Showing papers by "St Bartholomew's Hospital published in 2019"
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Abbott Northwestern Hospital1, University of Freiburg2, St George's Hospital3, Henry Ford Hospital4, Clínica Alemana5, University of Sydney6, Tunis University7, Jagiellonian University Medical College8, University of Cologne9, St. Michael's Hospital10, University of Lisbon11, Aarhus University Hospital12, Vita-Salute San Raffaele University13, Brigham and Women's Hospital14, Southern Illinois University School of Medicine15, Peking Union Medical College16, Newcastle University17, Imperial College London18, Complutense University of Madrid19, University of Palermo20, Fudan University21, Sanjay Gandhi Post Graduate Institute of Medical Sciences22, Memorial Hospital of South Bend23, Belfast Health and Social Care Trust24, University of Graz25, Wellington Hospital26, University of Amsterdam27, University of Cambridge28, Harvard University29, University Health System30, National Taiwan University31, Columbia University32, Cairo University33, VU University Medical Center34, Rabin Medical Center35, McMaster University36, University of Ulsan37, Harbin Medical University38, University of New South Wales39, University of Washington40, Golden Jubilee National Hospital41, Lund University42, AHEPA University Hospital43, St Bartholomew's Hospital44, St. George's University45, Columbia University Medical Center46, Bristol Royal Infirmary47, University of Szeged48, University of Alberta49, Torrance Memorial Medical Center50, University of Western Ontario51, Beth Israel Deaconess Medical Center52, Tongji University53, McGill University Health Centre54
TL;DR: In this paper, the authors identified seven common principles that are widely accepted as best practices for chronic total occlusion percutaneous coronary intervention (PCI) in CTO-PCI.
Abstract: Outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have improved because of advancements in equipment and techniques. With global collaboration and knowledge sharing, we have identified 7 common principles that are widely accepted as best practices for CTO-PCI. 1. Ischemic symptom improvement is the primary indication for CTO-PCI. 2. Dual coronary angiography and in-depth and structured review of the angiogram (and, if available, coronary computed tomography angiography) are key for planning and safely performing CTO-PCI. 3. Use of a microcatheter is essential for optimal guidewire manipulation and exchanges. 4. Antegrade wiring, antegrade dissection and reentry, and the retrograde approach are all complementary and necessary crossing strategies. Antegrade wiring is the most common initial technique, whereas retrograde and antegrade dissection and reentry are often required for more complex CTOs. 5. If the initially selected crossing strategy fails, efficient change to an alternative crossing technique increases the likelihood of eventual PCI success, shortens procedure time, and lowers radiation and contrast use. 6. Specific CTO-PCI expertise and volume and the availability of specialized equipment will increase the likelihood of crossing success and facilitate prevention and management of complications, such as perforation. 7. Meticulous attention to lesion preparation and stenting technique, often requiring intracoronary imaging, is required to ensure optimum stent expansion and minimize the risk of short- and long-term adverse events. These principles have been widely adopted by experienced CTO-PCI operators and centers currently achieving high success and acceptable complication rates. Outcomes are less optimal at less experienced centers, highlighting the need for broader adoption of the aforementioned 7 guiding principles along with the development of additional simple and safe CTO crossing and revascularization strategies through ongoing research, education, and training.
228 citations
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TL;DR: A framework of clinical scenarios in which screening for ATTR-CM is recommended, as well as diagnostic "red flags" that can assist in its diagnosis among the wider population of patients with heart failure are proposed.
Abstract: Highlights •ATTR-CM is a life-threatening, progressive disease that is often underdiagnosed and misdiagnosed. •Certain clinical scenarios have been identified that now warrant screening for ATTR-CM. •Once ATTR-CM is suspected, a definitive diagnosis can usually be achieved noninvasively. •Accurate, early diagnosis of ATTR-CM is key to enabling appropriate patient care.
185 citations
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20 May 2019
TL;DR: This work produced the first chronological map of human health with cumulative-incidence and period-prevalence estimates for multiple morbidities in parallel from birth to advanced age and developed phenotyping algorithms and codelists for physical and mental health conditions that involve intensive use of health-care resources.
Abstract: Summary Background To effectively prevent, detect, and treat health conditions that affect people during their lifecourse, health-care professionals and researchers need to know which sections of the population are susceptible to which health conditions and at which ages. Hence, we aimed to map the course of human health by identifying the 50 most common health conditions in each decade of life and estimating the median age at first diagnosis. Methods We developed phenotyping algorithms and codelists for physical and mental health conditions that involve intensive use of health-care resources. Individuals older than 1 year were included in the study if their primary-care and hospital-admission records met research standards set by the Clinical Practice Research Datalink and they had been registered in a general practice in England contributing up-to-standard data for at least 1 year during the study period. We used linked records of individuals from the CALIBER platform to calculate the sex-standardised cumulative incidence for these conditions by 10-year age groups between April 1, 2010, and March 31, 2015. We also derived the median age at diagnosis and prevalence estimates stratified by age, sex, and ethnicity (black, white, south Asian) over the study period from the primary-care and secondary-care records of patients. Findings We developed case definitions for 308 disease phenotypes. We used records of 2 784 138 patients for the calculation of cumulative incidence and of 3 872 451 patients for the calculation of period prevalence and median age at diagnosis of these conditions. Conditions that first gained prominence at key stages of life were: atopic conditions and infections that led to hospital admission in children ( Interpretation We have produced the first chronological map of human health with cumulative-incidence and period-prevalence estimates for multiple morbidities in parallel from birth to advanced age. This can guide clinicians, policy makers, and researchers on how to formulate differential diagnoses, allocate resources, and target research priorities on the basis of the knowledge of who gets which diseases when. We have published our phenotyping algorithms on the CALIBER open-access Portal which will facilitate future research by providing a curated list of reusable case definitions. Funding Wellcome Trust, National Institute for Health Research, Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Department of Health and Social Care (England), Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), Economic and Social Research Council, Engineering and Physical Sciences Research Council, National Institute for Social Care and Health Research, and The Alan Turing Institute.
