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1.
Eur J Orthop Surg Traumatol ; 34(1): 339-345, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37498351

RESUMEN

PURPOSE: The relationship between preoperative blood pressure (BP) and intraoperative mean arterial pressure (MAP) and estimated blood loss (EBL) in pediatric spine surgery is currently unknown. The objectives of this study were to determine if elevated preoperative BP is associated with elevated intraoperative MAP, EBL, and percentage estimated blood volume (EBV) lost, and to determine if intraoperative MAP is associated with percentage of EBV lost during posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). METHODS: This is a retrospective cohort analysis of 209 patients undergoing PSF for AIS between 2016 and 2019 by a single surgeon. Data extracted included demographic characteristics, preoperative systolic and diastolic BP, continuous intraoperative MAP measured by arterial line, EBL, radiographic, and surgical characteristics. Time points of interest for MAP included incision and exposure. Elevated BP was defined as > 1 standard deviation above the mean BP of patients included in the study, and elevated MAP was defined as > 65 mmHg. RESULTS: Elevated preoperative systolic BP was associated with elevated MAP at incision (p = 0.002). Patients with elevated preoperative diastolic BP had significantly higher MAP at exposure and throughout the procedure (p = 0.04). MAP > 65 at incision was associated with a 5% increase in EBV lost (p < 0.001). CONCLUSIONS: Patients with elevated preoperative BP parameters have increased MAPs at incision, exposure, and throughout surgery. Elevated MAP at incision is associated with an increased percentage of EBV lost in a small number of patients undergoing PSF for AIS.


Asunto(s)
Cifosis , Escoliosis , Fusión Vertebral , Humanos , Adolescente , Niño , Escoliosis/cirugía , Estudios Retrospectivos , Presión Arterial , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Presión Sanguínea , Pérdida de Sangre Quirúrgica , Resultado del Tratamiento
2.
Hand (N Y) ; : 15589447231205615, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37876175

RESUMEN

BACKGROUND: Preoperative anemia has been shown to be associated with complications after numerous orthopedic procedures. No studies to our knowledge have examined its impact on outcomes after open reduction internal fixation (ORIF) of distal radius fracture (DRF). We hypothesized that patients with preoperative anemia would have increased likelihood of adverse outcomes, and likelihood would increase with severity of anemia. METHODS: A total of 14 136 patients underwent ORIF for DRF over 2012-2021, identified in the National Surgical Quality Improvement Program database. Patients were classified by World Health Organization criteria as nonanemic (hematocrit >36% for women, >39% for men), mildly anemic (hematocrit 33%-36% for women, 33%-39% for men), or moderately to severely anemic (hematocrit <33% for women or men). Multivariable regressions adjusted for age, sex, race, and comorbidities statistically different between anemic and nonanemic patients were used to examine the effect of anemia on postoperative outcomes. RESULTS: Mildly anemic patients had significantly longer length of stay and were significantly more likely to experience readmission and sepsis (P < .05 all). Moderately to severely anemic patients had significantly longer length of stay and were significantly more likely to experience readmission, postoperative transfusion, septic shock, and any adverse event (P < .05 all). CONCLUSIONS: Preoperative anemia is associated with increased likelihood of adverse outcomes after ORIF for DRF, and likelihood increases with severity of anemia. Surgeons should monitor patients for preoperative anemia and endeavor to identify the source of and, if safe and possible, correct the anemia preoperatively or manage and educate patients postoperatively.

3.
J Surg Educ ; 80(6): 806-816, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37019709

RESUMEN

OBJECTIVE: Improving diversity in healthcare is a widely recognized national goal. The diversity of medical student matriculants has increased, yet this trend is not seen in the composition of competitive residency programs. In this review, we examine racial and ethnic disparities in medical student grading during clinical years and explore the consequences of how this may exclude minority students from accessing competitive residency positions. DESIGN: Following PRISMA guidelines, we searched PubMed, Embase, Scopus, and ERIC databases using variations of the terms "race," "ethnicity," "clerkship," "rotation," "grade," "evaluation", or "shelf exam." Of 391 references found using the criteria, 29 were related to clinical grading and race/ethnicity and included in the review. The GRADE criteria were used to determine the quality of evidence. SETTING: Johns Hopkins School of Medicine, Baltimore MD. RESULTS: Five studies examining a total of 107,687 students from up to 113 different schools found racial minority students receive significantly fewer Honors grades in core clerkships compared to White students. Three studies examining 94,814 medical student evaluations from up to 130 different schools found significant disparities in the wording of written clerkship evaluations based on race and/or ethnicity. CONCLUSIONS: A large body of evidence suggests the presence of racial bias in subjective clinical grading and written clerkship evaluations of medical students. Grading disparities can disadvantage minority students when applying to competitive residency programs and may contribute to a lack of diversity in these fields. As low minority representation has a negative impact on patient care and research advancement, strategies to resolve this issue must be further explored.


