Highlights • Donation-related HRQoL among older sibling HSC donors >60 is similar to that of their younger counterparts 18-60. • Among older sibling HSC donors 61-76, there is no evidence that ...increasing age is associated with poorer donation-related HRQoL. • These data support the current practice of HSC donation by sibling donors above age 60, and provide no evidence of worsening HRQoL up to one year after donation in this group.
This report summarizes the progress since 1991 of two agreements on “global and regional climate change” studies between the U.S. Department of Energy (DOE) and two state agencies of the People’s ...Republic of China. The first agreement is the DOE–Chinese Academy of Science joint project on the “Study of the Greenhouse Effect” and the second agreement is the DOE–China Meteorological Administration joint project on the “Study of Regional Climate.” While development of general circulation climate models and analysis of climate data over China continues, the joint research produced several unique Chinese climate datasets, including the reconstruction of 2000 years of historical climate, quality assured instrumental climate data, and an archive of methane emissions from rice fields in southern China.
The goal of the Department of Energy (DOE) Carbon Dioxide Research Program is to identify possible policy options for government action in response to effects of increased CO2. The achievement of ...this goal requires a significant increase in our scientific knowledge of the atmosphere, the biosphere, the oceans, and the cryosphere—their interactions and the effects that increasing atmospheric CO2 and other trace gases will have on them. To identify and specify valid choices, a program of directed research is required. The research areas include: • Projection of future atmospheric CO2 concentrations • Estimation of CO2-induced global/regional climate changes • Estimation of crop and ecosystem response to CO2-induced changes • Estimation of the effect of CO2-induced climate changes on sea level, fisheries, and human health. This paper describes the present DOE plan to address the questions related to the global and regional rate of CO2-induced climate change. The objective of the plan is to define the key questions in such a way that research is directed at experiments where answers are needed rather than at experiments where answers can be easily obtained. Only through this kind of focus can we expect to provide the climate-change estimates required for the policy process.
Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. ...Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P<0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT.
Risk factors for non-Aspergillus mold infection (NAMI) and the impact on transplant outcome are poorly assessed in the current era of antifungal agents. Outcomes of 124 patients receiving allogeneic ...hematopoietic cell transplantation (HCT) diagnosed with either mucormycosis (n=72) or fusariosis (n=52) between days 0 and 365 after HCT are described and compared with a control cohort (n=11 856). Patients with NAMI had more advanced disease (mucormycois: 25%, fusariosis: 23% and controls: 18%; P=0.004) and were more likely to have a Karnofsky performance status (KPS) <90% at HCT (mucormycosis: 42%, fusariosis: 38% and controls: 28%; P=0.048). The 1-year survival after HCT was 22% (15-29%) for cases and was significantly inferior compared with controls (65% (64-65%); P<0.001). Survival from infection was similarly dismal regardless of mucormycosis: 15% (8-25%) and fusariosis: 21% (11-33%). In multivariable analysis, NAMI was associated with a sixfold higher risk of death (P<0.0001) regardless of the site or timing of infection. Risk factors for mucormycosis include preceding acute GvHD, prior Aspergillus infection and older age. For fusariosis, increased risks including receipt of cord blood, prior CMV infection and transplant before May 2002. In conclusion, NAMI occurs infrequently, is associated with high mortality and appears with similar frequency in the current antifungal era.
Summary
Community respiratory viral infections (CRVIs) are associated with pulmonary function impairment, alloimmune lung syndromes and inferior survival in human leucocyte antigen (HLA)‐matched ...allogeneic haematopoietic stem cell transplant (HCT) recipients. Although the incidence of viral infections in HLA‐haploidentical HCT recipients who receive post‐transplant cyclophosphamide (PTCy)‐based graft‐versus‐host disease (GVHD) prophylaxis is reportedly increased, there are insufficient data describing the incidence of CRVIs and the impact of donor source and PTCy on transplant outcomes. Analysing patients receiving their first HCT between 2012 and 2017 for acute myeloid leukaemia, acute lymphoblastic leukaemia and myelodysplastic syndromes, we describe comparative outcomes between matched sibling transplants receiving either calcineurin‐based GVHD prophylaxis (SibCNI, N = 1605) or PTCy (SibCy, N = 403), and related haploidentical transplants receiving PTCy (HaploCy, N = 757). The incidence of CRVIs was higher for patients receiving PTCy, regardless of donor type. Patients in the HaploCy cohort who developed a CRVI by day +180 had both a higher risk of treatment‐related mortality hazard ratio (HR) 2⋅14, 99% confidence interval (CI) 1⋅13–4⋅07; P = 0⋅002 and inferior 2‐year overall survival (HR 1⋅65, 99% CI 1⋅11–2⋅43; P = 0⋅001) compared to SibCNI with no CRVI. This finding justifies further research into long‐term antiviral immune recovery, as well as development of preventive and treatment strategies to improve long‐term outcomes in such patients.