176 citations
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University of Cambridge1, University of Edinburgh2, Imperial College London3, UCL Institute of Child Health4, Great Ormond Street Hospital for Children NHS Foundation Trust5, John Radcliffe Hospital6, University College London7, St Mary's Hospital8, University of Manchester9, Newcastle University10, Newcastle upon Tyne Hospitals NHS Foundation Trust11, St Bartholomew's Hospital12, Guy's and St Thomas' NHS Foundation Trust13, Cambridge University Hospitals NHS Foundation Trust14, Papworth Hospital15, UCL Institute of Neurology16, King's College London17, University of Oxford18, Moorfields Eye Hospital19, UCL Institute of Ophthalmology20, Imperial College Healthcare21, Queen Mary University of London22
TL;DR: The characteristics of mtDNA in the human population are shaped by selective forces acting on heteroplasmy within the female germ line and are influenced by the nuclear genetic background, as indicated by population genetic evidence that selection shapes the evolving mtDNA phylogeny.
Abstract: Approximately 2.4% of the human mitochondrial DNA (mtDNA) genome exhibits common homoplasmic genetic variation. We analyzed 12,975 whole-genome sequences to show that 45.1% of individuals from 1526 mother-offspring pairs harbor a mixed population of mtDNA (heteroplasmy), but the propensity for maternal transmission differs across the mitochondrial genome. Over one generation, we observed selection both for and against variants in specific genomic regions; known variants were more likely to be transmitted than previously unknown variants. However, new heteroplasmies were more likely to match the nuclear genetic ancestry as opposed to the ancestry of the mitochondrial genome on which the mutations occurred, validating our findings in 40,325 individuals. Thus, human mtDNA at the population level is shaped by selective forces within the female germ line under nuclear genetic control, which ensures consistency between the two independent genetic lineages.
162 citations
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Great Ormond Street Hospital1, University College London2, Royal Children's Hospital3, University of Melbourne4, Boston Children's Hospital5, Foundation University, Islamabad6, Leiden University Medical Center7, University of Barcelona8, University of Girona9, Children's of Alabama10, Hospital General Universitario Gregorio Marañón11, University Hospital of Wales12, Leeds General Infirmary13, Hebron University14, Bristol Royal Hospital for Children15, John Radcliffe Hospital16, Glenfield Hospital17, Southampton General Hospital18, Universidad Francisco de Vitoria19, Aarhus University Hospital20, Ghent University Hospital21, Kōchi University22, Mater Dei Hospital23, Odense University Hospital24, Freeman Hospital25, St Bartholomew's Hospital26
TL;DR: This new, validated risk stratification model for SCD in childhood HCM may provide individualized estimates of risk at 5 years using readily obtained clinical risk factors.
Abstract: Importance Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM), but there is no validated algorithm to identify those at highest risk. Objective To develop and validate an SCD risk prediction model that provides individualized risk estimates. Design, Setting, and Participants A prognostic model was developed from a retrospective, multicenter, longitudinal cohort study of 1024 consecutively evaluated patients aged 16 years or younger with HCM. The study was conducted from January 1, 1970, to December 31, 2017. Exposures The model was developed using preselected predictor variables (unexplained syncope, maximal left-ventricular wall thickness, left atrial diameter, left-ventricular outflow tract gradient, and nonsustained ventricular tachycardia) identified from the literature and internally validated using bootstrapping. Main Outcomes and Measures A composite outcome of SCD or an equivalent event (aborted cardiac arrest, appropriate implantable cardioverter defibrillator therapy, or sustained ventricular tachycardia associated with hemodynamic compromise). Results Of the 1024 patients included in the study, 699 were boys (68.3%); mean (interquartile range [IQR]) age was 11 (7-14) years. Over a median follow-up of 5.3 years (IQR, 2.6-8.3; total patient years, 5984), 89 patients (8.7%) died suddenly or had an equivalent event (annual event rate, 1.49; 95% CI, 1.15-1.92). The pediatric model was developed using preselected variables to predict the risk of SCD. The model’s ability to predict risk at 5 years was validated; the C statistic was 0.69 (95% CI, 0.66-0.72), and the calibration slope was 0.98 (95% CI, 0.59-1.38). For every 10 implantable cardioverter defibrillators implanted in patients with 6% or more of a 5-year SCD risk, 1 patient may potentially be saved from SCD at 5 years. Conclusions and Relevance This new, validated risk stratification model for SCD in childhood HCM may provide individualized estimates of risk at 5 years using readily obtained clinical risk factors. External validation studies are required to demonstrate the accuracy of this model's predictions in diverse patient populations.
