Giant ganglioneuroma of the posterior mediastinum

We report the case of a 45-year-old female referred to us with progressive shortness of breath and a huge left mediastinal mass. Computed tomography of the chest revealed a mass occupying the posterior mediastinum and extending from the apex caudally to the left hemidiaphragm. Further magnetic resonance imaging demonstrated tumor extension to the left interverteberal foramina of T5-T6 and T6-T7. Excision of the mass was performed through a left posterolateral thoracotomy. Histology confirmed a mediastinal ganglioneuroma. This is an unusual tumor with more than one extension in the spine. Ganglioneuromas are rare tumors of the peripheral nervous system. Most of these tumors are, however, retroperitoneal and are more common in children and young adults. Ganglioneuromas arise from neural crest cells. These tumors are mostly asymptomatic, but some may present with hypertension and flushing. Massive tumors can present with pressure symptoms.     

Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model

The use of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) in spine fusion has led to concerns regarding a potential accompanying inflammatory response. This study evaluates a combination therapy (TrioMatrix®; Pioneer Surgical, Inc., Marquette, MI) comprised of a demineralized bone matrix (DBM), hydroxyapatite, and a nanofiber‐based collagen scaffold in a rodent spine fusion model. Thirty‐six athymic rats that underwent a posterolateral intertransverse spinal fusion were randomly assigned to 1 of 5 treatment groups: absorbable collagen sponge alone (ACS, negative control), 10 µg rhBMP‐2 on ACS (positive control), TrioMatrix®, Grafton® (Osteotech, Inc., Eatontown, NJ), and DBX® (Synthes, Inc., West Chester, PA). Both TrioMatrix® and rhBMP‐2‐treated animals demonstrated 100% fusion rates as graded by manual palpation scores 8 weeks after implantation. This rate was significantly greater than those of the ACS, Grafton®, and DBX® groups. Notably, the use of TrioMatrix® as evaluated by microCT quantification led to a greater fusion mass volume when compared to all other groups, including the rhBMP‐2 group. T2‐weighted axial MRI images of the fusion bed demonstrated a significant host response associated with a large fluid collection with the use of rhBMP‐2; this response was significantly reduced with the use of TrioMatrix®. Our results therefore demonstrate that a nanocomposite therapy represents a promising, cost‐effective bone graft substitute that could be useful in spine fusions where BMP‐2 is contraindicated. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1812–1819, 2011     

Validation of the French version of the alcohol, smoking and substance involvement screening test (ASSIST)

Background: The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) was developed to detect substance use disorders. Aims: The objective of the present study was to evaluate the psychometric properties of the French version of ASSIST in various clinical groups with different levels of substance use. Methods: 150 subjects were recruited from clients attending primary health care, psychiatric and addiction treatment facilities. Measures included ASSIST, Addiction Severity Index (ASI), Mini-International Neuropsychiatric Interview (MINI-Plus), Alcohol Use Disorders Identification Test (AUDIT) and Revised Fagerstrom Tolerance Questionnaire-Smoking (RTQ). Results and Conclusion: Concurrent validity was demonstrated by significant correlations between ASSIST scores and scores from ASI, AUDIT and RTQ, as well as significantly greater ASSIST scores for patients with a MINI-Plus diagnosis of abuse or dependence. The ASSIST questionnaire was found to have high internal consistency for the total substance involvement as well as for specific substance involvement as assessed with Cronbach's α, ranging from 0.74 to 0.93. When possibly computed, ASSIST cutoff scores have interesting sensitivity and specificity for discrimination between use and abuse and between abuse and dependence. The findings demonstrated that the French version of ASSIST is a valid screening test for identifying substance use disorders in various health care settings, including psychiatric settings.     

Metastasis of Solid Tumors in Bone Marrow: A Study from Northern India

The metastasis of bone marrow by the solid tumors is a sign of advanced stage of disease and poor prognosis. The aim of this study was to assess the pattern of bone marrow involvement of different solid tumors and their correlation with hematological findings. In a retrospective study we evaluated 434 aspirates and 76 biopsy sections from 124 cases of different types of solid tumors previously diagnosed on the basis of their clinical and histopathological findings. The hematological profile of the patients was done and correlated with the bone marrow findings. The study was carried out at a medical college hospital of northern India. Out of 124 cases of solid tumors 31 (25%) have metastasized to bone marrow. The highest number 25 (36%) of bone marrow involvement was seen in carcinoma prostate followed by gastric carcinoma and melanoma (25%) The least number (14.2%) cases of bone marrow metastasis were observed in endometrial carcinoma. Anemia was found the commonest (71.4%) hematological finding followed by thrombocytopenia in 45.1% cases. The bone marrow examination is an easy, convenient, sensitive and cost effective procedure for assessment of staging and monitoring of prognosis of solid tumors.     

