| 1. |
- Tran, K. B., et al.
(author)
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The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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In: Lancet. - 0140-6736. ; 400:10352, s. 563-591
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Journal article (peer-reviewed)abstract
- Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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- Bravo, L, et al.
(author)
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- 2021
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| 13. |
- Tabiri, S, et al.
(author)
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- 2021
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| 14. |
- Ruilope, LM, et al.
(author)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 15. |
- Glasbey, JC, et al.
(author)
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- 2021
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| 21. |
- Karaye, Kamilu M., et al.
(author)
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Disparities in clinical features and outcomes of peripartum cardiomyopathy in high versus low prevalent regions in Nigeria
- 2021
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In: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 8:4, s. 3257-3267
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Journal article (peer-reviewed)abstract
- Aims: The prospective, multicentre Peripartum Cardiomyopathy in Nigeria (PEACE) registry originally demonstrated a high prevalence of peripartum cardiomyopathy (PPCM) among patients originating from Kano, North-West Nigeria. In a post hoc analysis, we sought to determine if this phenomenon was characterized by a differential case profile and outcome among PPCM cases originating elsewhere.Methods and results: Overall, 199 (81.6%) of a total 244 PPCM patients were recruited from three sites in Kano, compared with 45 patients (18.4%) from 11 widely dispersed centres across Nigeria. Presence and extent of ventricular myocardial remodelling during follow-up, relative to baseline status, were assessed by echocardiography. During median 17 months follow-up, Kano patients demonstrated significantly better myocardial reverse remodelling than patients from other sites. Overall, 50.6% of patients from Kano versus 28.6% from other regions were asymptomatic (P = 0.029) at study completion, with an accompanying difference in all-cause mortality (17.6% vs. 22.2% respectively, P = 0.523) not reaching statistical significance. Alternatively, 135/191 (84.9%) of Kano patients had selenium deficiency (<70 μg/L), and 46/135 (34.1%) of them received oral selenium supplementation. Critically, those that received selenium supplementation demonstrated better survival (6.5% vs. 21.2%; P = 0.025), but the supplement did not have significant impact on myocardial remodelling.Conclusions: This study has shown important non-racial regional disparities in the clinical features and outcomes of PPCM patients in Nigeria, that might partly be explained by selenium supplementation.
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- Senage, T., et al.
(author)
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The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration
- 2022
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28, s. 283-294
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Journal article (peer-reviewed)abstract
- Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-alpha 1,3-galactose (alpha Gal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 +/- 43 months of follow-up (0.1-182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in <5% of BHV recipients within 2 years. The levels of both anti-alpha Gal and anti-Neu5Gc IgGs significantly increased one month after BHV implantation. The levels of these IgGs declined thereafter but anti-alpha Gal IgG levels declined significantly faster in control patients compared to BHV recipients. Neu5Gc, anti-Neu5Gc IgG and complement deposition were found in calcified BHVs at much higher levels than in calcified native aortic valves. Moreover, in mice, anti-Neu5Gc antibodies were unable to promote calcium deposition on subcutaneously implanted BHV tissue engineered to lack alpha Gal and Neu5Gc antigens. These results indicate that BHVs manufactured using donor tissues deficient in alpha Gal and Neu5Gc could be less prone to immune-mediated deterioration and have improved durability. In a large cohort of patients who underwent aortic valve replacement, antibody responses to glycans present in bioprosthetic heart valves, notably galactose-alpha 1,3-galactose and N-glycolylneuraminic acid, were implicated in valve calcification and deterioration.
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| 23. |
- Arora, Y., et al.
(author)
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Location of Superior Vena Cava Tears in Transvenous Lead Extraction
- 2022
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In: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975. ; 113:4, s. 1165-1171
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Journal article (peer-reviewed)abstract
- BACKGROUND Superior vena cava (SVC) tears are rare but potentially lethal complications associated with transvenous lead extraction. When lacerations occur, surgeons need to be prepared for an emergent response. Nonetheless, little is known about the precise whereabouts of these lesions. Understanding the location and injury patterns enables a more anticipated and targeted surgical response.& nbsp;METHODS We collected data via physician interviews after an SVC laceration occurred. These physicians were identified through the US Food and Drug Administration's Manufacturer and User Facility Device Experience database and independent physician reports of adverse events. We identified 116 reports of SVC tears between July 1, 2016, and July 31, 2018. For an SVC tear to be included in our registry, a cardiothoracic surgeon had to be physically present to confirm the injury via emergent sternotomy. In each case, the surgeon recorded the SVC injury's exact location after a repair was attempted.& nbsp;RESULTS During the study period, 116 SVC tears were confirmed by sternotomy. Tears occurred in any combination of the following locations: SVC-innominate vein, body of the SVC, and SVC-right atrial junction. The majority of tears (n = 72; 62%) were located in the isolated body of the SVC, followed by the SVC-right atrial junction (n = 23;19.8%) and the SVC-innominate junction (n = 17;14.6%). Combined tears were rare, accounting for only 3.6% (n = 4) of the adverse events recorded.& nbsp;CONCLUSIONS Most SVC tears occurred in the isolated body of the SVC. The second most common location was the SVC-right atrial junction. The SVC-innominate junction was the third most common location for these injuries. Combined tears were uncommon. & nbsp;(C)& nbsp;2022 by The Society of Thoracic Surgeons
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| 24. |
- Drake, Thomas M., et al.
