Resultados de investigación

Therapies targeting the programmed cell death 1 (PD-1) receptor or its ligand (PD-L1), such as the humanized monoclonal antibody durvalumab, have shown durable clinical responses in several tumor types. However, concerns about the safety and feasibility of PD-1/PD-L1 blockade in HIV-1-infected individuals have led to the exclusion of these patients from clinical trials on cancer immunotherapies. To evaluate the feasibility and safety of durvalumab treatment in patients with advanced cancer and virologically controlled HIV-1 infection. The DURVAST study was a nonrandomized, open-label, phase 2 clinical trial in patients with any solid tumor type in which anti-PD-1 or anti-PD-L1 antibodies have approved indications or for which there are data of antitumoral activity with no other available curative therapy. All patients had basal undetectable plasma viremia while undergoing combination antiretroviral therapy. Treatment consisted of intravenous infusion of durvalumab (1500 mg every 4 weeks) until disease progression or unacceptable toxic effects. Adverse events were graded with the use of the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1. A total of 20 HIV-1-infected patients with advanced cancer were enrolled; 16 (80%) were male, the median (range) age was 54 (30-73) years, and 12 (60%) had progressed with previous cancer treatment lines. A median (range) of 4 (1-16) cycles of durvalumab were administered. Drug-related adverse events were observed in 50% of patients, and all were grade 1 and 2 (mainly diarrhea, asthenia, and arthromyalgia). Four of 16 response-evaluable patients (25%) had a partial response. Five patients (31%) had stable disease, including 4 with durable stable disease (disease control rate of 50%). CD4+ and CD8+ T-cell counts and plasma HIV-1 viremia remained stable throughout the study. Durvalumab treatment was feasible and safe in HIV-1-infected patients with cancer receiving combination antiretroviral therapy. HIV-1-infected patients on suppressive antiretroviral therapy with advanced cancer should have access to cancer immunotherapy treatments. ClinicalTrials.gov Identifier: NCT03094286., Si

Alcoholic fermentation of fruits has generated novel products with high concentrations of bioactive compounds and moderate alcohol content. The aim of this study was to evaluate the potential effect on cardiovascular risk factors of the regular consumption by healthy humans of a beverage obtained by alcoholic fermentation and pasteurization of orange juice. Thirty healthy volunteers were enrolled in a randomized controlled study. The experimental group (n = 15) drank 500 mL orange beverage (OB) per day for 2 weeks (intervention phase), followed by a 3-week washout phase. Blood samples were collected at baseline (E-T0) and at the end of the intervention (E-T1) and washout (E-T2) phases. Controls (n = 15) did not consume OB during a 2-week period. OB intake significantly increased oxygen radical absorbance capacity (43.9%) and reduced uric acid (-8.9%), catalase (CAT) (-23.2%), thiobarbituric acid reactive substances (TBARS) (-30.2%) and C-reactive protein (-2.1%) (E-T1 vs. E-T0). These effects may represent longer-term benefits, given the decreased uric acid (-8.9%), CAT (-34.6%), TBARS (-48.4%) and oxidized low-density lipoprotein (-23.9%) values recorded after the washout phase (E-T2 vs. E-T0). The regular consumption of OB improved antioxidant status and decreased inflammation state, lipid peroxidation and uric acid levels. Thus OB may protect the cardiovascular system in healthy humans and be considered a novel functional beverage., Si

Background: Extra virgin olive oil (EVOO) has shown beneficial effects on the lipid profile and inflammatory parameters in general population. Our goal is to analyze these changes together with those of intestinal microbiota in human immunodeficiency virus (HIV)-infected patients over 50 years of age. Methods: Experimental single arm open study. HIV patients over the age of 50 with undetectable viral load were selected. EVOO was distributed among the patients so that each one consumed 50 g daily for 12 weeks. Lipid profile, C-reactive protein (CRP), and intestinal microbiota composition were analyzed at the beginning and at the end of the intervention. Results: Total cholesterol decreased significantly (5 mg/dL), and a nonsignificant decrease in low-density lipoprotein cholesterol (12 mg/dL), triglycerides (21 mg/dL), and CRP (1.25 mg/dL) was observed. There was a significant increase in alpha diversity after the intervention in men and a decrease in proinflammatory genera such as Dethiosulfovibrionaceae was observed. Differences were also observed in the microbiota of men and women and according to the type of antiretroviral treatment. Conclusion: Sustained consumption of 50 g of EVOO in elderly HIV-infected patients might be associated with an improvement in lipid profile and alfa diversity of intestinal microbiota., The authors thank the patients who collaborated in the development of this project and to the olive company Bravoliva S.L., who selflessly donated the extra virgin olive oil necessary for the project. The authors thank the Grants from Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER (RD16/0025/0040; http://www.isciii.es/isciii/es/contenidos/fd-investigacion/fd-ejecucion/fd-centros-participados/centros-participados-redesretics.shtml) and Fondo de Investigación Sanitaria (PI 18/00819) for the financial support. And the authors also thank Josefa López-Bueno for assistance in the analysis of the microbiota by next generation sequencing., Si

