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    Myocardial perfusion imaging in advanced coronary artery disease
    (Wiley, 2025-03-18)
    Roel Hoek
    ;
    Pepijn A. van Diemen
    ;
    Yvemarie B. O. Somsen
    ;
    Ruben W. de Winter
    ;
    Ruurt A. Jukema
    Myocardial perfusion imaging (MPI) is widely adapted as a noninvasive technique to assess the presence and extent of ischemia in patients with symptoms suggestive of obstructive coronary artery disease (CAD). However, as CAD advances, several factors can complicate the interpretation of MPI, subsequently impacting clinical decision‐making. This review focuses on the utility of MPI by means of cardiac magnetic resonance (CMR) imaging, single‐photon emission computed tomography (SPECT) and positron emission tomography (PET) in patients with advanced CAD—the latter characterized by documented CAD (i.e. prior myocardial infarction [MI] and/or percutaneous coronary intervention [PCI]), prior coronary artery bypass grafting (CABG) or the presence of a chronic total occlusion (CTO). It will discuss factors impacting the interpretation of MPI, the diagnostic performance for detecting obstructive CAD and coronary microvascular dysfunction (CMD), as well as the role of MPI in guiding revascularization.
    Scopus© Citations 1  2
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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
    ;
    Fabian Vega-Tapia
    ;
    Nathaly Elizalde
    ;
    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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      6Scopus© Citations 2
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    Machine learning-based identification of efficient and restrictive physiological subphenotypes in acute respiratory distress syndrome
    (Springer Science and Business Media LLC, 2025-03-01)
    Gabriela Meza-Fuentes
    ;
    ;
    Mario Barbé
    ;
    Ignacio Sánchez
    ;
    Acute respiratory distress syndrome (ARDS) is a severe condition with high morbidity and mortality, characterized by significant clinical heterogeneity. This heterogeneity complicates treatment selection and patient inclusion in clinical trials. Therefore, the objective of this study is to identify physiological subphenotypes of ARDS using machine learning, and to determine ventilatory variables that can effectively discriminate between these subphenotypes in a bedside setting with high performance, highlighting potential utility for future clinical stratification approaches.</jats:p> Methodology A retrospective cohort study was conducted using data from our ICU, covering admissions from 2017 to 2021. The study included 224 patients over 18 years of age diagnosed with ARDS according to the Berlin criteria and undergoing invasive mechanical ventilation (IMV). Data on physiological and ventilatory variables were collected during the first 24 h IMV. We applied machine learning techniques to categorize subphenotypes in ARDS patients. Initially, we employed the unsupervised Gaussian Mixture Classification Model approach to group patients into subphenotypes. Subsequently, we applied supervised models such as XGBoost to perform root cause analysis, evaluate the classification of patients into these subgroups, and measure their performance.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Our models identified two ARDS subphenotypes with significant clinical differences and significant outcomes. Subphenotype Efficient (<jats:italic>n</jats:italic> = 172) was characterized by lower mortality, lower clinical severity and presented a less restrictive pattern with better gas exchange compared to Subphenotype Restrictive (<jats:italic>n</jats:italic> = 52), which showed the opposite. The models demonstrated high performance with an area under the ROC curve of 0.94, sensitivity of 94.2% and specificity of 87.5%, in addition to an F1 score of 0.85. The most influential variables in the discrimination of subphenotypes were distension pressure, respiratory frequency and exhaled carbon dioxide volume.Conclusion This study presents an approach to improve subphenotype categorization in ARDS. The generation of clustering and prediction models by machine learning involving clinical, ventilatory mechanics, and gas exchange variables allowed for more accurate stratification of patients. These findings have the potential to optimize individualized treatment selection and improve clinical outcomes in patients with ARDS.</jats:p> Graphical Abstract
    Scopus© Citations 2  5
