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- 2019
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Journal article (peer-reviewed)
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- Horwich, A, et al.
(author)
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EAU–ESMO consensus statements on the management of advanced and variant bladder cancer - an international collaborative multi-stakeholder effort : under the auspices of the EAU and ESMO Guidelines Committees
- 2019
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In: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 30:11, s. 1697-1727
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Journal article (peer-reviewed)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.
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- Ademuyiwa, Adesoji O., et al.
(author)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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- Elkinany, Sherif, et al.
(author)
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Is Aortic Z-score an Appropriate Index of Beneficial Drug Effect in Clinical Trials in Aortic Aneurysm Disease?
- 2021
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In: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 143
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Journal article (peer-reviewed)abstract
- Aortic Z-score (Z-score) is utilized in clinical trials to monitor the effect of medications on aortic dilation rate in Marfan (MFS) patients. Z-scores are reported in relation to body surface area and therefore are a function of height and weight. However, an information void exists regarding natural, non-pharmacological changes in Z-scores as children age. We had concerns that Z-score decrease attributed to “therapeutic” effects of investigational drugs for Marfan disease connective tissue diseases might simply reflect normal changes (“filling out” of body contour) as children age. This investigation studies natural changes with age in Z-score in normal and untreated MFS children, teasing out normal effects that might erroneously be attributed to drug benefit. (1) We first compared body mass index (BMI) and Z-scores (Boston Children's Hospital calculator) in 361 children with “normal” single echo exams in four age ranges (0 to 1, 5 to 7, 10 to 12, 15 to 18 years). Regression analysis revealed that aging itself decreases ascending Z-score, but not root Z-score, and that increase in BMI with aging underlies the decreased Z-scores. (2) Next, we examined Z-score findings in both “normal” and Marfan children (all pharmacologically untreated) as determined on sequential echo exams over time. Of 27 children without aortic disease with sequential echos, 19 (70%) showed a natural decrease in root Z-score and 24 (89%) showed a natural decrease in ascending Z- score, over time. Of 25 untreated MFS children with sequential echos, 12 (40%) showed a natural decrease in root Z-score and 10 (33%) showed a natural decrease in ascending Z-score. Thus, Z-score is over time affected by natural factors even in the absence of any aneurysmal pathology or medical intervention. Specifically, Z-score decreases spontaneously as a natural phenomenon as children age and with fill out their BMI. Untreated Marfan patients often showed a spontaneous decrease in Z-score. In clinical drug trials in aneurysm disease, decreasing Z-score has been interpreted as a sign of beneficial drug effect. These data put such conclusions into doubt.
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- Norkin, Maxim, et al.
(author)
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Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation
- 2019
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In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 25:2, s. 362-368
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Journal article (peer-reviewed)abstract
- We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for ≥2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P < .001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and ≥55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-HCT compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD.
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- Nagueh, Sherif F., et al.
(author)
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Interobserver Variability in Applying American Society of Echocardiography/European Association of Cardiovascular Imaging 2016 Guidelines for Estimation of Left Ventricular Filling Pressure
- 2019
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In: Circulation Cardiovascular Imaging. - 1941-9651 .- 1942-0080. ; 12:1
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Journal article (peer-reviewed)abstract
- BACKGROUND:Assessment of left ventricular (LV) filling pressure is among the important components of a comprehensive echocardiographic report. Previous studies noted wide limits of agreement using 2009 American Society of Echocardiography/European Association of Echocardiography guidelines, but reproducibility of 2016 guidelines update in estimating LV filling pressure is unknown.METHODS:Echocardiographic and hemodynamic data were obtained from 50 patients undergoing cardiac catheterization for clinical indications. Clinical and echocardiographic findings but not invasive hemodynamics were provided to 4 groups of observers, including experienced echocardiographers and cardiology fellows. Invasively acquired LV filling pressure was the gold standard.RESULTS:In group I of 8 experienced echocardiographers from the guidelines writing committee, sensitivity for elevated LV filling pressure was 92% for all observers, and specificity was 93 +/- 6%. Fleiss kappa-value for the agreement in group I was 0.80. In group II of 4 fellows in training, sensitivity was 91 +/- 2%, and specificity was 95 +/- 2%. Fleiss kappa-value for the agreement in group II was 0.94. In group III of 9 experienced echocardiographers who had not participated in drafting the guidelines, sensitivity was 88 +/- 5%, and specificity was 91 +/- 7%. Fleiss kappa-value for the agreement in group III was 0.76. In group IV of 7 other fellows, sensitivity was 91 +/- 3%, and specificity was 92 +/- 5%. Fleiss kappa-value for the agreement in group IV was 0.89.CONCLUSIONS:There is a good level of agreement and accuracy in the estimation of LV filling pressure using the American Society of Echocardiography/European Association of Cardiovascular Imaging 2016 recommendations update, irrespective of the experience level of the observer.
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| 10. |
- Percival, Mary-Elizabeth, et al.
(author)
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Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation
- 2021
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In: Bone Marrow Transplantation. - : Springer Nature. - 0268-3369 .- 1476-5365. ; 56:9, s. 2108-2117
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Journal article (peer-reviewed)abstract
- Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13-1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR.
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