Background: Low-cardiac output syndrome (LCOS) after cardiac surgery secondary to systemic hypoperfusion is associated with a higher incidence of renal and neurological damage. A range of effective therapies are available for LCOS. The beneficial systemic effects of levosimendan persist even after cardiac output is restored, which suggests an independent cardioprotective effect. Methods: A double-blind clinical trial was conducted in patients with a confirmed diagnosis of LCOS randomized into two treatment groups (levosimendan vs. dobutamine). Monitoring of hemodynamic (cardiac index, systolic volume index, heart rate, mean arterial pressure, central venous pressure, central venous saturation); biochemical (e.g. creatinine, S100B protein, NT-proBNP, troponin I); and renal parameters was performed using acute kidney injury scale (AKI scale) and renal and brain ultrasound measurements [vascular resistance index (VRI)] at diagnosis and during the first 48 h. Results: Significant differences were observed between groups in terms of cardiac index, systolic volume index, NT-proBNP, and kidney injury stage at diagnosis. In the levosimendan group, there were significant variations in AKI stage after 24 and 48 h. No significant differences were observed in the other parameters studied. Conclusion: Levosimendan showed a beneficial effect on renal function in LCOS patients after cardiac surgery that was independent from cardiac output and vascular tone. This effect is probably achieved by pharmacological postconditioning., LG is supported by the Miguel Servet program from the ISCIII (Spain) (“Miguel Servet II” program, CPII18/00030) and Nicolas Monardes program from the Consejería de Salud de Andalucía (Spain) (C-0028-2018). CS is supported by a grant from the ISCIII (Spain) (“PFIS” program, FI16/00241). CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) is an ISCIII project (Spain)., Sí

The aim of this clinical trial (ID Number NCT01803347) was to determine the safety and efficacy of autologous adipose-derived stem cells (ASCs) for treatment of cryptoglandular fistula. This research was conducted following an analysis of the mistakes of a same previous phase III clinical trial. We designed a multicenter, randomized, single-blind clinical trial, recruiting 57 patients. Forty-four patients were categorized as belonging to the intent-to-treat group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue (group A) and 21 received intralesional fibrin glue (group B), both after a deeper curettage of tracks and closure of internal openings. Fistula healing was defined as complete re-epithelialization of external openings. Those patients in whom the fistula had not healed after 16 weeks were eligible for retreatment. Patients were evaluated at 1, 4, 16, 36, and 52 weeks and 2 years after treatment. Results were assessed by an evaluator blinded to the type of treatment. After 16 weeks, the healing rate was 30.4% in group A and 42.8% in group B, rising to 55.0% and 63.1%, respectively, at 52 weeks. At the end of the study (2 years after treatment), the healing rate remained at 50.0% in group A and had reduced to 26.3% in group B. The safety of the cellular treatment was confirmed and no impact on fecal continence was detected. The main conclusion was that autologous ASCs for the treatment of cryptoglandular perianal fistula is safe and can favor long-term and sustained fistula healing., Si

Obesity hypoventilation syndrome (OHS) is treated with either non-invasive ventilation (NIV) or CPAP, but there are no long-term cost-effectiveness studies comparing the two treatment modalities. We performed a large, multicentre, randomised, open-label controlled study to determine the comparative long-term cost and effectiveness of NIV versus CPAP in patients with OHS with severe obstructive sleep apnoea (OSA) using hospitalisation days as the primary outcome measure. Hospital resource utilisation and within trial costs were evaluated against the difference in effectiveness based on the primary outcome (hospitalisation days/year, transformed and non-transformed in monetary term). Costs and effectiveness were estimated from a log-normal distribution using a Bayesian approach. A secondary analysis by adherence subgroups was performed. In total, 363 patients were selected, 215 were randomised and 202 were available for the analysis. The median (IQR) follow-up was 3.01 (2.91-3.14) years for NIV group and 3.00 (2.92-3.17) years for CPAP. The mean (SD) Bayesian estimated hospital days was 2.13 (0.73) for CPAP and 1.89 (0.78) for NIV. The mean (SD) Bayesian estimated cost per patient/year in the NIV arm, excluding hospitalisation costs, was €2075.98 (91.6), which was higher than the cost in the CPAP arm of €1219.06 (52.3); mean difference €857.6 (105.5). CPAP was more cost-effective than NIV (99.5% probability) because longer hospital stay in the CPAP arm was compensated for by its lower costs. Similar findings were observed in the high and low adherence subgroups. CPAP is more cost-effective than NIV; therefore, CPAP should be the preferred treatment for patients with OHS with severe OSA., Si

