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- Shepherd, L., et al.
(författare)
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Infection-related and -unrelated malignancies, HIV and the aging population
- 2016
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Ingår i: HIV Medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 17:8, s. 590-600
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. Methods: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. Results: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5–5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person-years over the same period. Conclusions: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV-infected populations.
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- Neesgaard, B, et al.
(författare)
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How to RESPOND to Modern Challenges for People Living with HIV: A Profile for a New Cohort Consortium
- 2020
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Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: the International Cohort Consortium of Infectious Disease (RESPOND) is a collaboration dedicated to research on HIV and other infectious diseases. Methods: RESPOND is a flexible organization, with several independent substudies operating under one shared governance. HIV-related variables, including full antiretroviral therapy (ART) history, are collected annually for all participants and merged with substudy specific data into a shared data pool. Incident clinical events are reported using standardized forms. Prospective follow-up started 1/10/17 (enrolment) with retrospective data collected back to 01/01/12. Results: Overall, 17 cohorts from Europe and Australia provided data on 26,258 people living with HIV (PLWH). The majority (43.3%) of the population were white, with men-sex-with-men accounting for 43.3% of the risk for HIV acquisition. The median age was 48 years (IQR 40–56) and 5.2% and 25.5% were known to be co-infected with hepatitis B or C. While 5.3% were ART-naïve, the median duration on ART was 10.1 years (4.8–17.6), with 89.5% having a VL <200 copies/mL and the median CD4 count being 621 cells/µL (438–830). Malignancies (n = 361) and cardiovascular disease (n = 168) were the predominant reported clinical events. Conclusion: RESPOND’s large, diverse study population and standardized clinical endpoints puts the consortium in a unique position to respond to the diverse modern challenges for PLWH.
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- Caby, F, et al.
(författare)
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CD4/CD8 Ratio and the Risk of Kaposi Sarcoma or Non-Hodgkin Lymphoma in the Context of Efficiently Treated Human Immunodeficiency Virus (HIV) Infection: A Collaborative Analysis of 20 European Cohort Studies
- 2021
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 73:1, s. 50-59
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH.MethodsPLWH from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load ≤ 500 copies/mL) within 9 months following cART and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations.ResultsWe included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range [IQR]) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296–552)/mm3, 936 (670–1304)/mm3, and 0.43 (0.28–0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2–37) and 18 (7–42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio [HR] = 2.02 [95% confidence interval {CI } = 1.23–3.31]) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 [95% CI = 1.58–6.22]) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 [95% CI = 1.60–6.56] for KS; HR = 5.28 [95% CI = 2.17–12.83] for NHL).ConclusionsLow CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3.
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- McFarland, B. K., et al.
(författare)
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Ultrafast X-ray Auger probing of photoexcited molecular dynamics
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4235-
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Tidskriftsartikel (refereegranskat)abstract
- Molecules can efficiently and selectively convert light energy into other degrees of freedom. Disentangling the underlying ultrafast motion of electrons and nuclei of the photoexcited molecule presents a challenge to current spectroscopic approaches. Here we explore the photoexcited dynamics of molecules by an interaction with an ultrafast X-ray pulse creating a highly localized core hole that decays via Auger emission. We discover that the Auger spectrum as a function of photoexcitation-X-ray-probe delay contains valuable information about the nuclear and electronic degrees of freedom from an element-specific point of view. For the nucleobase thymine, the oxygen Auger spectrum shifts towards high kinetic energies, resulting from a particular C-O bond stretch in the pi pi* photoexcited state. A subsequent shift of the Auger spectrum towards lower kinetic energies displays the electronic relaxation of the initial photoexcited state within 200 fs. Ab-initio simulations reinforce our interpretation and indicate an electronic decay to the n pi* state.
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- Thiel, U, et al.
(författare)
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Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: a retrospective assessment
- 2013
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Ingår i: British Journal of Cancer. - : Cancer Research UK. - 0007-0920 .- 1532-1827. ; 109:10, s. 2523-2532
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allogeneic haematopoietic stem cell transplantation (allo-SCT) may provide donor cytotoxic T cell-/NK cell-mediated disease control in patients with rhabdomyosarcoma (RMS). However, little is known about the prevalence of graft-vs-RMS effects and only a few case experiences have been reported. less thanbrgreater than less thanbrgreater thanMethods: We evaluated allo-SCT outcomes of 30 European Group for Blood and Marrow Transplantation (EBMT)-registered patients with advanced RMS regarding toxicity, progression-free survival (PFS) and overall survival (OS) after allo-SCT. Twenty patients were conditioned with reduced intensity and ten with high-dose chemotherapy. Twenty-three patients were transplanted with HLA-matched and seven with HLA-mismatched grafts. Three patients additionally received donor lymphocyte infusions (DLIs). Median follow-up was 9 months. less thanbrgreater than less thanbrgreater thanResults: Three-year OS was 20% (s. e.+/- 8%) with a median survival time of 12 months. Cumulative risk of progression was 67% (s. e.+/- 10%) and 11% (s. e.+/- 6%) for death of complications. Thirteen patients developed acute graft-vs-host disease (GvHD) and five developed chronic GvHD. Eighteen patients died of disease and four of complications. Eight patients survived in complete remission (CR) (median: 44 months). No patients with residual disease before allo-SCT were converted to CR. less thanbrgreater than less thanbrgreater thanConclusion: The use of allo-SCT in patients with advanced RMS is currently experimental. In a subset of patients, it may constitute a valuable approach for consolidating CR, but this needs to be validated in prospective trials.
