RIMASaud Institutional Repository of the Regional Health System
Not a member yet
61753 research outputs found
Sort by
Efficacy and safety of dolutegravir/lamivudine in virologically suppressed female participants: week 48 data from the pooled TANGO and SALSA studies.
No full text20.500.12530/87854Women represent >50% of people with HIV globally but have historically been underrepresented in clinical trials. We evaluated the efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) vs continuing their current antiretroviral regimen (CAR) by sex assigned at birth (female and male) in virologically suppressed adults with HIV-1 without prior virological failure in a pooled analysis of two randomized controlled trials. This analysis included 48-week data from the phase 3 TANGO and SALSA studies. Primary and key secondary endpoints included proportions of participants with HIV-1 RNA ≥50 and Of 1234 participants, 250 (DTG/3TC, n = 133; CAR, n = 117) were female at birth. Week 48 proportions of participants with Snapshot HIV-1 RNA ≥50 copies/mL were similar regardless of sex at birth (DTG/3TC vs CAR: female, Results confirm the robustness of DTG/3TC as a switch option in virologically suppressed females with HIV-1, with outcomes similar to those in males
COVID-19 Outcomes in Patients with Hematologic Malignancies in the Era of COVID-19 Vaccination and the Omicron Variant.
No full text20.500.12530/87909A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64-2.87), with >1 comorbidity (2.44, 1.85-3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19-2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2-0.37) or BA.4/BA.5 (0.13, 0.08-0.19) periods and among patients vaccinated with one or two (0.51, 0.34-0.75) or three or four (0.22, 0.16-0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03-3.25) and Omicron (3.19, 95% CI 1.59-6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients
PVR (CD155) epigenetic status mediates immunotherapy response in multiple myeloma.
No full text20.500.12530/8791
Creation of an Isogenic Human iPSC-Based RGC Model of Dominant Optic Atrophy Harboring the Pathogenic Variant c.1861C>T (p.Gln621Ter) in the OPA1 Gene.
No full text20.500.12530/87912Autosomal dominant optic atrophy (ADOA) is a rare progressive disease mainly caused by mutations in OPA1, a nuclear gene encoding for a mitochondrial protein that plays an essential role in mitochondrial dynamics, cell survival, oxidative phosphorylation, and mtDNA maintenance. ADOA is characterized by the degeneration of retinal ganglion cells (RGCs). This causes visual loss, which can lead to legal blindness in many cases. Nowadays, there is no effective treatment for ADOA. In this article, we have established an isogenic human RGC model for ADOA using iPSC technology and the genome editing tool CRISPR/Cas9 from a previously generated iPSC line of an ADOA plus patient harboring the pathogenic variant NM_015560.3: c.1861C>T (p.Gln621Ter) in heterozygosis in OPA1. To this end, a protocol based on supplementing the iPSC culture media with several small molecules and defined factors trying to mimic embryonic development has been employed. Subsequently, the created model was validated, confirming the presence of a defect of intergenomic communication, impaired mitochondrial respiration, and an increase in apoptosis and ROS generation. Finally, we propose the analysis of OPA1 expression by qPCR as an easy read-out method to carry out future drug screening studies using the created RGC model. In summary, this model provides a useful platform for further investigation of the underlying pathophysiological mechanisms of ADOA plus and for testing compounds with potential pharmacological action
Influence of smoking on cardiometabolic profile and surgical outcomes in patients with primary aldosteronism: a cohort study.
No full textTo evaluate the influence of smoking on cardiometabolic profile and surgical outcomes in patients with primary aldosteronism (PA). Multicentre retrospective study of patients with PA evaluated in 36 Spanish tertiary hospitals with available information on smoking habits [smokers and non-smokers (never smokers and ex-smokers)]. A total of 881 patients were included, of whom 180 (20.4%) were classified as smokers and 701 as non-smokers. At diagnosis, smokers and non-smokers did not differ in blood pressure or serum potassium levels between. However, smokers had a higher prevalence of left ventricular hypertrophy (LVH) than non-smokers [odds ratio (OR) 2.0, 95% confidence interval (CI) 1.23-3.25], and smokers were more likely to have severe LVH than non-smokers (12.5% vs 6.6%, P = .164). A larger mean tumour size of the adrenal nodule/s was observed in the smoking group (18.6 ± 9.66 vs 15.8 ± 8.66 mm, P = .002). In addition, the odds of mild autonomous cortisol secretion (MACS) was greater in smokers than in non-smokers (OR 2.1, 95% CI 1.14-4.06), but these differences disappeared when adjusted for the size of the adrenal nodule/s (adjusted OR 1.6, 95% CI 0.76-3.37). The rate of biochemical and hypertension cure was similar in both groups; however, hypertension cure tended to be more frequent in the non-smoker group (41.2% vs 29.9%, P = .076). Patients with PA who smoke have a higher prevalence of LVH and MACS and larger adrenal nodule/s than non-smokers. Smoking has no significant effect on the probability of hypertension response after adrenalectomy in patients with PA; however, a tendency to a lower probability of hypertension cure is observed in smokers compared to non-smokers
HER2DX genomic test in early-stage HER2-positive breast cancer.
