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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
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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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Spatial navigation entropy suggests allocentric dysfunction in PPPD
(Frontiers Media SA, 2025-05-16)
Felipe Faúndez
;
Camilo Arévalo-Romero
;
Karen Villarroel
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Gustavo Vial
;
Claudio Lavín
Persistent postural-perceptual dizziness (PPPD) is a common chronic dizziness disorder with an unclear pathophysiology. It is hypothesized that PPPD may involve functional dysfunction of the construction of inner cognitive maps, leading to disrupted spatial cognition processes as a core feature. The present studies attempt to unravel the neural mechanisms that underlie spatial navigation in PPPD.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Fifty-two participants completed the study: 19 PPPD patients, 20 control subjects with vestibular disorders but without PPPD (with comparable peripheral vestibular function to the PPPD group, and 13 healthy volunteers). All underwent a virtual Morris Water Maze (vMWM) task in both, non-immersive (NI) and virtual reality (VR) modalities, assessing spatial navigation performance, gaze behavior, and head kinematics.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>PPPD patients exhibited significantly worse navigation performance than both control groups across all metrics, with greater impairments in predominantly allocentric tasks. They also showed increased exploratory gaze behavior, unaffected by NI vs. VR modality or task condition. Head kinematics did not significantly differ between the three groups, though a non-significant trend indicated reduced head movement in both PPPD and vestibular controls. VR intolerance was highest in PPPD patients, followed by vestibular controls, with healthy volunteers showing the lowest discomfort.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>Our findings suggest that PPPD involves deficits in allocentric spatial navigation, likely due to predictive coding errors and impaired internal model updating, rather than sensory input dysfunction. Increased gaze scanning may reflect compensatory mechanisms for spatial uncertainty. Notably, VR immersion did not alter navigation performance, suggesting visuo-vestibular conflict is not the primary driver of PPPD-related spatial deficits. These findings offer new insights into PPPD as a disorder of spatial cognition, opening avenues for novel diagnostic and therapeutic approaches.
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
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Fabian Vega-Tapia
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Nathaly Elizalde
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Ivan Flores
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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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Prevalence, Causal Classification, and Prognosis of Patent Foramen Ovale in Young Patients With Embolic Strokes of Undetermined Source
(Ovid Technologies (Wolters Kluwer Health), 2025-05-06)
Abhilekh Srivastava
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Kate Tsiplova
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Amanda Taylor
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Aleksandra Pikula
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Jennifer Mandzia
1
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Automated urine culture system with reduced turnaround time: A prospective real-world evaluation
(Elsevier BV, 2025-07)
PORTE TORRE, LORENA ISABEL
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María Jesús Alfaro
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Carmen Varela
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Jorge Reyes
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WEITZEL, THOMAS
6Scopus© Citations 2
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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
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Oslando Padilla
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Pablo M. Santoro
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Maria Alejandra Alarcón
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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 < 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
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Influence of renal function on blood pressure control and outcome in thrombolyzed patients after acute ischemic stroke: post-hoc analysis of the ENCHANTED trial
(Frontiers Media SA, 2024-12-09)
Xinwen Ren
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Chen Chen
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Xia Wang
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Qiang Li
;
Yang Zhao
