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Chondrosarcoma is a common primary bone malignancy whose phenotype increases with its histologic grade. They are relatively resistant to chemotherapy and radiation therapy limiting curative options for disseminated disease. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface proteoglycan that is highly expressed across various human cancers, including chondrosarcoma, and has restricted distribution in healthy tissues, making it an attractive target for the antibody-based therapy. CSPG4 specific chimeric antigen receptor (CAR) T cell therapies have been shown to be effective in treating other cancers such as melanoma and triple negative breast cancer. The goal of this study was to assess the prevalence of CSPG4 in human chondrosarcoma and to assess the efficacy of CSPG4 specific CAR T cells in lysing chondrosarcoma cells in vitro. Using immunohistochemistry (IHC), we stained a tissue microarray containing primary conventional and dedifferentiated chondrosarcoma from 76 patients with CSPG4 specific monoclonal antibodies (mAbs). In addition, we incubated 2 chondrosarcoma cell lines with CSPG4-targeting CAR T cells and subsequently evaluated cell survival. Our results showed medium to high expression of CSPG4 in 29 of 41 (71%) conventional chondrosarcoma tumors and in 3 of 20 (15%) dedifferentiated chondrosarcoma tumors. CSPG4 expression showed a positive association with time to metastasis and survival in both subtypes. CSPG4 CAR T treated cell lines showed a lysis of respectively >80% and 70% demonstrating CSPG4-targeted CAR T cells effective in killing CSPG4-positive chondrosarcoma tumors.

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PURPOSE: The aim of this study was to characterize chondrosarcoma tumor infiltration by immune cells and the expression of immunologically relevant molecules. This information may contribute to our understanding of the role of immunological events in the pathogenesis of chondrosarcoma and to the rational design of immunotherapeutic strategies. PATIENTS AND METHODS: A tissue microarray (TMA) containing 52 conventional and 24 dedifferentiated chondrosarcoma specimens was analyzed by immunohistochemical staining for the expression of parameters associated with tumor antigen-specific immune responses, namely, CD4+ and CD8+ tumor infiltrating lymphocytes (TILs) and the expression of HLA class I heavy chain, beta-2 microglobulin (ß2m), HLA class II and immune checkpoint molecules, B7-H3 and PD-1/PD-L1. The results were correlated with histopathological characteristics and the clinical course of the disease. RESULTS: CD8+ TILs were present in 21% of the conventional and 90% of the dedifferentiated chondrosarcoma tumors tested. B7-H3 was expressed in 69% of the conventional and 96% of the dedifferentiated chondrosarcoma tumors tested. PD-1 and PD-L1 were expressed 53% and 33% respectively of the dedifferentiated tumors tested. PD-L1 expression was associated with shorter time to metastasis. CONCLUSION: The tumor infiltration by lymphocytes suggests that chondrosarcoma is immunogenic. Defects in HLA class I antigen and expression of the checkpoint molecules B7-H3 and PD-1/PD-L1 suggest that tumor cells utilize escape mechanisms to avoid immune recognition and destruction. This data implies that chondrosarcoma will benefit from strategies that enhance the immunogenicity of tumor antigens and/or counteract the escape mechanisms.

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BACKGROUND: There are no effective systemic therapies for chordoma. The recent successes of immunotherapeutic strategies in other cancers have resulted in a resurgence of interest in using immunotherapy in chordoma. These approaches rely on a functional interaction between the host's immune system and the expression of tumor peptides via the human leukocyte antigen (HLA) Class I antigen. It is not known whether chordoma cells express the HLA Class I antigen. QUESTIONS/PURPOSES: (1) Do chordoma tumors exhibit defects in HLA Class I antigen expression? (2) What is the pattern of lymphocyte infiltration in chordoma tumors? METHODS: Patients with chordoma treated at Massachusetts General Hospital between 1989 and 2009 were identified with permission from the institutional review board. Of the 75 patients who were identified, 24 human chordoma tumors were selected from 24 distinct patients based on tissue availability. Histology slides from these 24 formalin-fixed paraffin-embedded chordoma tissue samples were deparaffinized using xylene and ethanol and underwent heat-induced antigen retrieval in a citrate buffer. Samples were incubated with monoclonal antibodies directed against HLA Class I antigen processing machinery components. Antibody binding was detected via immunohistochemical staining. Staining intensity (negative, weakly positive, strongly positive) was assessed semiquantitatively and the percentage of chordoma cells stained for HLA Class I antigen subunits was assessed quantitatively. Hematoxylin and eosin-stained histology slides from the same 24 chordoma samples were assessed qualitatively for the presence of tumor-infiltrating lymphocytes and histologic location of these lymphocytes. Immunohistochemical staining with monoclonal antibodies directed against CD4 and CD8 was performed in a quantitative manner to identify the lymphocyte subtype present in chordoma tumors. All results were scored independently by two investigators and were confirmed by a senior bone and soft tissue pathologist. RESULTS: Seven of 24 chordoma samples exhibited no staining by the anti-HLA-A heavy chain monoclonal antibody HC-A2, two had weak staining intensity, and eight had a heterogeneous staining pattern, with fewer than 60% of chordoma cells exhibiting positive staining results. Four of 24 samples tested were not stained by the anti-HLA-B/C heavy chain monoclonal antibody HC-10, five had weak staining intensity, and 11 displayed a heterogeneous staining pattern. For the anti-ß-2-microglobulin monoclonal antibody NAMB-1, staining was detected in all samples, but 11 had weak staining intensity and four displayed a heterogeneous staining pattern. Twenty-one of 24 samples tested had decreased expression in at least one subunit of HLA Class I antigens. No tumors were negative for all three subunits. Lymphocytic infiltration was found in 21 of 24 samples. Lymphocytes were primarily found in the fibrous septae between chordoma lobules but also within the tumor lobules and within the fibrous septae and tumor lobules. Twenty-one of 24 tumors had CD4+ T cells and 11 had CD8+ T cells. CONCLUSION: In chordoma tissue samples, HLA Class I antigen defects commonly were present, suggesting a mechanism for escape from host immunosurveillance. Additionally, nearly half of the tested samples had cytotoxic CD8+ T cells present in chordoma tumors, suggesting that the host may be capable of mounting an immune response against chordoma tumors. The resulting selective pressure imposed on chordoma tumors may lead to the outgrowth of chordoma cell subpopulations that can evade the host's immune system. CLINICAL RELEVANCE: These findings have implications in the design of immunotherapeutic strategies for chordoma treatment. T cell recognition of tumor cells requires HLA Class I antigen expression on the targeted tumor cells. Defects in HLA Class I expression may play a role in the clinical course of chordoma and may account for the limited or lack of efficacy of T cell-based immunity triggered by vaccines and/or checkpoint inhibitors.

