The role of perceived patient injustice on pain related and functional outcomes in orthopaedic patients; a systematic review.

Introduction: Higher levels of perceived patient injustice has been associated with higher levels of pain and poor functional outcomes in patients with chronic musculoskeletal pain. We wanted to investigate if there was any evidence of this association in patients who underwent orthopaedic surgery. Materials and methods: A systematic search of the literature was performed independently by two researchers on the electronic databases of MEDLINE, EMBASE, Google Scholar, Web of Science, and the Cochrane Database of Systematic Reviews and data extracted in accordance with PRISMA guidelines for systematic reviews. Outcomes of interest were pain, pain intensity, pain interference, opiate use, disability, physical function, return to work, quality of life, depression, anxiety, post-traumatic stress, social functioning and quality of life. Results: Five studies were identified for qualitative analysis involving elective and trauma orthopaedic patients. All studies identified a positive correlation between higher levels of perceived injustice and depression, pain intensity and interference as well as reduced function and higher levels of disability. Conclusions: Higher levels of perceived patient injustice is associated with worse pain and functional outcomes in patients who undergo orthopaedic surgery in the traumatic and elective setting. Further research is warranted to further elucidate this association and identify potential therapeutic interventions.

Thromboembolic Events Associated with Thalidomide and Multimodality Therapy for Soft Tissue Sarcomas: Results of RTOG 0330.

Introduction. RTOG 0330 was developed to address the toxicity of RTOG 9514 and to add thalidomide (THAL) to MAID chemoradiation for intermediate/high grade soft tissue sarcomas (STSs) and to preoperative radiation (XRT) for low-grade STS. Methods. Primary/locally recurrent extremity/trunk STS: ≥8 cm, intermediate/high grade (cohort A): >5 cm, low grade (cohort B). Cohort A: 3 cycles of neoadjuvant MAID, 2 cycles of interdigitated THAL (200 mg/day)/concurrent 22 Gy XRT, resection, 12 months of adjuvant THAL. Cohort B: neoadjuvant THAL/concurrent 50 Gy XRT, resection, 6 months of adjuvant THAL. Planned accrual 44 patients. Results. 22 primary STS patients (cohort A/B 15/7). Cohort A/B: median age of 49/47 years; median tumor size 12.8/10 cm. 100% preoperative THAL/XRT and surgical resection. Three cycles of MAID were delivered in 93% cohort A. Positive margins: 27% cohort A/29% cohort B. Adjuvant THAL: 60% cohort A/57% cohort B. Grade 3/4 venous thromboembolic (VTE) events: 40% cohort A (1 catheter thrombus and 5 DVT or PE) versus 0% cohort B. RTOG 0330 closed early due to cohort A VTE risk and cohort B poor accrual. Conclusion. Neoadjuvant MAID with THAL/XRT was associated with increased VTE events not seen with THAL/XRT alone or in RTOG 9514 with neoadjuvant MAID/XRT.

Antineutrophil autoantibodies in Graves' disease. Implications of thyrotropin binding to neutrophils.

The hyperthyroidism of Graves' disease may be caused by autoantibodies to thyrotropin (TSH) receptors. We have found that patients with this disease have autoantibodies to neutrophils as well, which can be displaced by TSH. Using a radiochemical opsonic assay, we found serum antibodies against homologous neutrophils in 6 of 11 Graves' patients. With a staphylococcal protein A-binding assay, we detected circulating antibodies to homologous neutrophils in 10 of 20 patients, while finding cell-bound antibody on autologous neutrophils in 7 of 8 (including 2 with negative serum tests). Use of human 125I-TSH in a radioligand binding assay revealed that TSH bound to neutrophils rapidly (maximum binding within 10 min at 22 degrees C, pH 7.4), specifically (less than 20% nonspecific binding), and reversibly. Adding TSH to the radiochemical assay resulted in a dose-dependent inhibition of opsonic antibody activity in serum from patients with Graves' disease. In contrast, TSH did not inhibit antibody activity of serum from patients with immune neutropenia not associated with thyroid disease. Our findings suggest a basis for the association of Graves' disease with neutropenia. Furthermore, the discovery of such antineutrophil antibodies in Graves' disease permits detection of cell-bound antibody when free antibody is not present.

Treatment of the patient with stage M0 soft tissue sarcoma.

