IR-Sant Pau - Sant Pau Institute of Biomedical Research

Introduction: Dexketoprofen/tramadol 25/75 mg (DKP/TRAM) is a fixed-dose combination of a cyclooxygenase inhibitor and opioid receptor agonist. To better understand the efficacy and safety of DKP/TRAM in the treatment of moderate to severe acute lower back pain (LBP) with or without radiculopathy, we carried out a large explorative phase IV international, multicenter, prospective, randomized, double-blind, parallel group, placebo-controlled study (DANTE). Methods: A total of 538 patients with or without a history of LBP and experiencing acute LPB of moderate to severe intensity [Numerical Rating Scale-Pain Intensity (NRS-PI) score > 5] were randomized 4:4:1:1 to DKP/TRAM 25/75 mg every 8 h (n = 211), tramadol (TRAM) 100 mg (n = 207), placebo-matched DKP/TRAM (n = 59), or placebo-matched TRAM (n = 61). Results: The proportion of patients achieving the primary endpoint, defined as the time to first achieve NRS-PI score < 4 or pain intensity reduction ≥ 30% from drug intake up to 8 h after the first dose, was higher in the DKP/TRAM arm than in the placebo group, but the difference was not statistically significant (46.1% vs. 42.6%, respectively; hazard ratio 1.11; 95% confidence interval 0.775, 1.595; p = 0.566). DKP/ TRAM achieved superiority over TRAM in total pain relief at 4, 6, and 8 h (p < 0.05). Conversely, in relation to the secondary endpoints, a significantly greater reduction in NRS-PI score was seen with DKP/TRAM versus placebo starting from 1 h, and this reduction remained numerically lower throughout 8 h. Summed pain intensity difference values were also significantly lower at 4, 6, and 8 h with DKP/TRAM compared to TRAM (p < 0.05). Overall, DKP/TRAM was well tolerated. Conclusion: Although the primary endpoint was not met, secondary efficacy analyses suggest the superiority of DKP/TRAM over placebo and TRAM alone in terms of total pain relief. DKP/TRAM can be considered to be an effective and safe option for the treatment of moderate to severe acute LBP.

Purpose To compare three methods for identifying patient preferences (MIPPs) at the point of decision-making: analysis of video-recorded patient-clinician encounters, post-encounter interviews, and post-encounter surveys. Patients and Methods For the decision of whether to use a spinal cord stimulator device (SCS), a video coding scheme, interview guide, and patient survey were iteratively developed with 30 SCS decision-making encounters in a tertiary academic medical center pain clinic. Burke’s grammar of motives was used to classify the attributed source or justification for a potential preference for each preference block. To compare the MIPPs, 13 patients’ encounters with their clinician were video recorded and subsequently analyzed by 4 coders using the final video coding scheme. Six of these patients were interviewed, and 7 surveyed, immediately following their encounters. Results For videos, an average of 66 (range 33–106) sets of utterances potentially indicating a patient preference (a preference block), surveys 33 (range 32–34), and interviews 25 (range 18–30) were identified. Thirty-eight unique themes (75 subthemes), each a preference topic, were identified from videos, surveys 19 themes (12 subthemes), and interviews 39 themes (54 subthemes). The proportion of preference blocks that were judged as expressing a preference that was clearly important to the patient or affected their decision was highest for interviews (72.8%), surveys (68.0%), and videos (27.0%). Videos mostly attributed preferences to the patient’s situation (scene) (65%); interviews, the act of receiving or living with SCS (43%); surveys, the purpose of SCS (40%). Conclusion MIPPs vary in the type of preferences identified and the clarity of expressed preferences in their data sets. The choice of which MIPP to use depends on projects’ goals and resources, recognizing that the choice of MIPP may affect which preferences are found.

Background Mosaic Down syndrome is a triplication of chromosome 21 in some but not all cells. Little is known about the epidemiology of mosaic Down syndrome. We described prevalence of mosaic Down syndrome and the co‐occurrence of common chronic conditions in 94,533 Medicaid enrolled adults with any Down syndrome enrolled from 2016 to 2019. Methods We identified mosaic Down syndrome using the International Classification of Diseases and Related Health Problems, tenth edition code for mosaic Down syndrome and compared to those with nonmosaic Down syndrome codes. We identified chronic conditions using established algorithms and compared prevalence by mosaicism. Results In total, 1966 (2.08%) had claims for mosaic Down syndrome. Mosaicism did not differ by sex or race/ethnicity with similar age distributions. Individuals with mosaicism were more likely to present with autism (13.9% vs. 9.6%) and attention deficit hyperactivity disorder (17.7% vs. 14.0%) compared to individuals without mosaicism. In total, 22.3% of those with mosaic Down syndrome and 21.5% of those without mosaicism had claims for Alzheimer's dementia (Prevalence difference: 0.8; 95% Confidence interval: −1.0, 2.8). The mosaic group had 1.19 times the hazard of Alzheimer's dementia compared to the nonmosaic group (95% CI: 1.0, 1.3). Discussion Mosaicism may be associated with a higher susceptibility to certain neurodevelopmental and neurodegenerative conditions, including Alzheimer's dementia. Our findings challenge previous assumptions about its protective effects in Down syndrome. Further research is necessary to explore these associations in greater depth.