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    CCTA-Guided Selective Invasive Coronary Catheterization: A Strategy to Reduce Contrast Volume and Improve Efficiency
    (MDPI AG, 2025-04-01)
    Jorge Dahdal
    ;
    Ruurt Jukema
    ;
    Aernout G. Somsen
    ;
    Eline Kooijman
    ;
    Ellaha Wahedi
    Background: Symptomatic patients with unilateral obstructive coronary artery disease (CAD) identified by coronary computed tomography angiography (CCTA), involving either the right or left coronary artery, typically undergo per-protocol bilateral coronary visualization during invasive coronary angiography (ICA). However, a selective visualization approach may be sufficient. Objectives: The objectives of this study were to assess the accuracy of CCTA in excluding hemodynamically significant coronary stenosis in patients with unilateral CAD and to evaluate whether a CCTA-guided selective ICA strategy can reduce procedure time and contrast agent use. Methods: In this cross-sectional cohort study, 454 patients with clinically suspected stable CAD who underwent CCTA prior to ICA were included. The study population consisted of 190 patients with unilateral obstructive CAD, defined as ≥50% diameter stenosis on CCTA, and an absence of obstructive CAD on the contralateral side. ICA with invasive functional assessment was used as the reference standard. Results: CCTA demonstrated a high accuracy, 97.4% (95% CI: 94–99%), in excluding hemodynamically significant disease in the contralateral arteries without obstructive CAD. Compared to the conventional ICA approach, a CCTA-guided selective visualization strategy resulted in significant reductions in procedure time and contrast agent usage: procedure time and contrast agent usage were reduced by 27% (95% CI: 12.1–47.5%) and 46.8% (95% CI: 27.5–67.0%), respectively. Conclusions: In patients with unilateral obstructive CAD identified by CCTA, a CCTA-guided selective ICA visualization strategy is highly accurate in ruling out hemodynamically significant CAD on the contralateral side. Additionally, this unilateral ICA approach has the potential to reduce both contrast agent usage and procedure time compared to the conventional bilateral visualization strategy.
      2Scopus© Citations 2
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    The role of astrocytes in depression, its prevention, and treatment by targeting astroglial gliotransmitter release
    (2024)
    Yorley Duarte
    ;
    Daisy Quintana-Donoso
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    Rodrigo Moraga-Amaro
    ;
    Ivanka Dinamarca
    ;
    Yordan Lemunao
    <jats:p>The role of ventral hippocampus (vHipp) astroglial gliotransmission in depression was studied using chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) rodent models. CRS increased Cx43 hemichannel activity and extracellular glutamate levels in the vHipp and blocking astroglial Cx43 hemichannel-dependent gliotransmission during CRS prevented the development of depression and glutamate buildup. Moreover, the acute blockade of Cx43 hemichannels induced antidepressant effects in rats previously subjected to CRS or CUMS. This antidepressant effect was prevented by coinjection of glutamate and D-serine. Furthermore, Cx43 hemichannel blockade decreased postsynaptic NMDAR currents in vHipp slices in a glutamate and D-serine-dependent manner. Notably, chronic microinfusion of glutamate and D-serine, L-serine, or the NMDAR agonist NMDA, into the vHipp induced depressive-like symptoms in nonstressed rats. We also identified a small molecule, cacotheline, which blocks Cx43 hemichannels and its systemic administration induced rapid antidepressant effects, preventing stress-induced increases in astroglial Cx43 hemichannel activity and extracellular glutamate in the vHipp, without sedative or locomotor side effects. In conclusion, chronic stress increases Cx43 hemichannel-dependent release of glutamate and D-/L-serine from astrocytes in the vHipp, overactivating postsynaptic NMDARs and triggering depressive-like symptoms. This study highlights the critical role of astroglial gliotransmitter release in chronic stress-induced depression and suggests it can be used as a target for the prevention and treatment of depression.</jats:p>
    Scopus© Citations 5  8
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    The value of Clinical signs in the diagnosis of Degenerative Cervical Myelopathy - A Systematic review and Meta-analysis
    (2023)
    Zhilin Jiang
    ;
    Benjamin Davies
    ;
    Carl Zipser
    ;
    Konstantinos Margetis
    ;
    Allan Martin
