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Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment.
20.500.12530/87857Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment. We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs. Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR = 2.3 ×10-7) as the most significant biological processes, and hemoglobin binding (FDR = 0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR = 0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3). We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs
Fight Retinal Blindness SPAIN. Report 3: clinical outcomes of vascular endothelial growth factor inhibitors in low vision eyes with neovascular age-related macular degeneration. A national database study.
20.500.12530/87887To compare visual outcomes for low vision eyes (LVE) (35 letters LogMAR or >20/200 Snellen) at the time of the first injection in a clinical practice setting. Subgroup analysis of a multicenter national database of treatment- naïve eyes neovascular age related macular degeneration (nAMD) treated with anti-VEGF intravitreal injections divided into LVE and NLVE. Demographics, visual acuity (VA) at baseline and subsequent timepoints (12, 24, and 36 months), number of injections and visits data were collected using a validated web-based tool (Fight Retinal Blindness!). 3138 eyes were included, 705 LVE and 2433 NLVE. The LVE group had the greatest VA gain (p Findings of this study support the need for ongoing therapy in patients with initial visual acuity less than 35 letters since sustained visual improvements can be achieved and maintained for the first 3 years of treatment
National survey on perioperative monitoring of direct oral anticoagulants: MonACOD survey.
20.500.12530/8787
ProsTAV, a clinically useful test in prostate cancer: an extension study.
20.500.12530/87912To assess the clinical performance of ProsTAV®, a blood-based test based on telomere associate variables (TAV) measurement, to support biopsy decision-making when diagnosing suspicious prostate cancer (PCa). Preliminary data of a prospective observational pragmatic study of patients with prostate-specific antigen (PSA) levels 3-10 ng/ml and suspicious PCa. Results were combined with other clinical data, and all patients underwent prostate biopsies according to each center's routine clinical practice, while magnetic resonance imaging (MRI) before the prostate biopsy was optional. Sensitivity, specificity, positive and negative predicted values, and subjects where biopsies could have been avoided using ProsTAV were determined. The mean age of the participants (n = 251) was 67.4 years, with a mean PSA of 5.90 ng/ml, a mean free PSA of 18.9%, and a PSA density of 0.14 ng/ml. Digital rectal examination was abnormal in 21.1% of the subjects, and according to biopsy, the prevalence of significant PCa was 47.8%. The area under the ROC curve of ProsTAV was 0.7, with a sensitivity of 0.90 (95% CI, 0.85-0.95) and specificity of 0.27 (95% CI, 0.19-0.34). The positive and negative predictive values were 0.53 (95% CI, 0.46-0.60) and 0.74 (95% CI, 0.62-0.87), respectively. ProsTAV could have reduced the biopsies performed by 27% and showed some initial evidence of a putative benefit in the diagnosis pathway combined with MRI. ProsTAV increases the prediction capacity of significant PCa in patients with PSA between 3 and 10 ng/ml and could be considered a complementary tool to improve the patient diagnosis pathway
Introduction to iodinated contrasts: Properties, intravenous administration and distribution throughout the body.
20.500.12530/87908Iodinated contrast media enable greater attenuation of vascular and visceral structures in radiological studies and are widely used due to their high degree of safety, easy administration, acceptable level of tolerance, wide distribution and rapid excretion, qualities determined by their composition. Automated power injectors are used to administer contrast media. Once injected, contrast is distributed throughout the body, remaining in the intravascular space during its first passage before reaching the organs and spreading into the extracellular interstitial space, followed by a recirculation phenomenon. In CT studies, the level of contrast enhancement obtained is determined by multiple factors including patient-related factors, contrast medium characteristics, method of administration, equipment and technique. Different methods are available for determining the scan timing depending on the aim of the exploration
Independent role of atherosclerotic plaque composition and extension in predicting the risk of cardiac events: a CLIMA substudy.
To investigate two different approaches to determine patient risk to develop cardiac events: the burden of coronary atherosclerosis, as assessed by the Gensini score, and plaque morphology, as assessed by intracoronary optical coherence tomography (OCT). We assessed the Gensini score and OCT features of plaque vulnerability in 847 patients from the CLIMA registry. Patients were divided into four Gensini quartiles. The main study endpoint was the 1-year composite of cardiac death, myocardial infarction (MI) and/or target vessel revascularization (TVR). A total of 56 patients (6.6%) experienced the one-year main composite endpoint. The composite endpoint was significantly affected by the Gensini score (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.11-1.81, p = 0.005), with a low incidence in the first Gensini quartile (Q1 1.3%) and a higher incidence in the remaining groups (Q2 8.3%, Q3 8.9% and Q4 8.3%). At the multivariable analysis, the combined four OCT criteria (HR 6.4, 95%CI 3.0-13.7, p 180° (HR 2.1, 95%CI 1.2-3.6, p = 0.010), minimum lumen area
High-dose short-term creatine supplementation without beneficial effects in professional cyclists: a randomized controlled trial.