Surrogate endpoints that predict complications are necessary for assessment and approval of NASH therapies. We assessed associations between histologic and noninvasive tests (NITs) of fibrosis with liver-related complications in patients with NASH cirrhosis. Patients with compensated cirrhosis due to NASH were enrolled in two placebo-controlled trials of simtuzumab and selonsertib. Liver fibrosis at baseline and week 48 (W48) was staged by NASH Clinical Research Network (CRN) and Ishak classifications and a machine learning (ML) approach, hepatic collagen and alpha-smooth muscle actin (α-SMA) expression were quantified by morphometry, liver stiffness (LS) was measured by transient elastography, and serum NITs (enhanced liver fibrosis [ELF], NAFLD fibrosis score [NFS], and Fibrosis-4 index [FIB-4]) were calculated. Cox regression determined associations between these parameters at baseline and their changes over time with adjudicated liver-related clinical events. Among 1,135 patients, 709 (62%) had Ishak stage 6 fibrosis, and median ELF and LS were 10.66 and 21.1 kPa, respectively. During a median follow-up of 16.6 months, 71 (6.3%) had a liver-related event; associated baseline factors included Ishak stage 6 fibrosis, and higher hepatic collagen, α-SMA expression, ML-based fibrosis parameters, LS, ELF, NFS, and FIB-4. Cirrhosis regression observed in 16% (176/1,135) between BL and W48 was associated with a lower risk of events versus nonregression (1.1% [2/176] vs. 7.2% [69/957]; HR, 0.16; 95% CI, 0.04, 0.65 [p = 0.0104]). Conversely, after adjustment for baseline values, increases in hepatic collagen, α-SMA, ML-based fibrosis parameters, NFS, and LS were associated with an increased risk of events. In patients with compensated cirrhosis due to NASH, regression of fibrosis is associated with a reduction in liver-related complications. These data support the utility of histologic fibrosis regression and NITs as clinical trial endpoints for NASH cirrhosis., Si

Background. Snow reflectivity and altitude increase the exposure of ski resort workers to solar ultraviolet radiation. The aim was to assess the presence of skin cancer in ski resorts workers and compare it with other groups of outdoor workers reviewing published studies. Methods. An observational cross-sectional prospective study was conducted in the three largest ski resorts in Spain: Baqueira Beret, Lleida; Formigal, Huesca and Sierra Nevada, Granada. All outdoor workers including ski instructors were invited to participate in the study. The participants completed a validated questionnaire about sun exposure and underwent a skin examination. Results. 219 workers were included in the study (80% male; mean age 43.8 (SD 11.31) years). Actinic keratosis (AK) but no other skin cancers were detected in 32 participants (14.62%). Those with AK worked in the Southernmost ski resort, were more likely to have light colour hair, and were older and with higher photoaging grade than those without them. Conclusion. Compared to other studies, outdoor workers on ski resorts show a higher prevalence of AK than general population but a lower prevalence than other groups of outdoor workers., This work was supported by the B18_17D Dermatology and Photobiology research group, as recognized by the Government of Aragon (Spain) and by the Medical School of Granada University (Granada, Spain). The authors would like to thank all the participants in the study and also the directors of the ski resorts for their collaboration., Sí

Objectives: The use of intraosseous (IO) access is recommended in cardiac arrest when peripheral venous access is not accessible. Various methodologies exist that are used for teaching and learning about cannulation of the IO route both in education and in research. The purpose of the present study was to compare self-efficacy in the cannulation technique for IO access through different techniques. Methods: A randomized comparative study was conducted. A total of 118 nursing students participated. The participants were randomly distributed into 2 intervention groups: chicken bone and egg. A checklist was used for data collection to evaluate the IO cannulation technique in nursing students and another to analyze self-efficacy. Results: The average total score of self-efficacy for all participants was 8.84 (standard deviation (SD) = 0.98). No statistically significant differences were found when comparing the total self-efficacy score and the intervention group ( U = 1604.500; z = -0.733; P = 0.463). No statistically significant differences were found between both groups for the average total score of the procedure ( U = 6916.500; z = -0.939; P = 0.348). The egg group carried out the IO cannulation procedure in a significantly less amount of time (M = 126.88, SD = 82.18) than the chicken bone group (M = 183.77, SD = 108.28), finding statistically significant differences ( U = 4983.500; z = -5.326; P < 0.001). Conclusions: Using an egg to teach and learn about IO access could be considered a methodology that is equally effective as using a chicken bone, with the advantage of achieving IO access in a lesser amount of time., Yes

Biomarkers of cardiac damages, such as troponin T (TnT) and the amino-terminal fragment of brain natriuretic peptide (NT-proBNP), may be useful as early predictors of cardiac dysfunction. The role of these biomarkers in patients receiving lapatinib and/or trastuzumab before anthracyclines is unknown. This study explores TnT and NT-proBNP as predictors of early cardiac toxicity in neoadjuvant breast cancer patients. This sub-study of the NEOALTTO trial tested if changes in the levels of TnT and NT-proBNP occurred after 2 weeks of anti-HER2 therapy (lapatinib, trastuzumab or their combination) alone and/or after 18 weeks of anti-HER2 therapy plus weekly paclitaxel. 173 and 172 were tested at all three timepoints for NT-proBNP and TnT, respectively. The incidence of biomarker elevation was overall low at all timepoints for all the three treatment arms. A total of 13 CEs in 11 patients occurred. Biomarker elevations in patients with CEs were very rare; only one patient with subsequent CE had a NT-proBNP elevation at baseline and at week 2. These results suggest that TnT and proBNP may not be useful as early predictors of cardiac toxicity in anthracycline-naïve patients receiving trastuzumab and/or lapatinib., Si