Asunto(s)

Cordoma/inmunología , Antígenos HLA/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Monitorización Inmunológica , Anticuerpos Monoclonales/inmunología , Linfocitos T CD8-positivos/inmunología , Humanos

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BACKGROUND: No consensus exists on the best method of articular reconstruction in patients who require proximal humerus resection for the management of primary bone sarcomas, soft-tissue sarcomas extending into the bone, benign and locally aggressive primary bone tumors, and metastatic disease. METHODS: We identified patients from two institutions who underwent wide resection of the proximal humerus along with oncologic reconstruction using osteoarticular allografts (OAs), endoprostheses, or allograft-prosthesis composites. We prospectively collected functional outcomes and retrospectively assessed complications and implant survival. RESULTS: A total of 150 patients were included in this study. The average Disabilities of the Arm, Shoulder and Hand questionnaire score was 26 for 25 patients, of which we gathered their functional data, with no differences in physical function among the three constructional methods according to the Disabilities of the Arm, Shoulder and Hand questionnaire, upper extremity Toronto Extremity Salvage Score, upper extremity Musculoskeletal Tumor Society, and Patient-Reported Outcomes Measurement Information System scores. Overall, the survival rate of the prosthesis was >50%. A trend was noted for a higher risk of failure in the OA group secondary to the allograft fracture. DISCUSSION: All three articular oncologic shoulder reconstructions were comparable in terms of function. This large series confirms a higher fracture rate in OAs, which explains the observed higher revision rate and apparent lower survival rate in this subgroup.

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Artroplastía de Reemplazo de Hombro/efectos adversos , Húmero/cirugía , Procedimientos de Cirugía Plástica/efectos adversos , Complicaciones Posoperatorias/fisiopatología , Prótesis de Hombro/efectos adversos , Adulto , Anciano , Artroplastía de Reemplazo de Hombro/métodos , Neoplasias Óseas/fisiopatología , Neoplasias Óseas/cirugía , Trasplante Óseo/métodos , Femenino , Humanos , Húmero/fisiopatología , Masculino , Persona de Mediana Edad , Osteosarcoma/fisiopatología , Osteosarcoma/cirugía , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Estudios Prospectivos , Rango del Movimiento Articular , Procedimientos de Cirugía Plástica/métodos , Recuperación de la Función , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Sarcoma/fisiopatología , Sarcoma/cirugía , Resultado del Tratamiento

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BACKGROUND: Candidates for migraine surgery are chronic pain patients with significant disability. Currently, migraine-specific questionnaires are used to evaluate these patients. Analysis tools widely used in evaluation of better understood pain conditions are not typically applied. This is the first study to include a commonly used pain questionnaire, the Pain Self-Efficacy Questionnaire (PSEQ) that is used to determine patients' pain coping abilities and function. It is an important predictor of pain intensity/disability in patients with musculoskeletal pain, as low scores have been associated with poor outcome. METHODS: Ninety patients were enrolled prospectively and completed the Migraine Headache Index and PSEQ preoperatively and at 12 months postoperatively. Scores were evaluated using paired t tests and Pearson correlation. Representative PSEQ scores for other pain conditions were chosen for score comparison. RESULTS: All scores improved significantly from baseline (p < 0.01). Mean preoperative pain coping score (PSEQ) was 18.2 ± 11.7, which is extremely poor compared with scores reported for other pain conditions. Improvement of PSEQ score after migraine surgery was higher than seen in other pain conditions after treatment (112 percent). Preoperative PSEQ scores did not influence postoperative outcome. CONCLUSIONS: The PSEQ successfully demonstrates the extent of debility in migraine surgery patients by putting migraine pain in perspective with other known pain conditions. It further evaluates functional status, rather than improvement in migraine characteristics, which significantly adds to our understanding of outcome. Poor preoperative PSEQ scores do not influence outcome and should not be used to determine eligibility for migraine surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

