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BACKGROUND: Patients with symptomatic cholelithiasis are often discharged from the Emergency Department (ED) and asked to follow-up for elective cholecystectomy. We aimed to identify the social determinants of health (SDOH) that serve as barriers to elective cholecystectomy and to assess the associated impact on patient outcomes. METHODS: We conducted a multi-institutional, retrospective cohort study of patients discharged from the ED with symptomatic cholelithiasis. Univariable logistic regression was used to assess for variables associated with re-presenting to the ED rather than for elective cholecystectomy. P values â< â0.05 identified significance. RESULTS: Univariate analysis identified lack of a primary care physician, Black race, self-pay, language other than English as the primary language, and unemployed status to be independently associated with re-presentation to the ED for biliary disease. CONCLUSIONS: Socially disadvantaged populations would benefit from surgery at the time of presentation to the ED versus being sent home for elective follow-up.
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PURPOSE: Previous reports in the literature demonstrate racial and ethnic disparities for children diagnosed with acute appendicitis, with minorities experiencing worse outcomes. At our institution, we have developed an evidence based patient driven protocol for children following laparoscopic appendectomy. However, the influence of such protocol on mitigating racial and ethnic disparities in outcomes remains unknown. The purpose of our study is to assess the impact of our protocol by evaluating the influence of race and ethnicity on surgical outcomes among children treated for acute appendicitis. MATERIAL AND METHODS: A retrospective review of prospectively collected data was conducted. Children undergoing a laparoscopic appendectomy at our freestanding children's hospital between December 2015 and July 2017 were included. Demographic data, post-operative length of stay, same day discharge rates and hospital readmission rates were abstracted from patient medical records. Patients were classified by their race and ethnic background. Comparative analysis was performed in STATA with a p value <.05 determined as significant. RESULTS: A total of 786 children were included, with the majority being either White (70%, nâ¯=â¯547), Black (8%, nâ¯=â¯62) or Hispanic (17%, nâ¯=â¯133); 569 patients (72%) were found to have non-perforated appendicitis. There was no statistically significant difference in the rates of same day discharge among White, Black or Hispanic children respectively (88% vs. 77% vs. 86%, pâ¯=â¯.126). Of the 217 children with perforated appendicitis, Hispanic children had increased rates of perforation (41%, nâ¯=â¯55) compared to White and Black children respectively (23%, nâ¯=â¯128 and 29%, nâ¯=â¯18, pâ¯=â¯.001). However, average post-operative length of stay were similar among White, Black and Hispanic children (96â¯h vs. 95â¯h vs. 98â¯h, pâ¯=â¯.015). On multivariate analysis, the only significant risk factor for an elevated post-operative length of stay was the presence of a perforation. CONCLUSION: Our evidence based patient driven protocol effectively mitigates racial and ethnic disparities found in children with acute appendicitis. Further prospective investigation into the role of such patient-driven protocols to mitigate healthcare disparities is warranted. LEVELS OF EVIDENCE: Therapeutic study; Level 3.
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Apendicitis , Enfermedad Aguda , Apendicectomía , Apendicitis/cirugía , Niño , Humanos , Tiempo de Internación , Readmisión del Paciente , Estudios RetrospectivosRESUMEN
BACKGROUND: The preferred method of dialysis for children is chronic peritoneal dialysis (CPD), and these children may require delayed gastrostomy tube (GT) placement. Investigators have reported a high risk of fungal peritonitis, early bacterial peritonitis, and catheter loss when percutaneous endoscopic gastrostomy is performed in children already undergoing CPD. Current International Society for Peritoneal Dialysis guidelines recommend only open GT for these patients. We sought to report the safety of laparoscopic gastrostomy (LG) among children already receiving PD. MATERIALS AND METHODS: We conducted a retrospective chart review of children who had initiated CPD before GT placement between 2010 and 2017 at our pediatric hospital. Demographic data, clinical details, and peritonitis rates were recorded. Peritonitis was defined as peritoneal WBC count >100/mm3 and >50% neutrophils, with or without a positive peritoneal culture. RESULTS: Twenty-three subjects had both undergone CPD and had a GT placed in the study period. Of these, 13 had a GT placed after CPD had been initiated. One of these was excluded for open technique and another excluded because of no overlap of GT and PD catheter, leaving 11 for analysis. Median age at the time of LG was 1.32 y and median weight-for-age z-score was -1.86 (IQR -2.9, -1.3). Median days to PD catheter and GT use after LG were 2 (range 0-4) and 1 (range 0-2). Median weight z-score change at 90 d was +0.5 (IQR -0.1, +0.9). All patients received antifungal and antibiotic coverage at time of GT placement. No subjects developed fungal peritonitis or early bacterial peritonitis, although one developed bacterial peritonitis within 30 d. The overall rate of peritonitis after laparoscopic gastrostomy tube was 0.35 episodes/patient-year. This was similar to a rate of 0.45 episodes/patient-year during PD but before laparoscopic gastrostomy tube in the same patients (P = 0.679). Four subjects required periods of hemodialysis, two of which were because of PD catheter removal due to infection. One of the latter was due to a relapse of pre-LG peritonitis and the patient later resumed PD. The other was due to remote post-LG peritonitis and the patient continued hemodialysis until renal transplant, both after 6 mo. CONCLUSIONS: We found that, in children already receiving PD, LG is similar in safety profile, efficacy, and technical principle to open gastrostomy. LG is therefore an appropriate and safe alternative to open gastrostomy in this setting.
