Systemic Inflammation in Oncologic Patients Undergoing Systemic Treatment and Receiving Whey Protein-Based Nutritional Support.

There is increasing evidence about the role of inflammation in sarcopenia and tumor progression; thus, its modulation would represent a valuable strategy for improving clinical outcomes in patients with cancer. Several studies have reported that whey protein has significant anti-inflammatory and antioxidant characteristics in humans. We aimed to evaluate the effects of whey protein-based oral nutritional support on circulating cytokines in patients with solid tumors undergoing systemic treatment. Forty-six patients with solid tumors of different origin and undergoing systemic treatment were evaluated. Nutritional support with two daily whey protein-based oral supplements was administered. Circulating levels of IL-6, IL-8, IL-10, MCP-1 and IP-10 were determined. Nutritional evaluation included anthropometric, instrumental and biochemical parameters. Over 63% of the evaluated patients underwent surgery, 56.5% required chemotherapy and almost 50% received combined treatment. Patients with resected primary tumor presented with lower baseline IL-6 (p < 0.05) and IP-10 (p < 0.001); after three months of nutritional support, they presented with lower IL-8 (p < 0.05) and tended to present lower IL-6 and IP-10 (p = 0.053 and 0.067, respectively). Significant positive correlations between circulating cytokines, C-reactive protein and ferritin were observed; similarly, negative correlations with anthropometric and biochemical nutritional parameters were noticed (p < 0.05). We did not observe significant changes in circulating cytokine levels (IL-6, IL-8, IL-10, MCP-1 and IP-10) in patients with cancer undergoing systemic treatment after three months of nutritional support with whey protein-based oral supplements. According to a univariate analysis in our cohort, circulating IL-8 was associated with mortality in these patients, additionally, MCP-1 and IP-10 tended to correlate; but an age- and sex-adjusted multivariate analysis revealed that only baseline MCP-1 was significantly associated with mortality (OR 1.03 (95% CI: 1.00-1.05)). In conclusion, surgery of the primary solid tumor and combination treatment allow significant reduction in circulating cytokine levels, which remained stable while patients received nutritional support with whey protein-based oral supplements over three months. The role of MCP-1 as an independent factor for mortality in these patients should be further evaluated.

Impact of telenurse-led intervention in clinical trials on health literacy, empowerment, and health outcomes in patients with solid tumours: a pilot quasi-experimental study.

BACKGROUND: During the COVID-19 pandemic, decentralised clinical trials incorporated self-monitoring, self-reporting, and telenursing tools to address health literacy and health empowerment of patients enrolled in clinical trials. We aimed to determine the impact of an educational intervention using telenursing consultations on health literacy, health empowerment, and health-related quality of life in cancer patients enrolled in clinical trials by measuring the level of satisfaction with the care received and assessing the views of healthcare professionals concerning the advanced practice nurse (APN) role in oncology clinical trials. METHODS: In this pilot analytical, descriptive, longitudinal, quasi-experimental, and pre-post test study, an educational intervention was conducted by 5 visits with an APN using synchronous teleconsultation in patients starting cancer treatment for the first time in a clinical trial (n = 60), and health professionals working with the APN (n = 31). A descriptive analysis of the samples and questionnaires were utilised along with statistical comparisons. RESULTS: After the intervention, patients' health literacy (31.7%), health empowerment (18.3%), and health-related quality of life (33.3%) increased (p < 0.05), with a decrease and trend towards resolution of care needs (p < 0.05). Satisfaction with the quality and care received in terms of perceived convenience, transition, and continuity of care showed positive results in 64.9 ± 20.7, 77.6 ± 19.5, and 72.1 ± 20.4 of respondents, respectively. On the overall assessment of the APN role, healthcare professionals expressed a high level of agreement with the statements related to their work performance. CONCLUSIONS: The data indicates that a clinical trial APN-led telenursing educational intervention results in an overall increase in health literacy, an improvement in health empowerment and health-related quality of life, and a decrease in care needs of oncology clinical trials patients. Patients stated that they received a high quality of care and health professionals indicated high levels of acceptance with APNs. Based on these results, we suggest that the APN role should gain more recognition in the Spanish healthcare system and their professional competencies should be aligned with those of other countries.

Comparative Study of the Efficacy of EHO-85, a Hydrogel Containing Olive Tree (Olea europaea) Leaf Extract, in Skin Wound Healing.

