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BACKGROUND: Disseminated intravascular coagulation (DIC) is a rare but serious complication of pediatric scoliosis surgery; sparse current evidence warrants more information on causality and prevention. This systematic review sought to identify incidence of DIC in pediatric patients during or shortly after corrective scoliosis surgery and identify any predictive factors for DIC. METHODS: Medline/PubMed, EMBASE, and Ovid databases were systematically reviewed through July 2017 to identify pediatric patients with DIC in the setting of scoliosis surgery. Patient demographics, medical history, surgery performed, clinical course, suspected causes of DIC, and outcomes were collected. RESULTS: Eleven studies met inclusion criteria. Thirteen cases from 1974 to 2012 (mean age: 15.3 ± 4.3 years, 72% women) were identified, with neuromuscular (n = 7; 54%) scoliosis as the most common indication. There were no prior bleeding disorder histories; all preoperative labs were within normal limits. Procedures included 8 posterior segmental fusions (54%), 3 Harrington rods (31%), 1 Cotrel-Dubousset, and 1 unit rod. Eight patients experienced DIC intraoperatively and 5 patients experienced DIC postoperatively. Probable DIC causes included coagulopathy following intraoperatively retrieved blood reinfusion, infection from transfusion, rhabdomyolysis, hemostatic matrix application, heparin use, and hypovolemic shock. Most common complications included increased intraoperative blood loss (n = 8) and hypotension (n = 7). The mortality rate was 7.69%; one fatality occurred in the acute postoperative period. CONCLUSIONS: Prior bleeding disorder status notwithstanding, this review identified preliminary associations between variables during corrective scoliosis surgery and DIC incidence among pediatric patients, suggesting multiple etiologies for DIC in the setting of scoliosis surgery. Further investigation is warranted to quantify associated risk. CLINICAL RELEVANCE: This study brings awareness to a previously rarely discussed complication of pediatric scoliosis surgery. Further cognizance of DIC by scoliosis surgeons may help identify and prevent causes thereof.
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OBJECTIVE: To investigate the incidence of youth ice hockey-related concussions preceding and following the implementation of new body-checking and head contact rules by USA hockey in 2011. We hypothesized a decrease in concussions after the rule change. DESIGN: Retrospective analysis. SETTING: United States emergency department (ED) data queried in the National Electronic InjurySurveillance System (NEISS). PATIENTS: National Electronic Injury Surveillance System reported male youth (≤18 years) ice hockey concussion cases from January 1, 2002, to December 31, 2016. In total, 848 players were diagnosed with concussion, representing a national estimate of 17 374 cases. INDEPENDENT VARIABLES: Time, specifically years. MAIN OUTCOME MEASURES: Incidences and incidence rates (measured per 10 000 person-years) of male youth ice hockey concussions. Annual trends were analyzed using descriptive and linear or polynomial regression analysis. RESULTS: The national estimate of youth ice hockey-related concussions seen in US emergency departments (EDs) increased significantly from 656 in 2007 to 2042 in 2011 (P < 0.01). During the same period, their respective incidence increased significantly from 21.8 to 66.8 per 10 000, before dropping through 2016 (P < 0.05). After 2011, concussions decreased from 1965 in 2012 to 1292 in 2016 (P = 0.055). The gap in concussion incidence between the 11 to 12 and 13 to 14 divisions widened after 2011 (before 2011: 41 vs 49 per 10 000 person-years [P = 0.80]; after 2011: 45 and 89, respectively [P < 0.01]). CONCLUSIONS: US EDs experienced a significant increase in youth ice hockey concussion visits from 2007 to 2011. After the 2011 rule changes, concussion visits decreased significantly from 2012 to 2016.