Asunto(s)
Facultades de Medicina , Estudiantes de Medicina , Humanos , Prácticas Clínicas , Evaluación Educacional , Etnicidad , Grupos Minoritarios
4.
J Child Orthop ; 16(4): 285-289, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35992520

RESUMEN

Purpose: Serial casting is an effective treatment for infantile idiopathic scoliosis. The most common casting table types are Mehta, Risser, and spica tables. We compared major curve correction between patients with infantile idiopathic scoliosis treated using pediatric hip spica tables versus Risser or Mehta tables. Methods: In this multicenter retrospective study, we included 52 children younger than 3 years (mean ± standard deviation age, 1.6 ± 0.68 years) treated with ≥2 consecutive casts for infantile idiopathic scoliosis between September 2011 and July 2018. We compared major curve angle (measured using the Cobb method) before and after treatment and improvement in curve angle between the spica tables group (n = 12) and the Risser or Mehta tables group (n = 40). The primary outcome was the difference in percentage correction of the major curve according to radiographs taken after first casting and at final follow-up. Results: The mean major curve was 47° ± 18° before casting. A median of six casts (range: 2-14) were applied. Mean follow-up after treatment initiation was 22 months (range: 7-86 months). At baseline, the major curve was significantly larger in the spica tables group (58°) than in the Risser or Mehta tables group (43°) (p = 0.01). We found no differences in the percentage curve correction in the spica tables group versus Risser or Mehta tables group after first casting or at final follow-up. Conclusion: Serial casting was associated with substantial major curve correction in patients with infantile idiopathic scoliosis. Curve correction did not differ between patients treated with a spica table versus a Risser or Mehta table. Level of Evidence: Level III, retrospective cohort study.

5.
J Pediatr Orthop ; 42(9): e943-e948, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-35941092

RESUMEN

BACKGROUND: High costs and lack of price transparency for common pediatric orthopaedic procedures create financial burden for patients. We assessed (1) how patient medical debt after anterior cruciate ligament reconstruction (ACLR) correlates with health insurance type; and (2) factors associated with patient financial burden and worry after ACLR. METHODS: We reviewed records of 122 patients aged below 18 years who underwent ACLR at our US academic hospital from 2016 to 2020. Patients were grouped by health insurance type: private (n=80) or public (n=42). A telephone survey about ACLR-related financial burden and worry was administered to patients' parents (45% response rate). Primary outcomes were patient medical debt and patient-reported financial burden measured by the financial burden composite score (0 to 6, with 6 representing highest burden) and dichotomized worry score (1 to 3, low worry; 4 to 5, high worry). We used univariate analyses to compare financial outcomes and multivariable regressions to determine factors associated with reported financial burden (alpha=0.05). RESULTS: Debt after ACLR was reported by 10 of 122 patients (8%), all of whom had private insurance ( P =0.045). Of 55 survey respondents, treatment-related financial burden was reported by 32 (58%). Mean±SD financial burden composite scores were higher for privately insured (1.8±2.0) versus publicly insured patients (0.74±1.2) ( P =0.02), but rates of high financial worry were similar (private, 8% vs. public, 21%) ( P =0.22). A higher proportion of patients with private insurance (31%) reported having to use savings after ACLR compared with publicly insured patients (5%) ( P =0.04). The most frequently cited reason for financial burden was the cost of postoperative physical therapy (PT) (n=21). Number of PT visits was independently associated with financial burden composite scores ( P =0.02). Insurance type was not independently associated with financial burden ( P >0.05). CONCLUSION: Although a small proportion of patients generated medical debt after ACLR (greater for those privately vs. publicly insured), the majority reported treatment-related financial burden primarily driven by PT costs. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Lesiones del Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior/métodos , Niño , Estrés Financiero , Humanos , Seguro de Salud , Articulación de la Rodilla/cirugía , Periodo Posoperatorio
6.
BMC Health Serv Res ; 22(1): 851, 2022 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-35778738

