Glendenning J.,Kings College London |
Cook G.,Biomedical Imaging Center |
Cook G.,Clinical Center
Seminars in Nuclear Medicine | Year: 2013
The skeleton is commonly affected in the context of metastatic breast cancer and is a cause of significant morbidity in these individuals. Therapeutic options include systemic therapy, radiotherapy, and surgery given with the intent of preserving function and quality of life. As the spectrum of available therapies increases, key challenges comprise reliable diagnosis of bony metastatic disease and accurate evaluation of response that permits rapid therapeutic transition in those responding inadequately prior to development of significant skeletal morbidity. The 99mTc-diphosphonate bone scan remains one of the most commonly requested investigations for skeletal evaluation in patients with breast cancer. However a time lag of 3-6 months for accurate response evaluation from the start of treatment limits its utility for response evaluation in routine clinical practice or as a progression end point in the research setting. Functional imaging strategies using more tumor-specific radiopharmaceuticals show promise as an effective means of imaging response at a clinically relevant time point and are the subject of this review. © 2013 Elsevier Inc.
Pavlovic N.M.,Clinical Center
Clinical Kidney Journal | Year: 2013
Balkan endemic nephropathy (BEN), originally described in 1956, is a unique familial, chronic renal disease encountered with a high-prevalence rate in Serbia, Bulgaria, Romania, Croatia and Bosnia and Herzegovina. The most prominent features of the disease are its endemic nature, long-incubation period, familial clustering of the disease and an unusually high incidence of associated upper urothelial cancer (UUC). There are no clear-cut data on BEN incidence and prevalence, since the studies carried out in different endemic areas yielded contradictory information. In spite of intermittent variations, the incidence of new cases has remained stable over time. It has been estimated that almost 100 000 people are at risk of BEN, whereas 25 000 have the disease. The clinical signs and symptoms of BEN are non-specific and often remain unrecognized for years. There are no pathognomonic diagnostic features of BEN, but the set of epidemiological, clinical and biochemical data along with the pattern of pathologic injury in the absence of any other renal diseases are highly suggestive of this entity. Although the aetiology has been extensively studied, fostering the publication of various hypotheses, only one of them has provided conclusive evidence related to the aetiology of BEN. Studies conducted over the past decade have provided particularly strong arguments that BEN and UUC are caused by chronic poisoning with aristolochic acids (AAs). In light of these later studies, one can raise the question whether AAs could be responsible for previously and currently widespread unrecognized global renal disease and UUC. © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Lee D.W.,U.S. National Cancer Institute |
Kochenderfer J.N.,Experimental Transplantation and Immunology Branch |
Stetler-Stevenson M.,Laboratory of Pathology |
Cui Y.K.,U.S. National Cancer Institute |
And 16 more authors.
The Lancet | Year: 2015
Background Chimeric antigen receptor (CAR) modified T cells targeting CD19 have shown activity in case series of patients with acute and chronic lymphocytic leukaemia and B-cell lymphomas, but feasibility, toxicity, and response rates of consecutively enrolled patients treated with a consistent regimen and assessed on an intention-to-treat basis have not been reported. We aimed to define feasibility, toxicity, maximum tolerated dose, response rate, and biological correlates of response in children and young adults with refractory B-cell malignancies treated with CD19-CAR T cells. Methods This phase 1, dose-escalation trial consecutively enrolled children and young adults (aged 1-30 years) with relapsed or refractory acute lymphoblastic leukaemia or non-Hodgkin lymphoma. Autologous T cells were engineered via an 11-day manufacturing process to express a CD19-CAR incorporating an anti-CD19 single-chain variable fragment plus TCR zeta and CD28 signalling domains. All patients received fludarabine and cyclophosphamide before a single infusion of CD19-CAR T cells. Using a standard 3-+-3 design to establish the maximum tolerated dose, patients received either 1-×-106 CAR-transduced T cells per kg (dose 1), 3-×-106 CAR-transduced T cells per kg (dose 2), or the entire CAR T-cell product if sufficient numbers of cells to meet the assigned dose were not generated. After the dose-escalation phase, an expansion cohort was treated at the maximum tolerated dose. The trial is registered with ClinicalTrials.gov, number NCT01593696. Findings Between July 2, 2012, and June 20, 2014, 21 patients (including eight who had previously undergone allogeneic haematopoietic stem-cell transplantation) were enrolled and infused with CD19-CAR T cells. 19 received the prescribed dose of CD19-CAR T cells, whereas the assigned dose concentration could not be generated for two patients (90% feasible). All patients enrolled were assessed for response. The maximum tolerated dose was defined as 1-×-106 CD19-CAR T cells per kg. All toxicities were fully reversible, with the most severe being grade 4 cytokine release syndrome that occurred in three (14%) of 21 patients (95% CI 3·0-36·3). The most common non-haematological grade 3 adverse events were fever (nine [43%] of 21 patients), hypokalaemia (nine [43%] of 21 patients), fever and neutropenia (eight [38%] of 21 patients), and cytokine release syndrome (three [14%) of 21 patients). Interpretation CD19-CAR T cell therapy is feasible, safe, and mediates potent anti-leukaemic activity in children and young adults with chemotherapy-resistant B-precursor acute lymphoblastic leukaemia. All toxicities were reversible and prolonged B-cell aplasia did not occur. Funding National Institutes of Health Intramural funds and St Baldrick's Foundation. © 2015 Elsevier Ltd.