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Traumatismos en Atletas , Conmoción Encefálica , Hockey , Adolescente , Traumatismos en Atletas/epidemiología , Traumatismos en Atletas/etiología , Conmoción Encefálica/complicaciones , Hockey/lesiones , Humanos , Incidencia , Masculino , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
INTRODUCTION: Parkinson's disease (PD) patients experience chronic pain related to osteoarthritis at comparable rates to the general population. While total hip arthroplasty (THA) effectively improves pain, functionality, and quality of life in PD patients, long-term outcomes following THA are under-reported. This study sought to investigate whether PD patients have an increased risk of complications and revision following THA in comparison to the general population. METHODS: Utilising New York State's Statewide Planning and Research Cooperative System, all PD patients who underwent THA from 2009 to 2011 with minimum 2-year follow-up were identified. A control group (no-PD) was created via 1:1 propensity score-matching by age, gender, and Charlson/Deyo score. Univariate analysis compared demographics, complications, and revisions. Multivariate binary stepwise logistic regression identified independent predictors of outcomes. RESULTS: 470 propensity score-matched patients (PD: n = 235; no-PD: n = 235) were identified. PD patients demonstrated higher rates of overall and postoperative wound infection (p < 0.05), with comparable individual and overall complication and revision rates. PD did not increase odds of complications or revisions. PD patients had lengthier hospital stay (4.97 vs. 4.07 days, p = 0.001) and higher proportion of second primary THA >2-years postoperatively (69.4% vs. 59.6%, p = 0.027). Charlson/Deyo index was the greatest predictor of any surgical complication (OR = 1.17, p = 0.029). Female sex was the strongest predictor of any medical complication (OR = 2.21, p < 0.001). DISCUSSION: Despite lengthier hospital stays and infection-related complications, PD patients experienced comparable complication and revision rates to patients from the general population undergoing THA.
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Artroplastia de Reemplazo de Cadera/métodos , Enfermedad de Parkinson/complicaciones , Complicaciones Posoperatorias/epidemiología , Puntaje de Propensión , Calidad de Vida , Anciano , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación/tendencias , Masculino , New York/epidemiología , Periodo Posoperatorio , Estudios Retrospectivos , Factores de TiempoRESUMEN
STUDY DESIGN: Retrospective review of a prospectively collected database. OBJECTIVES: This preliminary investigation sought to identify the quality of care adolescent idiopathic scoliosis (AIS) patients from our large, underserved community had received before presenting at this institution's clinic. SUMMARY OF BACKGROUND DATA: AIS affects 1% to 4% of children between ages 10 and 16. Barriers to health care for patients in underserved populations have not been well studied. METHODS: Patients who visited a single surgeon's clinic for primary AIS between June 2016 and January 2017 were enrolled. Patients had 36-inch full-spine radiographs and completed a survey of demographics, prior AIS care received (screening, bracing, etc), socioeconomic parameters, and patient-reported outcomes (PROs; Scoliosis Research Society [SRS]-30 Questionnaire and Body Image Disturbance Questionnaire [BIDQ]). Parametric and nonparametric analyses were used and percentages and mean/median values were reported. RESULTS: 47 patients (age: 15 ± 3 years; 82.7% female) were included. Overall, 25.5% of patients reported a family history of scoliosis, and 42.6% had no prior knowledge of scoliosis. Per Scoliosis Research Society (SRS) recommendations, 15 patients required observation (main Cobb angle: <25°), 22 patients were eligible for bracing (25°-45°), and 10 patients were surgical candidates (>45°). In addition, 21.3% of all patients were never screened for scoliosis; of these, 50% had a main scoliosis curve >25°. Seventy percent of surgical candidates never wore a brace, and 59.3% of screened patients who were eligible for bracing were not braced at initial presentation. Patients who were left unbraced when eligible exhibited worse BIDQ scores (1.7 vs. 1.4, p < .05). CONCLUSIONS: One of five children in our population was never screened for scoliosis, and nearly three of five children did not receive optimal care as recommended by SRS. AIS patients in our inner-city populations are potentially at risk of continuing to experience a significant disadvantage in health care access. LEVEL OF EVIDENCE: Level IV case series.
