A crowdsourcing database for the copy-number variation of the Spanish population.

Background: Despite being a very common type of genetic variation, the distribution of copy-number variations (CNVs) in the population is still poorly understood. The knowledge of the genetic variability, especially at the level of the local population, is a critical factor for distinguishing pathogenic from non-pathogenic variation in the discovery of new disease variants.

Results: Here, we present the SPAnish Copy Number Alterations Collaborative Server (SPACNACS), which currently contains copy number variation profiles obtained from more than 400 genomes and exomes of unrelated Spanish individuals.

Evaluation of lipoprotein(a) in the prevention and management of atherosclerotic cardiovascular disease: A survey among the Lipid Clinics Network.

Background And Aims: The European Atherosclerosis Society (EAS) Lipid Clinics Network promoted a survey in order to identify and understand how and when lipoprotein(a) [Lp(a)] is tested and clinically evaluated in lipid clinics throughout Europe, and the challenges that may prevent evaluation from being carried out.

Methods: This survey was divided into three areas of inquiry: background and clinical setting information of clinicians, questions for doctors who claimed not to measure Lp(a), in order to understand what were the reasons for not ordering the test, and questions for doctors who measure Lp(a), to investigate the use of this value in the management of patients.

Results: A total of 151 centres clinicians filled in the survey, out of 226 invited.

Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging.

ATP-citrate lyase is a central integrator of cellular metabolism in the interface of protein, carbohydrate, and lipid metabolism. The physiological consequences as well as the molecular mechanisms orchestrating the response to long-term pharmacologically induced Acly inhibition are unknown. We report here that the Acly inhibitor SB-204990 improves metabolic health and physical strength in wild-type mice when fed with a high-fat diet, while in mice fed with healthy diet results in metabolic imbalance and moderated insulin resistance.

Factors associated with the humoral response after three doses of COVID-19 vaccination in kidney transplant recipients.

Introduction: Kidney transplant recipients showed a weak humoral response to the mRNA COVID-19 vaccine despite receiving three cumulative doses of the vaccine. New approaches are still needed to raise protective immunity conferred by the vaccine administration within this group of high-risk patients.

Methods: To analyze the humoral response and identify any predictive factors within these patients, we designed a prospective monocentric longitudinal study of Kidney transplant recipients (KTR) who received three doses of mRNA-1273 COVID-19 vaccine.

Midterm outcomes of patellofemoral arthroplasty.

Background: The purpose of this study is the evaluation of the patellofemoral arthroplasty (PFA) survival and clinical and radiological outcomes in our institution.

Methods: A retrospective evaluation of our institution patellofemoral arthroplasty cases from 2006 to 2018 was performed; the n sample after applying exclusion and inclusion criteria was 21. All patients excepting one were female with a median age of 63 (20-78).

Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small-cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial.

Background: The APPLE trial aimed to evaluate the feasibility of longitudinal plasma epidermal growth factor receptor (EGFR) T790M monitoring for the best sequencing strategy of gefitinib and osimertinib.

Methods: APPLE is a randomized, non-comparative, phase II study in patients with common EGFR-mutant, treatment-naive non-small-cell lung cancer including three arms: arm A (osimertinib upfront until RECIST progression, PD), arm B [gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation by cobas EGFR test v2 or RECIST PD], and arm C (gefitinib until RECIST PD), and then switch to osimertinib in both arms. The primary endpoint is the progression-free survival (PFS) rate 'on osimertinib' at 18 months (PFSR-OSI-18) after randomization in arm B (H: PFSR-OSI-18 of ≤40%).

Polygenic risk scores enhance prediction of body mass index increase in individuals with a first episode of psychosis.

Background: Individuals with a first episode of psychosis (FEP) show rapid weight gain during the first months of treatment, which is associated with a reduction in general physical health. Although genetics is assumed to be a significant contributor to weight gain, its exact role is unknown.

Methods: We assembled a population-based FEP cohort of 381 individuals that was split into a Training ( = 224) set and a Validation ( = 157) set to calculate the polygenic risk score (PRS) in a two-step process.

Evaluation of Clinical Results regarding Peristomal Skin Health Associated with the Adjustment and Formulation of the New Moderma Flex One-Piece Ostomy Devices.

In order to determine the perception of ostomized patients about the performance and safety of the new one-piece device Moderma Flex, as well as the evolution of peristomal skin health after its use. The pre- and post-experimental multicenter study after the use of the Moderma Flex one-piece ostomy device on 306 ostomized people from 68 hospitals in Spain. We used a self-made questionnaire on the usefulness of different parts of the device and the perception of peristomal skin improvement.

Comparative Study of the Impact of Human Leukocyte Antigens on Renal Transplant Survival in Andalusia and the United States.

Renal transplantation is the treatment of choice for patients suffering from chronic renal disease, one of the leading causes of death worldwide. Among the biological barriers that may increase the risk of acute renal graft rejection is the presence of human leukocyte antigen (HLA) incompatibilities between donor and recipient. This work presents a comparative study of the influence of HLA incompatibilities on renal transplantation survival in the Andalusian (South of Spain) and United States (US) population.

Development of Antimicrobial Defined Daily Dose (DDD) for the Pediatric Population.

Antimicrobial stewardship programs (ASPs) optimize antimicrobial use, improve patient outcomes, and reduce resistance. To assess the effectiveness of ASPs, it is necessary to have indicators that can be widely used. Defined daily dose (DDD) was designed by WHO for the adult population as a consumption indicator.

Impact of Frailty on Outcomes of First-Line Pembrolizumab Monotherapy in a Real-World Population with Advanced Non-Small Cell Lung Cancer.

