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  • BMJ Publishing Group  (6)
  • American Society of Hematology (ASH)  (4)
  • The American Association for Cancer Research (AACR)  (3)
Document type
Years
  • 1
    Publication Date: 2013-08-18
    Description: Aims Osteoid osteoma and osteoblastoma have, in the past, been variously regarded as both similar and distinct entities. Currently, WHO classifies these tumours separately. We compared archetypal cases to identify novel histomorphological and immunohistochemical features attempting to clarify their mutual relationship. Methods and results 10 osteoid osteomas and 20 osteoblastomas (10 spinal and 10 non-spinal) were retrieved and reviewed clinically, radiologically and histologically. Immunohistochemistry was performed for: desmin, SMA, neurofilament, S100, vimentin, PGP9.5, GFAP, EMA, caldesmon, CD34, broad-spectrum cytokeratins, claudin-1. We identified features, common to both osteoid osteoma and osteoblastoma, namely, areas of lesional non-osteoblastic stroma and the presence of scattered, large cells with smudged/degenerate nuclei. Immunohistochemically, we confirmed the innervated status of osteoid osteomas, and found that osteoblastomas were similarly innervated. The non-osteoblastic lesional stroma was distinctive owing to expression of EMA and NSE by the mesenchymal spindle cells and expression of desmin, PGP9.5 and S100 by the scattered, large cells with ‘smudged’ nuclei. Conclusions Both osteoid osteoma and osteoblastoma are innervated bone-forming lesions which share novel histomorphological and immunohistochemical features supporting the view that separate classification is unjustified, and we offer a pathogenetic explanation for their apparent clinical and radiological variance.
    Keywords: Immunology (including allergy)
    Print ISSN: 0021-9746
    Electronic ISSN: 1472-4146
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 2
    Publication Date: 2013-07-25
    Description: Varicose veins in the lower limbs are a common problem, estimated to affect at least a third of the UK population.1 Although some individuals with varicose veins remain asymptomatic, others may...
    Keywords: Health policy, Clinical trials (epidemiology), Guideline summaries, Pain (neurology), Interventional cardiology, Venous thromboembolism, Radiology, Dermatology, Clinical diagnostic tests, Vascular surgery, Health economics, Health service research, Sociology
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 3
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    BMJ Publishing Group
    Publication Date: 2013-07-18
    Description: Howard Eaton Freeman Davies (known affectionately to his friends and colleagues as “HEF”) died after a brief illness, having been frail for some months as a result of worsening cardiac failure. Born...
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 4
    Publication Date: 2013-08-16
    Description: The safety and activity of obinutuzumab (GA101) plus chemotherapy in relapsed/refractory follicular lymphoma was explored in 56 patients. Participants received obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP; every 3 weeks for 6 to 8 cycles) or obinutuzumab plus fludarabine and cyclophosphamide (G-FC; every 4 weeks for 4 to 6 cycles). Patients were randomly assigned to either obinutuzumab 1600 mg on days 1 and 8 of cycle 1 followed by 800 mg on day 1 of subsequent cycles or 400 mg for all doses. Treatment responders were eligible for obinutuzumab maintenance every 3 months for up to 2 years. Grade 1/2 infusion-related reactions (IRRs) were the most common treatment-related adverse event (AE) (all grades: G-CHOP, 68%; G-FC, 82%). Grade 3/4 IRRs were rare (7%) and restricted to the first infusion. All patients received the planned obinutuzumab dose. Neutropenia was the most common treatment-related hematologic AE for G-CHOP (43%) and G-FC (50%). At induction end, 96% (27/28) of patients receiving G-CHOP (complete response [CR], 39% [11/28]) and 93% (26/28) receiving G-FC (CR, 50% [14 of 28]) achieved responses. G-CHOP and G-FC had an acceptable safety profile with no new or unexpected AEs, but G-FC was associated with more AEs than G-CHOP. Obinutuzumab plus chemotherapy resulted in 93% to 96% response rates, supporting phase 3 investigation. This trial was registered at www.clinicaltrials.gov as #NCT00825149.
