Showing papers by "St Bartholomew's Hospital published in 2016"
University of New South Wales1, University of Manchester2, University College London3, Cardiff University4, University College Hospital5, James Cook University Hospital6, Belfast City Hospital7, Qatar Airways8, Medical Research Council9, Bangor University10, Hamad Medical Corporation11, Royal Derby Hospital12, Derriford Hospital13, Royal Free Hospital14, St. Michael's GAA, Sligo15, St Bartholomew's Hospital16, Harvard University17, St Mary's Hospital18, University Hospital of Wales19, National Health Service20, Public Health England21, Nottingham City Hospital22, Queen Alexandra Hospital23, Brighton and Sussex Medical School24, London School of Economics and Political Science25
TL;DR: Although the mortality reduction was not significant in the primary analysis, it was noted a significant mortality reduction with MMS when prevalent cases were excluded, and encouraging evidence of a mortality reduction in years 7–14 was noted.
756 citations
TL;DR: The authors thank Sally B. Killick, Nick Bown, Jamie Cavenagh, Inderjeet Dokal, Theodora Foukaneli, Peter Hillmen, Robin Ireland, Austin Kulasekararaj, Ghulam Mufti, John A Snowden, Sujith Samarasinghe and Anna Wood for their help.
Abstract: Sally B. Killick (Writing Group Chair), Nick Bown, Jamie Cavenagh, Inderjeet Dokal, Theodora Foukaneli, Peter Hillmen, Robin Ireland, Austin Kulasekararaj, Ghulam Mufti, John A Snowden, Sujith Samarasinghe, Anna Wood (BCSH Task Force Member), Judith C.W. Marsh on behalf of the British Society for Standards in Haematology. The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, Northern Genetics Service, Newcastle upon Tyne, St Bartholomew’s Hospital, Barts Health NHS Trust, London, Barts and The London School of Medicine and Dentistry, Queen Mary University of London and Barts Health NHS Trust, London, Addenbrooks Hospital, University of Cambridge, Cambridge, Leeds Teaching Hospitals, Leeds, Kings College Hospital NHS Foundation Trust, London, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield Great Ormond Street Hospital for Children NHS Foundation Trust, London, West Hertfordshire NHS Trust, Watford.
464 citations
University of Coimbra1, University of Aberdeen2, Netherlands Cancer Institute3, University of Rennes4, University of Texas at Austin5, Charles University in Prague6, Hannover Medical School7, Radboud University Nijmegen8, St Bartholomew's Hospital9, Ludwig Maximilian University of Munich10, Umeå University11, University of Eastern Piedmont12
TL;DR: The results suggest that RTB has good accuracy in diagnosing renal cancer and its subtypes, and it appears to be safe, but better quality studies are required to provide a more definitive answer.
391 citations
Cornell University1, Ohio State University2, Hackensack University Medical Center3, Washington University in St. Louis4, University of Plymouth5, Stanford University6, University of Michigan7, Oregon Health & Science University8, Jagiellonian University9, St Bartholomew's Hospital10, University of Virginia11, Ludwig Maximilian University of Munich12, University of Rochester Medical Center13
TL;DR: A retrospective cohort study of all patients with MCL who experienced disease progression while receiving ibrutinib across 15 international sites, poor clinical outcomes were noted in the majority of patients with primary or secondary ibrUTinib resistance and treatments could not identify treatments that clearly improved outcomes.
211 citations
TL;DR: In this paper, the authors explored the prevalence of wild-type transthyretin amyloid in cAS by myocardial biopsy, its imaging phenotype and prognostic significance.
Abstract: Background— Calcific aortic stenosis (cAS) affects 3% of individuals aged >75 years, leading to heart failure and death unless the valve is replaced. Wild-type transthyretin cardiac amyloid is also a disorder of ageing individuals. Prevalence and clinical significance of dual pathology are unknown. This study explored the prevalence of wild-type transthyretin amyloid in cAS by myocardial biopsy, its imaging phenotype and prognostic significance.
Methods and Results— A total of 146 patients with severe AS requiring surgical valve replacement underwent cardiovascular magnetic resonance and intraoperative biopsies; 112 had cAS (75±6 years; 57% men). Amyloid was sought histologically using Congo red staining and then typed using immunohistochemistry and mass spectrometry; patients with amyloid underwent clinical evaluation including genotyping and 99mTC-3,3-diphosphono-1,2-propanodicarboxylic-acid (DPD) bone scintigraphy. Amyloid was identified in 6 of 146 patients, all with cAS and >65 years (prevalence 5.6% in cAS >65). All 6 patients had wild-type transthyretin amyloid (mean age 75 years; range, 69–85; 4 men), not suspected on echocardiography. Cardiovascular magnetic resonance findings were of definite cardiac amyloidosis in 2, but could be explained solely by AS in the other 4. Postoperative DPD scans demonstrated cardiac localization in all 4 patients who had this investigation (2 died prior). At follow-up (median, 2.3 years), 50% with amyloid had died (versus 7.5% in cAS; 6.9% in age >65 years). In univariable analyses, the presence of transthyretin amyloidosis amyloid had the highest hazard ratio for death (9.5 [95% confidence interval, 2.5–35.8]; P =0.001).
