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      2
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    Scopus© Citations 22  3
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    Emergency Department Workflow Times of Intravenous Thrombolysis with Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Prospective Cohort Study before and during the COVID-19 Pandemic
    (S. Karger AG, 2025-02-03)
    Matias Guzman
    ;
    LAVADOS GERMAIN, PABLO MANUEL  
    ;
    Gabriel Cavada
    ;
    Alejandro M. Brunser
    ;
    Veronica V. Olavarria
    Introduction: Tenecteplase (TNK) has demonstrated to be non-inferior to alteplase (ALT) for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). There are potential workflow benefits associated with TNK use, aiming to reduce patient length of stay in the emergency department. Our aim was to investigate whether the routine use of TNK during the COVID-19 pandemic influenced workflow times compared to historical use of ALT, while maintaining non-inferior clinical outcomes in a non-drip and ship scenario of a comprehensive stroke center. Methods: We included patients with AIS admitted from September 2019 to September 2022 and compared those treated with TNK during the COVID-19 pandemic to those treated with ALT in the period immediately before. We compared emergency department length of stay (EDLOS), door-to-needle time (DTN), door-to-groin puncture time (DTG), clinical and safety outcomes with adjusted general linear regression models. Results: 110 patients treated with TNK and 111 with ALT were included in this study. Mean EDLOS was 251 (SD = 164) min for TNK users versus 240 (SD = 148) min for ALT (p = 0.62). Mean DTN was 43 (SD = 25) min for TNK versus 46 (SD = 27) min for ALT users (p = 0.39). Mean DTN under 60 min was achieved in 86 (78.2%) patients and in 85 (76.5%) patients of the TNK and ALT groups, respectively (p = 1.0). DTN under 45 min was achieved in 65.4% and 58.6% (p = 0.65) of the TNK and ALT groups, respectively. DTG time was 114 (SD = 43) min for TNK versus 111 (58 = SD) min in the ALT group (p = 0.88). DTG under 90 min was achieved in 32% of the TNK group and 35% of the ALT group (p = 0.69). There were no differences in any of the clinical or safety outcomes between groups at 90 days. Conclusions: The adoption of TNK during COVID-19 pandemic did not result in a change in EDLOS, DTN, or DTG times when compared to ALT in this cohort. Safety and clinical outcomes were similar between groups. Probably a greater benefit could have been seen in a drip and ship thrombolysis setting. Further research is needed to assess the potential advantages of TNK in drip and ship scenarios of IVT.
    Scopus© Citations 2  2
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    Arsenic Exposure During Pregnancy and Childhood: Factors Explaining Changes over a Decade
    (MDPI AG, 2025-03-16)
    RUBILAR RAMIREZ, PAOLA ANDREA  
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    HIRMAS ADAUY, MACARENA SOLEDAD  
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    APABLAZA SALINAS, MAURICIO IVÁN  
    ;
    Camila Awad
    ;
    Xaviera Molina
    Arsenic chronic exposure, particularly in its inorganic form, represents a significant public health concern. This study was conducted in Arica, the northernmost city in the country, whose inhabitants have been exposed to inorganic arsenic both naturally through drinking water and anthropogenically due to a toxic waste disposal site. We explored changes in inorganic arsenic levels in a cohort of pregnant women and their children over a decade, identifying exposure trends and their determinants. We used data on arsenic exposure through maternal urine samples during pregnancy, collected by the Health Authority between 2013 and 2016 (measurement 1), and followed up with assessments of their children in 2023 (measurement 2). Temporal changes in inorganic arsenic concentration were analyzed using the Wilcoxon Signed-Rank test, and a mixed linear regression model was employed to determine which factors contributed to urinary inorganic arsenic levels. We did not observe significant differences in mean arsenic concentrations between the two-time points (p = 0.4026). The mixed linear regression model revealed that children consuming bottled water had 8.3% lower urinary inorganic arsenic concentrations than those drinking tap water (95% CI: −15.36 to −0.54%). Additionally, children from ethnic groups had 8.64% higher inorganic arsenic concentrations (95% CI: 0.49 to 17.5%), while those with caregivers with higher education showed a 13.67% reduction (95% CI: −25.06 to −0.56%). Despite mitigation efforts, these findings underscore the ongoing risk of inorganic arsenic exposure among vulnerable populations. They further emphasize the importance of addressing natural arsenic contamination in water and implementing targeted interventions to reduce disparities associated with socioeconomic and demographic factors.</jats:p>
    Scopus© Citations 1  6
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    IL-10 and IL-6/IL-10 as predictive biomarkers for treatment response in non-infectious uveitis
    (Frontiers Media SA, 2025-05-13)
    Rodrigo A. Valenzuela
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    Fabian Vega-Tapia
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    Nathaly Elizalde
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    Ivan Flores
    ;
    Felipe M. Rojas