Olive tree (Olea europaea) leaf extract (OELE) has important antioxidant and anti-inflammatory properties, supporting its use in human clinical practice. We recently designed an amorphous hydrogel called EHO-85 (EHO indicates olive leaf extract in Spanish) containing OELE for skin ulcer treatments. Yet, its effectiveness has not been previously compared with other products used in routine clinical practice. This is necessary to evaluate its potential translation to the human clinic. Thus, in this study, the effect of EHO-85 on healing was evaluated in comparison with treatments containing Indian/Asiatic pennywort (Centella asiatica), hyaluronic acid, or dexpanthenol in a rat model. The speed of wound closure and histological parameters after seven and 14 days were analyzed. All treatments accelerated wound closure, but there were differences between them. Dexpanthenol after seven days produced the highest epithelialization and the lowest inflammation and vascularization. EHO-85 also promoted epithelialization and reduced vascularization. After 14 days, wounds treated with EHO-85 showed less inflammation and higher levels of collagen in the extracellular matrix. This indicates a higher degree of maturity in the regenerated tissue. In conclusion, the effect of EHO-85 on healing was equal to or superior to that of other treatments routinely used in human clinical practice. Therefore, these results, together with previous data on the effects of this hydrogel on ulcer healing in humans, indicate that EHO-85 is a suitable, low-cost, and efficient therapeutic option for wound healing.

Early Use of Sarilumab in Patients Hospitalized with COVID-19 Pneumonia and Features of Systemic Inflammation: the SARICOR Randomized Clinical Trial.

The objective of this study was to investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalized adults with COVID-19. Methods included phase II, open-label, randomized, controlled clinical trial of hospitalized patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or d-dimer > 1,500 ng/mL. Participants were randomized (1:1:1) to receive SOC (control group), SOC plus a single subcutaneous dose of sarilumab 200 mg (sarilumab-200 group), or SOC plus a single subcutaneous dose of sarilumab 400 mg (sarilumab-400 group). The primary outcome variable was the development of acute respiratory distress syndrome (ARDS) requiring high-flow nasal oxygenation (HFNO), non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV) at day 28. One-hundred and 15 participants (control group, n = 39; sarilumab-200, n = 37; sarilumab-400, n = 39) were included. At randomization, 104 (90%) patients had supplemental oxygen and 103 (90%) received corticosteroids. Eleven (28%) patients in the control group, 10 (27%) in sarilumab-200, and five (13%) in sarilumab-400 developed the primary outcome (hazard ratio [95% CI] of sarilumab-400 vs control group: 0.41 [0.14, 1.18]; P = 0.09). Seven (6%) patients died: three in the control group and four in sarilumab-200. There were no deaths in sarilumab-400 (P = 0.079, log-rank test for comparisons with the control group). In patients recently hospitalized with COVID-19 pneumonia and features of systemic inflammation, early IL-6 blockade with a single dose of sarilumab 400 mg was safe and associated with a trend for better outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT04357860.).

Influence of antioxidant compounds, total sugars and genetic background on the chilling injury susceptibility of a non-melting peach (Prunus persica (L.) Batsch) progeny.

BACKGROUND: To identify genotypes with good organoleptic properties, antioxidant-rich content and low susceptibility to chilling injury (CI), fruits from 130 peach cultivars were studied over three consecutive years. Pomological traits, l-ascorbic acid, flavonoids, total phenolics, relative antioxidant capacity (RAC) and sugars were determined. Major symptoms of CI developed at 5 °C, such as leatheriness, flesh browning, bleeding and loss of flavor, were evaluated. RESULTS: The population exhibited wide phenotypic variation in agronomic and biochemical traits. Six genotypes with high total phenolics, RAC, flavonoids and total sugars were selected. The progeny also showed variability for all evaluated CI symptoms, and 16 genotypes showed considerably lower susceptibility to CI. After 2 weeks of cold storage, leatheriness and bleeding were the main CI symptoms observed, whereas flesh browning was predominant after 4 weeks. CONCLUSION: It was possible to find varieties with high phenolic concentration and relatively low or intermediate CI susceptibility (22, 33, 68, 80, 81, 96 and 120). However, the correlations observed between CI and phenolic contents highlight their potential influence on susceptibility to internal browning. This relationship should be considered in the current breeding programs to select cultivars with high bioactive compound contents, health-enhancing properties and good postharvest performance.