130 citations
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TL;DR: The number of patients receiving an allogeneic HCT for marrow failure is decreasing slightly, and genetically modified T cells is type of cell therapy with the fastest growth.
Abstract: Hematopoietic cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants done in Europe and associated countries continues to rise with 45,418 HCT in 41,100 patients [(17,155 allogeneic (42%) and 23,945 autologous (58%)] reported by 683 centers in 50 countries in 2017. Main indications were myeloid malignancies 10,147 (25%; 96% allogeneic), lymphoid malignancies 26,488 (64%; 19% allogeneic), solid tumors 1,607 (3.9%; 2% allogeneic), and nonmalignant disorders 2,667 (7%; 81% allogeneic). Trends in donor choice seen before continue, with growing numbers of haploidentical HCT and decreasing use of cord blood. Of interest is that after many years of continued growth, the number of patients receiving an allogeneic HCT for marrow failure is decreasing slightly (p < 0.001). Such a change may be explained by the use of thrombopoietin analogs in aplastic anemia patients. Other nonmalignant indications, however continue to grow, most importantly HCT for hemoglobinopathies by 36%, equally for thalassemias and sickle cell disease. Non-HCT cell therapies have increased by 28% since 2015 and genetically modified T cells is type of cell therapy with the fastest growth. These annual reports reflect current activity and trends and are useful for health-care planning.
121 citations
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TL;DR: This research presents a novel probabilistic approach that allows us to assess the importance of knowing the carrier and removal status of canine coronavirus, as a source of infection for other animals.
Abstract: Background: The genetic basis of left ventricular (LV) image-derived phenotypes, which play a vital role in the diagnosis, management, and risk stratification of cardiovascular diseases, is unclear...
121 citations
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Sheba Medical Center1, Goethe University Frankfurt2, Aix-Marseille University3, Utrecht University4, Medical University of Warsaw5, Boston Children's Hospital6, Leiden University7, St Bartholomew's Hospital8, University of Sheffield9, Nicolaus Copernicus University in Toruń10, Lille University of Science and Technology11
TL;DR: Overall survival following allogeneic stem cell transplantation is improving with substantial progress among recipients of haploidentical and cord blood HSCT, and the traditional donor hierarchy of matched sibling donors followed by matched unrelated donors and then other donors holds.
120 citations
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Paris Descartes University1, French Institute of Health and Medical Research2, University of Paris3, St Bartholomew's Hospital4, Aix-Marseille University5, Brigham and Women's Hospital6, François Rabelais University7, University of Nantes8, Queen Mary University of London9, University of Rennes10, university of lille11, Royal Melbourne Hospital12, Leiden University13, Necker-Enfants Malades Hospital14, Centre national de la recherche scientifique15, Paris Diderot University16, Pasteur Institute17, University of Lorraine18, University of Montpellier19, Université de Montréal20
TL;DR: In this paper, an accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverte...
Abstract: Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverte...
106 citations
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TL;DR: Recommendations for periconception, antenatal, and postnatal care for women following bariatric surgery are provided, and many recommendations are not supported by high‐quality evidence and warrant further research.
Abstract: The objective of the study is to provide evidence‐based guidance on nutritional management and optimal care for pregnancy after bariatric surgery. A consensus meeting of international and multidisciplinary experts was held to identify relevant research questions in relation to pregnancy after bariatric surgery. A systematic search of available literature was performed, and the ADAPTE protocol for guideline development followed. All available evidence was graded and further discussed during group meetings to formulate recommendations. Where evidence of sufficient quality was lacking, the group made consensus recommendations based on expert clinical experience. The main outcome measures are timing of pregnancy, contraceptive choice, nutritional advice and supplementation, clinical follow‐up of pregnancy, and breastfeeding. We provide recommendations for periconception, antenatal, and postnatal care for women following surgery. These recommendations are summarized in a table and print‐friendly format. Women of reproductive age with a history of bariatric surgery should receive specialized care regarding their reproductive health. Many recommendations are not supported by high‐quality evidence and warrant further research. These areas are highlighted in the paper.
99 citations
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TL;DR: In a multimodality imaging assessment of a large cohort of amyloidosis patients, CMR-derived TAPSE and indexed stroke volume are the strongest prognostic cardiac functional markers.
Abstract: Objectives: This cross-sectional study aimed to describe the functional and structural cardiac abnormalities that occur across a spectrum of cardiac amyloidosis burden and to identify the s...
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Université Paris-Saclay1, Queen Elizabeth Hospital Birmingham2, Cardiff University3, Academy for Urban School Leadership4, National and Kapodistrian University of Athens5, University of Barcelona6, Services Hospital7, St Bartholomew's Hospital8, University Hospital Centre Zagreb9, University of Ulm10, Hoffmann-La Roche11
TL;DR: Efficacy overall and in the IMvigor211-like subgroup is consistent with previous pivotal anti-PD-L1/PD-1 urothelial carcinoma trials, and results support the use of atezolizumab in urinary tract carcinoma, including patients with limited treatment options.
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TL;DR: The most defining characteristic is a subepicardial ring-like scar pattern in DSP/FLNC, which should be considered in future diagnostic criteria for ALVC, and cause more regionality in LV impairment.
