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    Teenagers and Adolescents with Hemophilia-Need for a Specific Approach.

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    20.500.12530/87857Adolescents with hemophilia are a patient population with special requirements, having to manage their condition alongside the typical challenges of adolescence. Given the psychosocial impact of hemophilia and a desire to fit in with non-hemophilic peers, they may perceive treatment as more of a burden than a benefit. This can result in low adherence and a high risk of hemophilia-related complications. Hemophilia management has changed over time. To best inform shared decision-making with adolescent patients and their families, healthcare professionals must consider all the currently available evidence, highlighting treatment benefits as appropriate. They should also appreciate the requirements of all adolescents affected by hemophilia, including individuals with non-severe disease and girls/women. We discuss specific issues relating to the management of adolescents with hemophilia: prevention and management of bleeds, treatment adherence, joint health and physical activity, and other health-related issues. A multidisciplinary approach is advocated, and the potential role of digital technology in helping to equip patients with self-management skills to fully engage with treatment is considered. Currently, available hemophilia management generally enables adolescents with hemophilia to lead normal lives, participating in physical activities while maintaining good joint health. However, more work is required to help address both actual and perceived limitations

    Identification of factors associated with sarcopenic obesity development: Literature review and expert panel voting.

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    20.500.12530/87908Sarcopenic obesity (SO) is defined as the combination of excess fat mass (obesity) and low skeletal muscle mass and function (sarcopenia). The identification and classification of factors related to SO would favor better prevention and diagnosis. The present article aimed to (i) define a list of factors related with SO based on literature analysis, (ii) identify clinical conditions linked with SO development from literature search and (iii) evaluate their relevance and the potential research gaps by consulting an expert panel. From 4746 articles screened, 240 articles were selected for extraction of the factors associated with SO. Factors were classified according to their frequency in the literature. Clinical conditions were also recorded. Then, they were evaluated by a panel of expert for evaluation of their relevance in SO development. Experts also suggested additional factors. Thirty-nine unique factors were extracted from the papers and additional eleven factors suggested by a panel of experts in the SO field. The frequency in the literature showed insulin resistance, dyslipidemia, lack of exercise training, inflammation and hypertension as the most frequent factors associated with SO whereas experts ranked low spontaneous physical activity, protein and energy intakes, low exercise training and aging as the most important. Although literature and expert panel presented some differences, this first list of associated factors could help to identify patients at risk of SO. Further work is needed to confirm the contribution of factors associated with SO among the population overtime or in randomized controlled trials to demonstrate causality

    Multivalent, calcium-independent binding of surfactant protein A and D to sulfated glycosaminoglycans of the alveolar epithelial glycocalyx.

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    Lung surfactant collectins, surfactant protein A (SP-A) and D (SP-D), are oligomeric C-type lectins involved in lung immunity. Through their carbohydrate recognition domain, they recognize carbohydrates at pathogen surfaces and initiate lung innate immune response. Here, we propose that they may also be able to bind to other carbohydrates present in typical cell surfaces, such as the alveolar epithelial glycocalyx. To test this hypothesis, we analyzed and quantified the binding affinity of SP-A and SP-D to different sugars and glycosaminoglycans (GAGs) by microscale thermophoresis (MST). In addition, by changing the calcium concentration, we aimed to characterize any consequences on the binding behavior. Our results show that both oligomeric proteins bind with high affinity (in nanomolar range) to GAGs, such as hyaluronan (HA), heparan sulfate (HS) and chondroitin sulfate (CS). Binding to HS and CS was calcium-independent, as it was not affected by changing calcium concentration in the buffer. Quantification of GAGs in bronchoalveolar lavage (BAL) fluid from animals deficient in either SP-A or SP-D showed changes in GAG composition, and electron micrographs showed differences in alveolar glycocalyx ultrastructure in vivo. Taken together, SP-A and SP-D bind to model sulfated glycosaminoglycans of the alveolar epithelial glycocalyx in a multivalent and calcium-independent way. These findings provide a potential mechanism for SP-A and SP-D as an integral part of the alveolar epithelial glycocalyx binding and interconnecting free GAGs, proteoglycans, and other glycans in glycoproteins, which may influence glycocalyx composition and structure.NEW & NOTEWORTHY SP-A and SP-D function has been related to innate immunity of the lung based on their binding to sugar residues at pathogen surfaces. However, their function in the healthy alveolus was considered as limited to interaction with surfactant lipids. Here, we demonstrated that these proteins bind to glycosaminoglycans present at typical cell surfaces like the alveolar epithelial glycocalyx. We propose a model where these proteins play an important role in interconnecting alveolar epithelial glycocalyx components

    Native Valve Infective Endocarditis with Severe Regurgitation: What Matters Is Heart Failure.

