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Investigating the Link between Intermediate Metabolism, Sexual Dimorphism, and Cardiac Autonomic Dysfunction in Patients with Type 1 Diabetes.
No full text20.500.12530/87908Sexual dimorphism influences cardiovascular outcomes in type 1 diabetes (T1D), with women facing a higher relative risk of macrovascular events compared to men, especially after menopause. This study hypothesizes that abnormalities in intermediate metabolism may be associated with cardiac autonomic neuropathy (CAN) in T1D. We aim to assess low molecular weight metabolites (LMWM) as markers of CAN in T1D, considering the effects of sexual dimorphism and age. In this cross-sectional study, we included 323 subjects with T1D (147 women and 176 men), with a mean age of 41 ± 13 years. A total of 44 women and 41 men were over 50 years old. CAN was assessed using Ewing's tests, and serum metabolites were analyzed by proton nuclear magnetic resonance spectroscopy (1H-NMR). Patients with CAN had lower levels of valine, isoleucine, and threonine, and higher levels of lactate, compared to those without CAN. These differences persisted after adjusting for BMI and estimated glucose disposal rate (eGDR). In a logistic regression model (R² = 0.178,
Management of vitamin D deficiency in clinical practice: results of a multidisciplinary study at national level
No full textIntroduction: In recent years, there has been a notable interest in vitamin D, both in relation to its physiological aspects and its deficiency, to the need or not to supplement patients, to the recommended doses and even to the type of metabolite to use. Material and methods: Given the absence of criteria universally accepted by all scientific societies and the enormous heterogeneity observed in routine clinical practice with respect to these issues, we have carried out a survey on a sample of 698 doctors from Spain from the specialties of Primary Care (PC), Internal Medicine, Rheumatology, Traumatology, Endocrinology, Gynecology and Geriatrics in order to know their opinions on various aspects of vitamin D management. Results: There is a notable disparity in the answers to the 8 questions regarding their routine clinical practice, both in terms of the possibility of requesting a vitamin D determination and in the way of prescribing it. Conclusion: Finally, the recommendations of the panel of experts who prepared the survey and analyzed its results are presented
Bridging the gap between molecular and genomic epidemiology in tuberculosis: inferring MIRU-VNTR patterns from genomic data.
No full text20.500.12530/87858The transition from MIRU-VNTR-based epidemiology studies in tuberculosis (TB) to genomic epidemiology has transformed how we track transmission. However, short-read sequencing is poor at analyzing repetitive regions such as the MIRU-VNTR loci. This causes a gap between the new genomic data and the large amount of information stored in historical databases. Long-read sequencing could bridge this knowledge gap by allowing analysis of repetitive regions. However, the feasibility of extracting MIRU-VNTRs from long reads and linking them to historical data has not been evaluated. In our study, an in silico arm, consisting of inference of MIRU patterns from long-read sequences (using MIRUReader program), was compared with an experimental arm, involving standard amplification and fragment sizing. We analyzed overall performance on 39 isolates from South Africa and confirmed reproducibility in a sample enriched with 62 clustered cases from Spain. Finally, we ran 25 consecutive incident cases, demonstrating the feasibility of correctly assigning new clustered/orphan cases by linking data inferred from genomic analysis to MIRU-VNTR databases. Of the 3,024 loci analyzed, only 11 discrepancies (0.36%) were found between the two arms: three attributed to experimental error and eight to misassigned alleles from long-read sequencing. A second round of analysis of these discrepancies resulted in agreement between the experimental and in silico arms in all but one locus. Adjusting the MIRUReader program code allowed us to flag potential in silico misassignments due to suboptimal coverage or unfixed double alleles. Our study indicates that long-read sequencing could help address potential chronological and geographical gaps arising from the transition from molecular to genomic epidemiology of tuberculosis. The transition from molecular epidemiology in tuberculosis (TB), based on the analysis of repetitive regions (VNTR-based genotyping), to genomic epidemiology transforms in the precision with which we track transmission. However, short-read sequencing, the most common method for performing genomic analysis, is poor at analyzing repetitive regions. This means that we face a gap between the new genomic data and the large amount of information stored in historical databases, which is also an obstacle to cross-national surveillance involving settings where only molecular data are available. Long-read sequencing could help bridge this knowledge gap by allowing analysis of repetitive regions. Our study demonstrates that MIRU-VNTR patterns can be successfully inferred from long-read sequences, allowing the correct assignment of new cases as clustered/orphan by linking new data extracted from genomic analysis to historical MIRU-VNTR databases. Our data may provide a starting point for bridging the knowledge gap between the molecular and genomic eras in tuberculosis epidemiology
COVID-19 clinical phenotypes in vaccinated and nonvaccinated solid organ transplant recipients: a multicenter validation study.
No full text20.500.12530/87858Clinical phenotypes of COVID-19, associated with mortality risk, have been identified in the general population. The present study assesses their applicability in solid organ transplant recipients (SOTR) hospital-admitted by COVID-19. In a cohort of 488 SOTR, nonvaccinated (n = 394) and vaccinated (n = 94) against SARS-CoV-2, we evaluated 16 demographic, clinical, analytical, and radiological variables to identify the clinical phenotypes A, B, and C. The median age was 61.0 (51-69) years, 330 (67.6%) and 158 (32.4%) were men and women, respectively, 415 (85%) had pneumonia, and 161 (33%) had SpO2
Safety and efficacy preliminary analysis of first-line systemic therapy with atezolizumab plus bevacizumab in Spanish patients with unresectable hepatocellular carcinoma not previously treated with systemic therapy: phase IIIb ATHECA trial
No full textAnalysis of tumoral, stromal and glycolitic markers in the response basal cell carcinoma and Bowen disease to photodynamic therapy in real life.
