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Keywords = inspired fraction of oxygen

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12 pages, 2952 KiB  
Communication
In Vitro/In Vivo Evaluation of a Portable Anesthesia Machine with an Oxygen Concentrator for Dogs Under General Anesthesia with Isoflurane
by Jungha Lee, Donghwi Shin, Taehoon Sung, Minha Kim, Changhoon Nam, Wongyun Son and Inhyung Lee
Animals 2025, 15(7), 973; https://doi.org/10.3390/ani15070973 - 27 Mar 2025
Viewed by 129
Abstract
This prospective, non-blinded study assessed the performance of a portable anesthesia machine with an oxygen concentrator (PAMOC) across various oxygen flow rates and vaporizer settings, incorporating both in vitro and in vivo experiments. The oxygen delivery test measured the time required [...] Read more.
This prospective, non-blinded study assessed the performance of a portable anesthesia machine with an oxygen concentrator (PAMOC) across various oxygen flow rates and vaporizer settings, incorporating both in vitro and in vivo experiments. The oxygen delivery test measured the time required to reach 90% fraction of inspired oxygen (FIO2) at various flow rates. The vaporizer test assessed the time to stabilize maximum fraction of inspired isoflurane (FIIso) concentration at various oxygen flow rate and vaporizer settings. In the in vivo test, six adult male Beagle dogs (11.4 ± 1.4 kg) were evaluated. The in vivo evaluation included monitoring physiological parameters during isoflurane anesthesia. The higher flow rates significantly reduced the time to plateau for FIO2 (p < 0.001). Maximum FIIso values were lower than the vaporizer dial settings, and increased oxygen flow rates significantly reduced the time required to reach target values (p < 0.001). Physiological parameters remained stable throughout anesthesia, confirming adequate oxygenation and anesthetic maintenance. The PAMoc, despite its lower pounds per square inch, yielded predictable outcomes consistent with those obtained in conventional anesthesia systems. These results demonstrated the viability of the PAMoc for anesthesia administration in the field and other challenging environments. Full article
(This article belongs to the Section Veterinary Clinical Studies)
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22 pages, 3342 KiB  
Article
Identification of Early Biomarkers of Mortality in COVID-19 Hospitalized Patients: A LASSO-Based Cox and Logistic Approach
by Anna Maria Fratta Pasini, Chiara Stranieri, Edoardo Giuseppe Di Leo, Lorenzo Bertolone, Antonino Aparo, Fabiana Busti, Annalisa Castagna, Alice Vianello, Fabio Chesini, Simonetta Friso, Domenico Girelli and Luciano Cominacini
Viruses 2025, 17(3), 359; https://doi.org/10.3390/v17030359 - 28 Feb 2025
Viewed by 544
Abstract
This study aimed to identify possible early biomarkers of mortality among clinical and biochemical parameters, iron metabolism parameters, and cytokines detected within 24 h from admission in hospitalized COVID-19 patients. We enrolled 80 hospitalized patients (40 survivors and 40 non-survivors) with COVID-19 pneumonia [...] Read more.