RESUMEN

BACKGROUND: Early initiation of physical therapy (PT) has been associated with lower healthcare costs and utilization; however, these studies have been limited to single institutions or healthcare systems. Our goal was to assess healthcare utilization and spending among patients who present for the first time with low back pain (LBP), according to whether they received early physical therapy (PT), using a large, nationwide sample; and geographic variation in rates of early PT and 30-day LBP-related spending. METHODS: Using the Truven MarketScan database, we identified nearly 980,000 US adults ages 18-64 years who initially presented with acute LBP from 2010 through 2014 and did not have nonmusculoskeletal causes of LBP. Approximately 110,000 patients (11%) received early PT (≤2 weeks after presentation). We compared healthcare utilization and spending at 30 days and 1 year after presentation between patients who received early PT and those who did not. Alpha = 0.05. RESULTS: At 30 days, early PT was associated with lower odds of chiropractor visits (odds ratio [OR] = 0.41, 95% confidence interval [CI] = 0.40-0.42), pain specialist visits (OR = 0.49, 95% CI = 0.47-0.51), emergency department visits (OR = 0.51, 95% CI = 0.49-0.54), advanced imaging (OR = 0.57, 95% CI = 0.56-0.58), orthopaedist visits (OR = 0.67, 95% CI = 0.66-0.69), and epidural steroid injections (OR = 0.68, 95% CI = 0.65-0.70). At 1 year, early PT was associated with less healthcare utilization. At 30 days, patients with early PT had lower mean LBP-related spending ($1180 ± $1500) compared with those without early PT ($1250 ± $2560) (P < 0.001). At 1 year, LBP-related spending was significantly less among patients who did not receive early PT ($2510 ± $3826) versus those who did ($2588 ± $3704). Early PT rates (range, 4-25%; P < 0.001) and 30-day LBP-related spending differed by state (range, $421 to -$410; P < 0.001). CONCLUSION: Early PT for acute LBP was associated with less 30-day and 1-year healthcare utilization and less 30-day LBP-related spending. Early PT rates and 30-day spending differed by US state. LEVEL OF EVIDENCE: IV.


Asunto(s)
Dolor de la Región Lumbar , Adolescente , Adulto , Atención a la Salud , Humanos , Dolor de la Región Lumbar/terapia , Persona de Mediana Edad , Aceptación de la Atención de Salud , Modalidades de Fisioterapia , Estudios Retrospectivos , Adulto Joven
7.
J Pediatr Orthop ; 42(2): 65-69, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34995256

RESUMEN

BACKGROUND: Patients with public health insurance have greater difficulty obtaining orthopaedic care than their privately insured counterparts because of lower reimbursements. However, the relationship between insurance status and financial burden for patients and treating institutions is unknown. We compared patient medical debt and uncompensated hospital costs by insurance type for pediatric patients who received nonoperative treatment for distal radius fractures (DRFs). METHODS: We reviewed medical records of 100 pediatric patients (above 18 y) treated nonoperatively at our US academic hospital for DRFs from 2016 to 2020. Patients were grouped according to insurance type at the time of treatment: preferred-provider organization (PPO), n=30; health maintenance organization (HMO), n=29; Medicaid, n=28; and uninsured, n=13. These groups were matched by number of encounters, total original charge, and total number of charges. The primary outcomes were patient medical debt and uncompensated costs to the hospital, comprising unpaid balance, uncollectible debt, and self-adjustments offered by the hospital. χ2 tests and analysis of variance were used to compare financial outcomes among subgroups (alpha=0.05). RESULTS: Patient medical debt (ie, uncollectible debt) was generated by 20% of PPO, 7.7% of uninsured, and 6.9% of HMO patients (P=0.06). Medicaid patients generated no patient medical debt, whereas PPO patients generated a mean (±SD) of $15±$39 and HMO patients generated $26±$130, which was not significantly different than that of uninsured patients ($25±$89) (P<0.0001). Uncompensated costs were generated by 54% of uninsured, 20% of PPO, 6.9% of HMO, and 0% of Medicaid patients (P<0.0001). Uncompensated costs were the same as uncollectible debt for privately insured and Medicaid patients, whereas uninsured patients generated an additional $550±$600 from self-adjustments (P<0.0001). CONCLUSION: Unlike the Medicaid group, the privately insured and uninsured groups incurred patient medical debt and uncompensated costs after nonoperative DRF treatment. Thus, orthopaedic providers should be cost conscious with privately insured patients, while publicly insured patients may provide more consistent-albeit lower-reimbursement for the hospital. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Medicaid , Fracturas del Radio , Niño , Estrés Financiero , Humanos , Cobertura del Seguro , Seguro de Salud , Pacientes no Asegurados , Estados Unidos
8.
JBJS Rev ; 9(7)2021 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-34257233