Conclusions— Occult wild-type transthyretin cardiac amyloid had a prevalence of 6% among patients with AS aged >65 years undergoing surgical aortic valve replacement and was associated with a poor outcome.
198 citations
TL;DR: A meta-epigenomic approach that combines DNA methylation profiles across many small pools of cells and performed single-cell methylome sequencing to assess cell-to-cell heterogeneity is used and contributes to a better understanding of human hematopoietic stem cell differentiation and provides a framework for studying blood-linked diseases.
197 citations
Ryon M. Bateman1, Michael D. Sharpe1, Justin E. Jagger1, Christopher G. Ellis1 +1872 more•Institutions (226)
TL;DR: This research presents a novel probabilistic procedure called “spot-spot analysis” that allows for real-time analysis of the response of the immune system to natural disasters.
Abstract: [This corrects the article DOI: 10.1186/s13054-016-1208-6.].
180 citations
TL;DR: It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD.
Abstract: It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional DSD team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional team acts commonly as the first point of contact. This clinician should be part of a multidisciplinary team experienced in management of DSD and should ensure that the affected person and parents have access to specialist psychological support and that their information needs are comprehensively addressed. The underlying pathophysiology of DSD and the strengths and weaknesses of the tests that can be performed should be discussed with the parents and affected young person and tests undertaken in a timely fashion. Finally, in the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration.
164 citations
TL;DR: A possible role for AF in its aetiology is suggested, possibly as a trigger for ventricular fibrosis, and restoring sinus rhythm by catheter ablation seems successful in the medium term and improves HF symptoms, functional capacity, and left ventricular function.
Abstract: Atrial fibrillation (AF) and heart failure (HF) are evolving epidemics, together responsible for substantial human suffering and health-care expenditure. Ageing, improved cardiovascular survival, and epidemiological transition form the basis for their increasing global prevalence. Although we now have a clear picture of how HF promotes AF, gaps remain in our knowledge of how AF exacerbates or even causes HF, and how the development of HF affects the outcome of patients with AF. New data regarding HF with preserved ejection fraction and its unique relationship with AF suggest a possible role for AF in its aetiology, possibly as a trigger for ventricular fibrosis. Deciding on optimal treatment strategies for patients with both AF and HF is increasingly difficult, given that results from trials of pharmacological rhythm control are arguably obsolete in the age of catheter ablation. Restoring sinus rhythm by catheter ablation seems successful in the medium term and improves HF symptoms, functional capacity, and left ventricular function. Long-term studies to examine the effect on rates of stroke and death are ongoing. Guidelines continue to evolve to keep pace with this rapidly changing field.
149 citations
TL;DR: The cardiovascular morbidity and mortality associated with WCH may be slightly higher compared with normotension but well below the risks associated with sustained HTN.
Abstract: Background:White-coat hypertension (WCH) is a frequent condition particularly in children and elderly individuals. The prognostic significance of WCH is still a matter of debate.Methods:The present study was designed to systematically review cohort studies and assess the effects of WCH compared with
142 citations
National Institute of Standards and Technology1, University of Twente2, University of Western Australia3, German National Metrology Institute4, Humboldt University of Berlin5, Cambridge University Hospitals NHS Foundation Trust6, Imperial College London7, University of Milan8, Vita-Salute San Raffaele University9, Queen Mary University of London10, University of Stirling11, Beth Israel Deaconess Medical Center12, University of Virginia Health System13, National Institutes of Health14, St Bartholomew's Hospital15, University College London16
TL;DR: A phantom-based quality assurance (QA) system for verification of measurement stability over time at individual sites, with further aims of generalization of results across sites, vendor systems, software versions and imaging sequences is developed.