    Keywords: Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2017-11-09
    Description: Background To investigate whether sharing and linking routinely collected violence data across health and criminal justice systems can provide a more comprehensive understanding of violence, establish patterns of under-reporting and better inform the development, implementation and evaluation of violence prevention initiatives. Methods Police violence with injury (VWI) crimed data and emergency department (ED) assault attendee data for South Wales were collected between 1 April 2014 and 31 March 2016 to examine the rates and patterns of VWI. Person identifiable data (PID) were cross-referenced to establish if certain victims or events were less likely to be reported to criminal justice services. Results A total of 18 316 police crimed VWI victims and 10 260 individual ED attendances with an assault-related injury were considered. The majority of ED assault attendances (59.0%) were unknown to police. The key demographic identified as under-reporting to police were young males aged 18–34 years, while a significant amount of non-reported assaults involved a stranger. The combined monthly age-standardised rates were recalculated and on average were 74.7 (95% CI 72.1 to 77.2) and 66.1 (95% CI 64.0 to 68.2) per 100 000 population for males and females, respectively. Consideration of the additional ED cases resulted in a 35.3% and 18.1% increase on the original police totals for male and female VWI victims. Conclusions This study identified that violence is currently undermeasured, demonstrated the importance of continued sharing of routinely collected ED data and highlighted the benefits of using PID from a number of services in a linked way to provide a more comprehensive picture of violence.
    Keywords: Open access
    Print ISSN: 0143-005X
    Electronic ISSN: 1470-2738
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 6
    Publication Date: 2018-05-11
    Description: This phase 1 study evaluated frontline brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (BV+CHP; 6 cycles, then up to 10 cycles of brentuximab vedotin monotherapy) in 26 patients with CD30 + peripheral T-cell lymphoma, including 19 with systemic anaplastic large cell lymphoma. All patients (100%) achieved an objective response, with a complete remission (CR) rate of 92%; none received a consolidative stem cell transplant. After a median observation period of 59.6 months (range, 4.6-66.0) from first dose, neither the median progression-free survival (PFS) nor the median overall survival (OS) was reached. No progression or death was observed beyond 35 months. The estimated 5-year PFS and OS rates were 52% and 80%, respectively. Eighteen of 19 patients (95%) with treatment-emergent peripheral neuropathy (PN) reported resolution or improvement of symptoms. Thirteen patients (50%) remained in remission at the end of the study, with PFS ranging from 37.8+ to 66.0+ months. Eight of these 13 patients received the maximum 16 cycles of study treatment. These final results demonstrate durable remissions in 50% of patients treated with frontline BV+CHP, suggesting a potentially curative treatment option for some patients. This trial was registered at www.clinicaltrials.gov as #NCT01309789.
    Keywords: Lymphoid Neoplasia, Brief Reports, Clinical Trials and Observations
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 7
    Publication Date: 2017-11-16
    Description: Purpose: Prostate cancer was recently classified to three clinically relevant subtypes (PCS) demarcated by unique pathway activation and clinical aggressiveness. In this preclinical study, we investigated molecular targets and therapeutics for PCS1, the most aggressive and lethal subtype, with no treatment options available in the clinic. Experimental Design: We utilized the PCS1 gene set and our model of enzalutamide (ENZ R ) castration-resistant prostate cancer (CRPC) to identify targetable pathways and inhibitors for PCS1. The findings were evaluated in vitro and in the ENZ R CRPC xenograft model in vivo . Results: The results revealed that ENZ R CRPC cells are enriched with PCS1 signature and that Forkhead box M1 (FOXM1) pathway is the central driver of this subtype. Notably, we identified Monensin as a novel FOXM1-binding agent that selectively targets FOXM1 to reverse the PCS1 signature and its associated stem-like features and reduces the growth of ENZ R CRPC cells and xenograft tumors. Conclusions: Our preclinical data indicate FOXM1 pathway as a master regulator of PCS1 tumors, namely in ENZ R CRPC, and targeting FOXM1 reduces cell growth and stemness in ENZ R CRPC in vitro and in vivo . These preclinical results may guide clinical evaluation of targeting FOXM1 to eradicate highly aggressive and lethal PCS1 prostate cancer tumors. Clin Cancer Res; 23(22); 6923–33. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 8
    Publication Date: 2016-08-19
    Description: Somatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility at initial diagnosis. However, the genetic landscape and its clinical utility at relapse are less well understood and have not been studied comprehensively. We analyzed cytogenetic data from 427 children with relapsed B-cell precursor ALL treated on the international trial, ALLR3. Also we screened 238 patients with a marrow relapse for selected copy number alterations (CNAs) and mutations. Cytogenetic risk groups were predictive of outcome postrelapse and survival rates at 5 years for patients with good, intermediate-, and high-risk cytogenetics were 68%, 47%, and 26%, respectively ( P 〈 .001). TP53 alterations and NR3C1 / BTG1 deletions were associated with a higher risk of progression: hazard ratio 2.36 (95% confidence interval, 1.51-3.70, P 〈 .001) and 2.15 (1.32-3.48, P = .002). NRAS mutations were associated with an increased risk of progression among standard-risk patients with high hyperdiploidy: 3.17 (1.15-8.71, P = .026). Patients classified clinically as standard and high risk had distinct genetic profiles. The outcome of clinical standard-risk patients with high-risk cytogenetics was equivalent to clinical high-risk patients. Screening patients at relapse for key genetic abnormalities will enable the integration of genetic and clinical risk factors to improve patient stratification and outcome. This study is registered at www.clinicaltrials.org as #ISCRTN45724312.
    Keywords: Pediatric Hematology, Free Research Articles, Lymphoid Neoplasia, CME article, Clinical Trials and Observations
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 9
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    BMJ Publishing Group
    Publication Date: 2014-05-24
    Description: General practitioner (b 1929; q St Thomas’ 1954; FRCGP, MBE), died from congestive cardiac failure on 14 January 2014.After Winchester College, Alexander John McMurrough Cavenagh (“Sandy”) went up to...
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 10
    Publication Date: 2016-10-08
    Description: Purpose: To evaluate the safety, preliminary efficacy, and pharmacokinetics of inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, in combination with the immunochemotherapeutic regimen, rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), in patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma (NHL). Experimental Design: In part 1 ( n = 16), patients received inotuzumab ozogamicin plus R-CVP on a 21-day cycle with escalating doses of cyclophosphamide first then inotuzumab ozogamicin. Part 2 ( n = 10) confirmed the safety and tolerability of the maximum tolerated dose (MTD), which required a dose-limiting toxicity rate of 〈33% in cycle 1 and 〈33% of patients discontinuing before cycle 3 due to treatment-related adverse events (AEs). Part 3 ( n = 22) evaluated the preliminary efficacy of inotuzumab ozogamicin plus R-CVP. Results: The MTD was determined to be standard-dose R-CVP plus inotuzumab ozogamicin 0.8 mg/m 2 . The most common treatment-related grade ≥3 AEs in the MTD cohort ( n = 38) were hematologic: neutropenia (74%), thrombocytopenia (50%), lymphopenia (42%), and leukopenia (47%). Among the 48 patients treated in the study, 13 discontinued due to AEs, most commonly thrombocytopenia ( n = 10). Overall, 13 patients died, including one death due to treatment-related pneumonia secondary to neutropenia. Among patients receiving the MTD ( n = 38), the overall response rate (ORR) was 84% ( n = 32), including 24% ( n = 9) with complete response; the ORR was 100% for patients with indolent lymphoma ( n = 27) and 57% for those with aggressive histology lymphoma ( n = 21). Conclusions: Inotuzumab ozogamicin at 0.8 mg/m 2 plus full dose R-CVP was associated with manageable toxicities and demonstrated a high rate of response in patients with relapsed/refractory CD22+ B-cell NHL. The study is registered at ClinicalTrials.gov (NCT01055496). Clin Cancer Res; 22(19); 4807–16. ©2016 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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