular models have been investigated, and the results are presented here for x = 9-14. The rate coefficients were determined with FT-ICR mass spectrometry under single-collision conditions at O2 pressures of ~10(-8) mbar. In this way, the qualitatively known differences in the reactivities of the even- and odd-numbered clusters toward O2 could be quantified experimentally. To obtain information about the elementary steps, we additionally performed density functional theory calculations. The results show that for both even- and odd-numbered clusters the formation of the most stable dioxide species, [M(x)O2](-), proceeds via the less stable peroxo species, [M(x)(+)···O2(2-)](-), which contains M-O-O-M moieties. We conclude that the formation of these peroxo intermediates may be a reason for the decreased reactivity of the metal clusters toward O2. This could be one of the main reasons why O2 reactions with metal surfaces proceed more slowly than Cl2 reactions with such surfaces, even though O2 reactions with both Al metal and Al clusters are more exothermic than are reactions of Cl2 with them. Furthermore, our results indicate that the spin-forbidden reactions of (3)O2 with closed-shell clusters and the spin-allowed reactions with open-shell clusters to give singlet [M(x)(+)···O2(2-)](-) are the root cause for the observed even/odd differences in reactivity.
RESUMEN
BACKGROUND & AIMS: Interleukin (IL)-8 has an important role in initiating inflammation in humans, attracting immune cells such as neutrophils through their receptors CXCR1 and CXCR2. IL-8 has been proposed to contribute to chronic inflammation and cancer. However, mice do not have the IL-8 gene, so human cancer cell lines and xenograft studies have been used to study the role of IL-8 in colon and gastric carcinogenesis. We generated mice that carry a bacterial artificial chromosome that encompasses the entire human IL-8 gene, including its regulatory elements (IL-8Tg mice). METHODS: We studied the effects of IL-8 expression in APCmin(+/-) mice and IL-8Tg mice given azoxymethane and dextran sodium sulfate (DSS). We also examined the effects of IL-8 expression in gastric cancer in INS-GAS mice that overexpress gastrin and IL-8Tg mice infected with Helicobacter felis. RESULTS: In IL-8Tg mice, expression of human IL-8 was controlled by its own regulatory elements, with virtually no messenger RNA or protein detectable under basal conditions. IL-8 was strongly up-regulated on systemic or local inflammatory stimulation, increasing mobilization of immature CD11b(+)Gr-1(+) myeloid cells (IMCs) with thioglycolate-induced peritonitis, DSS-induced colitis, and H. felis-induced gastritis. IL-8 was increased in colorectal tumors from patients and IL-8Tg mice compared with nontumor tissues. IL-8Tg mice developed more tumors than wild-type mice following administration of azoxymethane and DSS. Expression of IL-8 increased tumorigenesis in APCmin(+/-) mice compared with APCmin(+/-) mice that lack IL-8; this was associated with increased numbers of IMCs and angiogenesis in the tumors. CONCLUSIONS: IL-8 contributes to gastrointestinal carcinogenesis by mobilizing IMCs and might be a therapeutic target for gastrointestinal cancers.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Transformación Celular Neoplásica/metabolismo , Colitis/metabolismo , Neoplasias del Colon/metabolismo , Gastritis/metabolismo , Interleucina-8/metabolismo , Células Mieloides/efectos de los fármacos , ARN Mensajero/metabolismo , Animales , Azoximetano , Línea Celular Tumoral , Colitis/inducido químicamente , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/patología , Células Dendríticas/metabolismo , Sulfato de Dextran , Gastritis/microbiología , Infecciones por Helicobacter/complicaciones , Helicobacter felis , Humanos , Interleucina-8/genética , Interleucina-8/farmacología , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Ratones , Ratones Transgénicos , Células Mieloides/metabolismo , Cultivo Primario de Células , Carga Tumoral , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: Pediatric patients treated at trauma centers demonstrate improved outcomes, but investigation of optimal resource utilization surrounding the transfer is ongoing. We evaluated characteristics of operative pediatric trauma transfer patients for resource optimization. METHODS: A retrospective review of pediatric trauma patients transferred to a level 1 pediatric trauma center from 2009 to 2019 was performed. Patients were categorized by initial operative subspecialty. RESULTS: Of 4164 transferred patients, 33.9 â% required operative intervention. 65 â% of operations were performed on orthopedic patients, who were significantly less injured compared to other patients. General surgery patients were more likely to undergo surgery on day of transfer compared to orthopedic patients (39.4%vs 56.3 â%, OR 2.0, CI 1.4-2.8). CONCLUSIONS: One-third of pediatric trauma transfer patients required operative intervention. The majority of surgeries were on orthopedic patients, who were less likely to undergo surgery on day of transfer. Critical evaluation of this patient population is required to safely utilize a less resource-intensive transfer process.