(author)
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Outcomes following small bowel obstruction due to malignancy in the national audit of small bowel obstruction
- 2019
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 45:12, s. 2319-2324
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Journal article (peer-reviewed)abstract
- © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology Introduction: Patients with cancer who develop small bowel obstruction are at high risk of malnutrition and morbidity following compromise of gastrointestinal tract continuity. This study aimed to characterise current management and outcomes following malignant small bowel obstruction. Methods: A prospective, multicentre cohort study of patients with small bowel obstruction who presented to UK hospitals between 16th January and 13th March 2017. Patients who presented with small bowel obstruction due to primary tumours of the intestine (excluding left-sided colonic tumours) or disseminated intra-abdominal malignancy were included. Outcomes included 30-day mortality and in-hospital complications. Cox-proportional hazards models were used to generate adjusted effects estimates, which are presented as hazard ratios (HR) alongside the corresponding 95% confidence interval (95% CI). The threshold for statistical significance was set at the level of P ≤ 0.05 a-priori. Results: 205 patients with malignant small bowel obstruction presented to emergency surgery services during the study period. Of these patients, 50 had obstruction due to right sided colon cancer, 143 due to disseminated intraabdominal malignancy, 10 had primary tumours of the small bowel and 2 patients had gastrointestinal stromal tumours. In total 100 out of 205 patients underwent a surgical intervention for obstruction. 30-day in-hospital mortality rate was 11.3% for those with primary tumours and 19.6% for those with disseminated malignancy. Severe risk of malnutrition was an independent predictor for poor mortality in this cohort (adjusted HR 16.18, 95% CI 1.86 to 140.84, p = 0.012). Patients with right-sided colon cancer had high rates of morbidity. Conclusions: Mortality rates were high in patients with disseminated malignancy and in those with right sided colon cancer. Further research should identify optimal management strategy to reduce morbidity for these patient groups.
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| 25. |
- Paulus, A, et al.
(author)
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Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells
- 2016
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In: Blood cancer journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 6:11, s. e492-
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Journal article (peer-reviewed)abstract
- The survival of Waldenstrom macroglobulinemia (WM) tumor cells hinges on aberrant B-cell receptor (BCR) and MYD88 signaling. WM cells upregulate the proteasome function to sustain the BCR-driven growth while maintaining homeostasis. Clinically, two treatment strategies are used to disrupt these complementary yet mutually exclusive WM survival pathways via ibrutinib (targets BTK/MYD88 node) and bortezomib (targets 20 S proteasome). Despite the success of both agents, WM patients eventually become refractory to treatment, highlighting the adaptive plasticity of WM cells and underscoring the need for development of new therapeutics. Here we provide a comprehensive preclinical report on the anti-WM activity of VLX1570, a novel small-molecule inhibitor of the deubiquitinating enzymes (DUBs), ubiquitin-specific protease 14 (USP14) and ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5). Both DUBs reside in the 19 S proteasome cap and their inhibition by VLX1570 results in rapid and tumor-specific apoptosis in bortezomib- or ibrutinib-resistant WM cells. Notably, treatment of WM cells with VLX1570 downregulated BCR-associated elements BTK, MYD88, NFATC, NF-κB and CXCR4, the latter whose dysregulated function is linked to ibrutinib resistance. VLX1570 administered to WM-xenografted mice resulted in decreased tumor burden and prolonged survival (P=0.0008) compared with vehicle-treated mice. Overall, our report demonstrates significant value in targeting USP14/UCHL5 with VLX1570 in drug-resistant WM and carries a high potential for clinical translation.
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