Growing evidence supports the ergogenic effects of creatine supplementation on muscle power/strength, but its effects on endurance performance remain unclear. We assessed the effects of high-dose short-term creatine supplementation in professional cyclists during a training camp. The study followed a double-blind, randomized parallel design. Twenty-three professional U23 cyclists (19 ± 1 years, maximum oxygen uptake: 73.0 ± 4.6 mL/kg/min) participated in a 6-day training camp. Participants were randomized to consume daily either a recovery drink (containing carbohydrates and protein) with a 20-g creatine supplement (creatine group, n = 11) or just the recovery drink (placebo group, n = 12). Training loads and dietary intake were monitored, and indicators of fatigue/recovery (Hooper index, countermovement jump height), body composition, and performance (10-second sprint, 3-, 6-, and 12-minute time trials, respectively, as well as critical power and W') were assessed as study outcomes. The training camp resulted in a significant (p 0.05). High-dose short-term creatine supplementation seems to exert no consistent beneficial effects on recovery, body composition or performance indicators during a strenuous training period in professional cyclists
Age-related structural remodelling of the coronary circulation.
While it is broadly accepted that ageing is associated with impairment of coronary microvascular function, little is known about the underlying mechanisms. We investigated age-related changes in coronary microvascular structure in patients with stable angina without epicardial coronary stenoses. In an analysis of the IDEAL registry, a total of 165 vessels without coronary stenosis were interrogated with combined pressure/Doppler guidewires. We calculated diastolic microvascular conductance (DMVC) and backward expansion wave (BEW), and compared them between age tertiles. We calculated the prevalence of CMD, defined by reduced coronary flow reserve (CFR), and the prevalence of low BEW and low DMVC in each group. The three study groups were defined as having 37-53, 54-66, and 67-77 years of age, respectively. Oldest (3rd tertile) patients showed lower hyperemic flow velocity (46.7 ± 14.4 vs. 45.1 ± 12.4 vs. 38.4 ± 11.5 cm s-1, p = 0.019), lower DMVC (1.90 ± 0.71 vs. 1.44 ± 0.56 vs. 1.37 ± 0.67 cm s-1 mmHg-1, p Ageing is independently associated with structural microcirculatory remodeling that is reflected in BEW intensity and DMVC measurements, and with an increased prevalence of structural CMD. These results are important to understand non-obstructive mechanisms of myocardial ischemia in the elderly
2-Hydroxyethyl methacrylate (2-HEMA) sensitization, a global epidemic at its peak in Spain?
20.500.12530/87870A global epidemic of allergic contact dermatitis to (meth)acrylates has been described in relation to the widespread use of manicure products. To evaluate the frequency of sensitization to 2-hydroxyethyl methacrylate (2-HEMA) among consecutively patch tested patients with eczema in Spain; the percentage of current relevance; the MOAHLFA index; and, the potential sources of exposure to (meth)acrylates. From January 2019 to December 2022, 2-HEMA 2% pet. was prospectively patch tested in 24 REIDAC (Spanish Allergic Contact Dermatitis Registry) centres. Six thousand one hundred thirty-four patients were consecutively patch tested with 2-HEMA 2% pet. 265/6134 (4.3%) were positive. Positive reactions of current relevance were identified to involve 184/265 (69%). The efficiency (number of patch tests needed to detect relevant positive patch test reactions) was 34 (6134/184). The variable 'occupational' was found to be significantly associated with a higher risk for relevant positive reactions to 2-HEMA (OR: 10.9; 95% CI: 8.1-14.9). (Meth)acrylate sensitization is a prevalent health issue in Spain. 2-HEMA 2% pet. has been identified to be a highly effective (meth)acrylate allergy marker in the GEIDAC baseline series. The responsible authorities should implement policies guaranteeing accurate labelling of industrial, medical, and consumer materials while ensuring the enforcement of said labelling through appropriate legal means