<jats:sec><jats:title>Background</jats:title><jats:p>The effect of renal impairment in patients who receive intravenous thrombolysis for acute ischemic stroke (AIS) is unclear. We aimed to determine the associations of renal impairment and clinical outcomes and any modification of the effect of intensive versus guideline-recommended blood pressure (BP) control in the BP arm of the International Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted a <jats:italic>post-hoc</jats:italic> analysis of the ENCHANTED BP arm, which involved 2,196 thrombolyzed AIS patients. Logistic regression models were used to define the association between eGFR and clinical outcomes of death, death or major disability [modified Rankin scale (mRS) scores 3–6], and major disability (mRS 3–5) at 90 days.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Of the 2,151 patients with available baseline renal function data (mean age 66.9 years; 38% women), 993 (46.2%), 822 (38.2%), and 336 (15.6%) had normal (eGFR ≥ 90 mL/min/1.73 m<jats:sup>2</jats:sup>), mildly (60–89), and moderate-to-severely impaired (&lt;60) renal function, respectively. Compared with patients with normal eGFR, mortality was higher in those with moderate-to-severe renal impairment (adjusted odds ratio 1.77, 95% confidence interval 1.05–2.99; <jats:italic>p</jats:italic> = 0.031 for trend). However, the difference in death or major disability (mRS 3–6) was not significant between groups. There was no heterogeneity in the effect of intensive versus guideline-recommended BP-lowering treatment on death by grades of renal function (<jats:italic>p</jats:italic> for interaction = 0.545).</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>The presence of moderate-to-severe renal impairment is associated with increased mortality in thrombolyzed patients with AIS. Renal function does not modify the effect of early intensive BP-lowering treatment on death in this patient group.</jats:p></jats:sec>
2
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Clinical Profile of Stroke Chameleons Receiving Intravenous Thrombolysis: Insights from a Single-Center Experience
(S. Karger AG, 2024-11-13)
BRUNSER RABOVICH, ALEJANDRO MICHEL
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LAVADOS GERMAIN, PABLO MANUEL
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MUÑOZ VENTURELLI, PAULA ANDREA
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OLAVARRIA IANISZEWSKY, VERONICA VIVIANA
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Eloy Mansilla
<jats:p>Introduction: In emergency rooms (ERs), 5% of patients experiencing an acute ischemic stroke (AIS) receive an alternative diagnosis; these cases are known as stroke chameleons (SC). The percentage of SC treated with intravenous thrombolysis (IVT) and the characteristics have not been well described. We aimed at investigating the variables associated with the probability receiving IVT. Methods: In this prospective study, we included consecutive patients with SC admitted at the ER of Clínica Alemana between September 2014 and October 2023. Results: Among 1,193 stroke patients; sixty-three (5.2%) corresponded to SC. Ten of these cases (15.8%, 95% CI: 8.8–26.8) were treated with IVT, mean door-to-needle (DTN) time of 85.7 (SD 35) min, median of 73.5 (IQR 62–113) min. SCs who underwent IVT were younger (p = 0.01), with higher NIHSS (p = 0.05). They presented more frequently with altered level of consciousness in the NIHSS (p = 0.01), language abnormities (p = 0.001), and dysarthria (p = 0.01). In multivariate analysis, none of the variables were significantly associated with IVT. A secondary analysis showed that only time to brain imaging was significantly associated with IVT (OR: 0.99; 95% CI: 0.98–0.99; p = 0.01). Conclusions: Almost 1 out of every 7 SC could be treated with IVT but with a prolonged DTN time; the chance of being treated is associated with time to brain imaging. <p>Introduction: In emergency rooms (ERs), 5% of patients experiencing an acute ischemic stroke (AIS) receive an alternative diagnosis; these cases are known as stroke chameleons (SC). The percentage of SC treated with intravenous thrombolysis (IVT) and the characteristics have not been well described. We aimed at investigating the variables associated with the probability receiving IVT. Methods: In this prospective study, we included consecutive patients with SC admitted at the ER of Clínica Alemana between September 2014 and October 2023. Results: Among 1,193 stroke patients; sixty-three (5.2%) corresponded to SC. Ten of these cases (15.8%, 95% CI: 8.8–26.8) were treated with IVT, mean door-to-needle (DTN) time of 85.7 (SD 35) min, median of 73.5 (IQR 62–113) min. SCs who underwent IVT were younger (p = 0.01), with higher NIHSS (p = 0.05). They presented more frequently with altered level of consciousness in the NIHSS (p = 0.01), language abnormities (p = 0.001), and dysarthria (p = 0.01). In multivariate analysis, none of the variables were significantly associated with IVT. A secondary analysis showed that only time to brain imaging was significantly associated with IVT (OR: 0.99; 95% CI: 0.98–0.99; p = 0.01). Conclusions: Almost 1 out of every 7 SC could be treated with IVT but with a prolonged DTN time; the chance of being treated is associated with time to brain imaging. </p></jats:p>