The U.S. Department of Energy and the People's Republic of China's Academy of Sciences signed an agreement on 19 August 1987 to carry out a joint research program on the study of global warming due ...to enhanced greenhouse effect. The joint study is a first step toward providing opportunities for scientists in both countries to share climate information leading to a better understanding of the earth's climate system and to reliable regional climate prediction. The joint program has four tasks—analysis of general circulation models (GCMs), preparation and analysis of proxy and instrumental data, the study of the relationship between large- and regional-scale climates, and measuring and analyzing methane emissions from rice paddy fields in China. Significant progress is being made, and this paper summarizes the research progress since 1985, including two years of scientist-to-scientist collaboration. Overall, there are over 120 publications documenting project research. Highlights of the accomplishments are described and future collaborative work is outlined.
Febuxostat and allopurinol are urate-lowering therapies used to treat patients with gout. Following concerns about the cardiovascular safety of febuxostat, the European Medicines Agency recommended a ...post-licensing study assessing the cardiovascular safety of febuxostat compared with allopurinol.
We did a prospective, randomised, open-label, blinded-endpoint, non-inferiority trial of febuxostat versus allopurinol in patients with gout in the UK, Denmark, and Sweden. Eligible patients were 60 years or older, already receiving allopurinol, and had at least one additional cardiovascular risk factor. Those who had myocardial infarction or stroke in the previous 6 months or who had severe congestive heart failure or severe renal impairment were excluded. After a lead-in phase in which allopurinol dose was optimised towards achieving a serum urate concentration of less than 0·357 mmol/L (<6 mg/dL), patients were randomly assigned (1:1, with stratification according to previous cardiovascular events) to continue allopurinol (at the optimised dose) or start febuxostat at 80 mg/day, increasing to 120 mg/day if necessary to achieve the target serum urate concentration. The primary outcome was a composite of hospitalisation for non-fatal myocardial infarction or biomarker-positive acute coronary syndrome; non-fatal stroke; or cardiovascular death. The hazard ratio (HR) for febuxostat versus allopurinol in a Cox proportional hazards model (adjusted for the stratification variable and country) was assessed for non-inferiority (HR limit 1·3) in an on-treatment analysis. This study is registered with the EU Clinical Trials Register (EudraCT 2011-001883-23) and ISRCTN (ISRCTN72443728) and is now closed.
From Dec 20, 2011, to Jan 26, 2018, 6128 patients (mean age 71·0 years SD 6·4, 5225 85·3% men, 903 14·7% women, 2046 33·4% with previous cardiovascular disease) were enrolled and randomly allocated to receive allopurinol (n=3065) or febuxostat (n=3063). By the study end date (Dec 31, 2019), 189 (6·2%) patients in the febuxostat group and 169 (5·5%) in the allopurinol group withdrew from all follow-up. Median follow-up time was 1467 days (IQR 1029–2052) and median on-treatment follow-up was 1324 days (IQR 870–1919). For incidence of the primary endpoint, on-treatment, febuxostat (172 patients 1·72 events per 100 patient-years) was non-inferior to allopurinol (241 patients 2·05 events per 100 patient-years; adjusted HR 0·85 95% CI 0·70–1·03, p<0·0001). In the febuxostat group, 222 (7·2%) of 3063 patients died and 1720 (57·3%) of 3001 in the safety analysis set had at least one serious adverse event (with 23 events in 19 0·6% patients related to treatment). In the allopurinol group, 263 (8·6%) of 3065 patients died and 1812 (59·4%) of 3050 had one or more serious adverse events (with five events in five 0·2% patients related to treatment). Randomised therapy was discontinued in 973 (32·4%) patients in the febuxostat group and 503 (16·5%) patients in the allopurinol group.
Febuxostat is non-inferior to allopurinol therapy with respect to the primary cardiovascular endpoint, and its long-term use is not associated with an increased risk of death or serious adverse events compared with allopurinol.
Menarini, Ipsen, and Teijin Pharma Ltd.
Fibrotic interstitial pneumonias are more prevalent in males of advancing age, although little is known about the underlying mechanisms. To evaluate the contributions of age and sex to the ...development of pulmonary fibrosis, we intratracheally instilled young (8-12 wk) and aged (52-54 wk) male and female mice with bleomycin and assessed the development and severity of fibrotic lung disease by measurements of lung collagen levels, static compliance, leukocyte infiltration, and stereological quantification of fibrotic areas in histological sections. We also quantified proinflammatory and profibrotic chemokine and cytokine levels in the bronchoalveolar lavage fluid. Aged male mice developed more severe lung disease, indicated by increased mortality, increased collagen deposition, and neutrophilic alveolitis compared with aged female mice or young mice of either sex. Aged male mice also exhibited increased levels of transforming growth factor-β, IL-17A, and CXCL1 in their bronchoalveolar lavage fluid. Young male mice developed a more fibrotic disease after bleomycin instillation compared with female mice, regardless of age. There was no difference in fibrosis between young and aged female mice. Taken together, these findings suggest that the variables of advanced age and male sex contribute to the severity of pulmonary fibrosis in this model. Our findings also emphasize the importance of stratifying experimental groups on the basis of age and sex in experimental and epidemiological studies of this nature.
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