Thiopurines, an effective therapy for Crohn’s disease (CD), often lead to adverse events (AEs). Gene polymorphisms affecting thiopurine metabolism may predict AEs. This retrospective study in CD patients (n = 114) with TPMT activity > 5 Units/Red Blood Cells analyzed TPMT (c.238 G > C, c.460 G > A, c.719 A > G), ITPA (c.94 C > A, IVS2 + 21 A > C), and NUDT15 (c.415 C > T) polymorphisms. All patients received azathioprine (median dose 2.2 mg/kg) with 41.2% experiencing AEs, mainly myelotoxicity (28.1%). No NUDT15 polymorphisms were found, 7% had TPMT, and 31.6% had ITPA polymorphisms. AEs led to therapy modifications in 41.2% of patients. Multivariate analysis identified advanced age (OR 1.046, p = 0.007) and ITPA IVS2 + 21 A > C (OR 3.622, p = 0.015) as independent predictors of AEs. IVS2 + 21 A > C was also associated with myelotoxicity (OR 2.863, p = 0.021). These findings suggest that ITPA IVS2 + 21 A > C polymorphism and advanced age predict AEs during thiopurine therapy for CD with intermediate-normal TPMT activity.

INTRODUCTION Children are vulnerable to secondhand smoke (SHS) exposure, especially those with lower socioeconomic status. This study assesses the changes in prevalence and socioeconomic inequalities in SHS exposure in children younger than 12 years old in Spain between 2016 and 2019. METHODS We conducted two cross-sectional studies among representative samples of households with children aged <12 years in Spain, in 2016 (n=2411) and 2019 (n=2412). Families were interviewed to assess children’s SHS exposure in private settings and outdoor public venues and their adoption of home and car smoke-free rules. We used the education level of the home main earner as a proxy for socioeconomic position. Changes over time in the prevalence and socioeconomic inequalities of SHS exposure and smoke-free rules were estimated through adjusted Poisson regression models with robust variance according to sociodemographic covariates (adjusted prevalence ratios, APRs). RESULTS In 2019, 70.5% of children were exposed to SHS in Spain. No changes between 2016 and 2019 were found for overall SHS exposure, exposure at home, and at school entrances. SHS exposure increased at public transport stations (APR=1.24; 95% CI: 1.03–1.49) and outdoor hospitality venues (APR=1.17; 95% CI: 1.07–1.29) while it decreased in cars (APR=0.74; 95% CI: 0.56–0.98) and parks (APR=0.87; 95% CI: 0.77–0.98). Households with lower education level had higher prevalence of SHS exposure at home in 2019 compared with those with university studies (primary: APR=1.30; 95% CI: 1.11–1.51; secondary: APR=1.12; 95% CI: 1.00–1.25) and were less likely to adopt home indoor smoke-free rules (primary: APR=0.88; 95% CI: 0.79–0.99; secondary: APR=0.95; 95% CI: 0.89–1.02). Socioeconomic inequalities in SHS exposure at home persisted between 2016 and 2019 (p>0.05), while decreased in smoke-free rules in cars (p=0.039). CONCLUSIONS Reported SHS exposure among children in Spain remained high between 2016 and 2019. Inequalities persisted at home, highlighting the need for measures to reduce such exposure with an equity perspective.

Low-density lipoprotein receptor-related protein 5 (LRP5) is a constitutively expressed receptor with observed roles in bone homeostasis, retinal development, and cardiac metabolism. However, the function of LRP5 in the brain remains unexplored. This study investigates LRP5’s role in the central nervous system by conducting an extensive analysis using RNA-seq tools and in silico assessments. Two protein-coding Lrp5 transcripts are expressed in mice: full-length Lrp5-201 and a truncated form encoded by Lrp5-202. Wt mice express Lrp5-201 in the liver and brain and do not express the truncated form. Lrp5−/− mice express Lrp5-202 in the liver and brain and do not express Lrp5-201 in the liver. Interestingly, Lrp5−/− mouse brains show full-length Lrp5-201 expression, suggesting that LRP5 has a role in preserving brain function during development. Functional gene enrichment analysis on RNA-seq unveils dysregulated expression of genes associated with neuronal differentiation and synapse formation in the brains of Lrp5−/− mice compared to Wt mice. Furthermore, Gene Set Enrichment Analysis highlights downregulated expression of genes involved in retinol and linoleic acid metabolism in Lrp5−/− mouse brains. Tissue-specific alternative splicing of Lrp5 in Lrp5−/− mice supports that the expression of LRP5 in the brain is needed for the correct synthesis of vitamins and fatty acids, and it is indispensable for correct brain development.