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Adaptación Psicológica , Dolor Crónico/psicología , Dolor Crónico/cirugía , Trastornos Migrañosos/psicología , Trastornos Migrañosos/cirugía , Dimensión del Dolor/métodos , Autoeficacia , Dolor Crónico/diagnóstico , Estudios de Seguimiento , Humanos , Trastornos Migrañosos/diagnóstico , Periodo Preoperatorio , Estudios Prospectivos , Resultado del Tratamiento

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BACKGROUND: The main reconstruction techniques for proximal humerus tumors include osteoarticular allografts (OAs), endoprostheses (EPs), or allograft prosthetic composites (APCs). A common complication is infection, and constructs involving the use of allografts are believed to be at a higher risk of infection. Literature comparing infection rates between different modalities of reconstruction is scarce and underpowered. The study purposes were (1) to determine and compare the prevalence of infection in patients who underwent reconstruction of the proximal humerus including OAs, EPs, and APCs; (2) to identify preoperative, perioperative, and postoperative predictors of infection that might be modifiable; and (3) to present our protocol of treatment in patients with superficial and deep infections. METHODS: We reviewed 150 patients of all ages with proximal humerus tumors treated by an OA, EP, or APC at 2 tertiary institutions. The prevalence of infection for each modality was calculated and compared between groups. We identified potential predictors of infection with stepwise backward multivariate Cox regression analysis. RESULTS: An infection developed in 19 patients (12%): 5 of 45 (11%) in the OA group, 12 of 85 (14%) in the EP group, and 2 of 20 (10%) in the APC group (P = .740). A lower preoperative hemoglobin blood level and low preoperative albumin blood level were independently associated with infection. CONCLUSIONS: We found similar infection rates compared with previously reported series. However, we did not identify a higher infection prevalence in constructs using allografts. Patients with a lower preoperative hemoglobin or albumin level are at higher risk of infection and should undergo optimization before surgery.

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Artroplastia/métodos , Neoplasias Óseas/cirugía , Cabeza Humeral/cirugía , Infecciones/epidemiología , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Artroplastia/efectos adversos , Neoplasias Óseas/sangre , Trasplante Óseo/efectos adversos , Femenino , Hemoglobinas/metabolismo , Humanos , Infecciones/sangre , Infecciones/terapia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/terapia , Periodo Preoperatorio , Prevalencia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Albúmina Sérica/metabolismo , Articulación del Hombro/cirugía , Trasplante Homólogo/efectos adversos

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Background: Variation in pain intensity and magnitude of disability among patients with musculoskeletal illness is largely accounted for by variations in symptoms of depression, catastrophic thinking, and heightened illness concern. It is possible that patients with greater stress, distress, and less effective coping strategies might be more likely to seek the use of Complementary Health Approaches (CHA). This study addressed the primary null hypothesis that there are no demographic, illness-related, or psychological factors associated with CHA use among patients with upper extremity illness. Methods: A cohort of 170 patients completed a web-based Complementary and Alternative Medicine (CAM) questionnaire the Patient Reported Outcomes Measurement Information System (PROMIS) Depression and Pain Interference questionnaires. We evaluated differences between patients who sought CAM treatment regarding the PROMIS Pain Interference and PROMIS Depression scores. Ninety-four patients (56%) use or plan to use CAM treatment. A CAM provider was consulted by 61 patients (37%): most commonly a massage therapist (30/61), chiropractor (26/61), or acupuncturist (14/61). Results: In bivariate analysis patients who sought CAM reported greater average PROMIS Pain Interference than those who did not. In multivariable logistic regression, CAM use was associated with a higher Pain Interference Score and the specific surgeon. Conclusion: In conclusion, CHA use is prevalent amongst orthopaedic patients and associated with less effective coping strategies. Orthopaedic surgeons might consider asking patients about CHA use and determining whether those patients are interested in cognitive behavioral therapy.

