Universidad Camilo José Cela

Meattini I., Coles C.E., Tramm T., Borghesi S., Krug D., Montero A., Nardone V., Salvestrini V., Valzano M., Valentini V., Aristei C., Poortmans P., Arenas M., Boersma L.J., Bolukbasi Y., et. al.

ImportanceIntegration of molecular biomarker information into systemic therapy has become standard practice in breast cancer care. However, its implementation in guiding radiotherapy (RT) is slower. Although postoperative RT is recommended for most patients after breast-conserving surgery and, depending on risk factors, following mastectomy, emerging evidence has indicated that patients with low scores on gene expression signatures or selected clinical-pathological features may have very low local recurrence rates. This narrative review explored the potential of biomarker-directed personalized RT approaches, which may optimize treatment strategies and be associated with improved patient outcomes and experiences.ObservationsDistinctions between prognostic and predictive biomarkers were highlighted, emphasizing the importance of analytical and clinical validity in biomarker-based studies. Findings from studies investigating the prognostic and predictive value of various genomic signatures and immunohistochemical markers for guiding breast RT were presented. These included the Adjuvant Radiotherapy Intensification Classifier and the Profile for the Omission of Local Adjuvant Radiation, which have shown potential in predicting RT benefits. The genomic-adjusted radiation dose and role of tumor-infiltrating lymphocytes were also discussed. Ongoing clinical trials exploring the use of biomarkers in ductal carcinoma in situ and invasive breast cancer to refine RT decision-making were illustrated.Conclusions and RelevanceThe results of this narrative review suggest that evidence-based shared decision-making is crucial to optimize treatment according to the individual’s predicted benefits and risks along with their personal preferences. Incorporation of biomarker-directed approaches in RT for breast cancer may hold promise for personalized treatment, potentially facilitating omission of RT for patients at low risk of recurrence, while identifying those who may benefit from intensified therapy. This personalized RT approach may be associated with improved clinical outcomes and quality of life and facilitate decision-making for people with breast cancer. However, there remains a need for robust clinical and analytical validation of biomarkers to ensure reliability and clinical utility for RT optimization.

Peinado V., Shevlin M., Trucharte A., Contreras A., Valiente C.

García M.S., Peláez A., Punter R.M., López M.C., Carbajal C.M., Ancochea J., Bachiller J.M., Hernández A.S., Rodrigo-García M., Clemente M.G., Moreno R.M.

Abstract Background This study aimed to assess how Elexacaftor/Tezacaftor/Ivacaftor (ETI) influences lung function, Body Mass Index (BMI), Sweat Test (ST) and mental health of Cystic Fibrosis (CF) patients, emphasizing on depression and anxiety. Methods We conducted an observational, prospective, multicentre study including 108 patients over 18 years old who initiated ETI therapy between December 2019 and December 2023. Patients underwent regular evaluations, including clinical, functional, and microbiological assessments, alongside completion of quality of life, anxiety, and depression questionnaires. We evaluated whether there was a difference in anxiety and depression levels over time. Results After 12 months of treatment, significant improvements were noted in BMI, lung function (FEV1%), ST and various aspects of quality of life (CFQ-R). However, anxiety and depression levels did not differ significantly during the follow-up. When we stratified our sample by key groups, we observed that younger patients (under 28 years) and those with homozygous Phe508del mutations experienced significant higher anxiety with no differences on depression. Furthermore, anxiety and depression demonstrated a moderate correlation, strengthening over time. Conclusions Treatment with ETI establishes significant improvements in lung function, BMI, ST and quality of life in patients with CF. However, despite these positive outcomes, there were no significant changes observed in levels of anxiety and depression, except for individuals with homozygous mutation type and those younger than 28 years old, who exhibited significant higher levels of anxiety.

Martínez Avidad M.