Our aims were: (1) to characterize gay, bisexual and other men who have sex with men (GBMSM) and transgender (TG) populations using internet-based self-sampling services in the TESTATE project or attending community-based STI/HIV voluntary counselling and testing (CBVCT) services as alternative strategies to formal HIV testing within the Spanish national health system, and (2) to identify factors associated with repeat use of the same screening strategy from November 2018 to December 2021. Demographic, health, and behavioral characteristics of users using complementary strategies were analyzed. We developed a cross-sectional study, with descriptive analysis, HIV cascade, and a multivariate logistic model to identify factors associated with participants’ repeated use of the same screening strategy. We included 9939 users, of whom 94.1% were GBMSM (n = 9348) and 5.9% TG (n = 580), with a high representation of migrants. Reactive results were 3.4% (n = 340), with 3.0% in GBMSM (n = 277/9348) and 10.7% in TG (n = 63/591). 73.8% (n = 251) were confirmed HIV positive and 76.7% (n = 194) were linked to health services. Users repeated the online screening strategy more than CBVCT (44.3% vs. 31.8%), but TG population used face-to-face community services more (8.4% vs. 0.6%). Factors influencing the repetition of the online self-sampling strategy included older age, non-migrant status, and recent HIV testing. In the CBVCT strategy, factors included older age, TG identity, non-migrant status, condom use during the last sexual encounter, and recent HIV testing. In conclusion, both CBVCT and online-requested self-sampling at home are important alternatives to the health system for the provision of HIV testing to GBMSM and TG.

To analyze the predictive capacity for local disease control of the transcriptional expression of neogenin-1 (NEO1) gene in patients with head and neck squamous cell carcinoma (HNSCC). A retrospective study was performed on tumor biopsies from 107 patients with HNSCC treated surgically. The transcriptional expression of NEO1 was determined by RT-PCR. NEO1 transcriptional expression value was categorized according to local disease control by recursive partitioning analysis. Lower NEO1 transcriptional expression was associated with worse local control after surgical treatment. Patients with lower NEO1 expression (n = 25, 23.4%) had a 5-year local recurrence-free survival of 61.8% (95% CI: 42.1–81.5%), while patients with higher NEO1 expression (n = 82, 76.6%) had a 5-year local recurrence-free survival of 85.6% (95% CI: 77.6–93.6%), (P = 0.003). According to the result of multivariable analysis, patients with lower NEO1 expression had a 2.7-fold increased risk of local tumor recurrence (95% CI: 1.0–7.0, P = 0.043) compared to patients with higher NEO1 expression. HNSCC patients with a lower transcriptional expression of NEO1 have a significantly higher risk of local recurrence after surgical treatment.

Lipid functions can be influenced by genetics, age, disease states, and lifestyle factors, particularly dietary patterns, which are crucial in diabetes management. Lipidomics is an expanding field involving the comprehensive exploration of lipids from biological samples. In this cross-sectional study, 396 participants from a Mediterranean region, including individuals with type 1 diabetes (T1D), type 2 diabetes (T2D), and non-diabetic individuals, underwent lipidomic profiling and dietary assessment. Participants completed validated food frequency questionnaires, and lipid analysis was conducted using ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC/MS). Multiple linear regression models were used to determine the association between lipid features and dietary patterns. Across all subjects, acylcarnitines (AcCa) and triglycerides (TG) displayed negative associations with the alternate Healthy Eating Index (aHEI), indicating a link between lipidomic profiles and dietary habits. Various lipid species (LS) showed positive and negative associations with dietary carbohydrates, fats, and proteins. Notably, in the interaction analysis between diabetes and the aHEI, we found some lysophosphatidylcholines (LPC) that showed a similar direction with respect to aHEI in non-diabetic individuals and T2D subjects, while an opposite direction was observed in T1D subjects. The study highlights the significant association between lipidomic profiles and dietary habits in people with and without diabetes, particularly emphasizing the role of healthy dietary choices, as reflected by the aHEI, in modulating lipid concentrations. These findings underscore the importance of dietary interventions to improve metabolic health outcomes, especially in the context of diabetes management.