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Adaptación Psicológica , Terapias Complementarias/estadística & datos numéricos , Depresión/psicología , Dolor Musculoesquelético/psicología , Dolor Musculoesquelético/terapia , Medición de Resultados Informados por el Paciente , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Encuestas Epidemiológicas/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Estrés Psicológico/psicología , Extremidad Superior

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BACKGROUND: This study addresses the null hypothesis that there is no expansion of heterotopic ossification (HO) in the elbow beyond what can be seen early on. METHODS: The area of HO was measured on lateral radiographs of 38 consecutive patients that had operative treatment of HO between 2000 and 2013. Measurements from radiographs obtained between 3 to 7 weeks were compared to measurements from radiographs made 3 months or more after injury. RESULTS: There was no significant difference between the average area of HO on the first (median 2.8 square centimeters, Q1: 1.5, Q3: 5.1) and later radiographs (median of 2.8 square centimeters, Q1: 1.4, Q3: 5.0) (P = 0.99). CONCLUSION: According to our results the area of HO does not expand beyond what can be seen early in the disease process.

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BACKGROUND: Pain intensity and disability correlate with psychosocial factors such as depression and pain interference (the degree to which pain interferes with activities of daily living) as much or more than pathophysiology in upper extremity illness. However, other factors like emotional support (perception of being cared for and valued as a person), instrumental support (perception of availability of tangible assistance when needed), positive psychosocial impact (perception and focus on the positive side of a difficult situation, sometimes characterized as posttraumatic growth, benefit-finding, or meaning making), also might be associated with disability in patients with upper extremity orthopaedic illness. This is the first published study, to our knowledge, addressing the potential association of emotional support, instrumental support, and positive psychosocial illness impact with disability in patients with upper extremity illness. QUESTIONS/PURPOSES: We asked: (1) Is there a correlation between the QuickDASH and the Patient-reported Outcomes Measurement Information System (PROMIS(®)) emotional support Computer Adaptive Testing (CAT)? (2) Is there a correlation between the QuickDASH and PROMIS(®) instrumental support CAT? (3) Is there a correlation between the QuickDASH and PROMIS(®) positive psychosocial illness impact CAT? (4) Among the PROMIS(®) measures of depression, emotional support, instrumental support, positive illness impact, and pain interference, which accounts for the most variance in QuickDASH scores? METHODS: One hundred ninety-three patients with upper extremity illness (55% women; average age, 51 ± 18 years) of 213 approached (91% recruitment rate) completed the QuickDASH, and five different PROMIS(®) CATs: pain interference (the degree to which pain interferes with accomplishing one's goals), depression, emotional support, psychosocial illness impact, and instrumental support. We recruited patients from the practice of three surgeons in hand service of the department of orthopaedic surgery at a major urban university hospital. RESULTS: Pearson Product Moment Correlations showed that emotional support (r = -0.18; p = 0.014) and instrumental support (r = -0.19; p = 0.008) were weakly and inversely associated with the QuickDASH), while positive psychosocial illness impact was moderately and inversely associated with the QuickDASH (r = -0.36; p < 0.001). In multivariable analyses, pain interference, but not the social support measures, was the only psychosocial factor associated with the QuickDASH and alone explained 66% of variance. CONCLUSIONS: Emotional support, instrumental support and positive psychosocial illness impact are all individually associated with disability to a small degree, but pain interference (the degree to which pain interferes with accomplishing one's goals) has the strongest influence on magnitude of disability. LEVEL OF EVIDENCE: Level 1, prognostic study.

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Evaluación de la Discapacidad , Emociones , Accesibilidad a los Servicios de Salud , Dolor Musculoesquelético/diagnóstico , Apoyo Social , Extremidad Superior/fisiopatología , Actividades Cotidianas , Adaptación Psicológica , Adulto , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Costo de Enfermedad , Estudios Transversales , Depresión/diagnóstico , Depresión/fisiopatología , Depresión/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor Musculoesquelético/fisiopatología , Dolor Musculoesquelético/psicología , Dolor Musculoesquelético/terapia , Dimensión del Dolor , Evaluación del Resultado de la Atención al Paciente , Valor Predictivo de las Pruebas , Pronóstico , Encuestas y Cuestionarios , Adulto Joven

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BACKGROUND: BRAF(V600E)-mediated MAPK pathway activation is associated in melanoma cells with IFNAR1 downregulation. IFNAR1 regulates melanoma cell sensitivity to IFNα, a cytokine used for the adjuvant treatment of melanoma. These findings and the limited therapeutic efficacy of BRAF-I prompted us to examine whether the efficacy of IFNα therapy of BRAF(V600E) melanoma can be increased by its combination with BRAF-I. METHODS: BRAF/NRAS genotype, ERK activation, IFNAR1, and HLA class I expression were tested in 60 primary melanoma tumors from treatment-naive patients. The effect of BRAF-I on IFNAR1 expression was assessed in three melanoma cell lines and in four biopsies of BRAF(V600E) metastases. The antiproliferative, pro-apoptotic and immunomodulatory activity of BRAF-I and IFNα combination was tested in vitro and in vivo utilizing three melanoma cell lines, HLA class I-MA peptide complex-specific T-cells and immunodeficient mice (5 per group for survival and 10 per group for tumor growth inhibition). All statistical tests were two-sided. Differences were considered statistically significant when the P value was less than .05. RESULTS: The IFNAR1 level was statistically significantly (P < .001) lower in BRAF(V600E) primary melanoma tumors than in BRAF wild-type tumors. IFNAR1 downregulation was reversed by BRAF-I treatment in the three melanoma cell lines (P ≤ .02) and in three out of four metastases. The IFNAR1 level in the melanoma tumors analyzed was increased as early as 10 to 14 days following the beginning of the treatment. These changes were associated with: 1) an increased susceptibility in vitro of melanoma cells to the antiproliferative (P ≤ .04), pro-apoptotic (P ≤ .009) and immunomodulatory activity, including upregulation of HLA class I antigen APM component (P ≤ .04) and MA expression as well as recognition by cognate T-cells (P < .001), of BRAF-I and IFNα combination and 2) an increased survival (P < .001) and inhibition of tumor growth of melanoma cells (P < .001) in vivo by BRAF-I and IFNα combination. CONCLUSIONS: The described results provide a strong rationale for the clinical trials implemented in BRAF(V600E) melanoma patients with BRAF-I and IFNα combination.