RESUMEN

¼: Inborn errors of metabolism are disorders of carbohydrate, amino acid, organic acid, or purine and pyrimidine metabolism; disorders of fatty acid oxidation; disorders of metal metabolism; and lysosomal storage defects that can cause metabolic derangements that have secondary musculoskeletal effects. ¼: Orthopaedic surgeons should be aware that patients with inborn errors of metabolism may be at high risk for spasticity, which may cause joint subluxations, scoliosis, and contractures, as well as poor bone quality, which is caused by malnutrition or disordered bone growth. ¼: Multidisciplinary care and follow-up are important to identify musculoskeletal problems in a timely manner in order to provide effective treatment.


Asunto(s)
Errores Innatos del Metabolismo , Ortopedia , Humanos , Errores Innatos del Metabolismo/complicaciones , Errores Innatos del Metabolismo/terapia
9.
J Pediatr Orthop ; 41(6): e457-e463, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34096551

RESUMEN

INTRODUCTION: Organic acid disorders (OADs) are a subset of inborn errors of metabolism that result in a toxic accumulation of organic acids in the body, which can lead to metabolic derangements and encephalopathy. Patients with these disorders are managed by a team of biochemical geneticists and metabolic nutritionists. However, subspecialists such as neurologists and orthopaedic surgeons are often needed to help manage the sequelae of the metabolic derangements. The breadth of orthopaedic sequelae of these disease states is poorly understood. Herein, we describe orthopaedic problems associated with 5 types of OAD most commonly seen at our institution: maple syrup urine disease, methylmalonic aciduria, propionic aciduria, pyruvate dehydrogenase deficiency, and glutaric aciduria type 1. METHODS: We retrospectively reviewed medical records of 35 patients with an OAD who were seen at our academic tertiary care center from May 1999 to May 2020. Patients were grouped into cohorts according to OAD type and analyzed for orthopaedic presentations of hip, knee, or foot disorders, presence and severity of scoliosis, history of fracture, movement disorders, and osteopenia/osteoporosis. RESULTS: Of the 35 patients, 13 had maple syrup urine disease, 12 had methylmalonic aciduria, 4 had propionic aciduria, 4 had pyruvate dehydrogenase deficiency, and 2 had glutaric aciduria type 1. Associated orthopaedic problems included spasticity causing neuromuscular scoliosis and/or hip subluxation or dislocation (10 patients), fractures (7 patients), and osteopenia/osteoporosis (7 patients). Overall, 22 of 35 patients had some orthopaedic condition. CONCLUSIONS: Most in this cohort of patients with OAD also had an orthopaedic abnormality. It is important for physicians treating these patients to understand their propensity for musculoskeletal problems. When treating patients with OAD, it is important to initiate and maintain communication with specialists in several disciplines and to develop collaborative treatments for this unique population. LEVEL OF EVIDENCE: Level IV-prognostic study.