Strategies to enhance rituximab anti-tumor activity in the treatment of CD20-positive B-cell neoplasms

Rituximab is a chimeric monoclonal anti-CD20 antibody and was the first monoclonal antibody (mAb) therapy approved by FDA (Food and Drug Administration) for the treatment of B-cell lymphoma. It has revolutionized the treatment of patients with CD20-positive non-Hodgkin’s lymphoma and CLL. Rituximab is currently being used in virtually all patients with B-cell lymphomas either alone or in combination with chemotherapy. Despite its excellent safety and efficacy profile, only a small portion of B-cell lymphoma patients treated with rituximab as a single agent have sustained complete remissions. Combining rituximab with standard chemotherapy regimens is associated with higher response rates, and improved survival in a subset of patients. Unfortunately, a significant percentage of patients who initially respond to rituximab eventually relapse, and there are patients that demonstrate intrinsic resistance to initial therapy. In the last decade, ongoing scientific research has led to a better understanding of rituximab-associated cytotoxic mechanisms against lymphoma target cells. Scientific efforts are increasingly being focused in developing new strategies to improve mAb activity. Various strategies include the following: combining rituximab with different biologic agents (e.g. cytokines, immunomodulatory drugs); developing novel antibody constructs (including bi-specific antibodies); and/or inhibiting signaling pathways associated with lymphomagenesis and immuno-chemotherapy resistance. In this review article, we will provide an overview of various rituximab-associated cytotoxic mechanisms and novel strategies to improve mAb activity against B-cell lymphoma.     

Chronic anemia and fatigue in elderly patients: results of a randomized, double-blind, placebo-controlled, crossover exploratory study with epoetin alfa

OBJECTIVES: To evaluate the effect of epoetin alfa treatment on hemoglobin (Hb), fatigue, quality of life (QOL), and mobility in elderly patients with chronic anemia. DESIGN: An exploratory, 32 week, randomized, double-blind, crossover treatment trial. PARTICIPANTS: Sixty-two community-dwelling individuals aged 65 and older with chronic anemia (Hb < or =11.5 g/dL). INTERVENTION: Subcutaneous epoetin alfa or placebo weekly for 16 weeks (Phase I) with crossover to the opposite treatment (Phase II). MEASUREMENTS: Hb and QOL scores from the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system. Mobility was assessed as a secondary outcome using the Timed Up and Go (TUG) test. RESULTS: Of the 62 subjects enrolled, complete data were analyzed for 58 in Phase I and 54 participants in Phase II. Of those enrolled, most were African American (95%) and female (85%) and had multiple comorbidities and a mean age+/-standard deviation of 76.1+/-7.2. Mean baseline Hb was 10.5+/-0.9 g/dL (7.3-11.5). In Phase I, 67% of those taking epoetin alfa, and in Phase II, 69% of those taking epoetin alfa had an increase in Hb of more than 2 g/dL, significantly more than those taking placebo (P<.001). Similarly, elderly participants significantly improved on the fatigue and anemia subscales of the FACIT across phases (all P<.05). No significant differences were found between treatment and placebo on TUG scores. Epoetin alfa was well tolerated. CONCLUSION: In this trial involving predominantly older African-American women with anemia, a direct relationship existed between increases in Hb during epoetin alfa therapy and improvements in fatigue and QOL.     

A cadaveric investigation into the links between macroscopic and microscopic osteoarthritic changes at the hip

Our objective was to investigate the frequency and distribution of osteoarthritic changes at the hip, including the relationship between osteoarthritic lesions on the femoral head surface and histological changes in articular cartilage, in 12 cadavers. Twelve embalmed cadavers (five males and seven females) were dissected, and the femoral head was removed from both sides (24 femoral heads). Any gross osteoarthritic changes were noted and graded (on a scale of 1-3). A circular disc was then removed from the equator of the femoral head and divided into nine regions. Out of 192 segments, 54 underwent sectioning and staining with haematoxylin and eosin to assess histological changes in cartilage. Osteoarthritis of the hip was present in all cadavers, with all males having bilateral OA and 50% having grade 2 or higher lesions (50% were grade 1), and four of the seven female specimens having bilateral OA and only 7% with grade 2 lesions (with 71% grade 1 and 21% normal). Chondrocyte clustering was most commonly observed in the deep layer of cartilage followed by the intermediate and superficial layers respectively, as the grade of the macroscopic lesion increased. Cartilage injury at the histological level precedes any visible denudation of the femoral head articular cartilage. This study supports the hypothesis that early osteoarthritic changes occur in the deep layer of cartilage near the tide mark and progress superficially concomitant with an overall increase in the osteoarthritic lesion size on the femoral head surface.