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Gastrostomía/efectos adversos , Laparoscopía/efectos adversos , Diálisis Peritoneal , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Atención Perioperativa , Peritonitis/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Lung biopsy is part of the diagnostic workup for multiple diseases. Although the morbidity of the procedure has decreased with the use of thoracoscopy, lung biopsy still holds substantial risk for patients. Therefore, we evaluated the likelihood of lung biopsies impacting treatment compared to complications. MATERIAL AND METHODS: This was a single-institution, retrospective chart review of patients less than aged 18 y undergoing lung biopsy from 2010 to 2016. Details of demographics, hospital course, adverse events, complications, pathology, and follow-up were recorded. All values are reported as medians with interquartile range. RESULTS: Thirty-seven patients met inclusion criteria. Median age was 7 y old (interquartile range 1.4, 15). Eighty-seven percent (33) of biopsies were performed thoracoscopically, with a 3% conversion rate. Adverse events occurred in 25% (9) of cases with the majority involving prolonged respiratory failure (n = 7). Complications occurred in 16% (6) of cases including pneumothorax (13%, n = 5) and cardiac arrest (3%, n = 1). A third of these complications (n = 2) required reoperation, and both were decompressions of tension pneumothoraces. Pathology established a diagnosis in 62% (n = 23) of cases, yet treatment was changed in only 43% of cases. No preoperative variables were associated with the pathology establishing a diagnosis or changing treatment. CONCLUSIONS: Lung biopsy for questionable pulmonary disease changed treatment in less than half of cases, with significant perioperative morbidity. Careful consideration should therefore be given to who would benefit most from lung biopsy.
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Toma de Decisiones Clínicas , Enfermedades Pulmonares/diagnóstico , Complicaciones Posoperatorias/epidemiología , Toracoscopía/efectos adversos , Adolescente , Biopsia/efectos adversos , Biopsia/métodos , Niño , Preescolar , Estudios de Seguimiento , Humanos , Lactante , Pulmón/patología , Pulmón/cirugía , Enfermedades Pulmonares/patología , Enfermedades Pulmonares/terapia , Complicaciones Posoperatorias/etiología , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo , Toracoscopía/métodosRESUMEN
BACKGROUND: In some institutions, urinary catheters (UCs) have been placed in all patients receiving opioid patient-controlled analgesia (PCA) because of the increased incidence of urinary retention. Our institutional data demonstrated no UC replacements in 48 children who had PCA for perforated appendicitis who had their catheters removed before discontinuation of the PCA. As part of a quality improvement initiative, we discontinued the practice of requiring UC with PCA for perforated appendicitis. MATERIALS AND METHODS: A prospective list of patients with perforated appendicitis was maintained. Data were gathered regarding 60 consecutive patients. UC placement was allowed for specific indications including urinary retention and surgeon discretion. RESULTS: Sixteen patients (27%) received a UC with 14 of these being placed in the operating room (OR). Two UCs were placed outside the OR for urinary retention. Patients who underwent UC placement in the OR weighed significantly more than those who did not (33 versus 42 kg, P = 0.05). No patients required replacement of the catheter once removed. There were no postoperative urinary tract infections. Median PCA duration was 68 h (50, 98) for patients with UC placed in the OR compared with 60 h (47, 78) (P = 0.42). Median postoperative length of stay for patients with UC placed in the OR was 95 h (76, 140) compared with 90 h (70, 113) (P = 0.09). CONCLUSIONS: UC can be withheld from patients with perforated appendicitis who are placed on PCA with a very low placement rate. UC placement at time of operation did not lengthen time receiving PCA or length of stay.