Asunto(s)
Ortopedia , Herida Quirúrgica , Humanos , Niño , Centros Traumatológicos , Estudios Retrospectivos , Transferencia de PacientesRESUMEN
Altered branching and aberrant expression of N-linked glycans is known to be associated with disease states such as cancer. However, the complexity of determining such variations hinders the development of specific glycomic approaches for assessing disease states. Here, we examine a combination of ion mobility spectrometry (IMS) and mass spectrometry (MS) measurements, with principal component analysis (PCA) for characterizing serum N-linked glycans from 81 individuals: 28 with cirrhosis of the liver, 25 with liver cancer, and 28 apparently healthy. Supervised PCA of combined ion-mobility profiles for several, to as many as 10 different mass-to-charge ratios for glycan ions, improves the delineation of diseased states. This extends an earlier study [J. Proteome Res.2008, 7, 1109-1117] of isomers associated with a single glycan (S(1)H(5)N(4)) in which PCA analysis of the IMS profiles appeared to differentiate the liver cancer group from the other samples. Although performed on a limited number of test subjects, the combination of IMS-MS for different combinations of ions and multivariate PCA analysis shows promise for characterizing disease states.
Asunto(s)
Cirrosis Hepática/sangre , Neoplasias Hepáticas/sangre , Polisacáridos/sangre , Espectrometría de Masa por Ionización de Electrospray/métodos , Adolescente , Adulto , Biología Computacional/métodos , Glicoproteínas/sangre , Glicoproteínas/química , Humanos , Polisacáridos/química , Polisacáridos/clasificación , Análisis de Componente Principal , Estadísticas no Paramétricas , Espectrometría de Masas en TándemRESUMEN
Introduction: Firearm injuries are a major public health concern. Safe firearm storage is recommended by multiple medical organizations. However, rates of firearm safety counseling are particularly low among trauma providers. Educational initiatives for other provider groups have proven to be effective. We hypothesized that educating trauma providers to offer safety counseling would be similarly effective. Methods: We developed a didactic session around safe firearm storage counseling for trauma providers consisting of a lecture followed by an interactive session with standardized patients. Session participants completed pre- and postsurveys evaluating their knowledge about firearm storage, self-efficacy in providing firearm storage counseling, and attitudes towards firearm safety. We compared differences between pre- and postsurvey data using chi-square tests. Results: The didactic session was delivered to target trauma providers: three trauma nurse practitioners, 42 general surgery residents, and 26 emergency medicine residents. After the session, participants were more likely to know the optimal way to safely store a firearm and to be confident in effectively counseling patients about safe firearm storage. Learners were not more likely to believe that providers have a responsibility to counsel patients on firearm safety. Discussion: A didactic session on safe firearm storage counseling was associated with increased rates of knowledge and self-efficacy. The session did not change attitudes among trauma providers, although, prior to the session, most providers already believed they had a responsibility to counsel patients on safe firearm storage. Similar curricula should be piloted at other trauma centers.