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    20.500.12530/87885Background/Objectives: Heart failure worsens the prognosis of patients with infective endocarditis (IE) and is mainly caused by severe valvular regurgitation. The aim of our investigation is to describe the clinical, epidemiological, microbiological, and echocardiographic characteristics of patients with native left-sided infective endocarditis (NLSIE) with severe valvular regurgitation; to describe the prognosis according to the therapeutic approach; and to determine the prognostic factors of in-hospital mortality. Methods: We prospectively recruited all episodes of possible or definite NLSIE diagnosed at three tertiary hospitals between 2005 and 2022. Patients were divided into two groups: patients with severe valvular regurgitation at the time of admission or during hospitalization and patients without severe valvular regurgitation. We analyzed up to 85 variables concerning epidemiological, clinical, analytical, microbiological, and echocardiographic data. Results: We recovered 874 patients with NLSIE, 564 (65%) of them with severe valvular regurgitation. There were no differences in mortality among patients with and without severe regurgitation (30.2% vs. 26.5%, p = 0.223). However, mortality increased when patients with severe regurgitation developed heart failure (33% vs. 11.4%,

    Immune response against the SARS-CoV-2 spike protein in cancer patients after COVID-19 vaccination during the Omicron wave: a prospective study.

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    20.500.12530/87858Cancer patients often have weakened immune systems, resulting in a lower response to vaccines, especially those receiving immunosuppressive oncological treatment (OT). We aimed to assess the impact of OT on the humoral and T-cell response to the B.1 lineage and Omicron variant following COVID-19 vaccination in patients with solid and hematological neoplasms. We conducted a prospective study on cancer patients, stratified into OT and non-OT groups, who received a two-dose series of the COVID-19 mRNA vaccine and a booster six months later. The outcomes measured were the humoral (anti-SARS-CoV-2 S IgG titers and ACE2-S interaction inhibition capacity) and cellular (SARS-CoV-2 S-specific T-cell spots per million PBMCs) responses against the B.1 lineage and Omicron variant. These responses were evaluated four weeks after the second dose (n = 98) and eight weeks after the booster dose (n = 71). The humoral response after the second vaccine dose against the B.1 lineage and Omicron variant was significantly weaker in the OT group compared to the non-OT group (q-value Cancer patients, particularly those receiving immunosuppressive oncological treatments, should require booster doses and adapted COVID-19 vaccines for new SARS-CoV-2 variants like Omicron. Future studies should evaluate the durability of the immune response and the efficacy of individualized regimens

    Nutritional and Morphofunctional Assessment of Post-ICU Patients with COVID-19 at Hospital Discharge: NutriEcoMuscle Study.

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    20.500.12530/87910This paper presents baseline results from the NutriEcoMuscle study, a multicenter observational study conducted in Spain which focused on changes in nutritional status, body composition, and functionality in post-intensive care unit (ICU) COVID-19 patients following a nutritional intervention. Assessments at hospital discharge included Subjective Global Assessment (SGA), Global Leadership Initiative on Malnutrition (GLIM) criteria, the Barthel index, handgrip strength (HGS) and the Timed Up-and-Go test, bioelectrical impedance analysis (BIA), and nutritional ultrasound (US). The study involved 96 patients (71.9% male, mean age 58.8 years, mean BMI 28.8 kg/m2, 36.5% obese). All patients were malnourished at discharge according to GLIM and SGA. Functional status declined from admission up to hospital discharge. A total of 33.3% of patients had a low fat-free mass index (FFMI) and 29.5% had a low phase angle (PhA). Myosteatosis was observed in 83.7% of the population. There was a positive correlation between rectus femoris cross-sectional area, PhA, FFMI, and HGS. In conclusion, post-critically ill COVID-19 patients commonly suffer from malnutrition and reduced muscle mass, causing a loss of independence at hospital discharge. BIA and US could be valuable tools for assessing body composition in these patients. The NutriEcoMuscle study highlights the need for a thorough nutritional and morphofunctional status assessment of post-ICU patients

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