This study aimed to identify possible early biomarkers of mortality among clinical and biochemical parameters, iron metabolism parameters, and cytokines detected within 24 h from admission in hospitalized COVID-19 patients. We enrolled 80 hospitalized patients (40 survivors and 40 non-survivors) with COVID-19 pneumonia and acute respiratory failure. The median time from the onset of COVID-19 symptoms to hospital admission was lower in non-survivors than survivors (p < 0.05). Respiratory failure, expressed as the ratio of arterial oxygen partial pressure to the fraction of inspired oxygen (P/F), was more severe in non-survivors than survivors (p < 0.0001). Comorbidities were similar in both groups. Among biochemical parameters and cytokines, eGFR and interleukin (IL)-1β were found to be significantly lower (p < 0.05), while LDH, IL-10, and IL-8 were significantly higher in non-survivors than in survivors (p < 0.0005, p < 0.05 and p < 0.005, respectively). Among other parameters, LDH values distribution showed the most significant difference between study groups (p < 0.0001). LASSO feature selection combined with Cox proportional hazards and logistic regression models was applied to identify features distinguishing between survivors and non-survivors. Both approaches highlighted LDH as the strongest predictor, with IL-22 and creatinine emerging in the Cox model, while IL-10, eGFR, and creatinine were influential in the logistic model (AUC = 0.744 for Cox, 0.723 for logistic regression). In a similar manner, we applied linear regression for predicting LDH levels, identifying the P/F ratio as the top predictor, followed by IL-10 and eGFR (NRMSE = 0.128). Collectively, these findings underscore LDH’s critical role in mortality prediction, with P/F and IL-10 as key determinants of LDH increases in this Italian COVID-19 cohort. Full article
(This article belongs to the Special Issue Basic Sciences for the Conquest of COVID-19)
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15 pages, 2669 KiB  
Article
Acute Severe Hypoxia Decreases Mitochondrial Chain Complex II Respiration in Human Peripheral Blood Mononuclear Cells
by Marianne Riou, Anne-Laure Charles, Irina Enache, Charles Evrard, Cristina Pistea, Margherita Giannini, Anne Charloux and Bernard Geny
Int. J. Mol. Sci. 2025, 26(2), 705; https://doi.org/10.3390/ijms26020705 - 15 Jan 2025
Viewed by 837
Abstract
Peripheral blood mononuclear cells’ (PBMCs) mitochondrial respiration is impaired and likely involved in myocardial injury and heart failure pathophysiology, but its response to acute and severe hypoxia, often associated with such diseases, is largely unknown in humans. We therefore determined the effects of [...] Read more.
Peripheral blood mononuclear cells’ (PBMCs) mitochondrial respiration is impaired and likely involved in myocardial injury and heart failure pathophysiology, but its response to acute and severe hypoxia, often associated with such diseases, is largely unknown in humans. We therefore determined the effects of acute hypoxia on PBMC mitochondrial respiration and ROS production in healthy volunteers exposed to controlled oxygen reduction, achieving an inspired oxygen fraction of 10.5%. We also investigated potential relationships with gene expression of key biomarkers of hypoxia, succinate and inflammation, as hypoxia and inflammation share common mechanisms involved in cardiovascular disease. Unlike global mitochondrial respiration, hypoxemia with a spO2 ≤ 80% significantly reduced PBMC complex II respiration (from 6.5 ± 1.2 to 3.1 ± 0.5 pmol/s/106 cell, p = 0.04). Complex II activity correlated positively with spO2 (r = 0.63, p = 0.02) and inversely correlated with the succinate receptor SUCNR1 (r = −0.68), the alpha-subunit of the hypoxia-inducible factor (HIF-1α, r = −0.61), the chemokine ligand-9 (r = −0.68) and interferon-stimulated gene 15 (r = −0.75). In conclusion, severe hypoxia specifically impairs complex II respiration in association with succinate, inflammation and HIF-1α pathway interactions in human PBMCs. These results support further studies investigating whether modulation of complex II activity might modify the inflammatory and metabolic alterations observed in heart failure. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Pathophysiology of Myocardial Disease)
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13 pages, 1281 KiB  
Article
Effects of Automated Versus Conventional Ventilation on Quality of Oxygenation—A Substudy of a Randomized Crossover Clinical Trial
by Michela Botta, David M. P. van Meenen, Tobias D. van Leijsen, Jitske R. Rogmans, Stephanie S. List, Pim L. J. van der Heiden, Janneke Horn, Frederique Paulus, Marcus J. Schultz and Laura A. Buiteman-Kruizinga
J. Clin. Med. 2025, 14(1), 41; https://doi.org/10.3390/jcm14010041 - 25 Dec 2024
Viewed by 737
Abstract
Background/Objectives: Attaining adequate oxygenation in critically ill patients undergoing invasive ventilation necessitates intense monitoring through pulse oximetry (SpO2) and frequent manual adjustments of ventilator settings like the fraction of inspired oxygen (FiO2) and the level of positive end-expiratory [...] Read more.
