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- Zhu, RJ, et al.
(författare)
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Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms
- 2021
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Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:12, s. 1244-1262
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Tidskriftsartikel (refereegranskat)abstract
- The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.
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- Ruilope, LM, et al.
(författare)
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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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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)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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- Zhang, JR, et al.
(författare)
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Systematic bias between blinded independent central review and local assessment: literature review and analyses of 76 phase III randomised controlled trials in 45 688 patients with advanced solid tumour
- 2018
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 8:9, s. e017240-
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Tidskriftsartikel (refereegranskat)abstract
- Unbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments.DesignLiterature review, pooling analysis and correlation analysis.Data sourcesPubMed, from 1 January 2010 to 30 June 2017.Eligibility criteria for selecting studiesEligible articles are phase III RCTs comparing anticancer agents for advanced solid tumours. Additionally, the articles should report objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) or time to progression (TTP); the treatment effect of these endpoints, OR or HR, should be based on central and local assessments.ResultsOf 76 included trials involving 45 688 patients, 17 (22%) trials reported their endpoints with statistically inconsistent inferences (p value lower/higher than the probability of type I error) between central and local assessments; among them, 9 (53%) trials had statistically significant inference based on central assessment. Pooling analysis presented no systematic bias when comparing treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07), p=0.42, I2=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I2=0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I2=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I2=0%), regardless of funding source, mask, region, tumour type, study design, number of enrolled patients, response assessment criteria, primary endpoint and trials with statistically consistent/inconsistent inferences. Correlation analysis also presented no sign of systematic bias between central and local assessments (ORR, DCR, PFS: r>0.90, p<0.01; TTP: r=0.90, p=0.29).ConclusionsNo systematic bias could be found between local and central assessments in phase III RCTs on solid tumours. However, statistically inconsistent inferences could be made in many trials between both assessments.
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- Huang, JJ, et al.
(författare)
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Cancer Incidence and Mortality in Asian Countries: A Trend Analysis
- 2022
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Ingår i: Cancer control : journal of the Moffitt Cancer Center. - : SAGE Publications. - 1526-2359. ; 29, s. 10732748221095955-
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to evaluate the updated burden and temporal trends of cancer incidence and mortality in Asian countries. Methodology The data used in this study were retrieved from the Global Cancer Observatory, Cancer Incidence in Five Continents volumes I-XI, and the World Health Organization mortality database. These data were used to calculate the Average Annual Percentage Change (AAPC), with a 95% confidence interval (CI) by joinpoint regression analysis to determine the epidemiological trend in the past decade. Results In 2020, the cancer incidence in Asia was 169.1 per 1 00 000, accounting for 49.3% of the global cancer incidence. The most common cancers included lung (13.8%), breast (10.8%) and colorectal (10.6%) cancers. Its mortality was 101.6 per 1 00 000 (58.3% of the global cancer death) with lung (19.2%), liver (10.5%) and stomach (9.9%) cancers being the most common causes of cancer death. The cancer incidence had been increasing in female population, with Korea (AAPC = 5.73, 95% CI [5.30, 6.17], P < .001), Japan (AAPC = 2.67, 95% CI [2.12, 3.23], P < .001) and Kuwait (AAPC = 2.08, 95% CI [.49, 3.69], P = .016) showing the most significant increases in the past decade. The incidence increase was also observed among population aged <40 years old, with Korea (female AAPC = 8.42, 95% CI [7.40, 9.45], P < .001; male AAPC = 5.28, 95% CI [4.23, 6.33], P <.001), China (female AAPC = 2.94, 95% CI [2.07, 3.81], P < .001; male AAPC = 1.37, 95% CI [.57, 2.18], P = .004) and Japan (female AAPC = 2.88, 95% CI [1.88, 3.88], P = .016; male AAPC = 1.59, 95% CI [.40, 2.78], P = .015) showing the most significant increases. However, there was an overall decreasing trend of cancer mortality. Conclusions There was a substantial burden of cancer incidence and mortality in Asia. Although there was a decreasing trend in cancer mortality, its incidence had been increasing especially among female and younger populations. Future studies could be done to further investigate the potential reasons for these epidemiologic trends.
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- Huang, JJ, et al.
(författare)
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Global Burden, Risk Factors, and Trends of Esophageal Cancer: An Analysis of Cancer Registries from 48 Countries
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to examine the global burden, risk factors, and trends of esophageal cancer based on age, sex, and histological subtype. The data were retrieved from cancer registries database from 48 countries in the period 1980–2017. Temporal patterns of incidence and mortality were evaluated by average annual percent change (AAPC) using joinpoint regression. Associations with risk factors were examined by linear regression. The highest incidence of esophageal cancer was observed in Eastern Asia. The highest incidence of adenocarcinoma (AC) was found in the Netherlands, the United Kingdom, and Ireland. A higher AC/squamous cell carcinoma (SCC) incidence ratio was associated with a higher prevalence of obesity and elevated cholesterol. We observed an incidence increase (including AC and SCC) in some countries, with the Czech Republic (female: AAPC 4.66), Spain (female: 3.41), Norway (male: 3.10), Japan (female: 2.18), Thailand (male: 2.17), the Netherlands (male: 2.11; female: 1.88), and Canada (male: 1.51) showing the most significant increase. Countries with increasing mortality included Thailand (male: 5.24), Austria (female: 3.67), Latvia (male: 2.33), and Portugal (male: 1.12). Although the incidence of esophageal cancer showed an overall decreasing trend, an increasing trend was observed in some countries with high AC/SCC incidence ratios. More preventive measures are needed for these countries.
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