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

Effectiveness of antimicrobial photodynamic therapy mediated by butyl toluidine blue in preventing medication-related osteonecrosis of the jaws in rats.

Background: Medication-related osteonecrosis of the jaws (MRONJ) is difficult to treat, therefore, prevention would be the ideal clinical approach. This study evaluated the effectiveness of antimicrobial photodynamic therapy (aPDT), mediated by butyl toluidine blue (BuTB) in the prevention of MRONJ-like lesions after tooth extraction in rats. Methods: Twenty-eight senescent female rats were distributed in groups: VEH and VEH-aPDT, treated with vehicle, ZOL and ZOL-aPDT, treated with 100 µg/Kg of zoledronate, both treatments every three days over seven weeks. After three weeks from the commencement of treatment, the mandibular first molar was extracted. For the VEH and ZOL groups, no local treatment was performed, while with the VEH-aPDT and ZOL-aPDT groups, photodynamic treatment was carried out at 0, 2, and 4 days after extraction. For aPDT, 500μl of BuTB solution was deposited on the dental extraction site (0.5 mg/ml; 60 s), followed by irradiation with low-level laser (InGaAIP; 660 nm; 35 mW; 74.2 J/cm²; 60 s). After 28 postoperative days, euthanasia was performed. The hemimandibles were processed to: (1) histological analysis of tissue repair; (2) histometric analysis of the percentage of newly formed bone tissue (PNFBT) and percentage of non-vital bone tissue (PNVBT); (3) immunohistochemical analysis for tartrate-resistant acid phosphatase (TRAP). Results: The ZOL and ZOL-aPDT groups showed less TRAP-positive cells when compared with VEH and VEH-aPDT. The ZOL group demonstrated great compromise in the tissue repair process, consistent with MRONJ-like lesions. VEH, VEH-aPDT and ZOL-aPDT presented a favorable tissue repair process. PNFBT in the ZOL group was lower than in the VEH, VEH-aPDT and ZOL-aPDT groups, whereas PNVBT in the ZOL group was higher than in the VEH, VEH-aPDT and ZOL-aPDT groups. Conclusion: aPDT mediated by BuTB prevented the occurrence of MRONJ-like lesions after tooth extraction in rats

Cultivo hidropônico de tomate cereja utilizando-se efluente tratado de uma indústria de sorvete Hydroponic production of cherry tomatoes using treated effluent of ice cream industry

O objetivo deste trabalho foi avaliar o uso de doses de efluente oriundo de indústria de sorvete, na cultura do tomate cereja em relação ao consumo hídrico e no desenvolvimento vegetativo em sistema hidropônico. O delineamento experimental foi o inteiramente casualizado, com seis tratamentos e quatro repetições. Os tratamentos foram compostos pelo uso de doses de efluente (0, 25, 50, 75 e 100%) com complementação de nutrientes e com o uso de 100% de efluente sem complementação nutriente. O aumento das doses de efluente na solução nutritiva proporcionou redução linear no consumo hídrico. O efluente com 25% proporcionou a melhor produtividade. A adição de até 50% de efluente de sorvete à solução nutritiva permitiu o cultivo de tomate cereja sem redução na produtividade, com melhor eficiência do uso da água na produção de matéria seca da parte aérea, produção de frutos e máxima substituição de minerais solúveis na solução nutritiva.<br>The objective of this study was to evaluate the effect of ice cream raw effluent doses on consumption and vegetative development of cherry tomato under hydroponic system. The experiment was conducted in completely randomized design with six treatments and four replications. Treatments consisted of 5 different levels of effluent (0, 25, 50, 75 and 100%) complemented with the amount of nutrient recommended for growing tomatoes and 100% of effluent without nutrient complementation. Increasing doses of effluent provided linear reduction in water consumption.Addition of effluent in proportion of 25% provided best production results. Addition up to 50% ice cream effluent to nutrient solution allowed growth of cherry tomato without yield reduction providing better efficiency of water use in terms of dry weight of shoots and fruit production as well as maximum substitution of soluble mineral fertilizers in nutrient solution