In Spain, the gender gap in support for the far-right populist party VOX is notable, with two thirds of its voters being men. This article explores how VOX’s populist rhetoric around masculinity attracts male voters. It is argued that the collective identity promoted by the party aligns with hegemonic masculinity, which elevates male social status and serves as an effective strategy for capturing this electorate. To examine this dynamic, a critical discourse analysis was conducted on a sample of 34 videos from VOX’s YouTube channel. A deductive approach was employed, integrating categories that encompassed the masculine gender dimension and key concepts from the discursive approaches of populism. Overall, VOX discursively constructs a common identity around masculinity through populist rhetoric that combines victimization and recognition, which seems to have contributed to attracting male Spanish voters.

Peláez A., Jimeno S., Villarreal M., Gil M., Gutiérrez I., Sanz M., Martínez S.N.

Background/Objectives: Respiratory syncytial virus (RSV) represents a significant cause of acute respiratory infections (ARIs) in adults aged 60 years and older, often leading to severe clinical outcomes and high healthcare costs. This study aimed to evaluate the clinical and economic burden of RSV compared to other ARIs, focusing on specific age groups, comorbidities, and demographic factors. Methods: A retrospective observational study was conducted using the electronic medical records of adults aged ≥60 years hospitalized for ARIs, including RSV, in Spain. Direct costs related to hospitalizations, intensive care unit (ICU) admissions, and treatments were analyzed. The study also assessed demographic, clinical, and comorbidity-related factors influencing the economic burden. Results: RSV infections resulted in significantly higher direct costs compared to other ARIs, particularly in patients aged 70–80 years. Comorbidities such as asthma and smoking history were associated with increased costs in RSV cases. Although ICU costs were comparable between groups, hospitalizations for RSV required longer stays and more intensive treatments, amplifying the overall economic burden. Differences in costs by age and sex highlighted the need for tailored clinical management strategies. Conclusions: RSV poses a substantial economic and clinical burden on adults aged 60 years and older, particularly in those with comorbidities. Preventive measures, such as vaccination, could reduce healthcare costs and improve outcomes in this vulnerable population. These findings support the inclusion of RSV vaccines in immunization programs, especially in aging populations like Spain, to alleviate healthcare pressures during peak respiratory disease seasons.

Unzue L., Antón B.D., Laderas A.P., Polo L.M., Vázquez J.M., Rodrigo F.J., Jimenez F.J., Fernández‐Friera L., Mestre R.T., Fernández E.G.

ABSTRACTBackgroundCommissural misalignment (CMA) has demonstrated to difficult future coronary access in self‐expandable prosthesis and has been related with subclinical leaflet thrombosis and a potential increase in valve gradients and aortic regurgitation at follow‐up.AimsThe aim of our study was to assess the commissural alignment of the balloon expandable SAPIEN 3 valve (Edwards Lifesciences) and to evaluate its impact on transvalvular gradient and mortality at 5 years of follow‐up.MethodsConsecutive patients treated with SAPIEN 3 prosthesis guided with intraprocedural transesophageal echocardiogram (TEE) with a minimal follow‐up of 5 years were included. Commissural alignment between the prosthesis and the native valve was measured by TEE by two independent cardiologists using a standardized 3‐cusp view pre and post‐valve deployment. CMA was defined as a neocommissure deviation > 30° compared with native commissures. Echocardiographic gradients and clinical events were recorded during follow‐up and compared between groups.ResultsOne hundred and five patients (54% male, mean age 80.4 years) were included; 63 (40%) were classified as “aligned” (CMA < 30°) and 42 (60%) as “misaligned” (CMA > 30°). Patients with CMA > 30° presented smaller aortic annulus (23.8 vs. 20.7, p < 0.01) and received smaller valves. There was a slight increase of mean transvalvular gradient during follow‐up (9.2−10.3 mmHg, p < 0.05), without significant differences between groups. Mortality rate was 16.2% at 1 year and 49.5% at 5 years; and not related to commissural alignment.ConclusionsSignificant CMA is present in 40% of patients treated with SAPIEN 3 valves, however, we didn't find a significant association between CMA and gradient increase or mortality during long‐term follow‐up.

Serrano-Lobo J., Reigadas E., Muñoz P., Escribano P., Guinea J.