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Analgesia Controlada por el Paciente/efectos adversos , Apendicectomía/efectos adversos , Apendicitis/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Retención Urinaria/prevención & control , Adolescente , Analgésicos Opioides/administración & dosificación , Catéteres de Permanencia/efectos adversos , Niño , Preescolar , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Dolor Postoperatorio/etiología , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Cateterismo Urinario/efectos adversos , Cateterismo Urinario/instrumentación , Cateterismo Urinario/normas , Catéteres Urinarios/efectos adversos , Retención Urinaria/etiologíaRESUMEN
PURPOSE: Neonatal exploratory laparotomies are often performed with a transumbilical incision in our institution, so umbilical ostomy placement has become more common. The purpose of our study is to evaluate the outcomes of neonates with ostomy placement at the umbilicus in comparison to more traditional stoma locations. MATERIAL AND METHODS: Retrospective study of neonates that underwent an exploratory laparotomy with ostomy creation between January 2010 and September 2015. Demographics, presentation, feedings, ostomy position, postoperative complications, and outcomes were collected. Comparative analysis was performed in STATA with P-value <.05 determined as significant. Results reported as means ± standard deviation and medians with interquartile ranges. RESULTS: Fifty-four children were included, 37% (n = 20) had stomas at the umbilicus. Most common other stoma location was the right lower quadrant (63%, n = 34). Necrotizing enterocolitis (NEC) was the most common indication for surgery in both groups. Days to stoma output were similar between the two groups, [3 (1, 6) versus 2 (1, 5), P = .96]. Days to initiation of feeds were delayed in the umbilical ostomy group [15 (9.5, 23.5) versus 6 (4, 10), P = .02]. Comparing only NEC patients, initiation of feeds was similar [22 (14, 56) versus 15.5 (8, 43), P = .73]. Umbilical ostomies had an increase in prolapse/peristomal hernias (7 versus 3, P = .01), but no patients required operative revision. CONCLUSION: Umbilical ostomies had similar time to stoma function compared to other sites, but a delay in initiation of oral feeds likely secondary to a higher percentage of patients with NEC.
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Estomía/métodos , Estomas Quirúrgicos , Ombligo/cirugía , Nutrición Enteral , Enterocolitis Necrotizante/cirugía , Femenino , Hernia/etiología , Humanos , Lactante , Recién Nacido , Masculino , Estomía/efectos adversos , Complicaciones Posoperatorias/etiología , Prolapso , Estudios Retrospectivos , Estomas Quirúrgicos/efectos adversos , Estomas Quirúrgicos/fisiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The evolving demands of our current health care system for enhanced efficiency and safety while decreasing hospital length of stay has led to our institutional protocol for same-day discharge (SDD) after laparoscopic appendectomy. We have previously demonstrated a 28% rate of SDD in children with nonperforated appendicitis. The purpose of our study is to assess the effectiveness of a mature protocol for SDD by evaluating discharge success, duration of hospital stay, and readmission rates. MATERIALS AND METHODS: A retrospective review of prospectively collected data was conducted. All children undergoing a laparoscopic appendectomy for nonperforated appendicitis at Children's Mercy Hospital between December 2015 and July 2017 were included. Patients were classified according to whether they were discharged home the same day as their operation or had an overnight stay. Demographic data, time of day the procedure was completed, postoperative length of stay, and readmission rates were abstracted from patient medical records. Comparative analysis was performed in STATA using chi-squared or Fisher exact tests for categorical variables and t-test or Wilcoxon rank sum test for continuous variables. RESULTS: A total of 569 children were included, with 87% (n = 495) discharged home the same day as their appendectomy. Of the patients discharged home the same day of surgery, their median length of postoperative stay was 4 h (IQR: 3, 5) compared with 19 h for the patients who stayed overnight (IQR: 15, 25, P < 0.0001). Approximately two-thirds of patients who had their appendectomies after 6 PM stayed overnight. In addition, patients discharged home the same day had similar hospital readmission rates compared with patients who stayed overnight (2% vs. 4%, P = 0.155). CONCLUSIONS: After laparoscopic appendectomy in children with nonperforated appendicitis, SDD not only reduces postoperative length of stay but also is not associated with higher hospital readmission rates.