[Spontaneous hemoperitoneum and clear cell tumor of ovary]. / Hemoperitoneo espontáneo y carcinoma ovárico de células claras.

UNLABELLED: Hemoperitoneum is a rare cause of acute abdomen, which is usually due to liver, spleen, hematologic and vascular causes. We should consider gynecological origin in women in reproductive age, being a rare etiology in postmenopausal. CLINICAL CASE: We report the case of a spontaneous hemoperitoneum in a postmenopausal woman as the first manifestation of an ovarian tumor, with exceptional pathological lineage: clear cell carcinoma. Hemoperitoneum is a suspected diagnosis before clinical symptoms of hypovolemic shock and acute abdomen, with decrease in hemoglobin. To treating underlying cause, which in this case was surgical, it's important the clinical suspect and the appropriate hemodynamic support of the patient. Despite the resolution of the acute, it is particularly important the subsequent clinical monitoring of the patient by the peculiarities of this type of tumors.

Agronomical parameters, sugar profile and antioxidant compounds of "Catherine" peach cultivar influenced by different plum rootstocks.

The influence of seven plum rootstocks (Adesoto, Monpol, Montizo, Puebla de Soto 67 AD, PM 105 AD, St. Julien GF 655/2 and Constantí 1) on individual and total sugars, as well as on antioxidant content in fruit flesh of "Catherine" peaches, was evaluated for three years. Agronomical and basic fruit quality parameters were also determined. At twelve years after budding, significant differences were found between rootstocks for the different agronomic and fruit quality traits evaluated. The Pollizo plum rootstocks Adesoto and PM 105 AD seem to induce higher sweetness to peach fruits, based on soluble solids content, individual (sucrose, fructose and sorbitol) and total sugars. A clear tendency was also observed with the rootstock Adesoto, inducing the highest content of phenolics, flavonoids, vitamin C and relative antioxidant capacity (RAC). Thus, the results of this study demonstrate the significant effect of rootstock on the sugar profile and phytochemical characteristics of peach fruits. In addition, this work shows the importance of the sugar profile, because specific sugars play an important role in peach flavour quality, as well as the studied phytochemical compounds when looking for high quality peaches with enhanced health properties.

The Impact of Rootstock on "Big Top" Nectarine Postharvest Concerning Chilling Injury, Biochemical and Molecular Parameters.

Peaches and nectarines have a short shelf life even when harvested at appropriate physiological maturity. Market life is increased by storage at low temperatures. However, chilling injury symptoms can appear, causing physiological disorders and limiting shipping potential. The rootstock effect on the post-harvest quality has hardly been explored. Thus, the principal aim of this work was to study the influence of seven different Prunus rootstocks on the "Big Top" nectarine cv, considering harvest and post-harvest quality parameters and their correlation with chilling injury disorders. Basic fruit quality traits, individual sugars and organic acids analyzed by HPLC and other biochemical compounds such as relative antioxidant capacity, total phenolics content, flavonoids, anthocyanins, vitamin C and related enzyme activities (PAL, POD, PPO) were considered. In addition, correlations with possible candidate genes for chilling injury (CI) tolerance were searched by qPCR. Although a low susceptibility to CI symptoms has been found in "Big Top", rootstocks "PADAC 9902-01", "PADAC 99-05" and "ReplantPAC" exhibited lower CI symptoms. A statistically significant influence of the evaluated rootstocks was found concerning the parameters of this study. Phenols and anthocyanins seem to be important parameters to be considered in the prevention of chilling injury disorders. Moreover, PAL1, PPO4, PG2 and LDOX genes relative expressions were positively associated with chilling injury susceptibility. This study opens new perspectives for understanding peach fruit adaptation and response to cold storage temperatures during the post-harvest period.

Nutritional Support Reduces Circulating Cytokines in Patients with Heart Failure.