No full textPhotodynamic therapy (PDT) is a widely-used non-surgical treatment for non-melanoma skin cancers, including basal cell carcinoma (BCC), actinic keratoses (AK), and Bowen's disease (BD). PDT has high success rates, but various factors, can influence treatment response. This study investigates the clinical, histological, and molecular factors that affect the efficacy of methyl aminolevulinate PDT (MAL-PDT) for BCC and BD. Prospective observational multicentric study performed between May 2019 and January 2021 with 64 patients included. Clinical data such as tumor thickness, location, and histological subtype were recorded. Immunohistochemical analysis was performed on tumor samples to assess the expression of biomarkers including p53, β-catenin, and GLUT1. Tumor thickness was found to be a critical determinant of MAL-PDT response, with thicker nodular BCCs showing reduced response rates compared to thinner, superficial BCCs and BD lesions. Immunohistochemical analysis revealed that p53 positivity was associated with better treatment outcomes, while increased β-catenin and cytoplasmic GLUT1 expression correlated with resistance to PDT. On the other hand, the metabolic profile of the tumors indicated that tumors with higher glycolytic activity were less responsive to treatment, therefore, using metformin, a glycolytic inhibitor, as a potential adjuvant therapy to improve outcomes in resistant tumors should be considered. This study emphasizes the importance of personalized approaches in the use of MAL-PDT, tailoring treatment according to tumor-specific characteristics. Biomarkers such as p53, β-catenin, and GLUT1 can serve as predictive tools for PDT response, helping clinicians identify patients who may benefit from alternative or combined treatments to enhance therapeutic efficacy
A Phase 2 Randomized Open-label Study of Oral Darolutamide Monotherapy Versus Androgen Deprivation Therapy in Men with Hormone-sensitive Prostate Cancer (EORTC-GUCG 1532).
No full text20.500.12530/87854Darolutamide is an androgen receptor inhibitor that increases overall survival in combination with androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer (PCa). This phase 2 study assessed the efficacy and safety of darolutamide as monotherapy without ADT in patients with eugonadal testosterone levels. This was a 24-wk, open-label, randomized study of patients with hormone-sensitive, histologically confirmed PCa requiring gonadotropin-releasing hormone (GnRH); an Eastern Cooperative Oncology Group performance status score of 0/1; and life expectancy >1 yr. All patients received darolutamide 600 mg bid or a commercially available GnRH analog. The primary endpoint is a prostate-specific antigen (PSA) response, defined as a ≥80% decline at week 24 relative to baseline in the darolutamide study arm. The GnRH arm is used as an internal control. The secondary endpoints included changes in T levels, safety/tolerability, and quality of life. Among 61 men enrolled, the median (range) age was 72 yr (53-86 yr); 42.6% of them had metastases. In the darolutamide arm, the evaluable population with available PSA values at baseline and week 24 consisted of 23 patients. Twenty-three (100%) evaluable darolutamide patients achieved a PSA decline of >80% at week 24 (primary endpoint), with a median (range) decrease of -99.1% (-91.9%, -100%). Serum T levels increased by a median (range) of 44.3 (5.7-144.0) at week 24, compared with baseline. In the darolutamide arm, 48.4% of men reported drug-related adverse events (AEs; mostly grade 1 or 2). The most frequent treatment-emergent AEs included gynecomastia (35.5%), fatigue (12.9%), hot flush (12.9%), and hypertension (12.9%). Health-related quality of life measures are descriptive, and GnRH arm results will be presented as an internal reference. Darolutamide monotherapy was associated with a significant PSA response in nearly all men with hormone-naïve PCa. Testosterone-level changes and most common AEs (gynecomastia, fatigue, hypertension, and hot flush) were consistent with potent androgen receptor inhibition. In this study, we report the first use of darolutamide, a novel antiandrogen, as monotherapy without androgen deprivation therapy (ADT). The study shows that darolutamide induce a profound suppression of prostate-specific antigen in all patients, with a safety profile different from that of ADT
Is Antiviral Treatment with Remdesivir at the Acute Phase of SARS-CoV-2 Infection Effective for Decreasing the Risk of Long-Lasting Post-COVID Symptoms?
No full text20.500.12530/87849The aim of this study was to investigate the effects of administrating Remdesivir at the acute COVID-19 phase on developing post-COVID symptoms in previously hospitalized COVID-19 survivors by controlling factors such as age, sex, body mass index, and vaccination status. A case-control study was performed. Hospitalized COVID-19 survivors who had received intravenous Remdesivir during the acute phase (n = 216) were matched by age, sex, body mass index, and vaccination status with survivors who did not receive antiviral treatment (n = 216). Participants were asked to self-report the presence of any post-COVID symptom (defined as a symptom that started no later than three months after infection) and whether the symptom persisted at the time of study (mean: 18.4, SD: 0.8 months). Anxiety levels (HADS-A), depressive symptoms (HADS-D), sleep quality (PSQI), and severity/disability (FIC) were also compared. The multivariate analysis revealed that administration of Remdesivir at the acute COVID-19 phase was a protective factor for long-term COVID development (OR0.401, 95%CI 0.256-0.628) and specifically for the following post-COVID symptoms: fatigue (OR0.399, 95%CI 0.270-0.590), pain (OR0.368, 95% CI 0.248-0.548), dyspnea at rest (OR0.580, 95%CI 0.361-0.933), concentration loss (OR0.368, 95%CI 0.151-0.901), memory loss (OR0.399, 95%CI 0.270-0.590), hair loss (OR0.103, 95%CI 0.052-0.207), and skin rashes (OR0.037, 95%CI 0.005-0.278). This study supports the potential protective role of intravenous administration of Remdesivir during the COVID-19 acute phase for long-lasting post-COVID symptoms in previously hospitalized COVID-19 survivors