Background/Objectives: Attaining adequate oxygenation in critically ill patients undergoing invasive ventilation necessitates intense monitoring through pulse oximetry (SpO2) and frequent manual adjustments of ventilator settings like the fraction of inspired oxygen (FiO2) and the level of positive end-expiratory pressure (PEEP). Our aim was to compare the quality of oxygenation with the use of automated ventilation provided by INTELLiVENT–Adaptive Support Ventilation (ASV) vs. ventilation that is not automated, i.e., conventional pressure-controlled or pressure support ventilation. Methods: A substudy within a randomized crossover clinical trial in critically ill patients under invasive ventilation. The primary endpoint was the percentage of breaths in an optimal oxygenation zone, defined by predetermined levels of SpO2, FiO2, and PEEP. Secondary endpoints were the percentage of breaths in acceptable or critical oxygenation zones, the percentage of time spent in optimal, acceptable, and critical oxygenation zones, the number of manual interventions at the ventilator, and the number and duration of ventilator alarms related to oxygenation. Results: Of the 96 patients included in the parent study, 53 were eligible for this current subanalysis. Among them, 31 patients were randomized to start with automated ventilation, while 22 patients began with conventional ventilation. No significant differences were found in the percentage of breaths within the optimal zone between the two ventilation modes (median percentage of breaths during automated ventilation 19.4 [0.1–99.9]% vs. 25.3 [0.0–100.0]%; p = 0.963). Similarly, there were no differences in the percentage of breaths within the acceptable and critical zones, nor in the time spent in the three predefined oxygenation zones. Although the number of manual interventions was lower with automated ventilation, the number and duration of ventilator alarms were fewer with conventional ventilation. Conclusions: The quality of oxygenation with automated ventilation is not different from that with conventional ventilation. However, while automated ventilation comes with fewer manual interventions at the ventilator, it also comes with more ventilator alarms. Full article
(This article belongs to the Section Intensive Care)
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11 pages, 1135 KiB  
Article
Non-Invasive Ventilation Failure in Pediatric ICU: A Machine Learning Driven Prediction
by Maria Vittoria Chiaruttini, Giulia Lorenzoni, Marco Daverio, Luca Marchetto, Francesca Izzo, Giovanna Chidini, Enzo Picconi, Claudio Nettuno, Elisa Zanonato, Raffaella Sagredini, Emanuele Rossetti, Maria Cristina Mondardini, Corrado Cecchetti, Pasquale Vitale, Nicola Alaimo, Denise Colosimo, Francesco Sacco, Giulia Genoni, Daniela Perrotta, Camilla Micalizzi, Silvia Moggia, Giosuè Chisari, Immacolata Rulli, Andrea Wolfler, Angela Amigoni and Dario Gregoriadd Show full author list remove Hide full author list
Diagnostics 2024, 14(24), 2857; https://doi.org/10.3390/diagnostics14242857 - 19 Dec 2024
Viewed by 792
Abstract
Background/Objectives: Non-invasive ventilation (NIV) has emerged as a possible first-step treatment to avoid invasive intubation in pediatric intensive care units (PICUs) due to its advantages in reducing intubation-associated risks. However, the timely identification of NIV failure is crucial to prevent adverse outcomes. [...] Read more.