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Área sin Atención Médica , Escoliosis , Adolescente , Niño , Femenino , Humanos , Masculino , Medición de Resultados Informados por el Paciente , Calidad de la Atención de Salud , Calidad de Vida , Estudios Retrospectivos , Escoliosis/diagnóstico por imagen , Escoliosis/epidemiología , Escoliosis/patología , Escoliosis/terapia , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
STUDY DESIGN: Retrospective analysis. OBJECTIVE: To compare outcomes and complication rates between patients with and without Parkinson's disease (PD) patients undergoing surgery for adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: There is limited literature evaluating the impact of PD on long-term outcomes after thoracolumbar fusion surgery for ASD. METHODS: Patients admitted from 2009 to 2011 with diagnoses of ASD who underwent any thoracolumbar fusion procedure with a minimum 2-year follow-up surveillance were retrospectively reviewed using New York State's Statewide Planning and Research Cooperative System. A 1:1 propensity score-match by age, Deyo score, and number of fused vertebral levels was conducted before comparing surgical outcomes of patients with ASD with and without PD. Univariate analysis compared demographics, complications, and subsequent revision. Multivariate binary stepwise logistic regression models identified independent predictors of these outcomes (covariates: age, sex, Deyo Index score, and PD diagnosis). RESULTS: A total of 576 propensity score-matched patients were identified (PD: nâ=â288; no-PD: nâ=â288), with a mean age of 69.7 years (PD) and 70.2 years (no-PD). Each cohort had comparable distributions of age, sex, race, insurance provider, Deyo score, and number of levels fused (all P > 0.05). Patients with PD incurred higher total charges across ASD surgery-related visits ($187,807 vs. $126,610, P < 0.001), yet rates of medical complications (35.8% PD vs. 34.0% no-PD, Pâ=â0.662) and revision surgery (12.2% vs. 10.8%, P > 0.05) were comparable. Postoperative mortality rates were comparable between PD and no-PD cohorts (2.8% vs. 1.4%, Pâ=â0.243). Logistic regression identified nine-level or higher spinal fusion as a significant predictor for an increase in total complications (odds ratioâ=â5.64); PD was not associated with increased odds of any adverse outcomes. CONCLUSION: Aside from higher hospital charges incurred, patients with PD experienced comparable overall complication and revision rates to a propensity score-matched patient cohort without PD from the general population undergoing thoracolumbar fusion surgery. These results can support management of concerns and postoperative expectations in this patient cohort. LEVEL OF EVIDENCE: 3.
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Enfermedad de Parkinson/epidemiología , Puntaje de Propensión , Fusión Vertebral/estadística & datos numéricos , Anciano , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Masculino , New York/epidemiología , Complicaciones Posoperatorias/epidemiología , Reoperación/estadística & datos numéricos , Estudios RetrospectivosRESUMEN
Survey of 869 arthroscopists regarding joint-specific arthroscopic procedures and postoperative rehabilitative preferences revealed comparable support for use of supervised physical therapy (SPT) and home exercise programs (HEPs) but stronger preference for joint-specific HEP applications (wrist, knee). Among respondents utilizing HEPs, modality of delivery (verbal/handout/web-based) didn't differ by joint, yet only 2.9% utilized web-based HEPs. This is the first known study to identify postoperative rehabilitation preferences. With 1.77 million estimated arthroscopic procedures annually (mean: 325.4 procedures/respondent), this study highlights under-utilization of web-based HEPs. Reliable, web-based HEPs can improve post-arthroscopic outcomes for patients, arthroscopic surgeons, and rehabilitative specialists while being cost efficient.
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STUDY DESIGN: This is a meta-analysis. OBJECTIVE: To establish rates of (1) neurological complications, (2) bony-related complications, (3) complications delaying recovery, (4) reoperation, and (5) fatalities following posterior cervical arthrodesis in Down syndrome (DS) patients with atlantoaxial subluxation. To determine if presenting symptoms had any relationship to postoperative complications. SUMMARY OF BACKGROUND DATA: Posterior arthrodesis is commonly utilized to correct cervical instability secondary to atlantoaxial instability in DS patients. However, there has never been a global evaluation of postoperative complications associated with posterior cervical spinal arthrodesis in DS patients. METHODS: A comprehensive search of Medline/PubMed, EMBASE, and Ovid databases between January 1980 and July 2017 was utilized to identify DS patients with atlantoaxial subluxation who underwent posterior cervical arthrodesis. Data were sorted by neurological complications, complications delaying recovery, bony-related complications, reoperations, and fatalities. Patients were sorted into 2 groups based on presentation with or without neurological deficits. RESULTS: Twelve studies met inclusion criteria, including 128 DS patients. Mean age was 13.8 years (range: 6.7-32.7 y; 47.8% male). Mean follow-up was 31.7 months (range: 14.9-77 mo). All patients underwent primary posterior cervical arthrodesis with an average of 2.5 vertebrae fused. A total of 39.6% of patients had bony-related complications [95% confidence interval (CI), 31.4%-48.5%], 23.3% had neurological deficits (95% CI, 16.6%-31.6%), and 26.4% experienced complications delaying recovery (95% CI, 19.4%-34.9%). The reoperation rate was 34.9% (95% CI, 25.5%-45.6%). The mortality rate was 3.9% (95% CI, 1.5%-9.7%). Neurological complications were 4-fold (P<0.05) and reoperation was 5.5-fold (P<0.05) more likely in patients presenting with neurological deficits compared with those without. CONCLUSIONS: This study detailed global complication rates of posterior arthrodesis for DS patients, identifying bony-related complications and reoperations among the most common. Patients presenting with neurological symptoms and cervical instability have increased postoperative rates of neurological complications and reoperations than patients with instability alone. Further investigation into how postoperative complications effect patient independence is warranted.