Abstract: T1 mapping and extracellular volume (ECV) have the potential to guide patient care and serve as surrogate end-points in clinical trials, but measurements differ between cardiovascular magnetic resonance (CMR) scanners and pulse sequences. To help deliver T1 mapping to global clinical care, we developed a phantom-based quality assurance (QA) system for verification of measurement stability over time at individual sites, with further aims of generalization of results across sites, vendor systems, software versions and imaging sequences. We thus created T1MES: The T1 Mapping and ECV Standardization Program. A design collaboration consisting of a specialist MRI small-medium enterprise, clinicians, physicists and national metrology institutes was formed. A phantom was designed covering clinically relevant ranges of T1 and T2 in blood and myocardium, pre and post-contrast, for 1.5 T and 3 T. Reproducible mass manufacture was established. The device received regulatory clearance by the Food and Drug Administration (FDA) and Conformite Europeene (CE) marking. The T1MES phantom is an agarose gel-based phantom using nickel chloride as the paramagnetic relaxation modifier. It was reproducibly specified and mass-produced with a rigorously repeatable process. Each phantom contains nine differently-doped agarose gel tubes embedded in a gel/beads matrix. Phantoms were free of air bubbles and susceptibility artifacts at both field strengths and T1 maps were free from off-resonance artifacts. The incorporation of high-density polyethylene beads in the main gel fill was effective at flattening the B
1 field. T1 and T2 values measured in T1MES showed coefficients of variation of 1 % or less between repeat scans indicating good short-term reproducibility. Temperature dependency experiments confirmed that over the range 15–30 °C the short-T1 tubes were more stable with temperature than the long-T1 tubes. A batch of 69 phantoms was mass-produced with random sampling of ten of these showing coefficients of variations for T1 of 0.64 ± 0.45 % and 0.49 ± 0.34 % at 1.5 T and 3 T respectively. The T1MES program has developed a T1 mapping phantom to CE/FDA manufacturing standards. An initial 69 phantoms with a multi-vendor user manual are now being scanned fortnightly in centers worldwide. Future results will explore T1 mapping sequences, platform performance, stability and the potential for standardization.
TL;DR: Synthetic ECV provides validated noninvasive quantification of the myocardial extracellular space without blood sampling and is associated with cardiovascular outcomes.
Abstract: Objectives The authors sought to generate a synthetic extracellular volume fraction (ECV) from the relationship between hematocrit and longitudinal relaxation rate of blood. Background ECV quantification by cardiac magnetic resonance (CMR) measures diagnostically and prognostically relevant changes in the extracellular space. Current methodologies require blood hematocrit (Hct) measurement—a complication to easy clinical application. We hypothesized that the relationship between Hct and longitudinal relaxation rate of blood (R1 = 1/T1blood) could be calibrated and used to generate a synthetic ECV without Hct that was valid, user-friendly, and prognostic. Methods Proof-of-concept: 427 subjects with a wide range of health and disease were divided into derivation (n = 214) and validation (n = 213) cohorts. Histology cohort: 18 patients with severe aortic stenosis with histology obtained during valve replacement. Outcome cohort: For comparison with external outcome data, we applied synthetic ECV to 1,172 consecutive patients (median follow-up 1.7 years; 74 deaths). All underwent CMR scanning at 1.5-T with ECV calculation from pre- and post-contrast T1 (blood and myocardium) and venous Hct. Results Proof-of-concept: In the derivation cohort, native R1blood and Hct showed a linear relationship (R2 = 0.51; p Conclusions Synthetic ECV provides validated noninvasive quantification of the myocardial extracellular space without blood sampling and is associated with cardiovascular outcomes.
TL;DR: This randomized multicenter study demonstrated that CF data availability was associated with reduced acute PV reconnection but not improved 1-year success rates, procedural and fluoroscopy times, or complication rates.
Royal Sussex County Hospital1, University of Oxford2, University College London3, Central and North West London NHS Foundation Trust4, Imperial College London5, University of Liverpool6, Western General Hospital7, Imperial College Healthcare8, Royal Free Hospital9, Chelsea and Westminster Hospital NHS Foundation Trust10, St Bartholomew's Hospital11, Leicester Royal Infirmary12, King's College London13, North Manchester General Hospital14
TL;DR: Writing Group Duncan Churchill, Chair, Royal Sussex County Hospital, Brighton, Laura Waters, Vice Chair, Mortimer Market Centre, London, and Rob Horne, University College London are among the authors of this book.
Abstract: Writing Group Duncan Churchill, Chair, Royal Sussex County Hospital, Brighton, UK Laura Waters, Vice Chair, Mortimer Market Centre, London, UK Nadia Ahmed, Mortimer Market Centre, London, UK Brian Angus, University of Oxford, UK Marta Boffito, Chelsea and Westminster Hospital, London, UK Mark Bower, Chelsea and Westminster Hospital, London, UK David Dunn, University College London, UK Simon Edwards, Central and North West London NHS Foundation Trust, UK Carol Emerson, Royal Victoria Hospital, Belfast, UK Sarah Fidler, Imperial College School of Medicine at St Mary’s, London, UK †Martin Fisher, Royal Sussex County Hospital, Brighton, UK Rob Horne, University College London, UK Saye Khoo, University of Liverpool, UK Clifford Leen, Western General Hospital, Edinburgh, UK Nicola Mackie, Imperial College Healthcare NHS Trust, London, UK Neal Marshall, Royal Free Hospital NHS Trust, London, UK Fernando Monteiro, UK-CAB Mark Nelson, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
TL;DR: Clinicians are assisted in navigating clinical guidelines for HCM by highlighting important updates, current gaps in knowledge, differences in the recommendations, and challenges in implementing them, including aids and pitfalls in clinical and pathological evaluation.