No full text20.500.12530/87912Therapies targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer significantly impact patient outcomes, quality of life, and health care systems. While chemotherapy and trastuzumab improve survival in early-stage HER2-positive breast cancer, variability in clinical and biological characteristics leads to different response to therapies and outcomes. Clinical guidelines provide general recommendations, but significant uncertainty persists in identifying an optimal treatment plan for individual patients. The HER2DX genomic test informs treatment decisions for stage 1-3 HER2-positive breast cancer by integrating biological factors and clinical factors (tumor size and nodal status). It provides three scores relevant to patient management: long-term prognosis (risk score), likelihood of achieving pathological complete response (pCR score), and ERBB2 mRNA expression (ERBB2 score). This article offers an expert overview of HER2DX, covering score interpretation, clinical applications, ongoing studies, and future directions. By analyzing the genomic profiles of HER2-positive tumors, HER2DX provides independent information regarding therapeutic responses and disease prognosis, thereby enabling physicians to navigate the increasing complexity of managing patients with HER2-positive early breast cancer. Key findings show that HER2DX predicts relapse-free survival and probability of pCR to a variety of neoadjuvant therapy regimens, which aids in personalizing treatment plans that could reduce over-treatment and under-treatment. The article underscores expert recommendations to help integrate HER2DX into clinical practice, aiming to enhance decision making and clinical outcomes
REAL-WORLD EXPERIENCE OF THE EFFICACY AND SAFETY OF SECUKINUMAB DOSE INTENSIFICATION IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS
No full textDietary Intake of Polyunsaturated Fatty Acids Is Associated with Blood Glucose and Diabetes in Community-Dwelling Older Adults
No full text20.500.12530/87897Objectives: The present study was conducted to examine the cross-sectional associations between the dietary intake of polyunsaturated fatty acids (PUFAs) and cardiometabolic risk factors in a large sample of Italian community-dwelling older adults. Methods: This is a cross-sectional study. Longevity Check-up 8+ (Lookup 8+) is an ongoing project that started in June 2015. The project is conducted in unconventional settings (e.g., exhibitions, malls, and health promotion campaigns) across Italy with the aim of fostering the adoption of healthy lifestyles in the general population. For the present study, participants were eligible if they were 65+ years and provided written informed consent. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), and blood glucose and cholesterol levels were assessed. A 12-item food frequency questionary was used to estimate the dietary intake of PUFAs, which included omega-3 (alpha-linolenic acid [ALA], eicosapentaenoic acid [EPA], and docosahexaenoic acid [DHA]) and omega-6 fatty acids. Results: Data of 4461 older adults (female 56%, mean age: 72.9 years, mean body mass index [BMI]: 26.1 kg/m2, blood glucose: 109 mg/dL, total blood cholesterol: 198.5 mg/dL, ALA: 8.8%, EPA: 16.0%, and DHA: 26.1%) were cross-sectionally analyzed. Multilinear regression results indicated that a high consumption of EPA, DHA, and DHA+EPA was negatively and significantly associated with glucose levels. Furthermore, binary regression analysis indicated that the dietary intake of ALA and omega-6 PUFAs was inversely and significantly associated with the prevalence of diabetes. In contrast, BMI values were positively associated with ALA and omega-6 PUFAs, and negatively with the consumption of EPA and DHA+EPA. Conclusions: Findings of the present study indicate that the dietary intake of PUFAs was cross-sectionally, inversely, and significantly associated with blood glucose levels and the prevalence of diabetes in a large sample of Italian community-dwelling older adults
European Association of Urology Guidelines on Renal Transplantation: Update 2024.