Poudel-Tandukar K.,Clinical Center |
Bertone-Johnson E.R.,University of Massachusetts Amherst |
Palmer P.H.,Claremont Graduate University |
Poudel K.C.,University of Massachusetts Amherst
Brain, Behavior, and Immunity | Year: 2014
Background: Human Immunodeficiency Virus (HIV) infection has been frequently associated with chronic inflammation as well as depression. C-reactive protein (CRP) is positively associated with depression in people without HIV infection. We tested the hypothesis of an independent relationship between CRP and depression in a cohort of HIV-positive people. Methods: A cross-sectional survey was conducted among 316 HIV-positive people (181 men and 135 women) aged 18-60. years residing in the Kathmandu Valley, Nepal. The latex agglutination turbidimetric method was used to measure serum CRP concentrations and the Beck Depression Inventory (BDI)-I method was used to measure depression, with a cut off of ≥20 indicating likely depression. The relationship between CRP concentrations and depression symptoms was assessed using both multiple linear regression analysis and multiple logistic regression analysis, with adjustment for potential socio-demographic, cardiovascular, life-style, and HIV-related clinical and treatment confounding factors. Results: Twenty-six percent participants (men: 23%; women: 29%) met criteria for depression. In multiple regression analysis, the authors observed a linear relation between serum CRP concentrations and BDI score (beta for 1 unit change in ln(CRP). =. 1.13, p=. 0.001) in HIV-positive participants. In a logistic regression analysis, participants with serum CRP levels. >. 3. mg/L had a 2.3-fold higher odds of depression symptoms compared to those with serum CRP level. ≤. 3. mg/L (. p=. 0.005). In analyses stratified by sex, associations were stronger in men than in women. For example, CRP. >. 3. mg/L was associated with a 3.6-fold higher odds of depression in men (. p=. 0.002), while in women the odds ratio was 1.7 (. p=. 0.33). Conclusion: We found a linear relationship between serum CRP concentrations and depression symptoms score in HIV-positive people, and evidence that risk of depression is elevated among HIV-positive men with a high level of inflammation (CRP. >. 3. mg/L). Further prospective study to confirm the role of inflammation in depression among HIV-positive people is warranted. © 2014 Elsevier Inc..
Micic I.D.,Clinical Center
Clinics in orthopedic surgery | Year: 2010
Surgical treatment is the preferred method for treating subtrochanteric femoral fractures and the variety of extramedullary and intramedullary implants continues to evolve. The purpose of our study was to retrospectively evaluate the clinical and radiological results of subtrochanteric fractures that are treated with the Selfdynamisable internal fixator. From January 2000 to January 2004, we treated 49 consecutive patients who had subtrochanteric fractures. According to the AO classification, 8 (16.3%) fractures were type 32-A, 16 (32.7%) were type 32-B and 25 (51%) fractures were type 32-C. The mean follow-up time was 22.3 months. The average operating time was 45 minutes (range, 32 to 90 minutes). The average blood loss was 250 mL (range, 125 to 350 mL). The average hospital stay was 10 days (range, 7 to 59 days). Implant failure was not observed and union was achieved in all the patients. Deep infection occurred in one (2%) patient in the early postoperative period. Fracture union was achieved at a mean of 14 weeks. Varus malalignment less then 10 degree was noted in three (6.1%) patients at the end of follow-up. Thirty-five patients were pain-free and 14 had mild pain. The selfdynamisable internal fixator was successfully used for subtrochanteric fracture. It provides a short operative time, low blood loss, spontaneous biaxial dynamisation and healing in an optimal period of time without the need for secondary intervention.