Abstract: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, affecting 1 in 500 individuals worldwide. Existing epidemiological studies might have underestimated the prevalence of HCM, however, owing to limited inclusion of individuals with early, incomplete phenotypic expression. Clinical manifestations of HCM include diastolic dysfunction, left ventricular outflow tract obstruction, ischaemia, atrial fibrillation, abnormal vascular responses and, in 5% of patients, progression to a 'burnt-out' phase characterized by systolic impairment. Disease-related mortality is most often attributable to sudden cardiac death, heart failure, and embolic stroke. The majority of individuals with HCM, however, have normal or near-normal life expectancy, owing in part to contemporary management strategies including family screening, risk stratification, thromboembolic prophylaxis, and implantation of cardioverter-defibrillators. The clinical guidelines for HCM issued by the ACC Foundation/AHA and the ESC facilitate evaluation and management of the disease. In this Review, we aim to assist clinicians in navigating the guidelines by highlighting important updates, current gaps in knowledge, differences in the recommendations, and challenges in implementing them, including aids and pitfalls in clinical and pathological evaluation. We also discuss the advances in genetics, imaging, and molecular research that will underpin future developments in diagnosis and therapy for HCM.
TL;DR: IMH and residualMyocardial iron may be potential therapeutic targets for preventing adverse LV remodeling in reperfused ST-segment–elevation myocardial infarction patients.
Abstract: Background— The presence of intramyocardial hemorrhage (IMH) in ST-segment–elevation myocardial infarction patients reperfused by primary percutaneous coronary intervention has been associated with residual myocardial iron at follow-up, and its impact on adverse left ventricular (LV) remodeling is incompletely understood and is investigated here.
Methods and Results— Forty-eight ST-segment–elevation myocardial infarction patients underwent cardiovascular magnetic resonance at 4±2 days post primary percutaneous coronary intervention, of whom 40 had a follow-up scan at 5±2 months. Native T1, T2, and T2* maps were acquired. Eight out of 40 (20%) patients developed adverse LV remodeling. A subset of 28 patients had matching T2* maps, of which 15/28 patients (54%) had IMH. Eighteen of 28 (64%) patients had microvascular obstruction on the acute scan, of whom 15/18 (83%) patients had microvascular obstruction with IMH. On the follow-up scan, 13/15 patients (87%) had evidence of residual iron within the infarct zone. Patients with residual iron had higher T2 in the infarct zone surrounding the residual iron when compared with those without. In patients with adverse LV remodeling, T2 in the infarct zone surrounding the residual iron was also higher than in those without (60 [54–64] ms versus 53 [51–56] ms; P =0.025). Acute myocardial infarct size, extent of microvascular obstruction, and IMH correlated with the change in LV end-diastolic volume (Pearson’s rho of 0.64, 0.59, and 0.66, respectively; P =0.18 and 0.62, respectively, for correlation coefficient comparison) and performed equally well on receiver operating characteristic curve for predicting adverse LV remodeling (area under the curve: 0.99, 0.94, and 0.95, respectively; P =0.19 for receiver operating characteristic curve comparison).
Conclusions— The majority of ST-segment–elevation myocardial infarction patients with IMH had residual myocardial iron at follow-up. This was associated with persistently elevated T2 values in the surrounding infarct tissue and adverse LV remodeling. IMH and residual myocardial iron may be potential therapeutic targets for preventing adverse LV remodeling in reperfused ST-segment–elevation myocardial infarction patients.
TL;DR: Dose prediction models to predict the risk of heart valve disease in the future and newer radiation techniques to reduce the radiation dose to the heart are being developed.
Abstract: Radiation to the mediastinum is a key component of treatment with curative intent for a range of cancers including Hodgkin's lymphoma and breast cancer. Exposure to radiation is associated with a risk of radiation-induced heart valve damage characterised by valve fibrosis and calcification. There is a latent interval of 10-20 years between radiation exposure and development of clinically significant heart valve disease. Risk is related to radiation dose received, interval from exposure and use of concomitant chemotherapy. Long-term outlook and the risk of valve surgery are related to the effects of radiation on mediastinal structures including pulmonary fibrosis and pericardial constriction. Dose prediction models to predict the risk of heart valve disease in the future and newer radiation techniques to reduce the radiation dose to the heart are being developed. Surveillance strategies for this cohort of cancer survivors at risk of developing significant heart valve complications are required.