    <jats:sec><jats:title>Study Design</jats:title><jats:p> Delayed diagnosis of degenerative cervical myelopathy (DCM) is likely due to a combination of its subtle symptoms, incomplete neurological assessments by clinicians and a lack of public and professional awareness. Diagnostic criteria for DCM will likely facilitate earlier referral for definitive management. </jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p> This systematic review aims to determine (i) the diagnostic accuracy of various clinical signs and (ii) the association between clinical signs and disease severity in DCM? </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> A search was performed to identify studies on adult patients that evaluated the diagnostic accuracy of a clinical sign used for diagnosing DCM. Studies were also included if they assessed the association between the presence of a clinical sign and disease severity. The QUADAS-2 tool was used to evaluate the risk of bias of individual studies. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> This review identified eleven studies that used a control group to evaluate the diagnostic accuracy of various signs. An additional 61 articles reported on the frequency of clinical signs in a cohort of DCM patients. The most sensitive clinical tests for diagnosing DCM were the Tromner and hyperreflexia, whereas the most specific tests were the Babinski, Tromner, clonus and inverted supinator sign. Five studies evaluated the association between the presence of various clinical signs and disease severity. There was no definite association between Hoffmann sign, Babinski sign or hyperreflexia and disease severity. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> The presence of clinical signs suggesting spinal cord compression should encourage health care professionals to pursue further investigation, such as neuroimaging to either confirm or refute a diagnosis of DCM. </jats:p></jats:sec>
      3Scopus© Citations 37
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    Head-to-head comparison of CAMPYAIR aerobic culture medium versus standard microaerophilic culture for Campylobacter isolation from clinical samples
    (2023)
    Arturo Levican
    ;
    Carmen Varela
    ;
    ; ;
    Isabel Briceño
    <jats:p><jats:italic>Campylobacter</jats:italic> spp. are considered the most frequent cause of acute gastroenteritis worldwide. However, outside high-income countries, its burden is poorly understood. Limited published data suggest that <jats:italic>Campylobacter</jats:italic> prevalence in low- and middle-income countries is high, but their reservoirs and age distribution are different. Culturing <jats:italic>Campylobacter</jats:italic> is expensive due to laboratory equipment and supplies needed to grow the bacterium (e.g., selective culture media, microaerophilic atmosphere, and a 42°C incubator). These requirements limit the diagnostic capacity of clinical laboratories in many resource-poor regions, leading to significant underdiagnosis and underreporting of isolation of the pathogen. CAMPYAIR, a newly developed selective differential medium, permits <jats:italic>Campylobacter</jats:italic> isolation without the need for microaerophilic incubation. The medium is supplemented with antibiotics to allow <jats:italic>Campylobacter</jats:italic> isolation in complex matrices such as human feces. The present study aims to evaluate the ability of the medium to recover <jats:italic>Campylobacter</jats:italic> from routine clinical samples. A total of 191 human stool samples were used to compare the ability of CAMPYAIR (aerobic incubation) and a commercial <jats:italic>Campylobacter</jats:italic> medium (CASA, microaerophilic incubation) to recover <jats:italic>Campylobacter</jats:italic>. All <jats:italic>Campylobacter</jats:italic> isolates were then identified by MALDI-TOF MS. CAMPYAIR showed sensitivity and specificity values of 87.5% (95% CI 47.4%–99.7%) and 100% (95% CI 98%–100%), respectively. The positive predictive value of CAMPYAIR was 100% and its negative predictive value was 99.5% (95% CI 96.7%–99.9%); Kappa Cohen coefficient was 0.93 (95% CI 0.79–1.0). The high diagnostic performance and low technical requirements of the CAMPYAIR medium could permit <jats:italic>Campylobacter</jats:italic> culture in countries with limited resources.</jats:p>
    Scopus© Citations 3  1
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    Estado actual del diagnóstico de la displasia del desarrollo de las caderas en el siglo XXI
    (2023)
    Lizbet Pérez
    ;
    Javier Besomi
    ;
    Isabel Fuentealba
      20Scopus© Citations 2