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Bramham K.,Kings College London | Thomas M.,Guys and St. Thomas National Health Service NHS Foundation Trust | Nelson-Piercy C.,Foundation Medicine | Khamashta M.,Kings College London | Hunt B.J.,Thrombosis and Haemostasis and Lupus Unit
Blood | Year: 2011

The objective of this study was to assess pregnancy outcome in women with a history of refractory antiphospholipid antibody - associated pregnancy loss(es) who were treated with early low-dose prednisolone in addition to aspirin and heparin. Eighteen women with antiphospholipid antibodies who had refractory pregnancy loss(es) were given prednisolone (10 mg) from the time of their positive pregnancy test to 14 weeks' gestation. Before low-dose prednisolone was given as treatment, 4 (4%) of 97 pregnancies had resulted in live births. Among 23 pregnancies supplemented with prednisolone, 9 women had 14 live births (61%), including 8 uncomplicated pregnancies. The remainder were complicated by preterm delivery, preeclampsia, and/or small-for-gestational-age infants. There were 8 first-trimester miscarriages and 1 ectopic pregnancy. There were no fetal deaths after 10 weeks' gestation and no evidence of maternal morbidity. The addition of first-trimester low-dose prednisolone to conventional treatment is worthy of further assessment in the management of refractory antiphospholipid antibody - related pregnancy loss(es), although complications remain elevated. © 2011 by The American Society of Hematology.


Barrington S.F.,Kings College London | Kirkwood A.A.,University College London | Franceschetto A.,University of Modena and Reggio Emilia | Fulham M.J.,Royal Prince Alfred Hospital | And 20 more authors.
Blood | Year: 2016

International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design.PET-CTwasreported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2scans. TheRATHLand PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a k (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice. © 2016 by The American Society of Hematology.


Molife L.R.,Institute of Cancer | Rudman S.M.,Guys and St. Thomas National Health Service NHS Foundation Trust | Alam S.,Institute of Cancer | Tan D.S.-W.,Institute of Cancer | And 11 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2013

Purpose: Afatinib is an irreversible ErbB family blocker currently under evaluation in late-stage clinical trials. This study primarily assessed the cardiac safety, pharmacokinetics and antitumor activity of afatinib in cancer patients. Methods: In this multicenter, Phase II, open-label, single-arm trial, 60 patients with solid tumors who were expected to express epidermal growth factor receptor-1 and HER2 received oral afatinib 50 mg daily. QTcF intervals (QT interval corrected by the Fridericia formula) were evaluated based on electrocardiogram recordings time-matched with pharmacokinetic blood samples after single (Day 1) and continuous (Day 14; steady state) administration. Adverse events were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0; antitumor activity was assessed using RECIST 1.0. Results: There was a nonsignificant decrease of 0.3 ms (90 % confidence interval -2.8, 2.3; N = 49) in the mean of the average time-matched QTcF interval from baseline to steady state. The maximum plasma concentration for afatinib was seen at median t max 3 h after both single dose and at steady state. No relationship between afatinib plasma concentrations and time-matched QTcF, QT and heart rate change was found. The overall adverse event profile was consistent with the known safety profile of afatinib. One patient demonstrated a partial response (PR) and two patients unconfirmed PRs. Conclusions: Afatinib had no impact on cardiac repolarization, had a manageable safety profile and demonstrated antitumor activity in this uncontrolled study. © 2013 Springer-Verlag Berlin Heidelberg.


Sarwar K.N.,Guys and St. Thomas National Health Service NHS Foundation Trust | Huda M.S.B.,Guys and St. Thomas National Health Service NHS Foundation Trust | Van De Velde V.,Guys and St. Thomas National Health Service NHS Foundation Trust | Hopkins L.,Guys and St. Thomas National Health Service NHS Foundation Trust | And 5 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: Incidental pituitary hemorrhage, without full pituitary apoplexy, is a recognized radiological finding, but little information exists on its clinical behavior, with most reports describing surgically treated macroprolactinoma or nonfunctioning adenoma. Objective: Our aim was to characterize the prevalence, natural history, and risk factors associated with pituitary hemorrhage in a large clinic prolactinoma population. Design: The design consisted of a retrospective analysis of a clinic population. Setting: The setting was a tertiary endocrine center in a large teaching hospital. Patients: We studied three hundred sixty-eight patients with prolactinoma. The presence of hemorrhage was documented on magnetic resonance imaging. Main outcome measure: The main outcome measures were the prevalence, risk factors, and natural history of pituitary hemorrhage. Results: Pituitary hemorrhage was found in 25 patients, giving an overall prevalence of 6.8%, and was significantly higher in macroprolactinoma (20.3%) compared to microprolactinoma (3.1%, P < .0001). Three patients had classical pituitary apoplexy. The majority of patients in the hemorrhage group had macroprolactinomas (16/25 [64%]) and were women (22/25 [88%]). The proportion of women with macroprolactinoma was higher in the hemorrhage group (14/16 macroprolactinomas [87.5%]) than in the nonhemorrhage group (36/63 macroprolactinomas [57.1%], P = .02). The majority of pituitary hemorrhages (92%) were treated conservatively with dopamine agonist therapy for hyperprolactinemia. Eighty-seven percent of patients had complete resolution of their hemorrhage within 26.6 ± 23.3 (mean ± SD) months. The presence of macroprolactinoma (odds ratio 9.00 [95% CI 3.79-23.88], P < .001) and being female (odds ratio 8.03 [95% confidence interval 1.22-52.95], P = .03) were independently associated with hemorrhage. Conclusions: These data show that incidental hemorrhage in prolactinoma is not uncommon. It is more likely to occur in macroprolactinoma, where 1 in 5 develop hemorrhage, and is particularly common in women with macroprolactinoma. The majority are asymptomatic and resolve spontaneously. Copyright © 2013 by The Endocrine Society.

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