Abstract Gradient diffusion plastic strips are utilized for azole susceptibility testing against Aspergillus fumigatus in some clinical microbiology laboratories, however, they lack proper validation. We evaluated the performance of this method for detecting azole resistance in A. fumigatus sensu stricto and we assessed whether skipping filtration and inoculum adjustment of conidial suspensions negatively influenced its performance. A total of 98 A. fumigatus sensu stricto isolates, previously classified as azole-susceptible or resistant, were studied. Azole-resistant isolates had specific cyp51A gene mutations, including TR34-L98H ± S297T-F495I, G54R, TR46-Y121F-T289A, and G448S. Conidial suspensions were prepared following the principles of the E.Def 9.4 method or left unfiltered and unadjusted. Based on minimum inhibitory concentration (MIC) distributions obtained with the gradient diffusion plastic strip using both types of inoculum preparations, cut-off values were proposed to classify isolates as resistant: &gt;1 mg/L for itraconazole and voriconazole and &gt; 0.25 mg/L for posaconazole. These cut-offs coincided with EUCAST breakpoints and correctly classified all except one (TR46-Y121F-T289A) isolate. High essential agreement values (95.9%–98%) were obtained, regardless of inoculum preparation. Overall, sensitivity/specificity values of the gradient diffusion plastic strip using the proposed cut-off values for itraconazole (100%/98%), voriconazole (100%/100%), and posaconazole (100%/98%) to screen for azole resistance were not impacted by the inoculum preparation method. Thus, the gradient diffusion plastic strip is a reliable method for screening azole resistance in A. fumigatus isolates using the proposed MIC cut-offs and inoculum preparation without filtration and adjustment of conidial suspensions did not negatively influence the performance of the method.

Díaz Antón B., Lanza R.P., Virosta Gil E., Fernández Friera L.

Vena A., Tiseo G., Falcone M., Bartalucci C., Marelli C., Cesaretti M., Di Pilato V., Escribano P., Forniti A., Giacobbe D.R., Guinea J., Limongelli A., Lupetti A., Machado M., Mikulska M., et. al.

Abstract Background This study assesses the impact of fluconazole resistance on 30-day all-cause mortality and 1-year recurrence in patients with Candida parapsilosis bloodstream infections (BSI). Methods A multicenter retrospective study was performed at 3 hospitals in Italy and Spain between 2018 and 2022. Adult patients with positive blood cultures for C. parapsilosis who received appropriate targeted therapy with either echinocandins or fluconazole were included. Results Among 457 patients, 196 (42.9%) had fluconazole-resistant C. parapsilosis (FLZR-CP) BSI and 261 (57.1%) had fluconazole-susceptible C. parapsilosis (FLZS-CP) BSI. All FLZR-CP patients received targeted echinocandins, while FLZS-CP patients received either echinocandins (60.5%) or fluconazole (39.5%). Unadjusted 30-day all-cause mortality rates were 28.6% for FLZR-CP and 28.4% for FLZS-CP (log-rank test, P = .998). In multivariable analysis, increased mortality was associated with age (adjusted hazard ratio [aHR] 1.03 per year; 95% confidence interval [CI], 1.01–1.05; P = .0005), solid tumor (aHR 1.91; 95% CI, 1.06–3.46; P = .0302), previous antifungal treatment (aHR 1.84; 95% CI, 1.12–3.10; P = .0192), and septic shock (aHR 2.39; 95% CI, 1.42–4.06; P = .0010), but not fluconazole resistance (aHR 1.00; 95% CI, .62–1.63; P = .9864) nor the type of initial antifungal therapy (aHR 1.46; 95% CI, .69–3.06; P = .3202). Propensity score-matched analysis showed no 30-day all-cause mortality difference between echinocandin-treated FLZR-CP and fluconazole-treated FLZS-CP patients (HR 0.81; 95% CI, .37–1.75; P = .5915). However, a higher 1-year recurrence risk was observed in FLZR-CP patients (odds ratio, 7.37; 95% CI, 2.11–25.80; P = .0018). Conclusions Our results suggest that fluconazole resistance is not associated with a higher mortality risk in patients with C. parapsilosis BSI, though 1-year recurrence rates were higher in the FLZR-CP group.