TL;DR: Pembrolizumab 2mg/kg q3w is a safe option in UM patients and disease control rates, particularly in the subgroup of patients without progressive liver disease at the outset are promising; these results merit further investigation in clinical trials possibly incorporating liver targeted treatment modalities.
Abstract: Background: Untreated metastatic uveal melanoma (UM) carries a grave prognosis. Unlike cutaneous melanoma (CM), there are no established treatments known to significantly improve outcomes for a meaningful proportion of patients. Inhibition of the PD1–PDL1 axis has shown promise in the management of CM and we here report a two center experience of UM patients receiving pembrolizumab. Methods: To assess the efficacy and safety of pembrolizumab, we retrospectively analyzed outcome data of 25 consecutive UM patients participating in the MK3475 expanded access program (EAP) who received pembrolizumab at 2 mg/kg 3 weekly. Tumor assessment was evaluated using RECIST 1.1 and immune-related Response Criteria (irRC) by CT scanning. Toxicity was recorded utilizing Common Terminology Criteria for Adverse Events (“CTCAE”) v4.03. Results: Twenty-five patients were identified receiving a median of six cycles of treatment. Two patients achieved a partial response and six patients stable disease. After a median fo...
TL;DR: The early infusion of intracoronary BMC following PPCI for patients with AMI and regional wall motion abnormality leads to a small non-significant improvement in LVEF when compared with placebo; however, it may play an important role in infarct remodelling and myocardial salvage.
Abstract: Aims
Clinical trials suggest that intracoronary delivery of autologous bone marrow-derived cells (BMCs) 1–7 days post-acute myocardial infarction (AMI) may improve left ventricular (LV) function. Earlier time points have not been evaluated. We sought to determine the effect of intracoronary autologous BMC on LV function when delivered within 24 h of successful reperfusion therapy.
TL;DR: A new level set method for segmentation of cardiac left and right ventricles by extending the edge based distance regularized level set evolution (DRLSE) model to a two-level-set formulation, with the 0 and k-level set representing the endocardium and epicardium, respectively.
TL;DR: A recent systematic review as discussed by the authors found evidence supporting a dose-response type of association between chronic pain and cardiovascular disease, supported by a range of observational studies originating from different countries, including the US, Australia, Canada, and New Zealand.
TL;DR: Data imply that the occurrence of MVT should not rule out the possibility of Brugada syndrome, and this finding may also be relevant for ICD model selection and programming.
TL;DR: The findings suggest non-infective causes of diarrhoea in ICU predominate and pathophysiology of diarrhea in critically ill patients warrants further investigation.
Abstract: Diarrhoea is common in Intensive Care Unit (ICU) patients, with a reported prevalence of 15-38%. Many factors may cause diarrhoea, including Clostridium difficile, drugs (e.g. laxatives, antibiotics) and enteral feeds. Diarrhoea impacts on patient dignity, increases nursing workload and healthcare costs, and exacerbates morbidity through dermal injury, impaired enteral uptake and subsequent fluid imbalance. We analysed a cohort of 9331 consecutive patients admitted to a mixed general intensive care unit to establish the prevalence of diarrhoea in intensive care unit patients, and its relationship with infective aetiology and clinical outcomes. We provide evidence that diarrhoea is common (12.9% (1207/9331) prevalence) in critically ill patients, independently associated with increased intensive care unit length of stay (mean (standard error) 14.8 (0.26) vs 3.2 (0.09) days, p < 0.001) and mortality (22.0% (265/1207) vs 8.7% (705/8124), p < 0.001; adjusted hazard ratio 1.99 (95% CI 1.70-2.32), p < 0.001) compared to patients without diarrhoea even after adjusting for potential confounding factors, and infrequently caused by infective aetiology (112/1207 (9.2%)) such as Clostridium difficile (97/1048 (9.3%) tested) or virological causes (9/172 (5.7%) tested). Our findings suggest non-infective causes of diarrhoea in ICU predominate and pathophysiology of diarrhoea in critically ill patients warrants further investigation.
TL;DR: The response to ovarian stimulation in cancer patients before undergoing cancer treatment and to determine whether any difference can be attributed to underlying cancer diagnosis is analyzed, showing pregnancy outcomes in oncology patients undergoing FP.