Asunto(s)
Ortopedia , Acidemia Propiónica/complicaciones , Acidemia Propiónica/cirugía , Adolescente , Adulto , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Encefalopatías Metabólicas/complicaciones , Niño , Preescolar , Femenino , Glutaril-CoA Deshidrogenasa/deficiencia , Humanos , Masculino , Enfermedad de la Orina de Jarabe de Arce/complicaciones , Enfermedad de la Orina de Jarabe de Arce/cirugía , Persona de Mediana Edad , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/complicaciones , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/cirugía , Estudios Retrospectivos
10.
Orthop J Sports Med ; 9(1): 2325967120975410, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33553452

RESUMEN

BACKGROUND: Tibial spine fractures (TSFs) are typically treated nonoperatively when nondisplaced and operatively when completely displaced. However, it is unclear whether displaced but hinged (type 2) TSFs should be treated operatively or nonoperatively. PURPOSE: To compare operative versus nonoperative treatment of type 2 TSFs in terms of overall complication rate, ligamentous laxity, knee range of motion, and rate of subsequent operation. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We reviewed 164 type 2 TSFs in patients aged 6 to 16 years treated between January 1, 2000, and January 31, 2019. Excluded were patients with previous TSFs, anterior cruciate ligament (ACL) injury, femoral or tibial fractures, or grade 2 or 3 injury of the collateral ligaments or posterior cruciate ligament. Patients were placed according to treatment into the operative group (n = 123) or nonoperative group (n = 41). The only patient characteristic that differed between groups was body mass index (22 [nonoperative] vs 20 [operative]; P = .02). Duration of follow-up was longer in the operative versus the nonoperative group (11 vs 6.9 months). At final follow-up, 74% of all patients had recorded laxity examinations. RESULTS: At final follow-up, the nonoperative group had more ACL laxity than did the operative group (P < .01). Groups did not differ significantly in overall complication rate, reoperation rate, or total range of motion (all, P > .05). The nonoperative group had a higher rate of subsequent new TSFs and ACL injuries requiring surgery (4.9%) when compared with the operative group (0%; P = .01). The operative group had a higher rate of arthrofibrosis (8.9%) than did the nonoperative group (0%; P = .047). Reoperation was most common for hardware removal (14%), lysis of adhesions (6.5%), and manipulation under anesthesia (6.5%). CONCLUSION: Although complication rates were similar between nonoperatively and operatively treated type 2 TSFs, patients treated nonoperatively had higher rates of residual laxity and subsequent tibial spine and ACL surgery, whereas patients treated operatively had a higher rate of arthrofibrosis. These findings should be considered when treating patients with type 2 TSF.

11.
Pain Med ; 22(3): 740-745, 2021 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-33260217

RESUMEN

OBJECTIVE: Neck pain is a leading cause of years lived with disability and is often managed with opioid medications in primary care settings, though this is contraindicated by national guidelines. The aim of this study was to determine the prevalence of opioid prescription for neck pain at a primary care visit and to analyze the geographic variation and trends in opioid prescriptions between 2011 and 2017. METHODS: Using a prescription drug claims database, we identified 591,961 adult patients who presented for neck pain in primary care settings between 2011 and 2017. Patients who had outpatient specialty visits within 1 year before presentation, a concomitant diagnosis of a non-musculoskeletal cause of neck pain, or preexisting chronic opioid use were excluded. RESULTS: The mean age of the patients was 45 ± 12 years, and 64% were female. Fifteen percent of patients were prescribed opioids within 30 days of their encounter. Eleven percent of patients were prescribed moderate- to high-dose opioids (>20 morphine milligram equivalents). From 2011-2017, the proportion of both overall opioid prescriptions and moderate- to high-dose prescriptions given to first time presenters to an outpatient clinic for neck pain was highest in Mississippi (20%) and lowest in New Mexico (6%) (P < 0.001). In 2017, the proportion of both overall opioid prescriptions and moderate- to high-dose prescriptions was highest in the Midwest (10.4%) and lowest in the Northeast (4.9%). The proportion of patients with filled opioid prescriptions declined between 2011 (19%) and 2017 (13%) (P < 0.001), and the proportion of patients with moderate- to high-dose prescriptions declined from 2011 (13%) to 2017 (8%) (P < 0.001). first-time presenters of neck pain to an outpatient clinic. CONCLUSIONS: Opioid medication use for neck pain in the primary care setting is significant. Although opioid prescriptions are declining, there remains a need for further standardization in prescription practices.