García A.M., Arias Arias A.J., Muñoz F.L., García‐Rico E.

ABSTRACTIt would be highly valuable to possess a tool for evaluating disease progression and identifying patients at risk of experiencing a more severe clinical course and potentially worse outcomes. The concept of allostatic load, which represents the overall strain on the body from repeated stress responses, has been recognized as a precursor to the development of chronic illnesses. It functions as a cumulative measure of the body's capacity to adapt to stress. Numerous studies have demonstrated that elevated allostatic load levels are associated with various negative health outcomes, both physical and mental, and are more predictive of mortality than individual biomarkers. Leveraging the unique circumstances presented by the COVID‐19 pandemic, we evaluated different clinical and laboratory parameters in hospitalised COVID‐19 patients to assess allostatic load. Our results indicated that allostatic load acts as a strong predictor of prolonged hospitalisation, increased ICU days, and mortality. This highlights its efficacy as a precise gauge of biological dysregulation linked to the response to COVID‐19 during disease progression. Allostatic load is easily obtainable and provides an early, cost‐effective indication of disease prognosis. Additionally, it has the potential to forecast the necessity for ICU admission. As a result, this parameter, indicative of the comprehensive physiological disruption in response to stress, emerges as a promising prognostic marker for hospitalised patients, extending beyond COVID‐19.

Álvarez-Gallego R., Pazo-Cid R., López de San Vicente B., Macarulla T., Martinez E., Garicano F., Hernández I., Granja M., Ghanem I., Martinez J., Ribera P., Diaz R., Martin Valadés J.I., Angeles M.C., Cubillo A.

Treatment with pegylated nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (folinic acid; 5-FU/LV) has demonstrated remarkable efficacy for metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical trials. However, real-world data on the effectiveness of nal-IRI+5-FU/LV is heterogeneous and is lacking in Spain. To assess the effectiveness and safety of nal-IRI+5-FU/LV in real-life PDAC patients in Spain. A multicenter retrospective study was conducted. Patients aged ⩾18 years who had received at least one cycle of nal-IRI+5-FU/LV as second- or third-line therapy for PDAC were included. The primary endpoint was overall survival (OS) from nal-IRI+5-FU/LV treatment initiation and OS from the diagnosis of metastatic disease (metOS). Overall, 200 evaluable patients were included (⩾3 metastatic sites: 22%; liver/lung metastases: 71.5%/36.9%; and Eastern Cooperative Oncology Group 0–1: 87% at nal-IRI+5FU/LV treatment initiation). Patients received a median of four cycles of nal-IRI+5FU/LV for 2.8 months (range 1.4–7.2), and the treatment was received in the second line by 80% of the patients. The median OS was 7.2 months (6- and 12-month OS rates: 58.1% and 28.9%, respectively), with 27.2% of the patients achieving OS ⩾12 months. The median metOS was 17.5 months, with 30.2% of the patients experiencing metOS ⩾ 24 months. The median progression-free survival (PFS) was 3.7 months (6- and 12-month PFS rate: 37.6% and 15.3%, respectively). The disease control rate was 35.5%. The median CA 19-9 levels decreased by at least 50% in 28.2% of the cases during treatment. Overall, 36% of the patients experienced at least one grade 3–4 adverse event during treatment, the most common being diarrhea (42.6%) and asthenia (30.9%). This real-world study shows that treatment with nal-IRI+5-FU/LV for advanced or metastatic PDAC affords benefit in terms of survival, radiological and CA 19-9 response, and PFS comparable to that reported in the clinical trial setting with a manageable safety profile.

Giuliano F., Soriano M.A., Pino-Mulero V., González-García J.