Abstract: AIMS: Myocardial scar detected by cardiovascular magnetic resonance has been associated with sudden cardiac death in dilated cardiomyopathy (DCM). Certain genetic causes of DCM may cause a malignant arrhythmogenic phenotype. The concepts of arrhythmogenic left ventricular (LV) cardiomyopathy (ALVC) and arrhythmogenic DCM are currently ill-defined. We hypothesized that a distinctive imaging phenotype defines ALVC. METHODS AND RESULTS: Eighty-nine patients with DCM-associated mutations [desmoplakin (DSP) n = 25, filamin C (FLNC) n = 7, titin n = 30, lamin A/C n = 12, bcl2-associated athanogene 3 n = 3, RNA binding motif protein 20 n = 3, cardiac sodium channel NAv1.5 n = 2, and sarcomeric genes n = 7] were comprehensively phenotyped. Clustering analysis resulted in two groups: 'DSP/FLNC genotypes' and 'non-DSP/FLNC'. There were no significant differences in age, sex, symptoms, baseline electrocardiography, arrhythmia burden, or ventricular volumes between the two groups. Subepicardial LV late gadolinium enhancement with ring-like pattern (at least three contiguous segments in the same short-axis slice) was observed in 78.1% of DSP/FLNC genotypes but was absent in the other DCM genotypes (P < 0.001). Left ventricular ejection fraction (LVEF) and global longitudinal strain were lower in other DCM genotypes (P = 0.053 and P = 0.015, respectively), but LV regional wall motion abnormalities were more common in DSP/FLNC genotypes (P < 0.001). DSP/FLNC patients with non-sustained ventricular tachycardia (NSVT) had more LV scar (P = 0.010), whereas other DCM genotypes patients with NSVT had lower LVEF (P = 0.001) than patients without NSVT. CONCLUSION: DSP/FLNC genotypes cause more regionality in LV impairment. The most defining characteristic is a subepicardial ring-like scar pattern in DSP/FLNC, which should be considered in future diagnostic criteria for ALVC.
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NHS Greater Glasgow and Clyde1, Vanderbilt University2, Wake Forest University3, St Bartholomew's Hospital4, Intermountain Medical Center5, University of Pittsburgh6, Veterans Health Administration7, University of California, San Francisco8, Guy's and St Thomas' NHS Foundation Trust9, Albert Einstein College of Medicine10, Mayo Clinic11, Wake Forest Baptist Medical Center12, Indiana University13, University Hospitals of Cleveland14, University of Washington15, University of Kentucky16, University of Colorado Denver17, Vanderbilt University Medical Center18, Brigham and Women's Hospital19, University of Maryland, Baltimore20, Intermountain Healthcare21, Hospital of the University of Pennsylvania22, University of Michigan23
TL;DR: Several enablers and barriers to implementing ICU follow-up clinics and peer support groups should be taken into account and leveraged to improve ICU recovery.
Abstract: Objectives: Data are lacking regarding implementation of novel strategies such as follow-up clinics and peer support groups, to reduce the burden of postintensive care syndrome. We sought to discover enablers that helped hospital-based clinicians establish post-ICU clinics and peer support programs, and identify barriers that challenged them.
Design: Qualitative inquiry. The Consolidated Framework for Implementation Research was used to organize and analyze data.
Setting: Two learning collaboratives (ICU follow-up clinics and peer support groups), representing 21 sites, across three continents.
Subjects: Clinicians from 21 sites.
Measurement and Main Results: Ten enablers and nine barriers to implementation of “ICU follow-up clinics” were described. A key enabler to generate support for clinics was providing insight into the human experience of survivorship, to obtain interest from hospital administrators. Significant barriers included patient and family lack of access to clinics and clinic funding. Nine enablers and five barriers to the implementation of “peer support groups” were identified. Key enablers included developing infrastructure to support successful operationalization of this complex intervention, flexibility about when peer support should be offered, belonging to the international learning collaborative. Significant barriers related to limited attendance by patients and families due to challenges in creating awareness, and uncertainty about who might be appropriate to attend and target in advertising.
Conclusions: Several enablers and barriers to implementing ICU follow-up clinics and peer support groups should be taken into account and leveraged to improve ICU recovery. Among the most important enablers are motivated clinician leaders who persist to find a path forward despite obstacles.
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Heidelberg University1, Medical College of Wisconsin2, Center for International Blood and Marrow Transplant Research3, Fred Hutchinson Cancer Research Center4, City of Hope National Medical Center5, Augsburg College6, Hospital General Universitario Gregorio Marañón7, Johns Hopkins University8, Harvard University9, University of Texas MD Anderson Cancer Center10, Ludwig Maximilian University of Munich11, University of Milan12, St Bartholomew's Hospital13
TL;DR: HCT with PTCy seems to be a valuable alternative for patients with DLBCL considered for allo-HCT but lacking a matched donor, and was associated with a lower cumulative incidence of chronic GVHD compared with MSD, MUD TCD+/TCD-.
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TL;DR: This research presents a novel probabilistic approach that allows us to assess the importance of knowing the carrier and removal status of canine coronavirus as a source of infection for other animals.
Abstract: Rationale: Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long noncoding RNAs (lncRNAs), are proposed novel biomarkers of myocardial injury. Their release kine...
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TL;DR: Fibrosis progression is associated with adverse cardiac remodelling and predicts an increased risk of subsequent clinical events in HCM, and impaired energetics and perfusion abnormalities are possible mechanistic drivers of the fibrotic process.
Abstract: This study was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the British Heart Foundation. B.R., M.M., M.S. were funded by NIHR Oxford Biomedical Research Centre. R.A. was funded by a British Heart Foundation Clinical Research Training Fellowship (098436/Z/12/Z to R.A.). K.C was supported by an NIHR academic clinical fellowship. C.T.R. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society [098436/Z/12/B]. S.E.P. acknowledges support from the NIHR Barts Biomedical Research Centre. M.J.D. is supported by the Wellcome Trust (WT098519MA). A.J.L. is supported by the British Heart Foundation (FS/18/3/33292). E.O.O. acknowledges support from Cancer Research UK. S.N. and H.W. acknowledge support from the Oxford British Heart Foundation Center of Research Excellence. C.M.K., S.N. and H.W. are supported by U.S. National Institute of Heath (NIH) Grant/Contract (U01HL117006-01A1).
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TL;DR: Pulmonary vein isolation using high power delivered by SmartTouch Surround Flow catheters guided by ablation index (AI) was evaluated in a multicenter registry.
Abstract: BACKGROUND Pulmonary vein isolation (PVI) using high power delivered by SmartTouch Surround Flow (STSF) catheters guided by ablation index (AI) was evaluated in a multicenter registry. METHODS Patients with paroxysmal AF underwent PVI with STSF catheters using 30 W on the posterior wall and 40 W elsewhere. AI targets were 350 posterior walls and 450 elsewhere. Procedures were compared with controls using conventionally irrigated contact force-sensing catheters using conventional powers (25 W posterior wall and 30 W elsewhere) guided by force-time integral (no agreed targets). The waiting period of 30 minutes was observed before adenosine administration to assess acute pulmonary vein (PV) reconnection. RESULTS One hundred patients from four centers were included: 50 patients in the high power ablation index (HPAI) group and 50 controls. Procedure time was 22% shorter in the HPAI group (156 [133.8-179] vs 199 [178.5-227] minutes; P < 0.001). Duration of the radiofrequency application was 37% shorter in the HPAI group (27.2 [21.5-35.8] vs 43.2 [35.1-52.1] minutes; P < 0.001). Acute PV reconnection was reduced (28 of 200 [14%] vs 48 of 200 [24%] veins; P = 0.015). Reconnection was predicted by a largest interlesion distance greater than 6 mm, a lesion with impedance drop less than 2.5 Ω, contact force less than 6 g, or less than 68% of the regional AI target (all P < 0.001). Freedom from atrial arrhythmia at 1 year off antiarrhythmic drugs after a single procedure was 78% in the HPAI group vs 64% in the control group ( P = 0.186). CONCLUSION High-powered ablation guided by AI was safe and led to shorter procedure times with reduced acute PV reconnection compared with conventional ablation.
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St Bartholomew's Hospital1, University of London2, University of Padua3, Queen Mary University of London4, Johns Hopkins University School of Medicine5, University of Zurich6, Northwestern University7, Medical University of South Carolina8, University College London9, Beth Israel Deaconess Medical Center10, Utrecht University11, University Medical Center Utrecht12, University of Amsterdam13
TL;DR: The conclusions of an expert round table are presented that aimed to summarise the current state of the art in arrhythmogenic cardiomyopathies and to define future research priorities.
Abstract: It is 35 years since the first description of arrhythmogenic right ventricular cardiomyopathy (ARVC) and more than 20 years since the first reports establishing desmosomal gene mutations as a major cause of the disease. Early advances in the understanding of the clinical, pathological and genetic architecture of ARVC resulted in consensus diagnostic criteria, which proved to be sensitive but not entirely specific for the disease. In more recent years, clinical and genetic data from families and the recognition of a much broader spectrum of structural disorders affecting both ventricles and associated with a propensity to ventricular arrhythmia have raised many questions about pathogenesis, disease terminology and clinical management. In this paper, we present the conclusions of an expert round table that aimed to summarise the current state of the art in arrhythmogenic cardiomyopathies and to define future research priorities.
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TL;DR: In this article, the epidemiological basis of the obesity-AF relationship, consider its underlying pathophysiology and discuss new therapeutic opportunities on the horizon, while secondary prevention strategies targeting obesity as part of a comprehensive risk factor management program have been demonstrated to be highly effective.
Abstract: Obesity is already a major global public health issue, implicated in a vast array of conditions affecting multiple body systems. It is now also firmly established as an independent risk factor in the incidence and progression of AF. The rapidly rising morbidity, mortality and healthcare costs associated with AF despite implementation of the three pillars of AF management - anticoagulation, rate control and rhythm control - suggest other strategies need to be considered. Compelling data has unveiled novel insights into adipose tissue biology and its effect on arrhythmogenesis while secondary prevention strategies targeting obesity as part of a comprehensive risk factor management programme have been demonstrated to be highly effective. Here, the authors review the epidemiological basis of the obesity-AF relationship, consider its underlying pathophysiology and discuss new therapeutic opportunities on the horizon.