1
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Increased mortality in hospital- compared to community-onset carbapenem-resistant enterobacterales infections
(2024)
Angelique E Boutzoukas
;
Natalie Mackow
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Abhigya Giri
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Lauren Komarow
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Carol Hill
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>The CDC reported a 35% increase in hospital-onset (HO) carbapenem-resistant Enterobacterales (CRE) infections during the COVID-19 pandemic. We evaluated patient outcomes following HO and community-onset (CO) CRE bloodstream infections (BSI).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Patients prospectively enrolled in CRACKLE-2 from 56 hospitals in 10 countries between 30 April 2016 and 30 November 2019 with a CRE BSI were eligible. Infections were defined as CO or HO by CDC guidelines, and clinical characteristics and outcomes were compared. The primary outcome was desirability of outcome ranking (DOOR) 30 days after index culture. Difference in 30-day mortality was calculated with 95% CI.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Among 891 patients with CRE BSI, 65% were HO (582/891). Compared to those with CO CRE, patients with HO CRE were younger [median 60 (Q1 42, Q3 70) years versus 65 (52, 74); P &lt; 0.001], had fewer comorbidities [median Charlson comorbidity index 2 (1, 4) versus 3 (1, 5); P = 0.002] and were more acutely ill (Pitt bacteraemia score ≥4: 47% versus 32%; P &lt; 0.001). The probability of a better DOOR outcome in a randomly selected patient with CO BSI compared to a patient with HO BSI was 60.6% (95% CI: 56.8%–64.3%). Mortality at 30-days was 12% higher in HO BSI (192/582; 33%) than CO BSI [66/309 (21%); P &lt; 0.001].</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>We found a disproportionately greater impact on patient outcomes with HO compared to CO CRE BSIs; thus, the recently reported increases in HO CRE infections by CDC requires rigorous surveillance and infection prevention methods to prevent added mortality.</jats:p> </jats:sec>
Scopus© Citations 1 3
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Six-month post-intensive care outcomes during high and low bed occupancy due to the COVID-19 pandemic: A multicenter prospective cohort study
(2023)
CASTRO AVILA, ANA CRISTINA
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Catalina Merino-Osorio
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GONZALEZ SEGUEL, FELIPE ANDRES
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CAMUS MOLINA, AGUSTIN
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Felipe Muñoz-Muñoz
<jats:sec id="sec001"> <jats:title>Introduction</jats:title> <jats:p>The COVID-19 pandemic can be seen as a natural experiment to test how bed occupancy affects post-intensive care unit (ICU) patient’s functional outcomes. To compare by bed occupancy the frequency of mental, physical, and cognitive impairments in patients admitted to ICU during the COVID-19 pandemic.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods</jats:title> <jats:p>Prospective cohort of adults mechanically ventilated >48 hours in 19 ICUs from seven Chilean public and private hospitals. Ninety percent of nationwide beds occupied was the cut-off for low versus high bed occupancy. At ICU discharge, 3- and 6-month follow-up, we assessed disability using the World Health Organization Disability Assessment Schedule 2.0. Quality of life, mental, physical, and cognitive outcomes were also evaluated following the core outcome set for acute respiratory failure.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Results</jats:title> <jats:p>We enrolled 252 participants, 103 (41%) during low and 149 (59%) during high bed occupancy. Patients treated during high occupancy were younger (P<jats:sub>50</jats:sub> [P<jats:sub>25</jats:sub>-P<jats:sub>75</jats:sub>]: 55 [44–63] vs 61 [51–71]; p<0.001), more likely to be admitted due to COVID-19 (126 [85%] vs 65 [63%]; p<0.001), and have higher education qualification (94 [63%] vs 48 [47%]; p = 0.03). No differences were found in the frequency of at least one mental, physical or cognitive impairment by bed occupancy at ICU discharge (low vs high: 93% vs 91%; p = 0.6), 3-month (74% vs 63%; p = 0.2) and 6-month (57% vs 57%; p = 0.9) follow-up.</jats:p> </jats:sec> <jats:sec id="sec004"> <jats:title>Conclusions</jats:title> <jats:p>There were no differences in post-ICU outcomes between high and low bed occupancy. Most patients (>90%) had at least one mental, physical or cognitive impairment at ICU discharge, which remained high at 6-month follow-up (57%).</jats:p> </jats:sec> <jats:sec id="sec005"> <jats:title>Clinical trial registration</jats:title> <jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT04979897" xlink:type="simple">NCT04979897</jats:ext-link> (clinicaltrials.gov).</jats:p> </jats:sec>
3Scopus© Citations 3

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