    Uveitis, a group of heterogeneous diseases causing ocular inflammation, is a major contributor to vision loss globally. While systemic corticosteroids (CS) are the mainstay treatment, identifying CS-refractory patients remains a significant challenge. This study aimed to explore cytokine expression and Glucocorticoid Receptor (GR) levels as biomarkers for the early detection of CS-refractory cases in non-infectious uveitis. We assayed blood samples from 19 patients with non-infectious uveitis, for the expression of IL-6, IL-17A, TNF-α, IL-10 and GRα. The cohort included 11 refractory and 8 sensitive patients, categorized based on their clinical response to corticosteroids (prednisone 1 mg/kg/day). Blood draws were conducted at three time points (at baseline, day 7- and day 14 after CS initiation), and peripheral blood mononuclear cells (PBMCs) were isolated to measure cytokine and GRα transcript levels via real-time PCR. The expression levels of GRα and cytokines IL-6, IL-17A and TNF-α did not show significant changes between CS-sensitive and CS-refractory patients on the different days of treatment. However, IL-10 expression levels as the day14-to-day7 ratio were significantly higher in patients sensitive to CS therapy. A higher day14-to-day7 ratio was also found for the IL-6/IL-10, IL-17A/IL-10 and GRα/IL-10 ratios. ROC curve analysis demonstrated a robust predictive performance of IL-10 mRNA expression and the IL-6/IL-10 ratio for identifying CS-refractory patients. In conclusion, the expression of IL-10 and the IL-6/IL-10 ratio hold promise as early predictive biomarkers for CS treatment refractoriness in patients with non-infectious uveitis. These findings offer valuable insights into personalized treatment strategies, potentially leading to improved clinical outcomes.
    Scopus© Citations 6  1
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    Patient centered outcomes in stroke: utility-weighted modified Rankin Scale results in a community-based study
    (Frontiers Media SA, 2025-03-21)
    Carlos Delfino
    ;
    Gabriel Cavada
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    HOFFMEISTER ARCE, LORENA  
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    LAVADOS GERMAIN, PABLO MANUEL  
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    MUÑOZ VENTURELLI, PAULA ANDREA  
    Background and aims</jats:title><jats:p>The transformation of modified Rankin Scale (mRS) scores based on the corresponding utilities of health-related quality of life questionnaires can facilitate the capture of Patient-Centered Outcomes (PCO) in stroke. We aimed to derive utility-weighted modified Rankin Scale (UW-mRS) values by mapping mRS functional status to EQ-5D-3L scores in a population-based cohort of stroke patients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The UW-mRS was obtained by analyzing the EQ5-D-3 L and mRS scores at 180 days after any stroke in the ÑANDU study, a large prospective community-based study in Chile. The mRS prediction was estimated using a linear regression adjusted by the EQ-5D-3L value. Generalized linear and binary logistic regression models were constructed to determine influencing factors of the UW-mRS, using STATA software (version 18.0).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We included 773 patients presenting with any stroke during 2015–2016: 48% were female, with a mean age of 71 years (SD 13.8), and 85% had an acute ischemic stroke (AIS). 82% of patients had a low socioeconomic status, 50% had less than 12 years of formal education, and only 32% lived in urban areas. UW-mRS values for mRS categories 0–6 at 180 days were 0.913, 0.694, 0.425, 0.249, −0.102, −0.347 and 0, respectively. Multivariable analysis identified age &amp;gt; 70 years (Coefficient <jats:italic>β</jats:italic> [β] -0.038 [Standard error SE 0.018], <jats:italic>p</jats:italic> = 0.032), prior mRS score 3–5 (<jats:italic>β</jats:italic> −0.556 [SE 0.197], <jats:italic>p</jats:italic> &amp;lt; 0.001), ischemic stroke (β −0.066 [SE 0.025], <jats:italic>p</jats:italic> = 0.010), and National Institutes of Health Stroke Scale (NIHSS) at admission&amp;gt;5 (<jats:italic>β</jats:italic> −0.015 [SE 0.002], <jats:italic>p</jats:italic> &amp;lt; 0.001) as significant predictors of worse UW-mRS scores (R<jats:sup>2</jats:sup> = 70%) in the overall group. Sex-disaggregated analysis showed that age &amp;gt; 70 years was a significant predictor in males (β −0.069 [SE 0.024], <jats:italic>p</jats:italic> = 0.006), while presenting an AIS had a greater impact on female’s worse UW-mRS score (β −0.087 [SE 0.033], <jats:italic>p</jats:italic> = 0.010).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>These results present UW-mRS values derived from a population-based stroke study. Key determinants of health-related quality of life in post-stroke patients included age, prior disability, and stroke severity. Sex-disaggregated analysis revealed age being significant for males and AIS for females. Incorporating PCO as UW-mRS in stroke research can provide a more nuanced understanding of the impact of stroke on survivors, offering valuable insights for clinical decision-making and rehabilitation strategies across diverse healthcare contexts.<
    Scopus© Citations 1  6
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    Neuromyelitis optica spectrum disorder in Latin America: a global data share initiative
    (Elsevier BV, 2025-06)
    Juan I. Rojas
    ;
    Liliana Patrucco
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    Edgardo Cristiano
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    José I. Gortari
    ;
    Paola A. Ortiz Salas
    Scopus© Citations 2  1
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    Scopus© Citations 2  1
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    Return-to-sport tests: Do they reduce risk of re-rupture after anterior cruciate ligament reconstruction?