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Apendicectomía/normas , Apendicitis/cirugía , Vías Clínicas , Hospitales Pediátricos/organización & administración , Alta del Paciente/normas , Adolescente , Procedimientos Quirúrgicos Ambulatorios/efectos adversos , Procedimientos Quirúrgicos Ambulatorios/normas , Apendicectomía/efectos adversos , Niño , Femenino , Hospitales Pediátricos/normas , Hospitales Pediátricos/estadística & datos numéricos , Humanos , Laparoscopía/efectos adversos , Laparoscopía/normas , Tiempo de Internación/estadística & datos numéricos , Masculino , Alta del Paciente/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Periodo Posoperatorio , Evaluación de Programas y Proyectos de Salud , Estudios Prospectivos , Estudios Retrospectivos , Factores de TiempoRESUMEN
PURPOSE: We have previously demonstrated successful laparoscopic management after failed enema reduction of children with intussusception. The purpose of this study is to assess the effectiveness of our mature experience with laparoscopic reduction by evaluating operative success, duration of hospital stay, postoperative complications, and hospital readmission rates. MATERIALS AND METHODS: After IRB approval, a retrospective review was conducted on children (age 0-18 years) who failed enema reduction of intussusception between 2008 and 2017. Cases were classified as either open or laparoscopic. Demographic data, incidence of bowel resection, postoperative length of stay, complications, and hospital readmission rates were abstracted from patient medical records. Comparative analysis was performed in STATA with a P value <.05 determined as significant. RESULTS: A total of 81 children were included in our study with 63 patients (78%) undergoing a laparoscopic reduction and 18 patients (22%) undergoing an open operation. Laparoscopic reduction carried similar complication rates (11%) when compared with children undergoing an open reduction (11%, P = 1.00). Furthermore, both hospital readmission rates and returns to the operating room were similar between the two groups (P = .345 and P = .672, respectively). The median postoperative length of stay was shorter for patients undergoing a laparoscopic reduction (4 days, interquartile range [IQR], 2-5 days) than for patients undergoing an open reduction (5 days, IQR, 4-6 days, P = .001). Children undergoing a laparoscopic reduction had a decreased rate of bowel resection (43% versus 50%, P = .591) despite similar rate of pathological lead points (21% versus 22%, P = .884). CONCLUSION: Laparoscopic management of intussusception after failed radiographic reduction yields a reduced hospital length of stay with no increase in hospital readmission rates and reoperations.
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Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Intususcepción/cirugía , Laparoscopía/métodos , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Tiempo de Internación/estadística & datos numéricos , Masculino , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/cirugía , Periodo Posoperatorio , Reoperación , Estudios RetrospectivosRESUMEN
PURPOSE: Pain is the main factor that determines the postoperative course for patients undergoing pectus bar placement. Cryoablation of the intercostal nerves has been suggested to mitigate this pain. We instituted a protocol for using intercostal cryoablation and report our early results compared to our immediately previous cohort. MATERIALS AND METHODS: A retrospective study was conducted on patients undergoing minimally invasive repair for pectus excavatum between January 1, 2017, and August 21, 2017. Demographic data, anthropometrics, operative times, type and duration of patient analgesia, and postoperative length of stay were collected. Descriptive statistics were performed with all means reported ± standard deviations. Comparisons between groups were analyzed on STATA using T-tests with a P value <.05 determined as significant. RESULTS: Twenty-eight patients were treated for pectus excavatum during the study period with 9 (32%) undergoing cryoablation. Mean number of rib spaces ablated was 5 ± 0.53 with no reported intraoperative complications. Mean operative time was 30 minutes longer in the cryoablation group (P = .00). Days to only oral pain medication was shorter in the cryoablation group, (1.22 ± 0.66 day versus 2.63 ± 0.68 day, P = .00). Length of stay, in days, was shorter in the cryoablation group (1.4 ± 0.72 days versus 4.0 ± 1.0 days, P = .00). There were no reported complications from cryoablation or bar placement during the study period. Days to discontinuation of oral narcotics were less in the cryoablation group (8.2 ± 7.0 versus 18.2 ± 10.4, P = .00). CONCLUSION: Cryoablation after pectus bar placement dramatically decreases narcotic usage and postoperative length of stay.