Abstract: STUDY QUESTION: Does the type of cancer influence on the ovarian response to stimulation for fertility preservation (FP) in female oncology patients? SUMMARY ANSWER: Patients with gynaecological cancer have less number of retrieved mature oocytes compared with haematological and breast cancer patients. WHAT IS KNOWN ALREADY: Concerns about the impact of cancer therapy on future fertility have been raised and FP has become an important component in cancer management. Previous studies analysing FP results in cancer patients have shown conflicting findings. STUDY DESIGN, SIZE, DURATION: This was a retrospective analytical study performed in the Centre for Reproductive Medicine, at St Bartholomew's Hospital, between January 2000 and December 2014. The aim of this study was to analyse the response to ovarian stimulation in cancer patients before undergoing cancer treatment and to determine whether any difference can be attributed to underlying cancer diagnosis. We also report the pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 531 female patients recently diagnosed with cancer were referred for counselling on FP. A total of 306 patients underwent ovarian stimulation for oocyte or embryo cryopreservation. We compared the baseline characteristics and ovarian response in five main subgroups: breast cancer, haematological cancer, gynaecological cancer, gastrointestinal cancer and others. The primary outcome was the total number of mature oocytes retrieved and pregnancy outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: Themain cancer diagnosis was breast cancer with 145 patients (47.4%); 79 patients (25.8%) had haematological malignancies; 42 (13.7%) had gynaecological malignancies; 20 (6.5%) had gastrointestinal cancer and 20 (6.5%) had other types of cancer. Patients with breast cancer were older (P<0.001). Patients with haematological malignancies had higher number of mature oocytes retrieved (P = 0.003). The number of mature oocytes retrieved was lower in patients with gynaecological malignancy compared with haematological and breast cancer patients (P = 0.005 and P = 0.045, respectively). The fertilization rate and the number of cycles cancelled were comparable between all the groups. Thirty-two embryo transfer cycles have been done in 22 patients who have returned to attempt pregnancy. Pregnancy rate per transfer cycle was 43.75%, and cumulative pregnancy rate per patient was 54.5%. Live birth rate per patient was 22.72%. LIMITATIONS, REASONS FOR CAUTION: Apart from the retrospective nature of the study, patients were included over the period of 15 years, and over that time technology has changed and protocols have evolved. The results obtained from subcategory analyses should be interpreted with caution, as in each subgroup there are different types of malignancies with different number of patients in different age groups. Different ovarian stimulation protocols were applied. Only a few patients have come back to attempt pregnancy after being cured from their disease. We do not have follow-updata on these patients; as a result, we are not able to report the survival rate and the reason for non-return for embryo transfer. In addition, we cannot report information on spontaneous conceptions and births. Slow freezing used for embryo cryopreservation, high miscarriage rate and low live birth rate per transfer are other limitations of this study. WIDER IMPLICATIONS OF THE FINDINGS: The current study is the largest series analysing each group of cancer separately and showing pregnancy outcomes in oncology patients undergoing FP. These results provide valuable information about the success of this technique in oncology patients. STUDY FUNDING/COMPETING INTEREST(S): The authors have not received any funding to support this study. There are no conflicts of interest to declare.
Cornell University1, University of Düsseldorf2, Indiana University3, University of Toronto4, The Royal Marsden NHS Foundation Trust5, University of Hamburg6, Russian Academy7, University of Western Ontario8, Harvard University9, Karolinska Institutet10, University of Zurich11, St Bartholomew's Hospital12
TL;DR: High-dose chemotherapy and multimodality treatment seemed to improve survival probabilities in men with BM from GCT at relapse, particularly if additional risk factors are present.
Abstract: PurposeTo define characteristics, treatment response, and outcomes of men with brain metastases (BM) from germ cell tumors (GCT).Patients and MethodsData from 523 men with BM from GCT were collected retrospectively from 46 centers in 13 countries by using standardized questionnaires. Clinical features were correlated with overall survival (OS) as the primary end point.ResultsBM were present at initial diagnosis in 228 men (group A) and at relapse in 295 men (group B). OS at 3 years (3-year OS) was superior in group A versus group B (48% v 27%; P < .001). Multiple BM and the presence of liver or bone metastasis were independent adverse prognostic factors in both groups; primary mediastinal nonseminoma (group A) and elevations of α-fetoprotein of 100 ng/mL or greater or of human chorionic gonadotropin of 5,000 U/L or greater (group B) were additional independent adverse prognostic factors. Depending on these factors, the 3-year OS ranged from 0% to 70% in group A and from 6% to 52% in group B. In group A, 9...
TL;DR: New developments in cardiovascular magnetic resonance are galvanising CMR uptake and having a major translational impact on healthcare globally and it is steadily becoming key imaging tool.