No full text20.500.12530/87910The European Association of Urology (EAU) Panel on Renal Transplantation released an updated version of the renal transplantation (RT) guidelines. This report aims to present the 2024 EAU guidelines on RT. A broad and comprehensive scoping exercise covering all areas of RT guidelines published between May 31, 2020 and April 1, 2023 was performed. Databases covered by the search included Medline, Embase, and the Cochrane Libraries. Previous guidelines were updated, and levels of evidence and grades of recommendation were assigned. It is strongly recommended to offer pure or hand-assisted laparoscopic/retroperitoneoscopic surgery for living donor nephrectomy. One should not base decisions regarding the acceptance of a donor organ on histological findings alone, since this might lead to an unnecessary high rate of discarded grafts. For the ureterovesical anastomosis, a Lich-Gregoir-like extravesical technique protected by a ureteral stent is the preferred technique. A list of RT patients with a history of appropriately treated low-stage/grade renal cell carcinoma or prostate cancer should be made without additional delay. In the potential donor kidney, the main surgical tumoral approach is ex vivo tumor excision and finally transplantation. It is also strongly recommended to perform initial rejection prophylaxis with a combination therapy of a calcineurin inhibitor (preferably tacrolimus), mycophenolate, steroids, and an induction agent (either basiliximab or antithymocyte globulin). The long version of the guidelines is available at the EAU website (www.uroweb.org/guidelines). These abridged EAU guidelines present updated information on the clinical and surgical management of RT for incorporation into clinical practice. The European Association of Urology has released the renal transplantation guidelines. Implementation of minimally invasive surgery for organ retrieval and the latest evidence on transplant surgery as well as on immunosuppressive regimens are key to minimizing rejection and achieving long-term graft survival
Association of cumulative oxygen and carbon dioxide levels with neurologic outcome after pediatric cardiac arrest resuscitation: A multicenter cohort study.
No full text20.500.12530/87858We aimed to (1) determine the association between cumulative PaO2 and PaCO2 exposure 24 h post-return of circulation and survival with favorable neurologic outcome. And (2) to assess adherence to American Heart Association post-cardiac arrest care treatment goals (PaO2 75-100 mmHg and PaCO2 35-45 mmHg). Prospectively collected data were analysed from five Pediatric Resuscitation Quality collaborative sites supplemented with retrospective PaO2 and PaCO2 data. Children aged 1 day-17 years with return of circulation after cardiac arrest, admitted 2019-2022, with ≥ 4 arterial blood gasses spanning at least 12 h within 24 h post-return of ciculation, were eligible. Congenital cyanotic heart disease events were excluded. Area under the curve calculation provided hourly cumulative PaO2 and PaCO2 exposures per child and similarly guideline recommended cumulative ranges. The primary outcome was survival to hospital discharge with favorable neurologic outcome defined as a Pediatric Cerebral Performance Category 1-3, or no pre-arrest baseline difference. Among 292 included children (median age 2.6 years (IQR 0.4-10.9)), 57 % survived to discharge and 48 % had favorable neurologic outcome (88 % of survivors). Cumulative PaO2 and PaCO2 exposure 0-24 h post-return of circulation were not significantly associated with favorable neurologic outcome in multivariable analysis (OR 1.0, 95 %CI 0.98-1.02 and OR 0.97, 95 %CI 0.87-1.09 respectively). Cumulative PaO2 and PaCO2 remained within guideline recommended ranges for 24 % and 58 % of children respectively with median areas under the curve over 0 - 24 h of 2664 mmHg (2151 - 3249 mmHg) for PaO2 and 948 mmHg (853 - 1051 mmHg) for PaCO2. AHA post-cardiac arrest care guideline recommendations for PaO2 (1800-2400 mmHg) and PaCO2 (840-1080 mmHg) were recalculated as area under the curve ranges. Achieving both normoxia and normocapnia was observed in 12 % of children. Cumulative PaO2 and PaCO2 exposure in the first 24 h post-return of circulation was not associated with survival with favorable neurologic outcome. Pediatric AHA post-cardiac arrest care guideline normoxia and normocapnia goals were often not met. Larger cohort studies are necessary to improve the accuracy of cumulative exposure calculations, assess the long-term effects of PaO2 and PaCO2 exposure, and explore the influence of other post-cardiac arrest care therapeutic strategies