Hematopoietic Stem Cell Transplantation in Primary Immunodeficiencies in Brazil-a Survey of the Working Group on Paediatric Transplantation of the Brazilian Society of Bone Marrow Transplantation

Inst Crianca HCFMUSP, Sao Paulo, BrazilHosp Israelita Albert Einstein, Sao Paulo, BrazilInst Oncol Pediat, Sao Paulo, BrazilHosp Clin Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Parana, Bone Marrow Transplantat Unit, BR-80060000 Curitiba, Parana, BrazilCtr Oncol & Hematol, Jau, BrazilUSP Ribeirao Preto, Hosp Clin, Ribeirao Preto, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilUniv Fed Rio de Janeiro, Rio De Janeiro, BrazilCtr Nacl Transplate Medula Ossea CEMO, Inst Nacl Canc, Rio De Janeiro, BrazilUniv Fed Parana, Paediat Intens Care Unit, BR-80060000 Curitiba, Parana, BrazilNatl Inst Canc INCA, Rio De Janeiro, BrazilHosp Israelita Albert Einstein, Hematol & Bone Marrow Transplantat Dept, Sao Paulo, BrazilWeb of Scienc

H1N1pdm09 Adjuvanted Vaccination in HIV-Infected Adults: A Randomized Trial of Two Single versus Two Double Doses

Since human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from pandemic influenza A (H1N1pdm09), vaccination was recommended as a prevention strategy. The aim of the present study was to evaluate the safety, immunogenicity and persistence of the immune response after vaccination against pandemic influenza A (H1N1pdm09) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses.Open label, randomized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls (NCT01155037). HIV-infected participants were randomized to receive 2 single (3.75 µg hemagglutinin) or 2 double (7.5 µg hemagglutinin) doses of the vaccine, 21 days apart. Controls received one dose of the vaccine. The primary endpoint was seroconversion as measured by hemagglutination inhibition assay. Two hundred fifty six HIV-infected participants (129 and 127 randomized to single and double doses, respectively) and 71 HIV-negative controls were enrolled. Among HIV-infected participants, seroconversion increased from 46.7% and 51.7% after the first dose to 77.2% and 83.8% after the second dose of the vaccine using single and double doses, respectively. Participants aged >40 years showed higher seroconversion compared to younger participants. Seroconversion among HIV-infected women and those with nadir CD4<200 cells/mm(3) was significantly higher with double doses. Persistence of protective antibodies six months after vaccination was achieved by 80% and 89.9% of the HIV-infected participants who received single and double doses, respectively.Our results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals, particularly women, and those aged >40 years or with nadir CD4<200 cells/mm(3), to achieve antibody levels that are both higher and more sustained.ClinicalTrials.gov NCT01155037

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p&lt;0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p&lt;0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Phylogenetics and geography of speciation in New World Halichoeres wrasses

The New World Halichoeres comprises about 30 small to medium sized wrasse species that are prominent members of reef communities throughout the tropical Western Atlantic and Eastern Pacific. We conducted a phylogenetic analysis of this group and related lineages using new and previously published sequence data. We estimated divergence times, evaluated the monophyly of this group, their relationship to other labrids, as well as the time-course and geography of speciation. These analyses show that all members of New World Halichoeres form a monophyletic group that includes Oxyjulis and Sagittalarva. New World Halichoeres is one of numerous labrid groups that appear to have radiated rapidly about 32 Ma and form a large polytomy within the julidine wrasses. We reconstruct the tropical Western Atlantic to be the ancestral area of New World Halichoeres, with four invasions of the Eastern Pacific and one reversal from East Pacific to Western Atlantic. These five speciation events were spread across the history of the group, with none corresponding closely to the time of the closure of the Isthmus of Panama. Three speciation events within the Atlantic occurred across the Orinoco-Amazon outflow and within the Pacific, five involve splits between lineages that occupy coastal reef systems and offshore islands. Of eight sister species pairs, seven show complete allopatry and one is fully sympatric

Extreme drought triggers parallel shifts in wood anatomical and physiological traits in upper treeline of the Mediterranean Andes

Abstract Background Treeline ecotones of Mediterranean ecoregions have been affected by the increasing intensity and severity of droughts. Even though the effect of droughts on forest dynamics has been widely documented, knowledge is relatively scarce of how extreme climate episodes affect the hydraulic structure and, therefore, the physiology of woody plants. The Mediterranean Andes have experienced an uninterrupted period of drought since 2010, including an extremely dry year in 2019 with approximately 80% rainfall deficit. Here, we investigated shifts in wood anatomical and physiological traits of Kageneckia angustifolia, an endemic treeline species, in response to this drought period. Methods We evaluated the xylem plasticity of three K. angustifolia populations across their natural distribution (31–35° SL) based on anatomical (vessel structure and distribution) and physiological (intrinsic water-use efficiency) variables in the tree rings. We focused on the period 2000–2020 that corresponds to before the megadrought (2000–2007), (ii) megadrought (2008–2018) and (iii) hyperdrought (2019–2020). The variables were annualized and analyzed by linear mixed-effects models. Results Our results provide insights to the anatomical and physiological mechanisms underlying the resilience of treeline forests to persistent droughts in central Chile. We found that the extreme drought in 2019–2020 triggered shifts in vessel size and frequency that increased hydraulic safety. These significant shifts in vessel traits occurred in parallel with a decrease in pit aperture area and an increase in water-use efficiency, further increasing the resilience of K. angustifolia to extreme drought stress. Conclusions Our results revealed coordinated shifts in vessel size and frequency and water-use efficiency in response to the megadrought, thereby reducing vulnerability to hydraulic failure. The apparent resilience of K. angustifolia to extreme droughts suggests that this adaptation to drought stress may increase its ability to tolerate novel climatic conditions of treeline environments of the Mediterranean Andes, although it is not clear whether these adaptations will be sufficient to persist in scenarios that predict intensification of climate stress. Finally, our results provide empirical evidence that integrating wood anatomical and physiological traits facilitates the understanding of resilience mechanisms that treeline forests develop in the face of increasing drought stress