Abstract: Cardiovascular magnetic resonance (CMR) is a key imaging technique for cardiac phenotyping with a major clinical role. It can assess advanced aspects of cardiac structure and function, scar burden and other myocardial tissue characteristics but there is new information that can now be derived. This can fill many of the gaps in our knowledge with the potential to change thinking, disease classifications and definitions as well as patient care. Established techniques such as the late gadolinium enhancement technique are now embedded in clinical care. New techniques are coming through. Myocardial tissue characterisation techniques, particularly myocardial mapping can precisely measure tissue magnetisation-T1, T2, T2* and also the extracellular volume. These change in disease. Key biological pathways are now open for scrutiny including focal fibrosis (scar) and diffuse fibrosis, inflammation, metabolism and infiltration. Other new areas to engage in where major insights are growing include detailed assessments of myocardial mechanics and performance, spectroscopy and hyperpolarised CMR. In spite of the advances, challenges remain, particularly surrounding utilisation, technical development to improve accuracy, reproducibility and deliverability, and the role of multidisciplinary research to understand the detailed pathological basis of the MR signal changes. Collectively, these new developments are galvanising CMR uptake and having a major translational impact on healthcare globally and it is steadily becoming key imaging tool.
TL;DR: Long-term success rates for persistent (but not paroxysmal) AF ablation are significantly lower in HF patients, and recurrent arrhythmia strongly predicted stroke and death during follow-up.
Abstract: Aims Catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) can improve left ventricular (LV) function and HF symptoms. We aimed to investigate whether long-term maintenance of sinus rhythm impacts on hard outcomes such as stroke and death.
Methods and results An international multicentre registry was compiled from seven centres for consecutive patients undergoing catheter ablation of AF. Long-term freedom from AF was examined in patients with and without HF. The impact of maintaining sinus rhythm on rates of stroke and death was also examined. A total of 1273 patients were included: 171 with HF and 1102 without. Median follow-up was 3.1 years (IQR 2.0–4.3). The final procedure success rate was no different for paroxysmal AF (PAF) (78.7 vs. 85.7%, P = 0.186), but significantly different for persistent AF (57.3 vs. 75.8%, P < 0.001). Multivariate analysis showed that HF independently predicted recurrent arrhythmia [hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.2–2.4, P = 0.002]. New York Heart Association class decreased from 2.3 ± 0.7 at baseline to 1.5 ± 0.8 at follow-up ( P < 0.001). Left ventricular ejection fraction (LVEF) increased from 34.3 ± 9.0 to 45.8 ± 12.8% ( P < 0.001). Recurrent AF was strongly predictive of stroke or death in HF patients (HR 8.33, 95% CI 1.86–37.7, P = 0.001).
Conclusion Long-term success rates for persistent (but not paroxysmal) AF ablation are significantly lower in HF patients. Left ventricular function and HF symptoms were improved following ablation. In HF patients, recurrent arrhythmia strongly predicted stroke and death during follow-up.
TL;DR: It is found that there is no advantage in using a single dose of 6 mg/m2 of gemtuzumab ozogamicin in combination with induction chemotherapy when compared with a 3 mg/ m2 dose, with respect to response, disease-free and overall survival, either overall, or in any disease subgroup.
Abstract: Arecent source data meta-analysis of randomized trials in adults assessing the immunoconjugate gemtuzumab ozogamicin combined with standard chemotherapy in acute myeloid leukemia showed a significant survival benefit in patients without an adverse karyotype. It is not clear whether the optimal dose should be 3 mg/m(2) or 6 mg/m(2) In this study, we randomized 788 patients to a single dose of gemtuzumab ozogamicin 3 mg/m(2) or 6 mg/m(2) with the first course of induction therapy. We found that the rate of complete remission was higher with 3 mg/m(2) [82% vs 76%; odds ratio 1.46 (1.04-2.06); P=0.03], but this was balanced by a higher rate of complete remission with incomplete peripheral blood count recovery in the 6 mg/m(2) treatment (10% vs 7%) resulting in similar overall response rate [89% vs 86%; hazard ratio 1.34 (0.88-2.04); P=0.17]. There was no overall difference in relapse or survival at four years between the arms: 46% vs 54%; hazard ratio 1.17 (0.94-1.45), P=0.5, and 50% versus 47%; hazard ratio 1.10 (0.90-1.34), P=0.3, respectively. The 30- and 60-day mortality was significantly higher in the 6 mg/m(2) recipients: 7% versus 3%; hazard ratio 2.07 (1.11-3.87), P=0.02, and 9% versus 5%; hazard ratio 1.99 (1.17-3.39), P=0.01, respectively, which in addition was associated with a higher rate of veno-occlusive disease (5.6% vs 0.5%; P<0.0001). Our conclusion from this trial is that there is no advantage in using a single dose of 6 mg/m(2) of gemtuzumab ozogamicin in combination with induction chemotherapy when compared with a 3 mg/m(2) dose, with respect to response, disease-free and overall survival, either overall, or in any disease subgroup. (AML17 was registered as ISRCTN55675535).