Increased inflammation is associated with the pathogenesis of heart failure (HF). Increased circulating levels of cytokines have been previously reported and generally associated with worse clinical outcomes. In this context, the modulation of inflammation-related parameters seems to be a reasonable therapeutic option for improving the clinical course of the disease. Based on this, we aimed to compare changes in circulating cytokines when Mediterranean diet alone or in combination with hypercaloric, hyperproteic oral nutritional supplements (ONS), enriched with omega-3 (n-3) polyunsaturated fatty acids were administered to patients with HF. Briefly, patients were randomly assigned to receive Mediterranean Diet (control group) vs. Mediterranean Diet plus ONS (intervention group). We observed increased circulating levels of IL-6, IL-8, MCP-1 and IP-10. MCP-1 and IL-6 were associated with overweight and obesity (p = 0.01-0.01-0.04, respectively); IL-6 and IL-8 were positively correlated with fat mass and CRP serum levels (p = 0.02-0.04, respectively). Circulating levels of IL-8 significantly decreased in all patients treated with the Mediterranean diet, while IL-6 and IP-10 only significantly decreased in patients that received plus ONS. In the univariate analysis, MCP-1 and its combination with IL-6 were associated with increased mortality (p = 0.02), while the multivariate analysis confirmed that MCP-1 was an independent factor for mortality (OR 1.01, 95%ci 1.01-1.02). In conclusion, nutritional support using hypercaloric, hyperproteic, n-3 enriched ONS in combination with Mediterranean Diet was associated with decreased circulating levels of some cytokines and could represent an interesting step for improving heart functionality of patients with HF.

An Open-label Phase 2 Study of Eneboparatide, a Novel PTH Receptor 1 Agonist, in Hypoparathyroidism.

CONTEXT: Hypoparathyroidism is a rare disorder characterized by a deficiency in PTH resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria. Eneboparatide is an investigational peptide agonist of the PTH1 receptor for the treatment of chronic hypoparathyroidism (HP). OBJECTIVE: To evaluate the efficacy, safety, and tolerability of eneboparatide in HP patients. DESIGN: Open-label, phase 2 study. PARTICIPANTS: Twenty-eight patients (21 women, 7 men), mean age (range): 58 years (28-72), with HP were enrolled into 2 consecutive cohorts (C1, n = 12 and C2, n = 16). INTERVENTION: Following an optimization period, daily subcutaneous injections of eneboparatide were administered for 3 months at a 20 µg/day (C1) or 10 µg/day (C2) starting dose. Conventional therapy was progressively removed, and eneboparatide could be titrated up to 60 µg (C1) or 80 µg (C2). MAIN OUTCOMES: Proportion of patients achieving independence from conventional therapy, albumin-adjusted serum calcium (ADsCa), 24-h urine calcium (uCa), serum bone turnover markers (serum carboxy-terminal telopeptide of type I collagen and procollagen 1 intact N-terminal propeptide), bone mineral density (BMD), and adverse events (AEs). RESULTS: After 3 months, ≥ 88% of patients achieved independence from conventional therapy while mean ADsCa was maintained within target range (7.8-9 mg/dL). Eneboparatide induced a rapid and sustained reduction of mean 24-hour uCa, even among patients with hypercalciuria. Bone turnover markers slightly increased, and BMD remained unchanged, consistent with progressive resumption of physiologic bone turnover. Eneboparatide was well tolerated with no serious AEs. CONCLUSION: Eneboparatide allowed independence from conventional therapy and maintenance of serum calcium within a target range while normalizing uCa excretion and producing a balanced resumption of bone turnover.

Differences in the Evaluation of Malnutrition and Body Composition Using Bioelectrical Impedance Analysis, Nutritional Ultrasound, and Dual-Energy X-ray Absorptiometry in Patients with Heart Failure.