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French Institute of Health and Medical Research1, University of Texas MD Anderson Cancer Center2, Martin Luther University of Halle-Wittenberg3, Curie Institute4, University of Michigan5, Anhui Medical University6, Universidade Federal do Rio Grande do Sul7, National Institutes of Health8, University of São Paulo9, Odense University Hospital10, University of Southern Denmark11, University of Chile12, King Edward Memorial Hospital13, Queen Mary University of London14, St Bartholomew's Hospital15, Great Ormond Street Hospital16, Hungarian Academy of Sciences17, University of Lisbon18, Université de Montréal19, Hospital Italiano de Buenos Aires20, Claude Bernard University Lyon 121, University Medical Center Groningen22, Sapienza University of Rome23, University of Milan24, Centre Hospitalier Universitaire de Grenoble25, University of Florence26, University Hospital Centre Zagreb27, Cliniques Universitaires Saint-Luc28, University of Padua29, Institut Gustave Roussy30, Sapporo Medical University31, Charles University in Prague32, New York University33, Cleveland Clinic Lerner Research Institute34
TL;DR: Overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year, were determined and remission status was assessed.
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Monash University1, Vanderbilt University Medical Center2, Vanderbilt University3, Wake Forest University4, St Bartholomew's Hospital5, Primary Children's Hospital6, University of Utah7, University of Pittsburgh8, Veterans Health Administration9, University of California, San Francisco10, Guy's and St Thomas' NHS Foundation Trust11, Albert Einstein College of Medicine12, Mayo Clinic13, Wake Forest Baptist Medical Center14, Indiana University15, University Hospitals of Cleveland16, University of Washington17, NHS Greater Glasgow and Clyde18, University of Kentucky19, University of Glasgow20, University of Colorado Denver21, Brigham and Women's Hospital22, University of Maryland, Baltimore23, Brigham Young University24, Hospital of the University of Pennsylvania25, University of Michigan26, Glasgow Royal Infirmary27
TL;DR: The follow-up of patients and families in post-ICU care settings is perceived to improve care within the ICU via five key mechanisms, including changing clinician’s own understanding of patient experience.
Abstract: To identify the key mechanisms that clinicians perceive improve care in the intensive care unit (ICU), as a result of their involvement in post-ICU programs. Qualitative inquiry via focus groups and interviews with members of the Society of Critical Care Medicine’s THRIVE collaborative sites (follow-up clinics and peer support). Framework analysis was used to synthesize and interpret the data. Five key mechanisms were identified as drivers of improvement back into the ICU: (1) identifying otherwise unseen targets for ICU quality improvement or education programs—new ideas for quality improvement were generated and greater attention paid to detail in clinical care. (2) Creating a new role for survivors in the ICU—former patients and family members adopted an advocacy or peer volunteer role. (3) Inviting critical care providers to the post-ICU program to educate, sensitize, and motivate them—clinician peers and trainees were invited to attend as a helpful learning strategy to gain insights into post-ICU care requirements. (4) Changing clinician’s own understanding of patient experience—there appeared to be a direct individual benefit from working in post-ICU programs. (5) Improving morale and meaningfulness of ICU work—this was achieved by closing the feedback loop to ICU clinicians regarding patient and family outcomes. The follow-up of patients and families in post-ICU care settings is perceived to improve care within the ICU via five key mechanisms. Further research is required in this novel area.
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TL;DR: Bone scintigraphy (paired with exclusion of serum free light chains) is emerging as the technique of choice for distinguishing ATTR from light chain cardiac amyloidosis and other cardiomyopathies.
Abstract: Cardiac involvement drives prognosis and treatment choices in cardiac amyloidosis. Echocardiography is the first-line examination for patients presenting with heart failure, and it is the imaging modality that most often raises the suspicion of cardiac amyloidosis. Echocardiography can provide an assessment of the likelihood of cardiac amyloid infiltration versus other hypertrophic phenocopies and can assess the severity of cardiac involvement. Visualizing myocardial amyloid infiltration is challenging and, until recently, was restricted to the domain of the pathologist. Two tests are transforming this: cardiac magnetic resonance (CMR) imaging and bone scintigraphy. After the administration of contrast, CMR is highly sensitive and specific for the 2 main types of ventricular myocardial amyloidosis, light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). CMR structural and functional assessment combined with tissue characterization can redefine cardiac involvement by tracking different disease processes, ranging from amyloid infiltration, to the myocardial response associated with amyloid deposition, through the visualization and quantification of myocardial edema and myocyte response. Bone scintigraphy (paired with exclusion of serum free light chains) is emerging as the technique of choice for distinguishing ATTR from light chain cardiac amyloidosis and other cardiomyopathies; it has transformed the diagnostic pathway for ATTR, allowing noninvasive diagnosis of ATTR without the need for a tissue biopsy in the majority of patients. CMR with tissue characterization and bone scintigraphy are rewriting disease understanding, classification, and definition, and leading to a change in patient care.
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TL;DR: The study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and differentiation of subtypes of cardiac amyloidosis.