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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Interferón-alfa/farmacología , Melanoma/tratamiento farmacológico , Mutación , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/genética , Receptor de Interferón alfa y beta/metabolismo , Neoplasias Cutáneas/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica , Ácido Glutámico , Humanos , Inmunohistoquímica , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/genética , Melanoma/genética , Melanoma/metabolismo , Ratones , Ratones Endogámicos NOD , Ratones SCID , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Valina

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PURPOSE: More effective therapy is needed for intrahepatic cholangiocarcinoma (ICC). The encouraging clinical results obtained with checkpoint molecule-specific monoclonal antibodies (mAb) have prompted us to investigate whether this type of immunotherapy may be applicable to ICC. The aims of this study were to determine whether (i) patients mount a T-cell immune response to their ICC, (ii) checkpoint molecules are expressed on both T cells and tumor cells, and (iii) tumor cells are susceptible to recognition by cognate T cells. EXPERIMENTAL DESIGN: Twenty-seven ICC tumors were analyzed for (i) lymphocyte infiltrate, (ii) HLA class I and HLA class II expression, and (iii) PD-1 and PD-L1 expression by T cells and ICC cells, respectively. The results of this analysis were correlated with the clinicopathologic characteristics of the patients investigated. RESULTS: Lymphocyte infiltrates were identified in all tumors. PD-L1 expression and HLA class I antigen expression by ICC cells was observed in 8 and 11, respectively, of the 27 tumors analyzed. HLA class I antigen expression correlated with CD8(+) T-cell infiltrate. Furthermore, positive HLA class I antigen expression in combination with negative/rare PD-L1 expression was associated with favorable clinical course of the disease. CONCLUSIONS: ICC patients are likely to mount a T-cell immune response against their own tumors. Defects in HLA class I antigen expression in combination with PD-L1 expression by ICC cells provide them with an immune escape mechanism. This mechanism justifies the implementation of immunotherapy with checkpoint molecule-specific mAbs in patients bearing ICC tumors without defects in HLA class I antigen expression.

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Antígeno B7-H1/inmunología , Neoplasias de los Conductos Biliares/inmunología , Colangiocarcinoma/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/inmunología , Conductos Biliares Intrahepáticos/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Humanos , Inmunoterapia/métodos , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad

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Introduction. Chondrosarcomas are malignant bone tumors that are characterized by the production of chondroid tissue. Since radiation therapy and chemotherapy have limited effect on chondrosarcoma, treatment of most patients depends on surgical resection. We conducted this study to identify independent predictive factors and survival characteristics for conventional central chondrosarcoma and dedifferentiated central chondrosarcoma. Methods. A systematic literature review was performed in September 2014 using the Pubmed, Embase, and Cochrane databases. Subsequent to a beforehand-composed selection procedure we included 13 studies, comprising a total of 1114 patients. Results. The prognosis of central chondrosarcoma is generally good for the histologically low-grade tumors. Prognosis for the high-grade chondrosarcoma and the dedifferentiated chondrosarcoma is poor with lower survival rates. Poor prognostic factors in conventional chondrosarcoma for overall survival are high-grade tumors and axial/pelvic tumor location. In dedifferentiated chondrosarcoma the percentage of dedifferentiated component has significant influence on disease-free survival. Conclusion. Despite the fact that there are multiple prognostic factors identified, as shown in this study, there is a need for prospective and comparative studies. The resulting knowledge about prognostic factors and survival can give direction in the development of better therapies. This could eventually lead to an evidence-based foundation for treating chondrosarcoma patients.