BACKGROUND: Although malnutrition is frequently observed in patients with heart failure (HF), this diagnosis should be performed carefully since HF itself is associated with increased inflammatory activity, which affects body weight, functionality, and some nutritional parameters; thus, its isolated interpretation can erroneously identify surrogate markers of severity as markers of malnutrition. In this context, we aimed to evaluate the prevalence of malnutrition using different classification systems and perform a comprehensive nutritional evaluation to determine the reliability of different diagnostic techniques. PATIENTS AND METHODS: Eighty-three patients with a recent hospital admission due to HF were evaluated. GLIM diagnosis criteria and subjective global assessment (SGA) were performed; a comprehensive anthropometric, functional, and biochemical nutritional evaluation was performed, in which bioelectrical impedance analysis (BIA), nutritional ultrasound, and dual-energy X-ray absorptiometry (DXA) were performed. Additionally, mortality and additional admissions due to HF were determined after a mean follow up of 18 months. RESULTS: Malnutrition according to the GLIM criteria (54%) accurately distinguished patients with impaired functionality, lower lean mass, skeletal mass index, and appendicular muscle mass (BIA), as well as lower trunk fat mass, trunk lean mass, fat-free mass (DXA), and decreased albumin and increased C-reactive protein serum levels. According to SGA, there were significant changes in body composition parameters determined by BIA, muscle ultrasound, and functional tests between well-nourished patients and patients with risk of malnutrition (53.7%) or who had malnutrition (7.1%), but not when the last two groups were compared. BIA and DXA showed strong correlations when evaluating muscle and fat mass in HF patients, but correlations with nutritional ultrasound were limited, as well as functional tests. A multivariate analysis showed that no significant association was observed between body composition and mortality, but preperitoneal fat was associated with an increased risk of new hospital admissions (OR: 0.73). CONCLUSIONS: GLIM criteria identified a lower percentage of patients with HF and malnutrition compared with SGA; thus, SGA could have a role in preventing malnutrition in HF patients. Nutritional evaluation with BIA and DXA in patients with HF showed reliable results of body composition parameters in HF, and both help with the diagnosis of malnutrition according to the GLIM or SGA criteria and could provide complementary information in some specific cases.

Altered CELF4 splicing factor enhances pancreatic neuroendocrine tumors aggressiveness influencing mTOR and everolimus response.

Pancreatic neuroendocrine tumors (PanNETs) comprise a heterogeneous group of tumors with growing incidence. Recent molecular analyses provided a precise picture of their genomic and epigenomic landscape. Splicing dysregulation is increasingly regarded as a novel cancer hallmark influencing key tumor features. We have previously demonstrated that splicing machinery is markedly dysregulated in PanNETs. Here, we aimed to elucidate the molecular and functional implications of CUGBP ELAV-like family member 4 (CELF4), one of the most altered splicing factors in PanNETs. CELF4 expression was determined in 20 PanNETs, comparing tumor and non-tumoral adjacent tissue. An RNA sequencing (RNA-seq) dataset was analyzed to explore CELF4-linked interrelations among clinical features, gene expression, and splicing events. Two PanNET cell lines were employed to assess CELF4 function in vitro and in vivo. PanNETs display markedly upregulated CELF4 expression, which is closely associated with malignancy features, altered expression of key tumor players, and distinct splicing event profiles. Modulation of CELF4 influenced proliferation in vitro and reduced in vivo xenograft tumor growth. Interestingly, functional assays and RNA-seq analysis revealed that CELF4 silencing altered mTOR signaling pathway, enhancing the effect of everolimus. We demonstrate that CELF4 is dysregulated in PanNETs, where it influences tumor development and aggressiveness, likely by modulating the mTOR pathway, suggesting its potential as therapeutic target.

Impact of the COVID-19 pandemic on the self-care and health condition of the older adults. CUIDAMOS+75. A mixed methods study protocol.

Aims: To assess the impact of the COVID-19 pandemic on the health condition of people ≥75 years of age and on their family caregivers in Spain. Design: Multicentric, mixed method concurrent study. Methods: This work, which will be conducted within the primary care setting in 11 administrative regions of Spain, will include three coordinated studies with different methodologies. The first is a population-based cohort study that will use real-life data to analyze the rates and evolution of health needs, care provision, and services utilization before, during, and after the pandemic. The second is a prospective cohort study with 18 months of follow-up that will evaluate the impact of COVID-19 disease on mortality, frailty, functional and cognitive capacity, and quality of life of the participants. Finally, the third will be a qualitative study with a critical social approach to understand and interpret the social, political, and economic dimensions associated with the use of health services during the pandemic. We have followed the SPIRIT Checklist to address trial protocol and related documents. This research is being funded by the Instituto de Salud Carlos III since 2021 and was approved by its ethics committee (June 2022). Discussion: The study findings will reveal the long-term impact of the COVID-19 pandemic on the older adults and their caregivers. This information will serve policymakers to adapt health policies to the needs of this population in situations of maximum stress, such as that produced by the COVID-19 pandemic. Trial Registration: Identifier: NCT05249868 [ClinicalTrials.gov].

Population Structure and Association Mapping for Agronomical and Biochemical Traits of a Large Spanish Apple Germplasm.

A basic knowledge of linkage disequilibrium and population structure is necessary in order to determine the genetic control and identify significant associations with agronomical and phytochemical compounds in apple (Malus × domestica Borkh). In this study, 186 apple accessions (Pop1), representing both Spanish native accessions (94) and non-Spanish cultivars (92) from the EEAD-CSIC apple core collection, were assessed using 23 SSRs markers. Four populations were considered: Pop1, Pop2, Pop3, and Pop4. The initial Pop1 was divided into 150 diploid (Pop2) and 36 triploid accessions (Pop3), while for the inter-chromosomal linkage disequilibrium and the association mapping analysis, 118 phenotype diploid accessions were considered Pop4. Thus, the average number of alleles per locus and observed heterozygosity for the overall sample set (Pop1) were 15.65 and 0.75, respectively. The population structure analysis identified two subpopulations in the diploid accessions (Pop2 and Pop4) and four in the triploids (Pop3). Regarding the Pop4, the population structure with K = 2 subpopulations segregation was in agreement with the UPGMA cluster analysis according to the genetic pairwise distances. Moreover, the accessions seemed to be segregated by their origin (Spanish/non-Spanish) in the clustering analysis. One of the two subpopulations encountered was quite-exclusively formed by non-Spanish accessions (30 out of 33). Furthermore, agronomical and basic fruit quality parameters, antioxidant traits, individual sugars, and organic acids were assessed for the association mapping analysis. A high level of biodiversity was exhibited in the phenotypic characterization of Pop4, and a total of 126 significant associations were found between the 23 SSR markers and the 21 phenotypic traits evaluated. This study also identified many new marker-locus trait associations for the first time, such as in the antioxidant traits or in sugars and organic acids, which may be useful for predictions and for a better understanding of the apple genome.

Standard Hypercaloric, Hyperproteic vs. Leucine-Enriched Oral Supplements in Patients with Cancer-Induced Sarcopenia, a Randomized Clinical Trial.

(1) Background: Malnutrition frequently affects patients with cancer, and it negatively impacts treatment tolerance, clinical outcomes and survival. Thus, appropriate nutritional screening and early nutrition support are extremely recommended. Currently, a significant number of oral supplements (OS) are commercially available; despite this, there is a lack of evidence for recommending specific OS, including leucine-enriched OS, for nutritional support in patients with cancer. (2) Aim: To compare the clinical evolution of patients with cancer (undergoing systemic treatment) that received standard hypercaloric, whey protein-based hyperproteic oral supplements vs. hypercaloric, hyperproteic leucine-enriched OS using a novel morphofunctional nutritional evaluation. (3) Patients and methods: This paper details an open-label, controlled clinical study in which patients were randomly assigned to receive nutritional treatment with whey protein-based hyperproteic oral supplements (control group) vs. hypercaloric, hyperproteic leucine-enriched OS (intervention group) during a twelve-week period. Forty-six patients were included; epidemiological, clinical, anthropometric, ultrasound (muscle echography of the rectus femoris muscle of the quadriceps and abdominal adipose tissue) and biochemical evaluation were performed. All patients received additional supplementation with vitamin D. (4) Results: Nutritional parameters (including bioimpedance, anthropometric, ultrasound and biochemical variables) of all included patients remained stable after the nutritional intervention. Extracellular mass tended to increase in the patients that received the leucine-enriched formula. Functionality (evaluated through the stand-up test) improved in both groups (p < 0.001). Prealbumin, transferrin levels and superficial adipose tissue increased in the control group (p < 0.05), while self-reported quality of life improved in all the evaluated patients (p < 0.001). (5) Conclusions: Nutritional support with hypercaloric, hyperproteic (with whey protein) OS and vitamin D supplementation were associated with the maintenance of body composition and improvements in functionality and in quality of life in the patients with cancer undergoing systemic treatment. No significant benefits were observed when a leucine-enriched formula was used.

Mediterranean Diet, Vitamin D, and Hypercaloric, Hyperproteic Oral Supplements for Treating Sarcopenia in Patients with Heart Failure-A Randomized Clinical Trial.

BACKGROUND: Malnutrition and sarcopenia frequently affect patients with heart failure (HF), in which clinical outcomes and survival is decreased. Thus, appropriate nutritional screening and early nutrition support are highly recommended. Currently, nutritional support is not a standard of care in patients with HF, and the use of commercially available oral supplements (OSs) could provide an additional benefit to medical treatment in these patients. AIM: To compare the effect of the Mediterranean diet in combination with hypercaloric, hyperproteic OS in patients with HF. PATIENTS AND METHODS: An open label, controlled clinical study in which patients were randomly assigned to receive a Mediterranean diet (control group) vs. hypercaloric, hyperproteic OS (intervention group) for twenty-four weeks. Thirty-eight patients were included; epidemiological, clinical, anthropometric, ultrasound (muscle echography of the rectus femoris muscle of the quadriceps and abdominal adipose tissue), and biochemical evaluations were performed. All patients received additional supplementation with vitamin D. RESULTS: Baseline malnutrition according to the GLIM criteria was observed in 30% of patients, while 65.8% presented with sarcopenia. Body cell mass, lean mass, and body mass increased in the intervention group (absolute increase of 0.5, p = 0.03, 1.2 kg, p = 0.03, and 0.1 kg, p = 0.03 respectively). In contrast, fat mass increased in the control group (4.5 kg, p = 0.05). According to the RF ultrasound, adipose tissue, muscle area, and circumference tended to decrease in the intervention group; it is probable that 24 weeks was too short a period of time for evaluating changes in muscle area or circumference, as previously observed in another group of patients. In contrast, functionality, determined by the up-and-go test, significantly improved in all patients (difference 12.6 s, p < 0.001), including the control (10 s improvement, p < 0.001) and the intervention group (improvement of 8.9 s, p < 0.001). Self-reported QoL significantly increased in all groups, from 68.7 ± 22.2 at baseline to 77.7 ± 18.7 (p = 0.01). When heart functionality was evaluated, LVEF increased in the whole cohort (38.7 ± 16.6 vs. 42.2 ± 8.9, p < 0.01); this increase was higher in the intervention group (34.2 ± 16.1 at baseline vs. 45.0% ± 17.0 after 24 weeks, p < 0.05). Serum values of NT-proBNP also significantly decreased in the whole cohort (p < 0.01), especially in the intervention group (p = 0.02). After adjusting by age and sex, nutritional support, baseline LVEF, NT-proBNP, and body composition parameters of functionality tests were not associated with mortality or new hospital admissions in this cohort. CONCLUSION: Nutritional support with hypercaloric, hyperproteic OS, Mediterranean diet, and vitamin D supplementation were associated with decreased NT-proBNP and improvements in LVEF, functionality, and quality of life in patients with HF, despite a significant decrease in hospital admissions.

Body composition and sexual hormones for the glucose control of autoimmune diabetes in males: are they necessary to predict diabetes-related complications?

Background: Glucose control in diabetes is essential for avoiding diabetes-related complications. Aim: To determine the impact of body composition and sexual hormones in glucose control and diabetes-related complications, in males with autoimmune diabetes. Patients and methods: Thirty-nine patients with autoimmune diabetes and flash glucose monitoring were included. A morphofunctional nutritional evaluation with bioelectrical impedance vector analysis (BIVA), abdominal adipose tissue ultrasound, rectus femoris ultrasound and biochemical parameters, was performed. Results: Strong, positive correlations were observed between body composition parameters, biochemical variables and sexual hormones (p<0.05). Adipose tissue measured by BIVA and ultrasound was more significantly associated with glucose control (including time in range >70%, glucose variability <36% determined by flash glucose monitoring; p<0.05) and the presence of microvascular/macrovascular complications (p<0.05) than lean mass. After adjusting by the duration of diabetes, BMI, abdominal circumference, fat mass and phase angle increased the risk for microvascular complications (OR 1.32(1.00 - 1.73), OR 1.06(1.00 - 1.12), OR 1.14(1.01 - 1.20), 0R 0.3(0.10 - 0.91) respectively; for macrovascular complications: BMI OR 1.38(1.04 - 1.84) and fat mass OR 1.26(1.00 - 1.58)]. Sexual hormone levels did not influence on glucose control or the development of diabetes-related complications. Conclusion: Anthrpometric parameters, especially adipose tissue, were associated with glucose control and variability determined by flash glucose monitoring. Furthermore, changes in fat and lean mass were associated with the presence of microvascular and macrovascular complications. Thus, a comprehensive nutritional evaluation might be useful for the evaluation of males with autoimmune diabetes, in order to identify patients with increased risk of complications.