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Artrodesis , Articulación Atlantoaxoidea/patología , Articulación Atlantoaxoidea/cirugía , Síndrome de Down/complicaciones , Síndrome de Down/cirugía , Luxaciones Articulares/complicaciones , Luxaciones Articulares/cirugía , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Complicaciones Posoperatorias/etiología , Reoperación , Resultado del Tratamiento , Adulto JovenRESUMEN
The routine workup of hallux valgus includes measurements of the distal metatarsal articular angle (DMAA). However, this angle may not be a reliable measurement when rotational deformities occur. Eight matched cadaveric feet were evaluated radiographically using fluoroscopy. The intermetatarsal angle (IMA), hallux valgus angle, and DMAA were evaluated as a baseline. Then, we assessed whether axial rotation of 15°, 30°, 45°, and 60° affected the accuracy of the IMA and the DMAA significantly. Statistical evaluation was performed using Student's t tests and analysis of variance. The IMA remained stable for each anterior-posterior image despite rotation of the distal segment, with a mean difference of less than 2.5°. However, the DMAA was not constant, having different angles of rotation through the osteotomy site. We were able to demonstrate that measurement of the DMAA varies significantly with rotation of the distal first metatarsal. Using the DMAA to assess first metatarsophalangeal joint congruency should be done cautiously because it may estimate unreliably and inaccurately the 3D deformity often encountered in pathologic hallux valgus.
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Hallux Valgus/diagnóstico por imagen , Huesos Metatarsianos/diagnóstico por imagen , Articulación Metatarsofalángica/diagnóstico por imagen , Cadáver , Fluoroscopía , Hallux Valgus/cirugía , Humanos , Osteotomía , RotaciónRESUMEN
STUDY DESIGN: Retrospective analysis. OBJECTIVE: To compare long-term outcomes between patients with and without mental health comorbidities who are undergoing surgery for adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: Recent literature reveals that one in three patients admitted for surgical treatment for ASD has comorbid mental health disorder. Currently, impacts of baseline mental health status on long-term outcomes following ASD surgery have not been thoroughly investigated. METHODS: Patients admitted from 2009 to 2013 with diagnoses of ASD who underwent more than or equal to 4-level thoracolumbar fusion with minimum 2-year follow-up were retrospectively reviewed using New York State's Statewide Planning and Research Cooperative System (SPARCS). Patients were stratified by fusion length (short: 4-8-level; long: ≥9 level). Patients with comorbid mental health disorder (MHD) at time of admission were selected for analysis (MHD) and compared against those without MHD (no-MHD). Univariate analysis compared demographics, complications, readmissions, and revisions between cohorts for each fusion length. Multivariate binary logistic regression models identified independent predictors of outcomes (covariates: fusion length, age, female sex, and Deyo score). RESULTS: Six thousand twenty patients (MHD: nâ=â1631; no-MHD: nâ=â4389) met inclusion criteria. Mental health diagnoses included disorders of depression (59.0%), sleep (28.0%), anxiety (24.0%), and stress (2.3%). At 2-year follow-up, MHD patients with short fusion had significantly higher complication rates (Pâ=â0.001). MHD patients with short or long fusion also had significantly higher rates of any readmission and revision (all Pâ≤â0.002). Regression modeling revealed that comorbid MHD was a significant predictor of any complication (odds ratio [OR]: 1.17, Pâ=â0.01) and readmission (OR: 1.32, Pâ<â0.001). MHD was the strongest predictor of any revision (OR: 1.56, Pâ<â0.001). Long fusion most strongly predicted any complication (OR: 1.87, Pâ<â0.001). CONCLUSION: ASD patients with comorbid depressive, sleep, anxiety, and stress disorders were more likely to experience surgical complications and revision at minimum of 2 years following spinal fusion surgery. Proper patient counseling and psychological screening/support is recommended to complement ASD treatment. LEVEL OF EVIDENCE: 3.