This study aimed to examine the intra- and inter-session reliability of kinetic variables in the isometric mid-thigh pull (IMTP) and isometric belt squat test (IBSqT) in strength-trained individuals. Fifteen men (26.9 ± 8.9 years; 1.78 ± 0.05 m; 86.9 ± 10.5 kg) and six women (23.8 ± 4.6 years; 1.66 ± 0.06 m; 65.8 ± 10.3 kg), experienced in strength training, completed a familiarization session followed by two experimental sessions. The peak force (PF) and relative peak force to body weight (RPF), were collected for both isometric tests. Additionally, force (F), impulse (I), and rate of force development (RFD) were analyzed across different time windows (50, 100, 150, 200, and 250 ms). The intraclass correlation coefficient (ICC), coefficient of variation (CV), standard error of measurement (SEM), smallest worthwhile change (SWC) and Bland-Altman plots were calculated and displayed. Intra-session reliability was excellent for PF and RPF (ICC ≥ 0.98, CV ≤ 10%) in both IMTP and IBSqT. However, RFD and IMP displayed higher variability (CV > 10%), with low to good reliability depending on time frames. Inter-session reliability was excellent for PF and RPF (ICC ≥ 0.96, CV ≤ 5.3%) in both tests. Force at various time points exhibited moderate to excellent reliability (ICC = 0.70–0.90). PF and RPF demonstrated the highest sensitivity to performance changes, with SWC0.2 values exceeding SEM. In contrast, RFD and impulse showed larger variabilities. These findings indicate that PF and RPF are the most reliable and sensitive metrics for monitoring performance. Coaches and practitioners can use IMTP and IBSqT to detect meaningful changes in maximal isometric force production.

La Touche R., García-Pastor T., Reina-Varona Á., Paris-Alemany A., Grande-Alonso M.

Previous research has focused on the possibility of cervical dysfunction in migraine patients, similar to what is observed in patients with tension-type headaches. However, there is no evidence concerning the physical function of other body regions, even though lower levels of physical activity have been reported among migraine patients. The aim of this study was to compare cervical and extra-cervical range of motion, muscular strength, and endurance, as well as overall levels of physical activity, between patients with chronic migraine (CM) and asymptomatic participants. The secondary objective included the analysis of associations between CM-related disability and various physical and psychological variables. A total of 90 participants were included in this cross-sectional study: 30 asymptomatic participants (AG) and 60 patients with CM. Cervical and lumbar range of motion, strength and endurance, as well as handgrip strength were measured. Headache-related disability, kinesiophobia, pain behaviors, physical activity level and headache frequency were assessed through a self-report. Lower values were found in CM vs AG for cervical and lumbar ranges of motion (p < 0.05; effect sizes ranging from 0.57 to 1.44). Also, for neck extension strength (p = 0.013; d = − 0.66), lumbar strength (p < 0.001; d = − 1.91) and handgrip strength (p < 0.001; d = − 0.98), neck endurance (p < 0.001; d = − 1.81) and lumbar endurance (p < 0.001; d = − 2.11). Significant differences were found for physical activity levels (p = 0.01; d = − 0.85) and kinesiophobia (p < 0.001; d = − 0.93) between CM and AG. Headache-related disability was strongly associated with headache frequency, activity avoidance, and rest, which together explained 41% of the variance. The main findings of this study suggest that patients with CM have a generalized fitness deficit and not specifically cervical dysfunction. These findings support the hypothesis that migraine patients have not only neck-related issues but also general body conditions.

García-Pastor T., Muñoz-Puente I., Pérez-Pelayo M., Púa I., Roberts J.D., Del Coso J.