During the period 1971 to 1985, 220 patients with soft tissue sarcoma of the extremities, torso, and head-neck region were managed by radiation and resectional surgery at the Massachusetts General Hospital (MGH). Actuarial 5-year local control and disease-free survival rates were 86% and 70%, respectively. The success rate improved during this time period. Namely, the local control rates for 1971 to 1975, 1976 to 1980, and 1981 to 1985 were 81%, 81%, and 94%, respectively. For the same time periods, the 5-year disease-free survival rates were 64%, 70%, and 76%. One hundred thirty-one patients were treated with postoperative radiation, and 89 with preoperative radiation. In the most recent 5-year period, the local control rates were 91% and 97% for the two groups (number of patients being 50 and 57 in the post- and preoperative groups, respectively). Treatment by preoperative radiation appears to have a major advantage for patients with very large sarcomas, ie, greater than 15 cm in maximum dimension. None of our patients with local control of grade 1 sarcoma have developed distant metastasis (DM). In contrast, among patients with grade 2 or 3 sarcomas, there is a relentless and progressive increase in the frequency of DM with size of the primary lesion, namely, 6% at less than or equal to 2.5 cm, congruent to 60% at 15 to 20 cm, and congruent to 80% at greater than 20 cm.

Lymphocyte surface markers in orbital lymphoid neoplasms.

Since the malignant nature of many orbital lymphoid infiltrates is difficult to assess from pathologic examination alone, over the past four years lymphocyte surface marker studies have been added to the evaluation of 23 such cases. Only 10 of the 23 could be confidently classified as malignant lymphoma by histology alone. However, monoclonal surface immunoglobulin was found in 15, supporting the pathologic diagnosis of malignancy in eight and adding seven that could not have been diagnosed otherwise. Clinical evaluation, including a median follow-up of 18 months, revealed manifestations of systemic lymphoma in six of those 15; two had been diagnosed only by surface markers. In contrast, only one of eight cases lacking monoclonal surface immunoglobulin exhibited clinical evidence of malignancy (that case was also indeterminate by histologic criteria). The addition of surface marker analysis permits more accurate diagnosis of orbital lymphoma than is possible from pathologic study alone. This technique can suggest the subtype of lymphoma.

Severe acute enteritis in a multiple myeloma patient receiving bortezomib and spinal radiotherapy: case report.

Proteasome inhibitors have been reported to enhance radiosensitivity in vitro. A case of potential clinical interaction between bortezomib, a proteasome inhibitor, and spine radiation is reported. A woman undergoing palliative radiotherapy to the T12 -S2 spine with concurrent bortezomib developed unexpectedly severe, acute radiation enteritis requiring hospital admission. Clinicians are advised to consider the potential for interactions of bortezomib with radiotherapy when the two agents are used simultaneously in the clinic.

Prognostic factors for local control of sarcomas of the soft tissues managed by radiation and surgery.

During the past decade, local control of primary sarcomas of the extremities by radiation and conservative surgery has supplanted more radical compartmental resections or amputations. Reviews of others and our published data show that the probability of achieving local control is highly dependent on achieving negative surgical margins. Other factors, such as pathological grade and size, histopathology, and concomitant chemotherapy may also affect local control, to a much lesser extent, although these are strongly correlated with the likelihood of distant metastatic disease. Appreciation of the importance of these different prognostic factors has been fundamental to the development of the current rationale for sarcoma management.

Ewing's sarcoma: surgical resection as a prognostic factor.

A retrospective review of 46 cases of Ewing's (43) and extraosseous Ewing's (3) sarcoma was performed to examine for prognostic factors. Follow-up ranged from 27 to 135 months with a mean of 77.6 months, 86% greater than 36 months. Nine (20%) patients presented with distant metastases, 98% received multiagent chemotherapy, and 98% received radiation therapy. Overall actuarial survival and local control at 5 years were .52 +/- .08 and .78 +/- .07, respectively. The freedom from relapse or treatment related mortality at 5 years was .46 +/- .08. In 12 (26%) patients, surgical resection of the involved bone or soft tissue was part of the initial treatment plan. Ninety-two percent (11/12) of these patients also received radiation therapy. In addition to surgical resection, tumor size (less than 500 cc vs. greater than or equal to 500 cc), primary site (central vs. other), and stage were also analyzed for prognostic significance, and where appropriate, were included in Cox multivariate analyses. Considering all patients, the 5-year actuarial survival was .92 +/- .08 vs. .37 +/- .09 for patients receiving and not receiving surgical resection, respectively (p = .001 by logrank, p = .02 by Cox). To make the groups more comparable, 8 patients with local failure and 5 patients with non-evaluable primary sites were excluded. After these exclusions, the presence or absence of surgical resection had decreased significance: .92 +/- .08 vs. .59 +/- .11, respectively; p = .01 by logrank, p = .07 by Cox. Only primary site remained statistically significant: .86 +/- .08 for noncentral sites vs. .38 +/- .16 for central sites, p less than .0002 by logrank, p = .0004 by Cox. Surgical resection when added to local irradiation has prognostic significance in this retrospective review. The reason for this is not clear, but may be related to a decrease in local failure after resection.