Asunto(s)
Analgésicos Opioides , Trastornos Relacionados con Opioides , Adulto , Analgésicos Opioides/uso terapéutico , Prescripciones de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor de Cuello/tratamiento farmacológico , Dolor de Cuello/epidemiología , Trastornos Relacionados con Opioides/tratamiento farmacológico , Pautas de la Práctica en Medicina , Atención Primaria de Salud
12.
Mol Cancer Res ; 14(1): 114-24, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26446920

RESUMEN

UNLABELLED: Sonic hedgehog (Shh) signaling is closely coupled with bioenergetics of medulloblastoma, the most common malignant pediatric brain tumor. Shh-associated medulloblastoma arises from cerebellar granule neuron precursors (CGNP), a neural progenitor whose developmental expansion requires signaling by Shh, a ligand secreted by the neighboring Purkinje neurons. Previous observations show that Shh signaling inhibits fatty acid oxidation although driving increased fatty acid synthesis. Proliferating CGNPs and mouse Shh medulloblastomas feature high levels of glycolytic enzymes in vivo and in vitro. Because both of these metabolic processes are closely linked to mitochondrial bioenergetics, the role of Shh signaling in mitochondrial biogenesis was investigated. This report uncovers a surprising decrease in mitochondrial membrane potential (MMP) and overall ATP production in CGNPs exposed to Shh, consistent with increased glycolysis resulting in high intracellular acidity, leading to mitochondrial fragmentation. Ultrastructural examination of mitochondria revealed a spherical shape in Shh-treated cells, in contrast to the elongated appearance in vehicle-treated postmitotic cells. Expression of mitofusin 1 and 2 was reduced in these cells, although their ectopic expression restored the MMP to the nonproliferating state and the morphology to a fused, interconnected state. Mouse Shh medulloblastoma cells featured drastically impaired mitochondrial morphology, restoration of which by ectopic mitofusin expression was also associated with a decrease in the expression of Cyclin D2 protein, a marker for proliferation. IMPLICATIONS: This report exposes a novel role for Shh in regulating mitochondrial dynamics and rescue of the metabolic profile of tumor cells to that of nontransformed, nonproliferating cells and represents a potential avenue for development of medulloblastoma therapeutics.


Asunto(s)
GTP Fosfohidrolasas/metabolismo , Proteínas Hedgehog/metabolismo , Mitofagia , Células-Madre Neurales/metabolismo , Animales , Animales Recién Nacidos , Proliferación Celular , Células Cultivadas , Neoplasias Cerebelosas , GTP Fosfohidrolasas/genética , Glucólisis , Meduloblastoma , Potencial de la Membrana Mitocondrial , Ratones , Mitocondrias/ultraestructura , Neoplasias Experimentales , Células-Madre Neurales/citología
13.
BMC Cancer ; 15: 118, 2015 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-25851054

RESUMEN

BACKGROUND: Malignant glioma is one of the most devastating tumors in adults with poor patient prognosis. Notably, glioma often exhibits resistance to conventional chemotherapeutic approaches, complicating patient treatments. However, the molecular mediators involved in tumor chemoresistance remain poorly defined, creating a barrier to the successful management of glioma. In the present study, we hypothesized that the antioxidant transcription factor, Nrf2 (nuclear factor erythroid-derived 2 like 2), attenuates glioma cytotoxicity to Carmustine (BCNU), a widely used chemotherapeutic agent known to modulate cellular oxidative balance. METHODS: To test the hypothesis, we employed human malignant glioma cell line, U87MG and overexpression of Nrf2 in glioma cells was achieved using both pharmacological and genetic approaches. RESULTS: Notably, induction of Nrf2 was associated with increased expression of heme oxygenase-1 (HO-1), a stress inducible enzyme involved in anti-oxidant defense. In addition, over expression of Nrf2 in U87MG cells significantly attenuated the cytotoxicity of Carmustine as evidenced by both cellular viability assay and flow cytometry analysis. Consistent with this, antioxidants such as glutathione and N-acetyl cysteine significantly reduced Carmustine mediated glioma cytotoxicity. CONCLUSIONS: Taken together, these data strongly implicate an unexplored role of Nrf2 in glioma resistance to Carmustine and raise the possible use of Nrf2 inhibitors as adjunct to Carmustine for the treatment of malignant glioma.


Asunto(s)
Antineoplásicos Alquilantes/farmacología , Carmustina/farmacología , Resistencia a Antineoplásicos/genética , Expresión Génica , Glioma/genética , Factor 2 Relacionado con NF-E2/genética , Antineoplásicos Alquilantes/toxicidad , Antioxidantes/farmacología , Carmustina/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Glioma/metabolismo , Humanos , Hidroquinonas/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos
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