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OBJECTIVES: To determine if closed reduction is worthwhile for the subset of patients who choose operative treatment before attempted reduction of their distal radius fracture. We hypothesize that there are no differences in (1) adverse events and (2) subsequent surgeries between patients treated with manipulative reduction compared with those that were splinted without reduction. DESIGN: Retrospective cohort study. SETTING: Three affiliated urban hospitals in a single city in the United States. PATIENTS/PARTICIPANTS: One thousand five hundred eleven consecutive adult patients who underwent open reduction and internal fixation of their distal radius fracture between January 1, 2007, and December 31, 2012, of whom 102 (7%) were not reduced before surgery. INTERVENTION: Manipulative reduction compared with splinting without reduction. MAIN OUTCOME MEASUREMENTS: Adverse events were defined as any infections, hematomas treated operatively, disproportionate finger stiffness, (transient) neuropathology after surgery, delayed carpal tunnel release, malunion, reoperation for loss of alignment, hardware removal, and tendon ruptures within 1 year after surgery. Outcome measures were grouped to determine the overall adverse event rate and subsequent surgery rate. RESULTS: We found no difference in specific adverse events between unreduced and reduced fractures. After adjusting for possible confounding variables by logistic regression, we found no difference in overall rates of adverse events (adjusted odds ratio unreduced fractures 1.2, 95% confidence interval 0.67-2.0) and subsequent surgeries (adjusted odds ratio unreduced fractures 0.65, 95% confidence interval 0.23-1.8). CONCLUSIONS: Leaving the fracture unreduced before surgery was not associated with increased adverse events or subsequent surgeries. For patients who make an informed decision to undergo operative treatment for their closed neurovascular intact displaced distal radius fracture, manipulative reduction may not be helpful.

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Fijación de Fractura/efectos adversos , Manipulación Ortopédica/efectos adversos , Fracturas del Radio/cirugía , Adulto , Anciano , Femenino , Fijación Interna de Fracturas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Fracturas del Radio/complicaciones , Fracturas del Radio/terapia , Estudios Retrospectivos , Férulas (Fijadores)

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BACKGROUND: Geographic and doctor-to-doctor variations in care are a focus of quality and safety efforts in medicine. This study addresses factors associated with variation in the rate of operative treatment of de Quervain tendinopathy. METHODS: We used a database including all patient encounters at 2 large medical centers, to study the experience of 10 hand surgeons and 1 physiatrist working in a hand surgery office in the treatment of 2,513 patients with de Quervain tendinopathy over a 12-year period. Survival analysis using the Kaplan-Meier method was used to compare surgery rates and time to surgery. Cox multivariable regression analysis was applied to identify factors associated with operative treatment. RESULTS: One hundred ninety nine (7.9%) patients had surgery. The odds of operative treatment were 1.7 times greater after corticosteroid injection and varied more than 10-fold among providers. There was substantial variation in the overall rate of surgery by provider. Corticosteroid injection delayed surgery slightly, but was associated with a higher rate of surgery. CONCLUSION: Providers have substantial influence on treatment of de Quervain tendinopathy. The use of decision aids and other methods that help involve the patient in decision-making merit investigation as interventions to help reduce doctor-to-doctor variation.

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Background Finger stiffness varies substantially in patients with hand and upper extremity illness and can be notably more than expected for a given pathophysiology. In prior studies, pain intensity and magnitude of disability consistently correlate with coping strategies such as catastrophic thinking and kinesiophobia, which can be characterized as overprotectiveness. In this retrospective study we address the primary research question whether patients with finger stiffness are more often overprotective when the primary pathology is outside the hand (e.g. distal radius fracture) than when it is located within the hand. Methods In an orthopaedic hand surgery department 160 patients diagnosed with more finger stiffness than expected for a given pathophysiology or time point of recovery between December 2006 and September 2012 were analyzed to compare the proportion of patients characterized as overprotective for differences by site of pathology: (1) inside the hand, (2) outside the hand, and (3) psychiatric etiology (e.g. clenched fist). Results Among 160 subjects with more finger stiffness than expected, 132 (82 %) were characterized as overprotective including 88 of 108 (81 %) with pathology in the hand, 39 of 44 (89 %) with pathology outside the hand, and 5 of 8 (63 %) with psychiatric etiology. These differences were not significant. Conclusions Overprotectiveness is common in patients with more finger stiffness than expected regardless the site and type of primary pathology. It seems worthwhile to recognize and treat maladaptive coping strategies early during recovery to limit impairment, symptoms, and disability.

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BACKGROUND: Illness (symptoms and disability) consistently correlates more with coping strategies and symptoms of depression than with pathophysiology or impairment. OBJECTIVE: This study tested the primary null hypothesis that there is no correlation between verbal and nonverbal communication of pain (pain behavior) and upper extremity-specific disability in patients with hand and upper extremity illness. METHODS: A total of 139 new and followed up adult patients completed the QuickDASH, an ordinal rating of pain, and 4 Patient-Reported Outcomes Measurement Information System (PROMIS) Computer Adaptive Testing instruments: (1) PROMIS pain behavior, (2) PROMIS pain interference (measuring the degree to which pain interferes with achieving ones physical goals), (3) PROMIS physical function, and (4) PROMIS depression. RESULTS: Factors associated with a higher QuickDASH score in bivariate analysis included a higher PROMIS pain behavior score, not working, being separated/divorced or widowed, having sought treatment before, having other pain conditions, a higher PROMIS pain interference score, a higher PROMIS depression score, and lower education level. The final multivariable model of factors associated with QuickDASH included PROMIS pain interference, having other pain conditions, and being separated/divorced or widowed, and it explained 64% of the variability. CONCLUSION: PROMIS pain behavior (verbal and nonverbal communication of pain) correlates with upper extremity disability, but PROMIS pain interference (the degree to which pain interferes with activity) is a more important factor. LEVEL OF EVIDENCE: Level IV, cross-sectional study.