TL;DR: Premenopausal RRSO appears to be extremely cost-effective at ≥4% lifetime OC risk, with ≥42.7 days gain in life expectancy if compliance with hormone replacement therapy is high, with benefits largely driven by reduction in BC risk.
Abstract: BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) is the most effective intervention to prevent ovarian cancer (OC). It is only available to high-risk women with >10% lifetime OC risk. This threshold has not been formally tested for cost-effectiveness. OBJECTIVE: To specify the OC risk thresholds for RRSO being cost-effective for preventing OC in premenopausal women. METHODS: The costs as well as effects of surgical prevention ('RRSO') were compared over a lifetime with 'no RRSO' using a decision analysis model. RRSO was undertaken in premenopausal women >40 years. The model was evaluated at lifetime OC risk levels: 2%, 4%, 5%, 6%, 8% and 10%. Costs and outcomes are discounted at 3.5%. Uncertainty in the model was assessed using both deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Outcomes included in the analyses were OC, breast cancer (BC) and additional deaths from coronary heart disease. Total costs and effects were estimated in terms of quality-adjusted life-years (QALYs); incidence of OC and BC; as well as incremental cost-effectiveness ratio (ICER). DATA SOURCES: Published literature, Nurses Health Study, British National Formulary, Cancer Research UK, National Institute for Health and Care Excellence guidelines and National Health Service reference costs. The time horizon is lifetime and perspective: payer. RESULTS: Premenopausal RRSO is cost-effective at 4% OC risk (life expectancy gained=42.7 days, ICER=£19 536/QALY) with benefits largely driven by reduction in BC risk. RRSO remains cost-effective at >8.2% OC risk without hormone replacement therapy (ICER=£29 071/QALY, life expectancy gained=21.8 days) or 6%if BC risk reduction=0 (ICER=£27 212/QALY, life expectancy gained=35.3 days). Sensitivity analysis indicated results are not impacted much by costs of surgical prevention or treatment of OC/ BC or cardiovascular disease. However, results were sensitive to RRSO utility scores. Additionally, 37%, 61%, 74%, 84%, 96% and 99.5% simulations on PSA are cost-effective for RRSO at the 2%, 4%, 5%, 6%, 8% and 10% levels of OC risk, respectively. CONCLUSIONS: Premenopausal RRSO appears to be extremely cost-effective at ≥4% lifetime OC risk, with ≥42.7 days gain in life expectancy if compliance with hormone replacement therapy is high. Current guidelines should be re-evaluated to reduce the RRSO OC risk threshold to benefit a number of at-risk women who presently cannot access risk-reducing surgery.
TL;DR: Patients with a higher ECVR emote and a lower myocardial salvage index (MSI) acutely were significantly associated with adverse LV remodeling whereas segments with higher ECVI nfarct were less likely to recover wall motion.
Abstract: Background Whether the remote myocardium of reperfused ST‐segment elevation myocardial infarction (STEMI) patients plays a part in adverse left ventricular (LV) remodeling remains unclear. We aimed to use automated extracellular volume fraction (ECV) mapping to investigate whether changes in the ECV of the remote (ECV R emote ) and infarcted myocardium (ECV I nfarct ) impacted LV remodeling. Methods and Results Forty‐eight of 50 prospectively recruited reperfused STEMI patients completed a cardiovascular magnetic resonance at 4±2 days and 40 had a follow‐up scan at 5±2 months. Twenty healthy volunteers served as controls. Mean segmental values for native T1, T2, and ECV were obtained. Adverse LV remodeling was defined as ≥20% increase in LV end‐diastolic volume. ECV R emote was higher on the acute scan when compared to control (27.9±2.1% vs 26.4±2.1%; P =0.01). Eight patients developed adverse LV remodeling and had higher ECV R emote acutely (29.5±1.4% vs 27.4±2.0%; P =0.01) and remained higher at follow‐up (28.6±1.5% vs 26.6±2.1%; P =0.02) compared to those without. Patients with a higher ECV R emote and a lower myocardial salvage index (MSI) acutely were significantly associated with adverse LV remodeling, independent of T1 Remote , T1 Core and microvascular obstruction, whereas a higher ECV I nfarct was significantly associated with worse wall motion recovery. Conclusions ECV R emote was increased acutely in reperfused STEMI patients. Those with adverse LV remodeling had higher ECV R emote acutely, and this remained higher at follow‐up than those without adverse LV remodeling. A higher ECV R emote and a lower MSI acutely were significantly associated with adverse LV remodeling whereas segments with higher ECV I nfarct were less likely to recover wall motion.