Abstract: Aims The study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and differentiation of subtypes of cardiac amyloidosis. Methods and results MEDLINE and Embase electronic databases were searched for studies evaluating the diagnostic performance of CMR or nuclear scintigraphy in detecting cardiac amyloidosis and subsequently in differentiating transthyretin amyloidosis (ATTR) from immunoglobulin light-chain (AL) amyloidosis. In this meta-analysis, histopathological examination of tissue from endomyocardial biopsy (EMB) or extra-cardiac organs were reference standards. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated, and a random effects meta-analysis was used to estimate diagnostic odds ratios. Methodological quality was assessed using a validated instrument. Of the 2947 studies identified, 27 met the criteria for inclusion. Sensitivity and specificity of CMR in diagnosing cardiac amyloidosis was 85.7% and 92.0% against EMB reference and 78.9% and 93.9% with any organ histology reference. Corresponding sensitivity and specificity of nuclear scintigraphy was 88.4% and 87.2% against EMB reference and 82.0% and 98.8% with histology from any organ. CMR was unable to reliably differentiate ATTR from AL amyloidosis (sensitivity 28.1-99.0% and specificity 11.0-60.0%). Sensitivity and specificity of nuclear scintigraphy in the differentiation of ATTR from AL amyloidosis ranged from 90.9% to 91.5% and from 88.6% to 97.1%. Pooled negative likelihood ratio and positive likelihood ratio for scintigraphy in this setting were 0.1 and 8, with EMB reference standard. Study quality assessed by QUADAS-2 was generally poor with evidence of bias. Conclusions Cardiac magnetic resonance is a useful test for diagnosing cardiac amyloidosis but is not reliable in further classifying the disease. Nuclear scintigraphy offers strong diagnostic performance in both the detection of cardiac amyloidosis and differentiating ATTR from AL amyloidosis. Our findings support the use of both imaging modalities in a non-invasive diagnostic algorithm that also tests for the presence of monoclonal protein.
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Salisbury NHS Foundation Trust1, University of Southampton2, University of Florence3, Heidelberg University4, Hull and East Yorkshire Hospitals NHS Trust5, University Hospitals of Leicester NHS Trust6, St James's University Hospital7, St Bartholomew's Hospital8, Nottingham University Hospitals NHS Trust9, Raigmore Hospital10, Poole Hospital11, University of Cambridge12, University College London13, University of Salford14, Barnet Hospital15, University of Manchester16, Royal Bournemouth Hospital17, Southmead Hospital18, St Mary's Hospital19
TL;DR: The finding of STAT5B N642H as a recurrent mutation in myeloid neoplasia with eosinophilia provides a new diagnostic and prognostic marker as well as a potential target for therapy.
Abstract: Determining the underlying cause of persistent eosinophilia is important for effective clinical management but remains a diagnostic challenge in many cases. We identified STAT5B N642H, an established oncogenic mutation, in 27/1715 (1.6%) cases referred for investigation of eosinophilia. Of the 27 mutated cases, a working diagnosis of hypereosinophilic syndrome (HES; n = 7) or a myeloid neoplasm with eosinophilia (n = 20) had been made prior to the detection of STAT5B N642H. Myeloid panel analysis identified a median of 2 additional mutated genes (range 0–4) with 4 cases having STAT5B N642H as a sole abnormality. STAT5B N642H was absent in cultured T cells of 4/4 positive cases. Individuals with SF3B1 mutations (9/27; 33%) or STAT5B N642H as a sole abnormality had a markedly better overall survival compared to cases with other additional mutations (median 65 months vs. 14 months; hazard ratio = 8.1; P < 0.001). The overall survival of STAT5B-mutated HES cases was only 30 months, suggesting that these cases should be reclassified as chronic eosinophilic leukemia, not otherwise specified (CEL-NOS). The finding of STAT5B N642H as a recurrent mutation in myeloid neoplasia with eosinophilia provides a new diagnostic and prognostic marker as well as a potential target for therapy.
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Heidelberg University1, Sheba Medical Center2, University of Cologne3, Erasmus University Rotterdam4, Martin Luther University of Halle-Wittenberg5, Katholieke Universiteit Leuven6, University of Freiburg7, University of Brescia8, Karolinska University Hospital9, University Hospital of Basel10, Maastricht University11, Goethe University Frankfurt12, Radboud University Nijmegen13, Nottingham University Hospitals NHS Trust14, St Bartholomew's Hospital15
TL;DR: While the relatively high post-transplant relapse risk in ibrutinib-exposed patients with CLL deserves further study, in patients with MCL consolidating disease responses to ibrUTinib with alloHCT seems to be a promising option.
Abstract: The aim of this retrospective study was to investigate the safety and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) in patients pre-treated with ibrutinib. Eligible were patients aged >18 years allotransplanted for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) after prior exposure to ibrutinib who were registered with the EBMT registry. Seventy patients (CLL 48, MCL 22) were included. At the time of alloHCT, 73% of the patients were ibrutinib responsive. All patients except one engrafted, and acute GVHD grade 2-4 (3-4) was observed in 49% (12%) of 68 evaluable patients. The cumulative incidence of chronic GVHD was 54% 1 year after transplant. In the CLL group, 12-month non-relapse mortality, relapse incidence (RI), progression-free survival (PFS), and overall survival (OS) were 10, 30, 60, and 72%, respectively, and in the MCL group 5, 19, 76, and 86%, respectively. Pre-transplant ibrutinib failure and poor performance status predicted inferior RI, PFS and OS in the CLL group. In conclusion, ibrutinib does not affect the safety of a subsequent alloHCT. While the relatively high post-transplant relapse risk in ibrutinib-exposed patients with CLL deserves further study, in patients with MCL consolidating disease responses to ibrutinib with alloHCT seems to be a promising option.