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Trastornos Mentales/epidemiología , Trastornos Mentales/cirugía , Vigilancia de la Población , Complicaciones Posoperatorias/epidemiología , Escoliosis/epidemiología , Escoliosis/cirugía , Adulto , Comorbilidad , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Vértebras Lumbares/cirugía , Masculino , Trastornos Mentales/diagnóstico , Salud Mental/tendencias , Persona de Mediana Edad , New York , Vigilancia de la Población/métodos , Complicaciones Posoperatorias/diagnóstico , Estudios Retrospectivos , Escoliosis/diagnóstico , Vértebras Torácicas/cirugía , Factores de TiempoRESUMEN
STUDY DESIGN: Retrospective review. OBJECTIVE: To investigate rates of in-hospital postsurgical complications among hepatitis C-infected patients after cervical spinal surgery in comparison with uninfected patients and determine independent risk factors. SUMMARY OF BACKGROUND DATA: Studying hepatitis C virus (HCV) as a possible risk factor for cervical spine postoperative complications is prudent, given the high prevalence of cervical spondylosis and HCV in older patients. Spine literature is limited with respect to the impact of chronic HCV upon complications after surgery. MATERIALS AND METHODS: Patients who underwent cervical spine surgery for cervical radiculopathy (CR) or cervical myelopathy (CM) from 2005 to 2013 were retrospectively reviewed using the Nationwide Inpatient Sample database. Patients were divided into CR and CM groups, with comparative subgroup analysis of HCV and no-HCV patients. Univariate analysis compared demographics and complications. Binary logistic stepwise regression modeling identified any independent outcome predictors (covariates: age, sex, Deyo score, and surgical approach). RESULTS: In total, 227,310 patients (HCV: n=2542; no-HCV: n=224,764) were included. From 2005 to 2013, HCV infection prevalence among all cervical spinal fusion cases increased from 0.8% to 1.2%. HCV patients were more likely to be African American or Hispanic and have Medicare and/or Medicaid (all P<0.001). Overall complication rates among HCV patients with CR or CM increased, specifically related to device (CR: 3.1% vs. 1.9%; CM: 2.9% vs. 1.3%), hematoma/seroma (CR: 1.1% vs. 0.4%; CM: 1.8% vs. 0.8%), and sepsis (CR: 0.4% vs. 0.1%; CM: 1.1% vs. 0.5%) (all P≤0.001). Among CR and CM patients, HCV significantly predicted increased complication rates [odds ratio (OR): 1.268; OR: 1.194], hospital stay (OR: 1.738; OR: 1.861), and hospital charges (OR: 1.516; OR: 1.732; all P≤0.044). CONCLUSIONS: HCV patients undergoing cervical spinal surgery were found to have increased risks of postoperative complications and increased risk associated with surgical approach. These findings should augment preoperative risk stratification and counseling for HCV patients and their spine surgeons. LEVEL OF EVIDENCE: Level III.
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Vértebras Cervicales/cirugía , Hepatitis C/epidemiología , Radiculopatía/complicaciones , Radiculopatía/virología , Enfermedades de la Médula Espinal/complicaciones , Enfermedades de la Médula Espinal/virología , Femenino , Costos de Hospital , Humanos , Tiempo de Internación/economía , Modelos Logísticos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Fusión Vertebral/economíaRESUMEN
INTRODUCTION: Ankylosing spondylitis (AS) is characterized by spinal inflammation and structural damage, primarily to the axial skeleton and sacroiliac joints. Between 25% and 70% of patients may experience progressive peripheral joint involvement, which, despite advancement in pharmacologic therapy, may necessitate surgical intervention. Total hip arthroplasty (THA) yields improved pain and functional outcomes for AS patients with hip involvement. It is unclear whether the annual rates of patients undergoing THA have changed due to newer pharmacologic management. Therefore, the purpose of this study was to evaluate the annual trends of AS patients who underwent THA. Specifically, we evaluated: 1) the annual trends of THAs due to AS in the United States population, and 2) the annual trends in the proportion of THAs due to AS in the United States. MATERIALS AND METHODS: This study used the Nationwide Inpatient Sample to identify all patients who underwent THA between 2002 and 2013 (n=3,135,904). Then, an additional query was performed to identify THA patients who had a diagnosis of AS, defined by the International Classification of Disease 9th revision diagnosis code 720. The incidence of THAs with a diagnosis of AS in the United States was calculated using the United States population as the denominator. Regression models were used to analyze the annual trends of AS in patients who underwent THA. RESULTS: Review of the database identified 5,562 patients with AS who underwent THA. The overall annual prevalence of THA in the AS population significantly decreased during the 12-year study period from 2.24 per 1,000 THAs in 2002 to 1.73 per 1,000 THAs in 2013 (R2=0.445; p=0.018). CONCLUSION: Annual THA trends in AS patients have significantly declined from 2002 to 2013. This decline may be attributed to improvements in medical management that delay the time from disease onset to requirement of a THA. Since THA is an option with advanced disease, the observed declining trends may indicate the efficacy of current medical management.