ICIs have been able to improve overall survival in advanced-stage lung cancer. The benefit of this therapy is limited in patients with poor ECOG PS. However, this scale is imprecise and can be influenced by different factors, such as frailty.

Severe equinus cavo-varus correction through triplanar tarsectomy and posterior tibial tendon transfer based on 3D-printed biomodel.

Surgery for severe equine cavo-varus is complex and must be individualized. The interindividual phenotypic variability demands a personalized planning of each foot to be operated. The study's primary goal was to evaluate the function and satisfaction of a series of patients with severe equinus cavo-varus deformity who underwent a triplanar tarsectomy and transposition of the posterior tibial tendon in a single stage surgery after a patient specific 3D biomodel planning.

VE-Cadherin modulates β-catenin/TCF-4 to enhance Vasculogenic Mimicry.

Vasculogenic Mimicry (VM) refers to the capacity to form a blood network from aggressive cancer cells in an independent way of endothelial cells, to provide nutrients and oxygen leading to enhanced microenvironment complexity and treatment failure. In a previous study, we demonstrated that VE-Cadherin and its phosphorylation at Y658 modulated kaiso-dependent gene expression (CCND1 and Wnt 11) through a pathway involving Focal Adhesion kinase (FAK). In the present research, using a proteomic approach, we have found that β-catenin/TCF-4 is associated with nuclear VE-cadherin and enhances the capacity of malignant melanoma cells to undergo VM in cooperation with VE-Cadherin; in addition, preventing the phosphorylation of Y658 of VE-cadherin upon FAK disabling resulted in VE-Cadherin/β-catenin complex dissociation, increased β-catenin degradation while reducing TCF-4-dependent genes transcription (C-Myc and Twist-1).

Rapid Detection of Piperacillin-Tazobactam Resistance in Klebsiella pneumoniae and Escherichia coli.

Rapid determination of susceptibility to piperacillin-tazobactam (TZP) is very important since the development of antibiotic resistance and inadequate treatment could increase the risk of clinical failure in infected patients, especially if such resistance is unknown to the clinician. Therefore, based on color change from orange to yellow of phenol red due to glucose metabolism (bacterial growth) in the presence of an adequate concentration of TZP (10 mg/L piperacillin and 5 mg/L tazobactam), the RapidTZP test has been developed to detect TZP resistance in Escherichia coli and Klebsiella pneumoniae isolates in a maximum of 3 h. A total of 140 isolates, 43 of E.

European Association for Endoscopic Surgery (EAES) consensus on Indocyanine Green (ICG) fluorescence-guided surgery.

Background: In recent years, the use of Indocyanine Green (ICG) fluorescence-guided surgery during open and laparoscopic procedures has exponentially expanded across various clinical settings. The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on this topic with the aim of creating evidence-based statements and recommendations for the surgical community.

Methods: An expert panel of surgeons has been selected and invited to participate to this project.

Generation of mesenchymal stromal cells from urine-derived iPSCs of pediatric brain tumor patients.

Human induced pluripotent stem cells (iPSCs) provide a virtually inexhaustible source of starting material for next generation cell therapies, offering new opportunities for regenerative medicine. Among different cell sources for the generation of iPSCs, urine cells are clinically relevant since these cells can be repeatedly obtained by non-invasive methods from patients of any age and health condition. These attributes encourage patients to participate in preclinical and clinical research.

Detection of High Level of Co-Infection and the Emergence of Novel SARS CoV-2 Delta-Omicron and Omicron-Omicron Recombinants in the Epidemiological Surveillance of Andalusia.

Recombination is an evolutionary strategy to quickly acquire new viral properties inherited from the parental lineages. The systematic survey of the SARS-CoV-2 genome sequences of the Andalusian genomic surveillance strategy has allowed the detection of an unexpectedly high number of co-infections, which constitute the ideal scenario for the emergence of new recombinants. Whole genome sequence of SARS-CoV-2 has been carried out as part of the genomic surveillance programme.

PCSK9 Inhibitors Have Apolipoprotein C-III-Related Anti-Inflammatory Activity, Assessed by 1H-NMR Glycoprotein Profile in Subjects at High or very High Cardiovascular Risk.

Atherosclerosis is a chronic inflammatory disease caused by the accumulation of cholesterol in the intima. Proprotein convertase subtilisin/kexin type 9 inhibitors (iPCSK9) can reduce low-density lipoprotein (LDL) cholesterol levels by 60%, but there is still no evidence that they can lower markers of systemic inflammation such as high-sensitivity C-reactive protein (hsCRP). Acute-phase serum glycoproteins are upregulated in the liver during systemic inflammation, and their role as inflammatory biomarkers is under clinical evaluation.

Stereotactic body radiation therapy for kidney cancer. Where do we stand?

At present, surgery is still the gold standard for the local treatment of renal cancer. Nonetheless, in several clinical scenarios, stereotactic body radiation therapy (SBRT) also known as stereotactic ablative body radiotherapy (SABR) is emerging as a highly effective ablative technique in fragile patients and those with significant comorbidities, as well as in cases where percutaneous therapy (cryoablation or radiofrequency) is not viable. However, considering the intrinsic radioresistance of renal tumors, the optimal treatment schemes have not been established.

Surgical management of complex perianal fistula revisited in a systematic review: a critical view of available scientific evidence.

Background: Treating complex perianal fistulas in Crohn's disease patients remains a challenge. Classical surgical treatments for Crohn's disease fistulas have been extrapolated from cryptoglandular fistulas treatment, which have different etiology, and this might interfere with its effectiveness, in addition, they increase fecal incontinence risk. Recently, new surgical techniques with support from biological approaches, like stem cells, have been developed to preserve the function of the sphincter.