Poor long-term survival in localized high-risk soft tissue sarcomas (STSs) of the extremities and trunk highlights the need to identify new prognostic factors. CXCR4 is a chemokine receptor involved in tumor progression, angiogenesis, and metastasis. The aim of this study was to evaluate the association between CXCR4 expression in tumor tissue and survival in STSs patients treated with neoadjuvant therapy. CXCR4 expression was retrospectively determined by immunohistochemical analysis in serial specimens including initial biopsies, tumors post-neoadjuvant treatment, and tumors after relapse. We found that a positive cytoplasmatic expression of CXCR4 in tumors after neoadjuvant treatment was a predictor of poor recurrence-free survival (RFS) (p = 0.003) and overall survival (p = 0.019) in synovial sarcomas. We also found that positive nuclear CXCR4 expression in the initial biopsies was associated with poor RFS (p = 0.022) in undifferentiated pleomorphic sarcomas. In conclusion, our study adds to the evidence that CXCR4 expression in tumor tissue is a promising prognostic factor for STSs.

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, accounting for 32% of global deaths, according to the World Health Organization (WHO) [...]

We developed a high content screening to investigate how Alzheimer disease (AD) genetic risk factors may impair synaptic mechanisms in rat primary neuronal cultures. Out of the gene targets identified, we found that shRNA-mediated downregulation of Plcg2 in mouse dentate gyrus neurons consistently impaired dendritic morphology and synaptic function. In human neuronal cultures (hNCs), PLCG2 downregulation also impaired synaptic function and was associated with increased levels of Aβ and Tau phosphorylation, potentially via the AKT/GSK3β axis. Very rare PLCG2 loss-of-functon(LoF) variants were associated with a 10-fold increased AD risk. PLCG2 LoF carriers exhibit low mRNA/protein PLCG2/PLCγ2 levels, consistent with nonsense-mediated mRNA decay mechanisms. Restoring PLCγ2 levels in shPLCG2-hNCs fully reversed the disease-related phenotypes. Our findings indicate that the downregulation of PLCγ2 increases the risk of AD by impairing synaptic function and increasing the levels of Aβ and Tau phosphorylation in neurons.

Introduction Patients’ decisions on prostate cancer (PCa) opportunistic screening may vary. This study aimed to assess how demographic and health-related characteristics may influence knowledge and decisions regarding PCa screening. Methods A cross-sectional survey was conducted among men aged over 40, randomly sampled from the Spanish population, 2022. The survey underwent development and content validation using a modified Delphi method and was administered via telephone. Binomial logistic regression was used to explore the relationship between respondents’ characteristics and participants’ knowledge and practices concerning PCa and the PSA test. Results Out of 1,334 men, 1,067 (80%) respondents were interviewed with a mean age of 58.6 years (sd 11.9). Most had secondary or university studies (787, 73.8%) and 61 (5.7%) self-reported their health status as bad or very bad. Most of the respondents (1,018, 95.4%) had knowledge regarding PCa with nearly 70% expressed significant concern about its potential development (720, 70.8%), particularly among those under 64 years (p = 0.001). Out of 847 respondents, 573 (67.7%) reported that they have knowledge regarding the PSA test: 374 (65.4%) reported receiving information from a clinicians, 324 (86.6%) information about the benefits of the test and 189 (49,5%) about its risks, with differences based on educational background. In a multivariable analysis (adjusted for age, educational level and previous prostate problems), respondents with higher levels of education were more likely to have higher knowledge regarding the PSA test (OR 1.75, 95%CI 1.24–2.50, p<0.001). Conclusions Although most of the patients reported to have knowledge regarding PCa, half of the interviewed men reported knowledge about PSA test. Differences in knowledge prostate cancer screening and undesirable consequences highlight the need to develop and provide tailored information for patients.

Background Intravitreal injections are a common ophthalmologic procedure. While infections following these injections are rare, they can lead to endophthalmitis, with potentially serious consequences. Various methods have been proposed to prevent endophthalmitis, including the use of antisepsis and antibiotics in patient preparation. Purpose To evaluate the antiseptic efficacy of aqueous chlorhexidine (CHX) and povidone-iodine (PI) when used alone and in combination with lidocaine gel (LG) in vitro. Methods Two independent experimental trials were conducted. The first trial determined the minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs) of CHX and PI against six bacterial strains. The second trial evaluated the bactericidal efficacy of the antiseptic agents (CHX 0.1% and PI 5%) and their combination with LG against the same bacterial strains. Results CHX was more effective than PI in reducing the number of colonies forming units (cfus) of the tested bacteria. The order in which the antiseptic and LG were administered affected their effectiveness, with CHX administered before LG resulting in greater reduction of bacterial growth. Conclusions CHX 0.1% is more effective than PI 5% as an antiseptic agent. Application of CHX and PI prior to the use of lidocaine gel results in a more effective reduction of microorganisms.

To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new‐onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma‐related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e‐cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new‐onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new‐onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new‐onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma‐related quality‐of‐life and LF (low certainty evidence).