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Criocirugía/métodos , Tórax en Embudo/cirugía , Nervios Intercostales/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Dolor Postoperatorio/cirugía , Adolescente , Analgésicos/uso terapéutico , Niño , Estudios de Cohortes , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Narcóticos/uso terapéutico , Tempo Operativo , Estudios RetrospectivosRESUMEN
BACKGROUND: Beta blockers, a class of medications that inhibit endogenous catecholamines interaction with beta adrenergic receptors, are often administered to patients hospitalized after traumatic brain injury (TBI). We tested the hypothesis that beta blocker use after TBI is associated with lower mortality, and secondarily compared propranolol to other beta blockers. METHODS: The American Association for the Surgery of Trauma Clinical Trial Group conducted a multi-institutional, prospective, observational trial in which adult TBI patients who required intensive care unit admission were compared based on beta blocker administration. RESULTS: From January 2015 to January 2017, 2,252 patients were analyzed from 15 trauma centers in the United States and Canada with 49.7% receiving beta blockers. Most patients (56.3%) received the first beta blocker dose by hospital day 1. Those patients who received beta blockers were older (56.7 years vs. 48.6 years, p < 0.001) and had higher head Abbreviated Injury Scale scores (3.6 vs. 3.4, p < 0.001). Similarities were noted when comparing sex, admission hypotension, mean Injury Severity Score, and mean Glasgow Coma Scale. Unadjusted mortality was lower for patients receiving beta blockers (13.8% vs. 17.7%, p = 0.013). Multivariable regression determined that beta blockers were associated with lower mortality (adjusted odds ratio, 0.35; p < 0.001), and propranolol was superior to other beta blockers (adjusted odds ratio, 0.51, p = 0.010). A Cox-regression model using a time-dependent variable demonstrated a survival benefit for patients receiving beta blockers (adjusted hazard ratio, 0.42, p < 0.001) and propranolol was superior to other beta blockers (adjusted hazard ratio, 0.50, p = 0.003). CONCLUSION: Administration of beta blockers after TBI was associated with improved survival, before and after adjusting for the more severe injuries observed in the treatment cohort. This study provides a robust evaluation of the effects of beta blockers on TBI outcomes that supports the initiation of a multi-institutional randomized control trial. LEVEL OF EVIDENCE: Therapeutic/care management, level III.
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Antagonistas Adrenérgicos beta/farmacología , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Enfermedad Crítica/terapia , Manejo de la Enfermedad , Sociedades Médicas , Centros Traumatológicos/estadística & datos numéricos , Traumatología , Anciano , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/epidemiología , Canadá/epidemiología , Femenino , Humanos , Incidencia , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Foregut duplication cysts are rare congenital anomalies that require surgical intervention with approximately 10%-15% of all gastrointestinal duplication cysts originating from the esophagus. Consensus is lacking among surgeons regarding closure of the esophageal muscle layer after resection of an esophageal duplication cyst and long-term outcomes are poorly documented. Therefore, we conducted the first study comparing complication rates in patients undergoing closure versus nonclosure of the esophageal muscle layer after esophageal duplication cyst resection. MATERIALS AND METHODS: A retrospective cohort study at Boston Children's Hospital, Massachusetts General Hospital, Brigham and Women's Hospital, and the Floating Hospital for Children at Tufts Medical Center was conducted. Patients undergoing resection of esophageal duplication cysts between 1990 and 2012 were classified according to whether the esophageal muscle layer was closed or left open. Demographic data, surgical technique, preoperative symptoms, and both short-term (<30 d) and long-term (≥30 d) complication rates were abstracted from patient medical records. RESULTS: Twenty-five patients were identified with a median age of 15-y old (range, 2 mo to 68-y old) and an average follow-up of 1 y. Eleven patients had the esophageal muscle layer closed after surgical resection (44%). Of those 11 patients, one developed a short-term complication, dysphagia (9%, 95% CI: 2%, 38%). Only one patient returned to the operating room, after 30 d, for an upper endoscopy after developing symptoms of gastroesophageal reflux disease. Of the 14 patients who had their muscle layer left open, three patients (21%, 95% CI: 8%, 48%) developed short-term complications, two of whom required surgical intervention within 30 d. Furthermore, two additional patients required surgical intervention after 30 d for a long-term complication (diverticulum and cyst recurrence). CONCLUSIONS: Surgical complications occurred more frequently in patients who had the muscle layer left open after resection of an esophageal duplication cyst. In addition, most patients requiring reoperation for both short-term and long-term complications occurred in this group. Though small, this study is the first to evaluate the complications after resecting esophageal duplication cysts. Our results suggest that closing the esophageal muscle layer after removal of an esophageal duplication cyst may be indicated to prevent both complications and the need for reoperations.