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Artroplastia de Reemplazo de Cadera/estadística & datos numéricos , Espondilitis Anquilosante/epidemiología , Espondilitis Anquilosante/cirugía , Humanos , Estudios RetrospectivosRESUMEN
INTRODUCTION: Although the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for spinal fusion has been fairly studied in the general population, relatively little research has been conducted on its use in the elderly patient demographic despite this population's growth. The authors sought to examine the clinical efficacy, complication rate, and cost-effectiveness of rhBMP-2 use in elderly patients undergoing spinal fusion surgery. EVIDENCE ACQUISITION: We conducted a systematic review of the published literature for elderly patients that underwent spinal fusion surgery with the use of rhBMP-2. A systematic search was performed utilizing the PUBMED and MEDLINE databases in order to identify all papers dealing with recombinant human Bone Morphogenic Protein-2 use in patients over the age of 60 years. EVIDENCE SYNTHESIS: Twenty-five papers were identified that met our inclusion criteria. While successful fusion, improvement in pain, and improved quality of life were encountered in elderly patients who were treated with fusions surgery along with rhBMP-2, there were several complications that were encountered including seroma formation, pleural effusions, and bone non-union. CONCLUSIONS: The literature demonstrated that BMP serves as a potent osteoinductive agent in the elderly with similar efficacy to bone autograft. Although use of BMP showed mixed results and had higher initial costs, when taken into account with complication correction and costs, BMP usage appears to be more economically beneficial overall. Future studies are needed to clarify the clinical significance of the complications encountered in elderly patients treated with rhBMP-2. Future research can assist in developing recommendations which can minimize these risks in the elderly patient demographic.
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Envejecimiento , Proteína Morfogenética Ósea 2/uso terapéutico , Proteínas Morfogenéticas Óseas/uso terapéutico , Vértebras Lumbares/cirugía , Fusión Vertebral , Factor de Crecimiento Transformador beta/uso terapéutico , Trasplante Óseo/métodos , Humanos , Proteínas Recombinantes/uso terapéuticoRESUMEN
BACKGROUND: There is a great interest in studying phosphotyrosine dependent protein-protein interactions in tyrosine kinase pathways that play a critical role in many aspects of cellular function. We previously established SH2 profiling, a phosphoproteomic approach based on membrane binding assays that utilizes purified Src Homology 2 (SH2) domains as a molecular tool to profile the global tyrosine phosphorylation state of cells. However, in order to use this method to investigate SH2 binding sites on a specific target in cell lysate, additional procedures such as pull-down or immunoprecipitation which consume large amounts of sample are required. RESULTS: We have developed PLA-SH2, an alternative in-solution modular domain binding assay that takes advantage of Proximity Ligation Assay and real-time PCR. The SH2-PLA assay utilizes oligonucleotide-conjugated anti-GST and anti-EGFR antibodies recognizing a GST-SH2 probe and cellular EGFR, respectively. If the GST-SH2 and EGFR are in close proximity as a result of SH2-phosphotyrosine interactions, the two oligonucleotides are brought within a suitable distance for ligation to occur, allowing for efficient complex amplification via real-time PCR. The assay detected signal across at least 3 orders of magnitude of lysate input with a linear range spanning 1-2 orders and a low femtomole limit of detection for EGFR phosphotyrosine. SH2 binding kinetics determined by PLA-SH2 showed good agreement with established far-Western analyses for A431 and Cos1 cells stimulated with EGF at various times and doses. Further, we showed that PLA-SH2 can survey lung cancer tissues using 1 µl lysate without requiring phospho-enrichment. CONCLUSIONS: We showed for the first time that interactions between SH2 domain probes and EGFR in cell lysate can be determined in a microliter-scale assay using SH2-PLA. The obvious benefit of this method is that the low sample requirement allows detection of SH2 binding in samples which are difficult to analyze using traditional protein interaction assays. This feature along with short assay runtime makes this method a useful platform for the development of high throughput assays to determine modular domain-ligand interactions which could have wide-ranging applications in both basic and translational cancer research.