Long-term results of combined modality therapy in primary bone lymphomas.

PURPOSE: To report the Massachusetts General Hospital experience in the management of patients with primary bone lymphoma (PBL) treated with combined modality therapy (CMT). METHODS AND MATERIALS: Records from 37 eligible patients were reviewed. Two patients were treated with complete resection of the tumor, while 35 patients underwent radiation therapy with a median total dose of 54 Gy (range 38.35-66.5). All patients received combination chemotherapy, which contained doxorubicin in 33 cases. We compared the current data with our previous experience in patients treated with local measures only. RESULTS: Actuarial disease-free survival (DFS) at 5 and 10 years is 78% and 73%, respectively, while overall survival (OS) is 91% and 87%, respectively. No local failures were seen. Pathologic fracture at presentation influenced DFS (p = 0.005) and OS (p = 0.017) adversely. OS was compromised in patients older than 60 years (p = 0.059) and DFS in patients with pelvic primaries (p = 0.015). CMT was associated with improved DFS (p = 0.0008) and OS p = 0.0001) compared to our historical controls. Ten patients (27%) developed complications requiring orthopedic procedures following completion of therapy at a median of 25.5 months (range 4-228). CONCLUSION: Patients with PBL have a favorable outcome with CMT, which appears superior to radiation therapy alone. Late complications can be seen, especially in weight-bearing bones.

Immunohistologic diagnosis of orbital lymphoid infiltrates.

The distinction between benign and malignant lymphoid infiltrates of the orbit may be impossible on routine histopathologic sections. However, the detection of monotypic immunoglobulin is useful in distinguishing neoplastic from benign infiltrates. Since diagnostic frozen sections are often performed on biopsies of orbital masses to determine the adequacy of the biopsy and to provide a preliminary diagnosis, we stained additional frozen sections of 20 predominantly lymphoid infiltrates by an immunoperoxidase technique with antisera to immunoglobulin heavy and light chains. On routine sections, nine cases were malignant lymphoma, three were follicular hyperplasia, and eight (42%) were dense lymphocytic infiltrates of indeterminate nature. The nine lymphomas had monotypic immunoglobulin staining. The three histologically benign lesions had polytypic immunoglobulin. Six of the eight indeterminate lesions had monotypic immunoglobulin, supporting a diagnosis of lymphoma; two had polytypic staining. There was evidence of disseminated lymphoma at the time of diagnosis in five of nine patients with histologically malignant lesions and three of five with monoclonal indeterminate lesions for whom the information was available. Staining with monoclonal antibodies to T-cells revealed variable numbers of T-cells in all cases; their number and distribution did not distinguish benign from malignant lesions. The immunoperoxidase technique on frozen sections permits optimal use of small biopsy specimens for both morphologic and immunologic diagnosis. The majority of histologically indeterminate orbital lymphoid infiltrates were shown to be monoclonal.

Primary lymphoma of bone. A B-cell neoplasm with a high frequency of multilobated cells.

Primary lymphoma of bone is an uncommon neoplasm that can be difficult to diagnose and subclassify. Only in a few cases has the immunophenotype been determined with monoclonal antibodies. We evaluated the histological features and immunophenotype of 12 cases of primary lymphoma of bone. The patients ranged in age from 16 to 80 years (mean, 41 years) with a male:female ratio of 1:1. The sites involved included femur (three cases), humerus (two cases), tibia (three cases), pelvis (two cases), ulna (one case), and scapula (one case). All cases were diffuse large-cell lymphomas: nine large-cleaved (eight with multilobated cells), two large-cell not otherwise specified, and one immunoblastic. Sclerosis was noted in six cases. Immunohistochemical studies on frozen-tissue sections demonstrated staining with the following antibodies: 11 of 11 with CD45, 12 of 12 with CD20, eight of 12 with monotypic immunoglobulin (six IgG, two IgM, seven kappa, one lambda). Tumor cells were negative for T-cell markers in each case. Ten patients are alive and well 0.5-4.5 years (median, 1.5 years) following treatment with radiation or chemotherapy. Two patients had recurrence at another site 0.75 years and 4 years after the initial diagnosis, respectively. Primary bone lymphoma is a B-lineage large-cell lymphoma with an unusually high incidence of large-cleaved and multilobated cells. The frequency of IgG heavy chain expression suggests a post-germinal center stage of differentiation. Frozen section immunohistologic studies are useful in the diagnosis of this tumor. Aggressive therapy has resulted in a favorable outcome in most cases.

