Malnutrition and Sarcopenia Combined Increases the Risk for Mortality in Older Adults on Hemodialysis

Aim: Sarcopenia and malnutrition are highly prevalent in older adults undergoing hemodialysis (HD) and are associated with negative outcomes. This study aimed to evaluate the role of sarcopenia and malnutrition combined on the nutritional markers, quality of life, and survival in a cohort of older adults on chronic HD. Methods: This was an observational, longitudinal, and multicenter study including 170 patients on HD aged >60 years. Nutritional status was assessed by 7-point-subjective global assessment (7p-SGA), body composition (anthropometry and bioelectrical impedance), and appendicular skeletal muscle mass (Baumgartner's prediction equation). Quality of life was assessed by KDQoL-SF. The cutoffs for low muscle mass and low muscle strength established by the 2019 European Working group on sarcopenia for Older People (EWGSOP) were used for the diagnosis of sarcopenia. Individuals with a 7p-SGA score 5 were considered malnourished, individuals with low strength or low muscle mass were pre-sarcopenic, and those with low muscle mass and low muscle strength combined as sarcopenic. The sample was divided into four groups: sarcopenia and malnutrition; sarcopenia and no-malnutrition; no-sarcopenia with malnutrition; and no-sarcopenia and no-malnutrition. Follow-up for survival lasted 23.5 (12.2; 34.4) months. Results: Pre-sarcopenia, sarcopenia, and malnutrition were present in 35.3, 14.1, and 58.8% of the patients, respectively. The frequency of malnutrition in the group of patients with sarcopenia was not significantly higher than in the patients without sarcopenia (66.7 vs. 51.2%; p = 0.12). When comparing groups according to the occurrence of sarcopenia and malnutrition, the sarcopenia and malnutrition group were older and presented significantly lower BMI, calf circumference, body fat, phase angle, body cell mass, and mid-arm muscle circumference. In the survival analysis, the group with sarcopenia and malnutrition showed a higher hazard ratio 2.99 (95% CI: 1.23: 7.25) for mortality when compared to a group with no-sarcopenia and no-malnutrition. Conclusion: Older adults on HD with sarcopenia and malnutrition combined showed worse nutritional parameters, quality of life, and higher mortality risk. In addition, malnutrition can be present even in patients without sarcopenia. These findings highlight the importance of complete nutritional assessment in patients on dialysis. (c) Copyright (c) 2021 Macedo, Amaral, Rodrigues, Santin and Avesani

Risk analysis in a Portuguese archive what has changed in five years?

The Cultural Property Risk Analysis Model was applied in 2006 to a Portuguese archive located in Lisbon. Its results highlighted the need for the institution to take care of risks related to fire, physical forces and relative humidity problems. Five years after this first analysis the results are revisited and a few changes are introduced due to recent events: fire and high humidity remain an important hazard but are now accompanied by a pressing contaminants problem. Improvements in storage systems were responsible for a large decrease in terms of calculated risk magnitude and proved to be very cost-effective

HIGH DOSE CARBOPLATIN, ETOPOSIDE, MELPHALAN and AUTOLOGOUS HEMATOPOIETIC STEM CELL RESCUE WITH for the TREATMENT of RELAPSED PEDIATRIC GERM CELL TUMORS

Inst Oncol Pediat, São Paulo, BrazilWeb of Scienc

Y-27632 is associated with corticosteroid-potentiated control of pulmonary remodeling and inflammation in guinea pigs with chronic allergic inflammation

Abstract\ud \ud Background\ud Previously, we showed that treatment with the Rho-kinase inhibitor Y-27632 was able to control airway responsiveness, inflammation, remodeling, and oxidative stress in an animal model of asthma, suggesting that this drug is beneficial in asthma. However, studies evaluating the effects of these inhibitors in conjunction with corticosteroids on chronic pulmonary inflammation have not been conducted. Therefore, we evaluated the effects of treatment with the Rho-kinase inhibitor Y-27632, with or without concurrent dexamethasone treatment, on airway and lung tissue mechanical responses, inflammation, extracellular matrix remodeling, and oxidative stress in guinea pigs with chronic allergic inflammation.\ud \ud \ud Methods\ud The guinea pigs were subjected to seven ovalbumin or saline inhalation exposures. Treatment with Y-27632 (1 mM) and dexamethasone (2 mg/kg) started at the fifth inhalation. Seventy-two hours after the seventh inhalation, the pulmonary mechanics were evaluated and exhaled nitric oxide (ENO) levels were determined. The lungs were removed and histological analysis was performed using morphometry.\ud \ud \ud Results\ud The treatment of guinea pigs with the Rho-kinase inhibitor and dexamethasone (ORC group) decreased ENO, the maximal mechanical responses after antigen challenge, inflammation, extracellular matrix remodeling and oxidative stress in the lungs.\ud This therapeutic strategy reduced the levels of collagen and IFN-γ in the airway walls, as well as IL-2, IFN-γ, 8-iso-PGF2α and NF-κB in the distal parenchyma, when compared to isolated treatment with corticosteroid or Rho-kinase inhibitor (P < 0.05) and reduced the number of TIMP-1-positive cells and eosinophils in the alveolar septa compared to corticosteroid-treated animals (P < 0.05). The combined treatment with the Rho-kinase inhibitor and the corticosteroid provided maximal control over the remodeling response and inflammation in the airways and parenchyma.\ud \ud \ud Conclusions\ud Rho-kinase inhibition, alone or in combination with corticosteroids, can be considered a future pharmacological tool for the control of asthma.We thank Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for their financial support

Isolation, Cloning and Structural Characterisation of Boophilin, a Multifunctional Kunitz-Type Proteinase Inhibitor from the Cattle Tick

Inhibitors of coagulation factors from blood-feeding animals display a wide variety of structural motifs and inhibition mechanisms. We have isolated a novel inhibitor from the cattle tick Boophilus microplus, one of the most widespread parasites of farm animals. The inhibitor, which we have termed boophilin, has been cloned and overexpressed in Escherichia coli. Mature boophilin is composed of two canonical Kunitz-type domains, and inhibits not only the major procoagulant enzyme, thrombin, but in addition, and by contrast to all other previously characterised natural thrombin inhibitors, significantly interferes with the proteolytic activity of other serine proteinases such as trypsin and plasmin. The crystal structure of the bovine α-thrombin·boophilin complex, refined at 2.35 Å resolution reveals a non-canonical binding mode to the proteinase. The N-terminal region of the mature inhibitor, Q16-R17-N18, binds in a parallel manner across the active site of the proteinase, with the guanidinium group of R17 anchored in the S1 pocket, while the C-terminal Kunitz domain is negatively charged and docks into the basic exosite I of thrombin. This binding mode resembles the previously characterised thrombin inhibitor, ornithodorin which, unlike boophilin, is composed of two distorted Kunitz modules. Unexpectedly, both boophilin domains adopt markedly different orientations when compared to those of ornithodorin, in its complex with thrombin. The N-terminal boophilin domain rotates 9° and is displaced by 6 Å, while the C-terminal domain rotates almost 6° accompanied by a 3 Å displacement. The reactive-site loop of the N-terminal Kunitz domain of boophilin with its P1 residue, K31, is fully solvent exposed and could thus bind a second trypsin-like proteinase without sterical restraints. This finding explains the formation of a ternary thrombin·boophilin·trypsin complex, and suggests a mechanism for prothrombinase inhibition in vivo

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs