Switchable CAR T cell strategy against osteosarcoma.

Immunotherapy with chimeric antigen receptor T (CAR T) cells has changed the treatment of hematological malignances, but they are still a challenge for solid tumors, including pediatric sarcomas. Here, we report a switchable CAR T cell strategy based on anti-FITC CAR T cells and a switch molecule conjugated with FITC for targeting osteosarcoma (OS) tumors. As a potential target, we analyzed the expression of B7-H3, an immune checkpoint inhibitor, in OS cell lines. In addition, we evaluate the capacity of an anti-B7-H3 monoclonal antibody conjugated with FITC (anti-B7-H3-FITC mAb) to control the antitumor activity of anti-FITC CAR T cells. The effector functions of anti-FITC CAR T cells against OS, measured in vitro by tumor cell killing activity and cytokine production, are dependent on the presence of the anti-B7-H3-FITC mAb switch. Moreover, OS cells stimulate anti-FITC CAR T cells migration. In vivo, anti-B7-H3 mAb penetrates in the tumor and binds 143B OS tumor cells. Furthermore, anti-FITC CAR T cells reach tumor region and exert antitumor effect in an OS NSG mouse model only in the presence of the switch molecule. We demonstrate that anti-B7-H3-FITC mAb redirects the cytotoxic activity of anti-FITC CAR T cells against OS tumors suggesting that switchable CAR T cell platforms might be a plausible strategy against OS.

[Socioeconomic determinants and gender gaps in depressive symptoms in Chile]. / Determinantes socioeconómicos y brechas de género de la sintomatología depresiva en Chile.

BACKGROUND: There are marked differences associated with socio-economic factors in the prevalence of depressive symptoms (DS) in men and women. AIM: To estimate the association between socioeconomic status and DS in Chile and to estimate the gender gaps in this association. MATERIAL AND METHODS: The Patient Health Questionnaire-9 (PHQ-9) was applied as part of a socioeconomic survey carried out in a representative community sample (n = 2913). Using this information, we analyzed the influence of social status (education level, occupation, household income) and other psychosocial factors (gender, perceived social support, stressful life events) on DS. RESULTS: The prevalence of DS was 23.2% in women and 13.4% in men. A socioeconomic gradient was found in the distribution of DS. This gradient was more pronounced for women than for men. Gender, social support and stressful life events were the most important predictors of severe DS, with an estimated risk twice as high among women and almost three times as high among those with low social support. CONCLUSIONS: There is a combined effect between socio-economic and gender inequalities on DS. This partially explains the greater vulnerability of poor women and the DS gap between men and women.

Antitumor virotherapy using syngeneic or allogeneic mesenchymal stem cell carriers induces systemic immune response and intratumoral leukocyte infiltration in mice.

Oncolytic virotherapy uses oncolytic viruses that selectively replicate in cancer cells. The use of cellular vehicles with migration ability to tumors has been considered to increase their delivery to target sites. Following this approach, the antitumor efficacy of the treatment Celyvir (mesenchymal stem cells infected with the oncolytic adenovirus ICOVIR-5) has been demonstrated in patients with neuroblastoma. However, the better efficacy of syngeneic or allogeneic mesenchymal stem cells as cell carriers and the specific role of the immune system in this therapy are still unknown. In this study we use our virotherapy Celyvir with syngeneic and allogeneic mouse mesenchymal stem cells to determine their antitumor efficacy in a C57BL/6 murine adenocarcinoma model. Adoptive transfer of splenocytes from treated mice to new tumor-bearing mice followed by a secondary adoptive transfer to a third group was performed. Similar reduction of tumor growth and systemic activation of the innate and adaptive immune system was observed in groups treated with syngeneic or allogeneic mesenchymal stem cells loaded with ICOVIR-5. Moreover, a different pattern of infiltration was observed by immunofluorescence in Celyvir-treated groups. While non-treated tumors presented higher density of infiltrating immune cells in the periphery of the tumor, both syngeneic and allogeneic Celyvir-treated groups presented higher infiltration of CD45+ cells in the core of the tumor. Therefore, these results suggest that syngeneic and allogeneic Celyvir induce systemic activation of the immune system, similar antitumor effect and a higher intratumoral infiltration of leukocytes.

Synthesis and pharmacophore modelling of 2,6,9-trisubstituted purine derivatives and their potential role as apoptosis-inducing agents in cancer cell lines.

A series of 2,6,9-trisubstituted purine derivatives have been synthesized and investigated for their potential role as antitumor agents. Twelve compounds were obtained by a three step synthetic procedure using microwave irradiation in a pivotal step. All compounds were evaluated in vitro to determine their potential effect on cell toxicity by the MTT method and flow cytometry analysis on four cancer cells lines and Vero cells. Three out of twelve compounds were found to be promising agents compared to a known and effective anticancer drug, etoposide, in three out of four cancer cell lines assayed with considerable selectivity. Preliminary flow cytometry data suggests that compounds mentioned above induce apoptosis on these cells. The main structural requirements for their activity for each cancer cell line were characterized with a preliminary pharmacophore model, which identified aromatic centers, hydrogen acceptor/donor center and a hydrophobic area. These features were consistent with the cytotoxic activity of the assayed compounds.

Exploring the impact of social protest on mental health: A study of the 2019 "Social Uprising" in Chile.

Socio-political conflicts, especially if accompanied by violent events, can affect the mental health of the population. This study aimed to estimate the causal effect of social protest-related violence on depressive symptoms during the 2019 social uprising in Chile. We collected population-representative data from a nationwide longitudinal survey (n = 2918), the fourth wave of which took place during the months of the social uprising in Chile (November 2019 and March 2020). Depressive symptoms were measured using the Patient Health Questionnaire-9, while violence related to social protest was measured as the perception of destruction at the neighbourhood level. To assess the casual relationship between destruction perception and depressive symptoms, we utilized an instrumental variable regression model. Our analysis controlled for relevant sociodemographic factors, participation in social protest, and history of mental health treatment. Results showed that perceived neighbourhood destruction during the 2019 social uprising significantly increased PHQ-9 score by 3.702 points, prevalence of moderate to severe depressive symptoms by 18.7%, and likelihood of having a Subthreshold or Major Depressive Episode by 15.2% (p < 0.01). The impact of perceived destruction on depressive symptoms varies by gender, with a significant effect found in men (an increase in depression indicators of 5.769 points, 26.8% and 23.0%, respectively, p < 0.05) but not in women. Stratified regression models by age demonstrate a positive association between the perception of neighbourhood destruction and depressive symptoms across all age groups, with a stronger effect observed among young adults. We found a casual effect of violence related to social protest on depressive symptoms. These findings have implications for the planning of social policies aimed at protecting the mental well-being of the population in times of increasing socio-political turmoil.

Effect of Mirror Therapy on Post-Needling Pain Following Deep Dry Needling of Myofascial Trigger Point in Lateral Elbow Pain: Prospective Controlled Pilot Trial.

Background: This prospective randomized, controlled pilot trial to explore the immediate effect of adding Mirror Visual Feedback Therapy on pain sensitivity and motor performance among subjects suffering from post-needling pain diagnosed as Lateral Elbow Pain. Methods: A total of 49 participants (23 female, 26 male) were enrolled and randomly allocated to either the experimental group, which received Deep Dry Needling in the m. Brachioradialis, Ischemic Compression, Cold Spray, Stretching, and Mirror Visual Feedback Therapy (n = 25), or a control group without Mirror Visual Feedback Therapy (n = 24). Pre- and post-treatment evaluations included assessments of post-needling pain intensity, pressure pain threshold, two-point discrimination threshold, and maximum hand grip strength. Results: Intergroup analysis revealed a statistically significant reduction in post-needling pain intensity favoring the experimental group (U = 188.00, p = 0.034). Additionally, intragroup analysis showed significant improvements in post-needling pain intensity (MD = 0.400, SEM = 0.271, W = 137.00, p = 0.047) and pressure pain threshold (MD = 0.148 Kg/cm2, SEM = 0.038, W = 262.00, p < 0.001) within the experimental group following the intervention. Conclusions: These findings suggest a potential benefit of integrating Mirror Visual Feedback Therapy into treatment protocols for individuals with Lateral Elbow Pain experiencing post-needling discomfort. Further research is necessary to fully elucidate the clinical implications of these findings.

Social contagion, violence, and suicide among adolescents.

PURPOSE OF REVIEW: Social Contagion is defined as the spread of behaviors, attitudes, and affect through crowds and other types of social aggregates from one member to another. Adolescents are prone to social contagion because they may be especially susceptible to peer influence and social media.In this article, we provide a brief review of the most recent findings on social contagion, violence, and suicide among adolescents. RECENT FINDINGS: Recent evidence support social contagion in gun violence, bullying, cyberbullying, violent offending, and suicide, but is inconclusive on the role of violent video game exposure on aggressive behavior. SUMMARY: The mechanisms underlying the contagion effect of violence and suicide are currently unclear. It has been argued that social learning, identification with significant others, and the normalization of specific norms play a role. All these mechanisms require understanding social contagion as a complex interaction between individual, relational and social factors. This is key if the social contagion perspective is to be used not only to investigate negative outcomes, but also as a framework for promoting prosocial attitudes and behaviors. Additionally, more research is needed on psychosocial interventions and public policies to minimize the potential spillover effect of violence and suicide.

Toll-like Receptor Signaling-deficient Cells Enhance Antitumor Activity of Cell-based Immunotherapy by Increasing Tumor Homing.

Cancer immunotherapy aims to activate the immune system. Some immunotherapeutic agents can be loaded in carrier cells for delivering to the tumors. However, a challenge with cell-based therapies is the selection of the appropriate cells to produce effective clinical outcomes. We hypothesize that therapies based on cells presenting a natural low proinflammatory profile ("silent cells") in the peripheral blood would result in better antitumor responses by increasing their homing to the tumor site. We studied our hypothesis in an immunotherapy model consisting of mesenchymal stromal cells (MSCs) carrying oncolytic adenoviruses for the treatment of immunocompetent mice. Toll-like receptor signaling-deficient cells (TLR4, TLR9, or MyD88 knockout) were used as "silent cells," while regular MSCs were used as control. Although in vitro migration was similar in regular and knockout carrier cells, in vivo tumor homing of silent cells was significantly higher after systemic administration. This better homing to the tumor site was highly related to the mild immune response triggered by these silent cells in peripheral blood. As a result, the use of silent cells significantly improved the antitumor efficacy of the treatment in comparison with the use of regular MSCs. While cancer immunotherapies generally aim to boost local immune responses in the tumor microenvironment, low systemic inflammation after systemic administration of the treatment may indeed enhance their tumor homing and improve the overall antitumor effect. These findings highlight the importance of selecting appropriate donor cells as therapeutic carriers in cell-based therapies for cancer treatment. Significance: Cells carrying drugs, virus, or other antitumor agents are commonly used for the treatment of cancer. This research shows that silent cells are excellent carriers for immunotherapies, improving tumor homing and enhancing the antitumor effect.

A Longitudinal Nationwide Study of Psychological Distress During the COVID-19 Pandemic in Chile.

Background: Despite numerous efforts to assess the impact of the COVID-19 pandemic on mental health, there are few longitudinal studies that examine the change in the burden of psychological distress over time and its associated factors, especially in developing countries. Objective: The primary aim of this study was to assess the levels of psychological distress at two time points during the COVID-19 outbreak based on a representative community sample in Chile. The secondary aim was to identify groups that are more vulnerable to psychological distress during the pandemic. Methods: A nationally representative, longitudinal telephone survey of Chilean adults was conducted. This study analyses panel data from two waves in 2020: May 30 to June 10 and September 15 to October 9. A total of 823 people participated in both surveys. Changes in mental health outcomes (anxiety and depressive symptoms) were assessed, estimating the effect of demographic characteristics, psychosocial and economic factors, household conditions, and health status. Results: There was a significant increase in psychological distress (PHQ-4 ≥ 6) between Waves 1 (22.6%) and 2 (27.0%), especially among younger participants. Overall, the results of this study show that being female, living in or near the capital, living in overcrowded households and having a perceived lack of space in the home, loneliness or perceived social isolation, and having received mental health treatment within the last year are significantly associated with psychological distress over time (p < 0.05). Conclusion: This study highlights the need to implement psychosocial programs to protect people's psychological well-being, as well as social policies to improve household living conditions and levels of social connectedness during the COVID-19 outbreak.

Suicide and quarantine during the COVID-19 pandemic: Do we know everything?

BACKGROUND: There is widespread concern over the impact of COVID-19 and lockdown measures on suicidal behaviour. We assessed their effects on suicide and hospitalization for attempted suicide during the initial phase of the pandemic in Chile. METHODS: We used panel data at the county and month level from January 1, 2016 to December 31, 2020 on suicides and related hospitalizations and a pandemic quarantine dataset. Poisson regression models and a difference-in-difference (DiD) methodology was used to estimate the impact of quarantine on both measures. FINDINGS: Suicide and hospitalizations for attempted suicide decreased (18% and 5.8%, respectively) during the COVID-19 outbreak in Chile (March-December 2020) compared to the same period in 2016-2019. The DiD analysis showed that there was at least a 13.2% reduction in suicides in quarantined counties relative to counties without such restrictions. This reduction was in male suicides and unaffected by age. There was no significant difference between quarantined and non-quarantined counties in terms of hospitalization for suicide attempts. CONCLUSIONS: This study shows a significant quarantine effect on reducing suicide during the initial phase of the COVID-19 pandemic in Chile. Changes in the number of hospitalizations for suicide attempts do not explain the differences between quarantined and non-quarantined counties.

Cellular Heterogeneity and Cooperativity in Glioma Persister Cells Under Temozolomide Treatment.

We have observed a drug-tolerant/persister state in a human glioblastoma (GBM) cell line after exposure to temozolomide, the standard-of-care chemotherapeutic agent for GBM. We used a multicolor lentiviral genetic barcode labeling to follow cell population evolution during temozolomide treatment. We observed no change in the distribution of the different colored populations of cells in persister or resistant cells suggesting that pre-existing minor subpopulations, which would be expected to be restricted to a single color, were not amplified/selected during the response to the drug. We have previously identified four genes (CHI3L1, FAT2, KLK5, and HB-EGF) that were over-expressed during the persister stage. Single-cell analysis of these four genes indicated that they were expressed in different individual cells ruling out the existence of a single persister-specific clone but suggesting rather a global answer. Even so, the transitory silencing of CHI3L1, FAT2, or KLK5 influenced the expression of the other three genes and the survival of U251 cells in absence of temozolomide. Since proteins encoded by the four genes are all localized in the extracellular matrix or interact within the extracellular compartment, we propose that cellular interactions and communications are important during the persister stage before the acquisition of chemo-resistance. Thus, persisters might be a new therapeutically relevant target in GBM.

One-Pot Thermal Synthesis of g-C3N4/ZnO Composites for the Degradation of 5-Fluoruracil Cytostatic Drug under UV-LED Irradiation.

Graphitic carbon nitride (g-C3N4) was used to enhance the photocatalytic activity of ZnO nanoparticles for the degradation of 5-fluorouracil (5-FU) cytostatic drug under UV-LED irradiation. CN/ZnO composites were synthetized by an easy one-pot thermal method, varying the g-C3N4 loading, i.e., from 10 to 67 wt% and a post-thermal exfoliation in air. The physicochemical and optical properties of the materials were analyzed by several techniques. CN/ZnO composites showed a coral-like structure of spherical ZnO wurtzite particles on the g-C3N4 structure. In general, the synergism and heterojunction interface between both phases allowed the enhancement of the mesoporosity, light absorption ability, and the aromaticity of the corresponding composites. Moreover, the photocatalytic activity of the CN/ZnO composites was increased with the addition of g-C3N4 in comparison with pristine ZnO. The highest activity was found for the composite containing 25 wt% of g-C3N4 (i.e., CN25/ZnO), reaching the total degradation of 5-FU and a mineralization of 48% at 180 min, as well as a good photostability during four reuse cycles. Experiments with different pH solutions and scavengers allowed for the assessment of the reactive oxygen species (ROS) involved in the 5-FU degradation pathway, with radicals and non-radical species as the main responsible active species. Furthermore, a tentative photocatalytic mechanism was proposed for CN/ZnO composites.

Psychological distress during the COVID-19 epidemic in Chile: The role of economic uncertainty.

Previous research has shown that the COVID-19 outbreak, social distancing, and lockdown can affect people's psychological well-being. The aims of this study were (1) to estimate the extent to which perceptions and expectations regarding the social, economic, and domestic effects of the COVID-19 outbreak are associated with psychological distress and (2) to identify some demographic, psychosocial, and economic factors associated with increased vulnerability to psychological distress during the COVID-19 outbreak in Chile. 1078 people participated in a telephone survey between May 30 and June 10, 2020. The sample is representative of the Chilean adult population. Psychological distress was assessed through a questionnaire of anxious and depressive symptoms (Patient Health Questionnaire-4). We analyzed the data set using ordinary least-squares regression models, first estimating models for the entire sample, and then stratifying the sample into different groups to explore differences by gender and age. 19.2% of participants displayed significant psychological distress (PHQ-4 ≥ 6), with moderate to severe anxiety-depression symptoms being more prevalent in women than in men (23.9% vs 14.1%, χ2 16.78, p<0.001). The results of this study suggest that being a woman, feeling lonely and isolated, living in the areas hit hardest by the pandemic and lockdown, expecting a lack of income due to having to stop working as a consequence of the pandemic, and having a history of diagnosed mental disorders are significantly associated with psychological distress (p<0.05). The results of this study highlight the need to implement psychosocial programs to guard people's psychological well-being and social policies to address economic uncertainty during the current COVID-19 outbreak in Chile.

Combination immunotherapy using G-CSF and oncolytic virotherapy reduces tumor growth in osteosarcoma.

BACKGROUND: Osteosarcoma is the most common malignant solid tumor that affects bones, however, survival rates of patients with relapsed osteosarcoma have not improved in the last 30 years. Oncolytic virotherapy, which uses viruses designed to selectively replicate in cancer cells, has emerged as a promising treatment for solid tumors. Our group uses mesenchymal stem cells (MSCs) to transport oncolytic adenoviruses (OAds) to the tumor site, a therapeutic strategy called Celyvir. This treatment has been already applied in human patients, canine patients and different mouse models. In parallel, previous results have probed that administration of granulocyte-colony stimulating factor (G-CSF) increased immune infiltration in tumors. We then hypothesized that the mobilization of immune cells by G-CSF may increase the antitumor efficacy of Celyvir treatment by increasing the immune infiltration into the tumors. METHODS: In this study, we use a murine version of Celyvir consisting in murine MSCs carrying the murine OAd dlE102-here called OAd-MSCs-in an immunocompetent model of osteosarcoma. We tested the antitumoral efficacy of the combination of OAd-MSCs plus G-CSF. RESULTS: Our results show that treatment with OAd-MSCs or the union of OAd-MSCs with G-CSF (Combination) significantly reduced tumor growth of osteosarcoma in vivo. Moreover, treated tumors presented higher tumor infiltration of immune cells-especially tumor-infiltrating lymphocytes-and reduced T cell exhaustion, which seems to be enhanced in tumors treated with the Combination. The comparison of our results to those obtained from a cohort of pediatric osteosarcoma patients showed that the virotherapy induces immunological changes similar to those observed in patients with good prognosis. CONCLUSIONS: The results open the possibility of using cellular virotherapy for the treatment of bone cancers. Indeed, its combination with G-CSF may be considered for the improvement of the therapy.

AKT and JUN are differentially activated in mesenchymal stem cells after infection with human and canine oncolytic adenoviruses.

There is increasing evidence about the use of oncolytic adenoviruses (Ads) as promising immunotherapy agents. We have previously demonstrated the clinical efficiency of mesenchymal stem cells (MSCs) infected with oncolytic Ads as an antitumoral immunotherapy (called Celyvir) in human and canine patients, using ICOVIR-5 or ICOCAV17 as human and canine oncolytic Ads, respectively. Considering the better clinical outcomes of canine patients, in this study we searched for differences in cellular responses of human and canine MSCs to Ad infection that may help understand the mechanisms leading to higher antitumor immune response. We found that infection of human and canine MSCs with ICOVIR-5 or ICOCAV17 did not activate the NF-κB pathway or the interferon regulatory factors IRF3 and IRF7. However, we observed differences in the profile of cytokines secretion, as infection of canine MSCs with ICOCAV17 resulted in lower secretion of several cytokines. Moreover, we showed that infection of human MSCs with ICOVIR-5 increased the phosphorylation of a number of proteins, including AKT and c-JUN. Finally, we demonstrated that differences in regulation of AKT and c-JUN in human and canine MSCs by ICOVIR-5 or ICOCAV17 are intrinsic to each virus. Our findings suggest that ICOCAV17 induces a more limited host response in canine MSCs, which may be related to a better clinical outcome. This result opens the possibility to develop new human oncolytic Ads with these specific properties. In addition, this improvement could be imitated by selecting specific human MSC on the basis of a limited host response after Ad infection.

Photocatalytic Perfomance of ZnO-Graphene Oxide Composites towards the Degradation of Vanillic Acid under Solar Radiation and Visible-LED.

Graphene oxide (GO) is used to enhance the photocatalytic activity of ZnO nanoparticles for the degradation of vanillic acid (VA) under simulated solar light and visible-LED (λ > 430 nm). ZnO-GO composites are prepared by a mixing and sonication process with different GO loadings (i.e., from 1.8 to 6.5 wt.%). The materials are extensively characterized by thermogravimetric analysis (TGA), physisorption of N2, X-ray diffraction (XRD), infrared spectroscopy (FTIR), scanning electron microscopy (SEM), point of zero charge (pHPZC), and UV-Vis diffuse reflectance spectroscopy (DRUV). The presence of GO increases the photocatalytic activity of all the prepared composites in comparison with the pristine ZnO. The highest photocatalytic activity is found for the composite containing 5.5 wt.% of GO (i.e., ZnO-GO5.5), reaching a VA degradation of 99% and 35% under solar light and visible-LED, respectively. Higher TOC removal/VA degradation ratios are obtained from the experiments carried out under visible-LED, indicating a more effective process for the mineralization of VA than those observed under simulated solar light. The influence of hole, radical, and non-radical scavengers is studied in order to assess the occurrence of the reactive oxygen species (ROS) involved in the photocatalytic mechanism. The study of the photo-stability during three reuse experiments indicates that the presence of GO in the composites reduces the photocorrosion in comparison with pristine ZnO.

Feasibility and Acceptability of "Cuida tu Ánimo" (Take Care of Your Mood): An Internet-Based Program for Prevention and Early Intervention of Adolescent Depression in Chile and Colombia.

The rapid internet penetration in Latin American countries has made it possible to implement digital mental health interventions. "Cuida tu Ánimo" (Take Care of Your Mood) is an internet-based program for the prevention and early intervention of depression in adolescents. A pilot study was conducted in Chile and Colombia to study the feasibility and acceptability of the program and estimate its effects. There were 199 participants (53.3% women; mean age = 14.8 years, SD = 1.0) recruited from two schools in Chile and two schools in Colombia. Qualitative and quantitative methods were applied for data collection and analyses. Although the levels of acceptance were moderate to high across all variables, adherence was lower than expected. The participants deemed important for an intervention of this type offered a higher level of interaction with team members through internet-based and face-to-face activities. Post-intervention outcomes show a reduction in depressive and anxious symptoms in adolescents in Chile, while there were no significant changes in the level of symptomatology in adolescents in Colombia. The women used the program more than the men. Results show the need to improve the intervention by increasing its levels of customization and developing strategies to achieve better adherence. The contradictory results of the program in Chile and Colombia suggest the importance of other variables beyond the content of the intervention, such as the setting or context of the intervention.

Acute responses of gastrointestinal hormones to both oral and parenteral intradialytic nutrition.

INTRODUCTION: Intradialytic nutrition (IDN) has been used to improve the nutritional status of malnourished hemodialysis (HD) patients. OBJECTIVE: To evaluate the different effects of parenteral IDN (IDPN) and oral IDN (IDON) on nutrition-related gastrointestinal hormones. PATIENTS AND METHODS: Seven clinically stable HD patients with malnutrition were included. All patients were treated for 1 month with either IDPN or IDON, with a 4-week period of no nutritional support between each type of therapy. On the first day of each nutritional support (IDON or IDPN) we analyzed the acute responses of insulin, ghrelin, and glucagon-like peptide 1 (GLP-1). We compared the areas under the secretory curves (AUC) and the maximum peaks of serum glucose, insulin, ghrelin, and GLP-1. A group of 6 clinically stable HD patients without any type of IDN served as the control group. RESULTS: The acute responses of glucose and insulin to IDN were significantly higher with IDPN than with IDON. The AUC of glucose (602 ± 81 vs. 495 ± 81 mg/dl/h, p < 0.01) and insulin (232 ± 103 vs. 73.8 ± 69 µU/ml/h, p < 0.01) as well as the maximum peaks of glucose (228 ± 41 vs. 177 ± 47 mg/dl, p < 0.05) and insulin (104 ± 46 vs. 29 ± 24 µU/ml, p < 0.01) were significantly higher after IDPN than after IDON. Ghrelin decreased after both IDPN and IDON; however, the decrease was significantly higher with IDPN compared to IDON. The ghrelin nadir was significantly lower in IDPN than in IDON (0.77 ± 0.5 vs. 1.5 ± 0.3, p < 0.05) although the AUC of ghrelin was not significantly different. GLP-1 was significantly increased at 1 h after starting both IDPN and IDON with no significant differences between the groups. CONCLUSION: IDPN induces a higher increase in serum glucose and insulin levels and a greater reduction in serum ghrelin concentrations compared with an equivalent orally administered nutritional supplement.

[Renal biopsy in patients aged 65 years or older: are there differences in the indication and histopathology compared to other patients?]. / La biopsia renal en pacientes de 65 o más años: ¿existen diferencias en la indicación y en la histopatología respecto al resto de pacientes?

BACKGROUND: Renal biopsy (RB) represents the gold standard for diagnosis of kidney diseases. In this paper we analyse whether the indication of RB and histopathology in patients 65 years or older is different from the other patients. MATERIAL AND METHODS: Retrospective study of 93 native renal biopsies performed in the General Hospital of Segovia in the period 2004-2008. The RB was performed percutaneously under ultrasound guidance in real time, using a 16G automatic needle. RESULTS: Mean age of biopsied patients was 56.89 ± 19 (range 14-89) , and 57% were males. A total of 39RB were performed on people aged 65 years or older. Overall, nephrotic syndrome (NS) is the most common indication of RB, and IgA glomerulonephritis the most common histology. In people ≥ 65 years, acute renal failure (ARF) is the most common indication for RB, and rapidly progressing (crescentic) glomerulonephritis/vasculitis the most detected the diagnosis. When taking age into account, no significant differences in the number of glomeruli obtained by RB or in the number of RB performed on the same patient. CONCLUSIONS: In people 65 years or older, ARF is the main indication of RB and crescentic glomerulonephritis/vasculitis the most frequent diagnosis.

[Estimation of glomerular filtration rate in persons aged 69 years or older: agreement between distinct calculation methods]. / Estimación del filtrado glomerular en personas de 69 años o más: concordancia entre diferentes métodos de cálculo.

MATERIAL: Estimation of glomerular filtration rate (eGFR) is the most widely accepted marker of renal function. Precise calculation is not routinely performed in clinical practice. Several methods have been developed for eGFR: creatinine clearance (CCr) calculation or the use of formulae derived from serum creatinine (sCr). The present study aimed to analyze the agreement between distinct methods of calculating eGFR. MATERIAL AND METHODS: We performed a cross-sectional study between January and April, 2006 in 32 stable elders, aged 69 years or older, evaluated in a general nephrology unit. eGFR was calculated by CCr (considered the gold standard), Cockcroft-Gault (CG) and Modification of Renal Diet in Disease (MDRD) equations. The Mann Whitney U-test, Spearman's correlation coefficient and the Kappa coefficient were used to compare means and determine the concordance between methods. RESULTS: The overall means+/-SD of GFRe for CCr were 36.14+/-16 ml/min (range 11.75-69.6); CG: 37.02+/-16 ml/min (range 13.3-72.3) and MDRD: 45.52+/-16 ml/min (range 19.2-75.36). Variations in eGFR on comparison of methods were CCr and MDRD: -9.37 ml/min (95% CI:-13.85, -4.9); CCr and CG:-2.54 ml/min (95% CI: -6.95, 1.80); MDRD and CG: 9.0 ml/min (95% CI: 5.96, 12). The correlation between the gold standard (CCr) and sCr-derived formulae was r=0.74 for MDRD (P<0.001) and r=0.77 for CG (P<0.001). The Kappa value for CCr and CG was 0.44 and was 0.35 for CCr and MDRD. When patients were classified by stage of chronic renal disease, discrepancies were found according to the method used: stage 5 (eGFR<15 ml/min) was diagnosed in 13.63% with CG while none were diagnosed with stage 5 with MDRD. CONCLUSIONS: In the estimation of the renal function in the elderly, eGFRe levels can differ in the same patient according to the method used: in view of the degree of concordance between CG and CCr, this mathematical formula should be used in preference to MDRD.