Asunto(s)

Comunicación , Evaluación de la Discapacidad , Dimensión del Dolor/métodos , Dolor/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Comunicación no Verbal , Adulto Joven

RESUMEN

BACKGROUND: Patients in other countries use fewer opioids than patients in the United States with satisfactory pain relief. OBJECTIVE: This study tested the null hypothesis that opioid intake after orthopedic surgery does not influence satisfaction with pain management. METHODS: A total of 232 orthopedic surgical inpatients completed measures of pain self-efficacy and symptoms of depression at enrollment and commonly used measures of pain intensity, satisfaction with pain relief, and satisfaction with hospital staff attention to pain approximately 14 days after surgery. Inpatient opioid intake per 24-hour period was quantified. RESULTS: At a phone evaluation approximately 2 weeks after discharge from the hospital, patients who were always satisfied with their pain relief in hospital and always satisfied with staff attention to pain used significantly less opioids on day 1 compared with patients who were not always satisfied. There were no differences in satisfaction by type of surgery. The final multivariable model for not always satisfied with pain relief included greater opioid use on day 1 (odds ratio = 1.2), and preadmission diagnosis of depression (odds ratio = 2.6). Greater opioid use on day 1 was the only factor associated with less than always satisfied with the staff attention to pain relief (odds ratio = 1.3). CONCLUSIONS: Patients who take more opioids report less satisfaction with pain relief and greater pain intensity. Evidence-based interventions to increase self-efficacy merit additional study for the management of postoperative pain. LEVEL OF EVIDENCE: Prognostic, Level 1.

Asunto(s)

Analgésicos Opioides/uso terapéutico , Ortopedia , Manejo del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológico , Satisfacción del Paciente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Relaciones Profesional-Paciente , Estudios Prospectivos , Autoeficacia , Encuestas y Cuestionarios

RESUMEN

BACKGROUND: Orthopaedic surgical site infections (SSIs) can delay recovery, add impairments, and decrease quality of life, particularly in patients undergoing spine surgery, in whom SSIs may also be more common. Efforts to prevent and treat SSIs of the spine rely on the identification and registration of these adverse events in large databases. The effective use of these databases to answer clinical questions depends on how the conditions in question, such as infection, are defined in the databases queried, but the degree to which different definitions of infection might cause different risk factors to be identified by those databases has not been evaluated. QUESTIONS/PURPOSES: The purpose of this study was to determine whether different definitions of SSI identify different risk factors for SSI. Specifically, we compared the International Classification of Diseases, 9th Revision (ICD-9) coding, Centers for Disease Control and Prevention (CDC) criteria for deep infection, and incision and débridement for infection to determine if each is associated with distinct risk factors for SSI. METHODS: In this single-center retrospective study, a sample of 5761 adult patients who had an orthopaedic spine surgery between January 2003 and August 2013 were identified from our institutional database. The mean age of the patients was 56 years (± 16 SD), and slightly more than half were men. We applied three different definitions of infection: ICD-9 code for SSI, the CDC criteria for deep infection, and incision and débridement for infection. Three hundred sixty-one (6%) of the 5761 surgeries received an ICD-9 code for SSI within 90 days of surgery. After review of the medical records of these 361 patients, 216 (4%) met the CDC criteria for deep SSI, and 189 (3%) were taken to the operating room for irrigation and débridement within 180 days of the day of surgery. RESULTS: We found the Charlson Comorbidity Index, the duration of the operation, obesity, and posterior surgical approach were independently associated with a higher risk of infection for each of the three definitions of SSI. The influence of malnutrition, smoking, specific procedures, and specific surgeons varied by definition of infection. These elements accounted for approximately 6% of the variability in the risk of developing an infection. CONCLUSIONS: The frequency of SSI after spine surgery varied according to the definition of an infection, but the most important risk factors did not. We conclude that large database studies may be better suited for identifying risk factors than for determining absolute numbers of infections. LEVEL OF EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Asunto(s)

Procedimientos Ortopédicos/efectos adversos , Columna Vertebral/cirugía , Infección de la Herida Quirúrgica/clasificación , Infección de la Herida Quirúrgica/epidemiología , Terminología como Asunto , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Centers for Disease Control and Prevention, U.S. , Comorbilidad , Minería de Datos , Bases de Datos Factuales , Desbridamiento , Femenino , Humanos , Incidencia , Clasificación Internacional de Enfermedades , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Infección de la Herida Quirúrgica/diagnóstico , Infección de la Herida Quirúrgica/microbiología , Infección de la Herida Quirúrgica/cirugía , Irrigación Terapéutica , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología , Adulto Joven