Non-Specific Inhibition of Dipeptidyl Peptidases 8/9 by Dipeptidyl Peptidase 4 Inhibitors Negatively Affects Mesenchymal Stem Cell Differentiation.

DPP4 may play a relevant role in MSC differentiation into osteoblasts or adipocytes. Dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4i), such as sitagliptin and vildagliptin, are used as antidiabetic drugs. However, vildagliptin is not a specific DPP4i and also inhibits DPP8/9, which is involved in energy metabolism and immune regulation. The aim of this study is to evaluate how sitagliptin, vildagliptin or 1G244 (a DPP8/9 specific inhibitor) may influence cell viability, as well as osteogenic and adipogenic differentiation in human mesenchymal stem cells (MSC). Viability, apoptosis, osteoblastogenesis and adipogenesis markers, as well as protein synthesis of ß-catenin, were studied in MSC cultures induced to differentiate into osteoblasts or adipocytes in the presence or absence of sitagliptin, vildagliptin or 1G244. The two tested DPP4i did not affect MSC viability, but 1G244 significantly decreased it in MSC and osteoblast-induced cells. Additionally, 1G244 and vildagliptin inhibited osteogenesis and adipogenesis, unlike sitagliptin. Therefore, inhibition of DPP4 did not affect MSC viability and differentiation, whereas inhibition of DPP8/9 negatively affected MSC. To the best of our knowledge, these results show for the first time that DPP8/9 have an important role in the viability and differentiation of human MSC. This data can be considered for human clinical use of drugs affecting DPP8/9 activity.

Professional competencies of oncology nurses: Recognizing advanced practice in nursing.

OBJECTIVE: To identify the competency profile of advanced practice nurses involved in the care process of cancer patients. METHODS: Cross-sectional and descriptive study. The study included all nurses involved in the cancer patient care process in a tertiary hospital in Barcelona. Competence profile data were collected using the instrument for defining the role of the advanced practice nurse (APRD), as well as sociodemographic and occupational variables. Sociodemographic and occupational data were compared against the performance of advanced practice activities. RESULTS: A total of 29 (82.9%) nurses participated with a mean age of 42.6±12.54 years. 9 (31%) nurses were identified as meeting the standard in all 6 domains on the APRD scale to be considered advanced practice nurses. Of these 9 (31%) nurses, 7 (24.1%) met the training standards required by the International Council of Nurses (ICN) with an official master's degree and 2 (6.9%) with a PhD. CONCLUSIONS: There are nurses who carry out their activity in the oncology field of the hospital analyzed with the EPA profile. The identification of advanced practice nurses (APNs) in our health system is essential to be able to recognize the competencies of these professionals and create specific positions that help to address chronicity, patients' quality of life, their survival, and the optimization of health resources. Our study highlights the importance of chronicity and cancer as areas for the development of the APNs.

Clinical Potential of Mesenchymal Stem Cell-Derived Exosomes in Bone Regeneration.

Bone metabolism is regulated by osteoblasts, osteoclasts, osteocytes, and stem cells. Pathologies such as osteoporosis, osteoarthritis, osteonecrosis, and traumatic fractures require effective treatments that favor bone formation and regeneration. Among these, cell therapy based on mesenchymal stem cells (MSC) has been proposed. MSC are osteoprogenitors, but their regenerative activity depends in part on their paracrine properties. These are mainly mediated by extracellular vesicle (EV) secretion. EV modulates regenerative processes such as inflammation, angiogenesis, cell proliferation, migration, and differentiation. Thus, MSC-EV are currently an important tool for the development of cell-free therapies in regenerative medicine. This review describes the current knowledge of the effects of MSC-EV in the different phases of bone regeneration. MSC-EV has been used by intravenous injection, directly or in combination with different types of biomaterials, in preclinical models of bone diseases. They have shown great clinical potential in regenerative medicine applied to bone. These findings should be confirmed through standardization of protocols, a better understanding of the mechanisms of action, and appropriate clinical trials. All that will allow the translation of such cell-free therapy to human clinic applications.