Asunto(s)
Medicina de Emergencia , Armas de Fuego , Heridas por Arma de Fuego , Consejo , Curriculum , Humanos , Heridas por Arma de Fuego/prevención & controlRESUMEN
BACKGROUND: Suicide is the second most common cause of death among adolescents and young adults. In the pediatric population, gunshot wounds (GSWs) and hangings are common mechanisms of pediatric suicide. Comorbid psychiatric illness is prevalent in this population, but psychiatric resource utilization after self-inflicted traumatic injury is not well characterized. METHODS: We analyzed patients < 18 years old presenting to a level 1 pediatric trauma center after suicide attempt by GSW, hanging, or jumping from a height from 2009 to 2019. The primary outcome was psychiatric resource utilization. Secondary outcomes included prior emergency department (ED) visits to identify prior opportunities for intervention. RESULTS: Of 6538 pediatric trauma patients, there were 219 GSWs, 7 hangings, and 7 jumps from height, for a total of 233 patients. Of these, 14 presented following a suicide attempt (four GSWs, six hangings, and four jumps, total 6.0%). Half of these patients died due to their injuries. Self-inflicted GSWs had the highest mortality (75%). Most surviving patients were placed on involuntary psychiatric holds (n = 5/7, 71.4%), and three patients were discharged to an inpatient psychiatric hospital (n = 3/7, 42.9%). Five of the 14 patients had prior ED visits (35.7%), and of these, 60% were for suicidal ideation or suicide attempts. CONCLUSIONS: Among pediatric trauma patients, suicide attempts are rare, but are highly lethal, with the highest mortality rate seen in self-inflicted GSWs. Psychiatric resource utilization is high both during and after the hospitalization. Prior ED visits may represent opportunities for depression and suicidality screening in this at-risk population.
RESUMEN
BACKGROUND: While fetal repair of myelomeningocele (MMC) revolutionized management, many children are still unable to walk independently. Preclinical studies demonstrated that research-grade placental mesenchymal stromal cells (PMSCs) prevent paralysis in fetal ovine MMC, however this had not been replicated with clinical-grade cells that could be used in an upcoming human clinical trial. We tested clinical-grade PMSCs seeded on an extracellular matrix (PMSC-ECM) in the gold standard fetal ovine model of MMC. METHODS: Thirty-five ovine fetuses underwent MMC defect creation at a median of 76 days gestational age, and defect repair at 101 days gestational age with application of clinical-grade PMSC-ECM (3 × 105 cells/cm2, n = 12 fetuses), research-grade PMSC-ECM (3 × 105 cells/cm2, three cell lines with n = 6 (Group 1), n = 6 (Group 2), and n = 3 (Group 3) fetuses, respectively) or ECM without PMSCs (n = 8 fetuses). Three normal lambs underwent no surgical interventions. The primary outcome was motor function measured by the Sheep Locomotor Rating scale (SLR, range 0: complete paralysis to 15: normal ambulation) at 24 h of life. Correlation of lumbar spine large neuron density with SLR was evaluated. RESULTS: Clinical-grade PMSC-ECM lambs had significantly better motor function than ECM-only lambs (SLR 14.5 vs. 6.5, p = 0.04) and were similar to normal lambs (14.5 vs. 15, p = 0.2) and research-grade PMSC-ECM lambs (Group 1: 14.5 vs. 15, p = 0.63; Group 2: 14.5 vs. 14.5, p = 0.86; Group 3: 14.5 vs. 15, p = 0.50). Lumbar spine large neuron density was strongly correlated with motor function (r = 0.753, p<0.001). CONCLUSIONS: Clinical-grade placental mesenchymal stromal cells seeded on an extracellular matrix rescued ambulation in a fetal ovine myelomeningocele model. Lumbar spine large neuron density correlated with motor function, suggesting a neuroprotective effect of the PMSC-ECM in prevention of paralysis. A first-in-human clinical trial of PMSCs in human fetal myelomeningocele repair is underway.