RESUMEN

BACKGROUND: To assess disability more efficiently with less burden on the patient, the National Institutes of Health has developed the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function-an instrument based on item response theory and using computer adaptive testing (CAT). Initially, upper and lower extremity disabilities were not separated and we were curious if the PROMIS Physical Function CAT could measure upper extremity disability and the Quick Disability of Arm, Shoulder and Hand (QuickDASH). QUESTIONS/PURPOSES: We aimed to find correlation between the PROMIS Physical Function and the QuickDASH questionnaires in patients with upper extremity illness. Secondarily, we addressed whether the PROMIS Physical Function and QuickDASH correlate with the PROMIS Depression CAT and PROMIS Pain Interference CAT instruments. Finally, we assessed factors associated with QuickDASH and PROMIS Physical Function in multivariable analysis. METHODS: A cohort of 93 outpatients with upper extremity illnesses completed the QuickDASH and three PROMIS CAT questionnaires: Physical Function, Pain Interference, and Depression. Pain intensity was measured with an 11-point ordinal measure (0-10 numeric rating scale). Correlation between PROMIS Physical Function and the QuickDASH was assessed. Factors that correlated with the PROMIS Physical Function and QuickDASH were assessed in multivariable regression analysis after initial bivariate analysis. RESULTS: There was a moderate correlation between the PROMIS Physical Function and the QuickDASH questionnaire (r=-0.55, p<0.001). Greater disability as measured with the PROMIS and QuickDASH correlated most strongly with PROMIS Depression (r=-0.35, p<0.001 and r=0.34, p<0.001 respectively) and Pain Interference (r=-0.51, p<0.001 and r=0.74, p<0.001 respectively). The factors accounting for the variability in PROMIS scores are comparable to those for the QuickDASH except that the PROMIS Physical Function is influenced by other pain conditions while the QuickDASH is not. CONCLUSIONS: The PROMIS Physical Function instrument may be used as an upper extremity disability measure, as it correlates with the QuickDASH questionnaire, and both instruments are influenced most strongly by the degree to which pain interferes with achieving goals. LEVEL OF EVIDENCE: Level III, diagnostic study. See the Instructions for Authors for a complete description of levels of evidence.

Asunto(s)

Evaluación de la Discapacidad , Enfermedades Musculoesqueléticas/diagnóstico , Dimensión del Dolor , Encuestas y Cuestionarios , Extremidad Superior/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Enfermedades Musculoesqueléticas/fisiopatología , Enfermedades Musculoesqueléticas/psicología , Valor Predictivo de las Pruebas , Pronóstico , Índice de Severidad de la Enfermedad , Adulto Joven

RESUMEN

BACKGROUND: Publication of a manuscript does not end an author's responsibilities. Reasons to contact an author after publication include clarification, access to raw data, and collaboration. However, legitimate questions have been raised regarding whether these responsibilities generally are being met by corresponding authors of biomedical publications. QUESTIONS/PURPOSES: This study aims to establish (1) what proportion of corresponding authors accept the responsibility of correspondence; (2) identify characteristics of responders; and (3) assess email address decay with time. We hypothesize that the response rate is unrelated to journal impact factor. METHODS: We contacted 450 corresponding authors throughout various fields of biomedical research regarding the availability of additional data from their study, under the pretense of needing these data for a related review article. Authors were randomly selected from 45 journals whose impact factors ranged from 52 to 0; the source articles were published between May 2003 and May 2013. The proportion of corresponding authors who replied, along with author characteristics were recorded, as was the proportion of emails that were returned for inactive addresses; 446 authors were available for final analysis. RESULTS: Fifty-three percent (190/357) of the authors with working email addresses responded to our request. Clinical researchers were more likely to reply than basic/translational scientists (51% [114/225] versus 34% [76/221]; p<0.001). Impact factor and other author characteristics did not differ. Logistic regression analysis showed that the odds of replying decreased by 15% per year (odds ratio [OR], 0.85; 95% CI, 0.79-0.91; p<0.001), and showed a positive relationship between clinical research and response (OR, 2.0; 95% CI, 1.3-2.9; p=0.001). In 2013 all email addresses (45/45) were reachable, but within 10 years, 49% (21/43) had become invalid. CONCLUSIONS: Our results suggest that contacting corresponding authors is problematic throughout the field of biomedical research. Defining the responsibilities of corresponding authors by journals more explicitly-particularly after publication of their manuscript-may increase the response rate on data requests. Possible other ways to improve communication after research publication are: (1) listing more than one email address per corresponding author, eg, an institutional and personal address; (2) specifying all authors' email addresses; (3) when an author leaves an institution, send an automated reply offering alternative ways to get in touch; and (4) linking published manuscripts to research platforms.

Asunto(s)

Autoria , Comunicación , Relaciones Interprofesionales , Correo Electrónico , Humanos , Factor de Impacto de la Revista , Modelos Logísticos