Liposarcoma: a soft tissue tumor with many presentations.

Liposarcoma is an uncommon connective tissue tumor arising from lipoblast cells. The lesion is located in body soft parts and rarely arises from the bones. The tumors are variable in presentation ranging from benign well-differentiated tumors to myxoid and round cell-dedifferentiated and pleomorphic forms which can present with metastases. The lesions are most often treated by surgical resection. Chemotherapy and radiation may be added to the treatment of the more malignant variants with some success.

Do patients with chronic low back pain have an altered level and/or pattern of physical activity compared to healthy individuals? A systematic review of the literature.

BACKGROUND: It is commonly assumed that patients with chronic low back pain are less active than healthy individuals. There has been a recent increase in the number of studies published comparing the physical activity levels of patients with chronic low back pain and healthy individuals. OBJECTIVES: The aim of this systematic review was to determine, based on the current body of evidence, if patients with chronic low back pain have a lower level and/or altered pattern of physical activity compared with asymptomatic, healthy individuals. DATA SOURCES: The electronic databases Embase, Medline, ISI Web of Knowledge, Cinahl, Sport Discus and Nursing and Allied Health were searched from the beginning of each database until the end of December 2009. REVIEW METHODS: Studies which compared the level and/or pattern of physical activity of patients with chronic low back pain and healthy controls were included. The quality of the included studies was assessed using an assessment tool based on the Newcastle-Ottawa Scale. The scale was modified for the purposes of this study. RESULTS: Seven studies were included in the final review. Four studies recruited adult patients (18-65 years), two studies examined older adults (≥65 years) and one study recruited adolescents (<18 years). Pooled data revealed no significant difference in the overall activity level of adults or adolescents with CLBP, however there is evidence that older adults with chronic low back pain are less active than controls. The results suggest that patients exhibit an altered pattern of physical activity over the course of a day compared to controls. Major methodological limitations were identified and are discussed. CONCLUSION: There is no conclusive evidence that patients with chronic low back pain are less active than healthy individuals. Based on a limited number of studies, there is some evidence that the distribution of activities over the course of a day is different between patients with chronic low back pain and controls.

Pleomorphic spindle cell sarcoma (PSCS) formerly known as malignant fibrous histiocytoma (MFH): a complex malignant soft-tissue tumor.

A presentation defining the nature, characteristics, causation, treatment and outcome of patients with lesions formerly known as malignant fibrous histiocytoma and now as pleomorphic spindle cell sarcoma is clearly a very difficult subject. Many authors do not believe that the tumor exists and instead describe them as forms of fibrosarcomas, fibromyxoid lesions, dedifferentiated chondrosarcomas or even leiomyosarcomas. The reasons for this confusion are presumably related to the fact that the malignant pleomorphic spindle cell sarcoma does not seem to be a distinct type of lesion with specific histologic and genetic characteristics. Instead, the tumor has at least four separate histologic variations and no specific gene signature and in fact does not seem to be either familial or ethnic in presentation. In view of the fact that the tumor was traditionally the most frequently encountered malignant soft-tissue neoplasm, the world of orthopedic oncology is clearly distressed by the problems that these patients have and is joined by the radiation oncologists and chemotherapists in seeking new solutions.

S100beta and nitric oxide product concentrations following cerebral aneurysm clipping in patients with subarachnoid haemorrhage: a pilot study.