Background/Objectives: Previous studies suggest that there is a genetically determined component of fat oxidation at rest and during exercise. To date, the FTO gene has been proposed as a candidate gene to affect fat oxidation during exercise because of the association of the “at-risk” A allele with different obesity-related factors such as increased body fat, higher appetite and elevated insulin and triglyceride levels. The A allele of the FTO gene may also be linked to obesity through a reduced capacity for fat oxidation during exercise, a topic that remains largely underexplored in the current literature. The aim of this study was to analyze the association between the FTO rs9939609 polymorphism with the rate of fat oxidation during exercise and metabolic syndrome criteria in healthy participants. Methods: A total of 80 healthy participants (41 men and 39 women) underwent comprehensive assessments, including measurements of anthropometric variables, blood pressure and blood measures of fasting glucose, triglycerides, low- and high-density lipoprotein cholesterol (LDL-c and HDL-c), insulin, interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations. Additionally, the Homeostatic Model Assessment (HOMA-IR) was used to evaluate insulin resistance. Peak oxygen uptake (VO2peak) and maximal fat oxidation rate (MFO) were also measured during an incremental cycling test. FTO rs9939609 genotyping (TT, AT, AA) was performed using genomic DNA samples obtained from a buccal swab and measured with PCR. Results: There were 32 participants (40.0%) with the TT genotype; 31 (38.8%) with the AT genotype; and 17 (21.2%) with the AA genotype. Age, body characteristics, VO2peak, blood pressure and blood variables were similar across all three genotypes. However, serum insulin concentration and HOMA-IR were associated with the FTO rs9939609 genotype with higher values in AA with respect to AT and TT participants (p < 0.050). Still, MFO was similar in TT, AT and AA participants (0.35 ± 0.13, 0.37 ± 0.11, 0.33 ± 0.11 g/min, p = 0.702). In the dominant model, there was no statistical difference between TT and A allele carriers. However, the recessive model revealed that AA participants had higher values of body mass, body mass index, blood insulin concentration and HOMA-IR than T allele carriers (p < 0.050), with no differences in MFO. Conclusions: In our sample of healthy individuals, the FTO rs9939609 polymorphism was associated with several phenotypes associated with obesity and insulin resistance, particularly under the AA vs. T allele/recessive model. However, the FTO rs9939609 polymorphism was not associated with MFO during exercise as fat oxidation was similar across genotypes. This suggests that reduced fat oxidation during exercise is unlikely to be a cause of the obesogenic influence of the FTO AA genotype. Clinically, these findings suggest that the obesogenic effects of the FTO AA genotype are unlikely driven by impaired fat oxidation during exercise. Instead, attention should focus on mechanisms like appetite regulation and energy intake. Moreover, exercise interventions may still effectively mitigate obesity risk, as AA individuals retain normal fat oxidation capacity during exercise.

Ladriñán-Maestro A., Sánchez-Infante J., Martín-Vera D., Sánchez-Sierra A.

The fatigue of the inspiratory musculature, particularly the diaphragm, has been demonstrated to exert systemic effects on the body, impacting cardiovascular and performance outcomes. This study aimed to evaluate the influence of an inspiratory muscle fatigue protocol on respiratory muscle strength, functionality, and muscle oxygen saturation in older adults. A single-blinded randomized controlled clinical trial was conducted on twenty-four older adults aged over 60 years, who met inclusion criteria were physically independent in terms of gait and functionality. Participants were randomly assigned to one of three groups: control group, inspiratory muscle fatigue group, or activation group. Diaphragmatic ultrasonography (diaphragmatic thickness, thickening fraction, diaphragm movement curve), maximal inspiratory mouth pressure, muscle oxygen saturation, and functionality (timed up and go test, for five times sit to stand test) were used to measure the study variables at two time points: pre-intervention (T1) and post-intervention (T2). In the maximum inspiratory pressure variable in the activation group an increase was found between baseline and post-treatment of 3.00 ± 0.93 cmH2O (P < 0.01), while in the inspiratory muscle fatigue a decrease of -6.75 ± 2.66 cmH2O (P < 0.01) was found. In addition, the inspiratory muscle fatigue group showed lower scores for respiratory and functional variables after performing the diaphragmatic fatigue intervention than the activation and control group (P < 0.05), on the other hand, the activation group showed more positive values for functional and respiratory capacity variables after performing the inspiratory muscle activation training (P < 0.05). Fatigue of the inspiratory musculature appears to negatively impact inspiratory muscle strength, peripheral muscle strength, muscular oxygenation, and functionality in older adults. Activation of the inspiratory musculature could contribute to improved respiratory muscle strength and function in these individuals. ClinicalTrials.gov ID: NCT06266013.