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Quiste Esofágico/congénito , Quiste Esofágico/cirugía , Esofagoplastia/métodos , Esófago/anomalías , Esófago/cirugía , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: To assess whether pediatric trauma patients initially evaluated at referring institutions met Massachusetts statewide trauma field triage criteria for stabilization and immediate transfer to a Pediatric Trauma Center (PTC) without pre-transfer CT imaging. METHODS: A 3-year retrospective cohort study was completed at our level 1 PTC. Patients with CT imaging at referring institutions were classified according to a triage scheme based on Massachusetts statewide trauma field triage criteria. Demographic data and injury profile characteristics were abstracted from patient medical records and our pediatric trauma registry. RESULTS: A total of 262 patients with 413 CT scans were reviewed from 2008 to 2011. 172 patients scanned (66%, 95% CI: 60%, 71%) met criteria for immediate transfer to a pediatric trauma center. Notably, 110 scans (27% of the total performed at referring institutions) were duplicated within four hours upon arrival to our PTC. GCS score <14 (45%) was the most common requirement for transfer, and CT scan of the head was the most frequent scan obtained (53%). CONCLUSION: The majority of pediatric trauma patients were subjected to CT scans at referring institutions despite meeting Massachusetts trauma triage guidelines that call for stabilization and immediate transfer to a pediatric trauma center without any CT imaging.
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Hospitales Pediátricos , Transferencia de Pacientes , Derivación y Consulta , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Centros Traumatológicos , Procedimientos Innecesarios/estadística & datos numéricos , Heridas y Lesiones/diagnóstico por imagen , Accidentes por Caídas/estadística & datos numéricos , Accidentes de Tránsito/estadística & datos numéricos , Adolescente , Niño , Preescolar , Estudios de Cohortes , Traumatismos Craneocerebrales/diagnóstico por imagen , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Femenino , Escala de Coma de Glasgow , Adhesión a Directriz , Humanos , Lactante , Recién Nacido , Masculino , Massachusetts , Transferencia de Pacientes/normas , Guías de Práctica Clínica como Asunto , Centros de Atención Terciaria , Triaje , Adulto JovenRESUMEN
Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad-) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor-free intervals in vivo after limiting dilution. Surprisingly, these cells are not only resistant to chemotherapeutics such as doxorubicin, but also are stimulated by it, as evidenced by the significantly increased number of colonies in treated 3+Ecad- cells. Similarly, proliferation of the 3+Ecad- cells in monolayer increased with treatment, by either doxorubicin or cisplatin, compared with the unseparated or cancer stem cell-depleted 3-Ecad+ cells. However, these cells are sensitive to Mullerian inhibiting substance (MIS), which decreased colony formation. MIS inhibits ovarian cancer cells by inducing G1 arrest of the 3+Ecad- subpopulation through the induction of cyclin-dependent kinase inhibitors. 3+Ecad- cells selectively expressed LIN28, which colocalized by immunofluorescence with the 3+ cancer stem cell markers in the human ovarian carcinoma cell line, OVCAR-5, and is also highly expressed in transgenic murine models of ovarian cancer and in other human ovarian cancer cell lines. These results suggest that chemotherapeutics may be stimulative to cancer stem cells and that selective inhibition of these cells by treating with MIS or targeting LIN28 should be considered in the development of therapeutics.