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TL;DR: The Surviving Sepsis Campaign group argues that the temporal nature of sepsis means benefit from even more rapid identification and intervention, and proposes a novel 1-hour care bundle, in contrast to the National Quality Forum 0-500 and the Sepsis CMS Core measures that defined 3and 6-hour target care bundles.
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TL;DR: Positive results with immune checkpoint inhibitors in metastatic renal cell carcinoma (RCC) suggest that these agents might also be effective adjuvant therapies and multidisciplinary management should be mandatory for almost all patients with radically resected kidney cancer.
Abstract: Approximately 70% of cases of kidney cancer are localized or locally advanced at diagnosis. Among patients who undergo surgery for these cancers, 30–35% will eventually develop potentially fatal metachronous distant metastases. Effective adjuvant treatments are urgently needed to reduce the risk of recurrence of kidney cancer and of dying of metastatic disease. To date, almost all of the tested adjuvant agents have failed to demonstrate any benefit. Only two trials of an autologous renal tumour cell vaccine and of the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor sunitinib have shown positive results, but these have been criticized for methodological reasons and conflicting data, respectively. The results of two additional trials of targeted agents as adjuvant therapies have not yet been published. Novel immune checkpoint inhibitors are promising approaches to adjuvant therapy in kidney cancer, and a number of trials are now underway. An important component of the management of patients with kidney cancer, particularly those who undergo radical resection for localized renal cell carcinoma, is the preservation of kidney function to reduce morbidity and mortality. The optimal management of these patients therefore requires a multidisciplinary approach involving nephrologists, oncologists, urologists and pathologists. Effective adjuvant therapies are needed to reduce the risk of recurrence of kidney cancer. Here, the authors discuss the results of adjuvant therapy trials, the potential of immune checkpoint inhibitors as adjuvant therapies and the need for multidisciplinary management of patients with resected kidney cancer.
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TL;DR: A list of poAF risk factors using expert opinion and based on published risk score models for poAF is created, which allows stratification of patients into risk groups and facilitates adherence to the evidence-based recommendations summarized in the graphical advisory tool.
Abstract: Postoperative atrial fibrillation (poAF) is the most common adverse event after cardiac surgery and is associated with increased morbidity, mortality, and hospital and intensive care unit length of stay. Despite progressive improvements in overall cardiac surgical operative mortality and postoperative morbidity, the incidence of poAF has remained unchanged at 30%-50%. A number of evidence-based recommendations regarding the perioperative management of atrial fibrillation (AF) have been released from leading cardiovascular societies in recent years; however, it is unknown how closely these guidelines are being followed by medical practitioners. In addition, many of these society recommendations are based on patient stratification into "normal" and "elevated" risk groups for AF, but criteria for that stratification have not been clearly defined. In an effort to improve the perioperative management of AF, the Society of Cardiovascular Anesthesiologists (SCA) Clinical Practice Improvement Committee developed a multidisciplinary Atrial Fibrillation Working Group that created a summary of current best practice based on a distillation of recent guidelines from professional societies involved in the care of cardiac surgical patients. An evidence-based set of survey questions was then generated to describe the current practice of perioperative AF management. Through collaboration with the European Association of Cardiothoracic Anaesthetists (EACTA), that survey was distributed to the combined memberships of both the SCA and EACTA, yielding 641 responses and resulting in the most comprehensive understanding to date of perioperative AF management in North America, Europe, and beyond. The survey data demonstrated the broad range of therapies utilized for the prevention and treatment of poAF, as well as a spectrum of adherence to published guidelines. With the goal of improving adherence, a graphical advisory tool was created with an easily accessible format that could be utilized for bedside management. Finally, given that no evidence-based threshold currently exists to differentiate patients at normal risk to develop poAF from those at elevated risk, the SCA/EACTA AF working group created a list of poAF risk factors using expert opinion and based on published risk score models for poAF. This approach allows stratification of patients into risk groups and facilitates adherence to the evidence-based recommendations summarized in the graphical advisory tool. It is our hope that these new additions to the clinical toolkit for the management of perioperative AF will improve the evidence-based care and outcomes of cardiac surgical patients worldwide.
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French Institute of Health and Medical Research1, University of Rennes2, Leiden University3, University Hospitals Bristol NHS Foundation Trust4, Oslo University Hospital5, Institute of Chartered Accountants of Nigeria6, Katholieke Universiteit Leuven7, University of Amsterdam8, University of Liège9, Aix-Marseille University10, St Bartholomew's Hospital11, University College London12
TL;DR: Recommendations for the use of multimodality imaging according to the clinical question are provided with the aim to underscore what is 'clinically relevant' and what are the tools that 'can be used'.
Abstract: Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to explain these changes. This is a heterogeneous disease frequently having a genetic background. Imaging is important for the diagnosis, the prognostic assessment and for guiding therapy. A multimodality imaging approach provides a comprehensive evaluation of all the issues related to this disease. The present document aims to provide recommendations for the use of multimodality imaging according to the clinical question. Selection of one or another imaging technique should be based on the clinical condition and context. Techniques are presented with the aim to underscore what is 'clinically relevant' and what are the tools that 'can be used'. There remain some gaps in evidence on the impact of multimodality imaging on the management and the treatment of DCM patients where ongoing research is important.