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- Krustrup, P., et al.
(författare)
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The Yo-Yo IE2 Test: Physiological Response for Untrained Men versus Trained Soccer Players
- 2015
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Ingår i: Medicine and Science in Sports and Exercise. - : Ovid Technologies (Wolters Kluwer Health). - 0195-9131. ; 47:1, s. 100-108
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Tidskriftsartikel (refereegranskat)abstract
- Purpose This study aimed to examine the physical capacity and physiological response to the Yo-Yo Intermittent Endurance level 2 test (IE2) for untrained individuals (UTR) and trained male soccer players (TR) and to investigate the determinants of intense intermittent exercise performance. Methods Thirty-four healthy UTR males and 15 age-matched TR performed a maximal incremental treadmill test and a Yo-Yo IE2 test. Muscle biopsies and blood samples were obtained, and heart rate (HR) was measured before, during, and after tests. Results UTR had a 67% lower (P < 0.01) Yo-Yo IE2 performance (665 271 vs 2027 +/- 298 m; effect size (ES), 4.8), 34% lower VO2max (P < 0.01), and 19% lower resting muscle glycogen (P < 0.05) than those of TR. Blood lactate concentration and HR during the first 560 m of the Yo-Yo IE2 test were higher (P < 0.01) in UTR than those in TR (560 m, 7.4 +/- 2.8 vs 2.4 +/- 0.8 mM; ES, 1.7-2.8; 188 +/- 11 vs 173 +/- 8 bpm; ES, 0.9-1.5), with no differences at exhaustion. Time >95% HRmax was lower (P < 0.01) in UTR than that in TR (1.0 +/- 1.1 vs 6.3 +/- 2.9 min; ES, 3.1). Mean rates of muscle creatine phosphate utilization (16.5 +/- 9.5 vs 4.3 +/- 2.7 mmolkg(-1) d.wmin(-1)), muscle lactate accumulation (16.8 +/- 9.1 vs 4.2 +/- 2.9 mmolkg(-1) d.w.min(-1)), and glycogen breakdown (29.6 +/- 14.2 vs 7.7 +/- 5.4 mmolkg(-1) d.w.min(-1)) were fourfold higher (P < 0.01; ES, 1.4-1.7) in UTR than those in TR. For UTR, correlations (P < 0.01) were observed between Yo-Yo IE2 performance and VO2max (r = 0.77), incremental treadmill test performance (r = 0.79), and muscle citrate synthase activity (r = 0.57) but not for TR (r = -0.12 to 0.50; P > 0.05). Conclusions The Yo-Yo IE2 test was shown to possess high construct validity by showing large differences in performance, HR, and anaerobic metabolism between UTR and TR. In addition, VO2max seemed to be important for intermittent exercise performance in UTR but not for TR.
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- Mohr, Magni, 1973, et al.
(författare)
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Muscle damage, inflammatory, immune and performance responses to three football games in 1 week in competitive male players.
- 2016
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 116:1, s. 179-93
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Tidskriftsartikel (refereegranskat)abstract
- We examined effects of a three-game, 1-week microcycle (G1, G2, G3) on recovery of performance and inflammatory responses in professional male footballers. Players were randomized into an experimental (EXP; N = 20) and a control group (CON; N = 20). Blood was drawn and repeated sprint ability (RSA), muscle soreness and knee range of motion (KJRM) were determined pre- and post-games and during recovery. High-intensity running during G2 was 7-14 % less compared to G1 and G3. RSA declined in EXP by 2-9 % 3 days post-game with G2 causing the greatest performance impairment. In EXP, game play increased muscle soreness (similar to sevenfold) compared to CON with G2 inducing the greatest rise, while KJRM was attenuated post-game in EXP compared to CON (5-7 %) and recovered slower post G2 and G3 than G1. CK, CRP, sVCAM-1, sP-Selectin and cortisol peaked 48 h post-games with G2 eliciting the greatest increase. Leukocyte count, testosterone, IL-1 beta and IL6 responses, although altered 24 h post each game, were comparable among games. Plasma TBARS and protein carbonyls rose by similar to 50 % post-games with G2 eliciting the greatest increase 48 h of recovery. Reduced to oxidized glutathione ratio declined for 24 h post all games with G2 displaying the slowest recovery. Total antioxidant capacity and glutathione peroxidase activity increased (9-56 %) for 48 h in response to game play. In summary, post-game performance recovery and inflammatory adaptations in response to a three-game weekly microcycle displayed a different response pattern, with strong indications of a largest physiological stress and fatigue after the middle game that was preceded by only a 3-day recovery.
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