OBJECTIVE: The objective of this investigation was to determine the efficacy of S100beta and nitric oxide product (nitrate and nitrite [NOx]) concentrations as markers of brain injury following cerebral aneurysm clipping in patients with spontaneous subarachnoid haemorrhage. METHODS: Fifteen patients with spontaneous subarachnoid haemorrhage were studied. Blood samples were obtained for estimation of serum S100beta (microg/L) and nitric oxide product (nitrate and nitrite [NOx]) (microM) concentrations immediately preoperatively (baseline) and then 10 minutes, 2, 6 and 12 hr postoperatively and daily thereafter for five days. Neurological outcome was assessed three months after surgery by the Glasgow Outcome Scale (GOS) (poor outcome, grade 1 - 3 and good outcome as grade 4 - 5). Data were analysed using the Mann-Whitney-U-test. RESULTS: S100beta concentrations were greater at two hours postoperatively compared to baseline (0.33 +/- 0.16 vs 0.25 +/- 0.04)(P = 0.02). S100beta concentrations were similar in good and poor neurological outcome groups as defined by GOS at three months. NOx concentrations were less at 12 hours postoperatively compared to baseline (9.81 +/- 3.25 vs 12.74 +/- 2.9)(P = 0.03). NOx concentrations were greater on the fourth and fifth postoperative days compared to baseline (t0) (17.22 +/- 7.9, 12.74 +/- 2.9 vs 9.81 +/- 3.25) (P < 0.05). NOx concentrations were greater in patients with a poor neurological outcome (n = 4) compared to the good outcome group (n = 11) (24.7 +/- 4.9 vs. 11.3 +/- 3.3)(P = 0.04). CONCLUSIONS: S100beta and NOx concentrations increase after cerebral aneurysm clipping in patients with spontaneous SAH. Increased nitric oxide product concentrations were associated with subsequent poor neurological outcome.

A staphylococcal slide test for detection of antineutrophil antibodies.

We describe a simple test for direct or indrect detection of antineutrophil antibodies. Sensitized leukocytes adherent to glass slides and fixed with paraformaldehyde can be stored in buffer for at least 3 wk. Killed Cowan I staphylococci, containing protein A, bind to sensitized but not control cells, and binding is ascertainable by light microscopy. Indirect tests were positive for 39/41 patients suspected of having immune neutropenia and found to have antineutrophil antibodies by an indirect radiochemical opsonic method. Fifty-four control sera from healthy persons, patients with bone marrow failure, or with immune complex diseases without neutropenia, gave negative indirect tests. Direct tests for cell-bound antibody could be done even during severe neutropenia by reacting fixed autologous cells with staphylococci in the absence of added serum. In some patients only the direct test was positive.

A slide test for detecting neutrophil-associated complement components.

Complement components deposited on neutrophils were detected by a new test that uses staphylococcal protein A and antisera against complement. Serum from three of 51 patients thought to have immune neutropenia deposited complement but not IgG on their own and normal neutrophils. Some cases of immune neutropenia may be caused primarily by complement-mediated neutrophil destruction.

The severity of immune neutropenia correlates with the maturational specificity of antineutrophil antibodies.

Sera from 15 patients with antineutrophil antibodies against peripheral blood neutrophils were incubated with normal bone marrow, and the reaction with marrow precursors was determined. Serum from controls did not deposit IgG on either peripheral blood or marrow myeloid cells. Serum from patients with moderate immune neutropenia with myeloid hyperplasia deposited IgG on neutrophils, bands and metamyelocytes, but not on earlier precursors. Serum from one patient with severe neutropenia and myeloid hypoplasia deposited IgG on myelocytes and promyelocytes as well as more mature cells. Serum from a patient with antineutrophil antibodies which impaired chemotaxis but who did not have neutropenia deposited IgG only on neutrophils and occasional bands. Immune neutropenia may become increasingly severe as antibodies become directed against earlier precursors.

Evaluation of case reports of aplastic anemia among patients treated with felbamate.

PURPOSE: Felbamate (FBM) is a new antiepileptic drug (AED) that is often effective in seizure disorders refractory to other treatments; its use has been greatly restricted after cases of aplastic anemia were reported. To elucidate the putative association between FBM and aplastic anemia, we made a detailed evaluation of the first 31 reports. METHODS: Hematologic review according to the criteria of the International Agranulocytosis and Aplastic Anemia Study (IAAAS) confirmed 23 cases (74%) as aplastic anemia; FBM was judged to be the only plausible cause for three; confounding (mostly by other drugs) was considered possible, but FBM remained the most likely cause for 11; and there was at least one other plausible cause for 9. RESULTS: Using a denominator from sales data of 110,000 persons exposed and a numerator of the cases for which FBM was considered the only plausible cause, we established a lower limit of incidence of 27 cases of aplastic anemia per million users as compared with the general population rate of 2.0 per million per year. With all confirmed cases used as the numerator, the upper limit of incidence was 209 per million. The 'most probable" incidence was estimated to be 127 per million. CONCLUSIONS: Intensive, systematic investigation can maximize the utility of case reports for assessing risks of newly released drugs. The present evaluation confirmed an association between FBM and aplastic anemia; however, confounding was significant for most cases and there was a tenfold range in the "best case" and "worst case" incidence estimates among users.