    (Elsevier BV, 2025-04)
    FIGUEROA POBLETE, DAVID HUMBERTO  
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    Waldo Gonzalez Duque
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    Daniela Landea Caroca
    ;
    Camila Tapia Castillo
    ;
    Daniela Erskine Ventura
    Scopus© Citations 1  1
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    Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer
    (MDPI AG, 2025-04-03)
    María José Maturana
    ;
    Oslando Padilla
    ;
    Pablo M. Santoro
    ;
    Maria Alejandra Alarcón
    ;
    Wilda Olivares
    Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated a non-invasive method based on the circulating methylated cell-free DNA (cfDNA) of Reprimo (RPRM), a tumor suppressor gene associated with the development of GC. Methylated RPRM cfDNA was analyzed in three de-identified cohorts: Cohort 1 comprised 81 participants with GC and 137 healthy donors (HDs); Cohort 2 comprised 27 participants with GC undergoing gastrectomy and/or chemotherapy analyzed at the beginning and after three months of treatment; and Cohort 3 comprised 1105 population-based participants in a secondary prevention program who underwent esophagogastroduodenal (EGD) endoscopy. This cohort includes 180 normal participants, 845 participants with premalignant conditions (692 with chronic atrophic gastritis [AG] and 153 with gastric intestinal metaplasia/low-grade dysplasia [GIM/LGD]), 21 with high-grade dysplasia/early GC [HGD/eGC], and 59 with advanced GC [aGC]). A nested case-control substudy was performed using a combination of methylated RPRM cfDNA and pepsinogens (PG)-I/II ratio. The dense CpG island of the promoter region of the RPRM gene was bisulfite sequenced and analyzed to develop a fluorescence-based real-time PCR assay (MethyLight). This assay allows the determination of the absolute number of copies of methylated RPRM cfDNA. A targeted sequence of PCR amplicon products confirmed the gastric origin of the plasma-isolated samples. In Cohort 1, the mean value of GCs (32,240.00 copies/mL) was higher than that of the HD controls (139.00 copies/mL) (p &lt; 0.0001). After dividing this cohort into training–validation subcohorts, we identified an area under the curve of 0.764 (95% confidence interval (CI) = 0.683–0.845) in the training group. This resulted in a cut-off value of 87.37 copies/mL (sensitivity 70.0% and specificity 80.2%). The validation subcohort predicted a sensitivity of 66.67% and a specificity of 83.33%. In Cohort 2 (monitoring treatment response), RPRM levels significantly decreased in responders (p = 0.0042) compared to non-responders. In Cohort 3 (population-based participants), 18.9% %, 24.1%, 30.7%, 47.0%, and 71.2% of normal, AG, GIM/LGD, HGD/eGC, and aGC participants tested positive for methylated RPRM cfDNA, respectively. Overall sensitivity and specificity in distinguishing normal/premalignant conditions vs. GC were 65.0% (95% CI 53.52% to 75.33%) and 75.9% (95% CI 73.16% to 78.49%), respectively, with an accuracy of 75.11% (95% CI 72.45% to 77.64%). Logistic regression analyses revealed an OR of 1.85 (95% CI 1.11–3.07, p = 0.02) and an odds ratio (OR) of 3.9 (95% CI 1.53–9.93, p = 0.004) for the risk of developing GIM/LGD and HGD/eGC, respectively. The combined methylated RPRM cfDNA and PG-I/II ratio reached a sensitivity of 78.9% (95% CI 54.43% to 93.95%) and specificity of 63.04% (95% CI 52.34% to 72.88%) for detecting HGD/eGC vs. three to six age- and sex-matched participants with premalignant conditions. Our results demonstrate that methylated RPRM cfDNA should be considered a direct biomarker for the non-invasive detection of GC and a predictive biomarker for treatment response.
      1Scopus© Citations 4