Background/Objectives: Non-invasive ventilation (NIV) has emerged as a possible first-step treatment to avoid invasive intubation in pediatric intensive care units (PICUs) due to its advantages in reducing intubation-associated risks. However, the timely identification of NIV failure is crucial to prevent adverse outcomes. This study aims to identify predictors of first-attempt NIV failure in PICU patients by testing various machine learning techniques and comparing their predictive abilities. Methods: Data were sourced from the TIPNet registry, which comprised patients admitted to 23 Italian Paediatric Intensive Care Units (PICUs). We selected patients between January 2010 and January 2024 who received non-invasive ventilation (NIV) as their initial approach to respiratory support. The study aimed to develop a predictive model for NIV failure, selecting the best Machine Learning technique, including Generalized Linear Models, Random Forest, Extreme Gradient Boosting, and Neural Networks. Additionally, an ensemble approach was implemented. Model performances were measured using sensitivity, specificity, AUROC, and predictive values. Moreover, the model calibration was evaluated. Results: Out of 43,794 records, 1861 admissions met the inclusion criteria, with 678 complete cases and 97 NIV failures. The RF model demonstrated the highest AUROC and sensitivity equal to 0.83 (0.64, 0.94). Base excess, weight, age, systolic blood pressure, and fraction of inspired oxygen were identified as the most predictive features. A check for model calibration ensured the model’s reliability in predicting NIV failure probabilities. Conclusions: This study identified highly sensitive models for predicting NIV failure in PICU patients, with RF as a robust option. Full article
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10 pages, 501 KiB  
Article
Enhancing ICU Outcomes Through Intelligent Monitoring Systems: A Comparative Study on Ventilator-Associated Events
by Jui-Fang Liu, Mei-Ying Kang, Hui-Ling Lin and Shih-Feng Liu
J. Clin. Med. 2024, 13(21), 6600; https://doi.org/10.3390/jcm13216600 - 3 Nov 2024
Viewed by 1571
Abstract
Background: Using intelligent monitoring systems can potentially improve the identification and management of ventilator-associated events (VAEs). This single-center retrospective observational study evaluated the impact of implementing intelligent monitoring systems on the clinical outcomes of patients with VAEs in an ICU setting. Method: An [...] Read more.
Background: Using intelligent monitoring systems can potentially improve the identification and management of ventilator-associated events (VAEs). This single-center retrospective observational study evaluated the impact of implementing intelligent monitoring systems on the clinical outcomes of patients with VAEs in an ICU setting. Method: An intelligent VAE monitoring system was integrated into electronic medical records to continuously collect patient data and alert attending physicians when a ventilated patient met the criteria for a ventilator-associated condition, which was defined as an increase of at least three cm H2O in positive end expiratory pressure (PEEP), an increase of at least 0.20 in the fraction of inspired oxygen (FiO2), or the FiO2 being over baseline for at least two consecutive days. This study covered two phases, consisting of before using the intelligent monitoring system (2021–2022) and during its use (2023–2024). Results: The results showed that patients monitored with the intelligent system experienced earlier VAE detection (4.96 ± 1.86 vs. 7.77 ± 3.35 days, p < 0.001), fewer ventilator-associated condition (VAC) occurrences, and a shorter total duration of VACs. Additionally, the system significantly reduced ventilator days, antibiotic use, and 14-day mortality. Conclusions: Intelligent monitoring systems enhance VAE management, improve clinical outcomes, and provide valuable insights into the future of critical care medicine. Full article
(This article belongs to the Special Issue Clinical Advances in Critical Care Medicine)
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13 pages, 1805 KiB  
Article
Predicting Survival Status in COVID-19 Patients: Machine Learning Models Development with Ventilator-Related and Biochemical Parameters from Early Stages: A Pilot Study
by Shin-Ho Chou, Cheng-Yu Tsai, Wen-Hua Hsu, Chi-Li Chung, Hsin-Yu Li, Zhihe Chen, Rachel Chien and Wun-Hao Cheng
J. Clin. Med. 2024, 13(20), 6190; https://doi.org/10.3390/jcm13206190 - 17 Oct 2024
Viewed by 974
Abstract
Objective: Coronavirus disease 2019 (COVID-19) can cause intubation and ventilatory support due to respiratory failure, and extubation failure increases mortality risk. This study, therefore, aimed to explore the feasibility of using specific biochemical and ventilator parameters to predict survival status among COVID-19 [...] Read more.
Objective: Coronavirus disease 2019 (COVID-19) can cause intubation and ventilatory support due to respiratory failure, and extubation failure increases mortality risk. This study, therefore, aimed to explore the feasibility of using specific biochemical and ventilator parameters to predict survival status among COVID-19 patients by using machine learning. Methods: This study included COVID-19 patients from Taipei Medical University-affiliated hospitals from May 2021 to May 2022. Sequential data on specific biochemical and ventilator parameters from days 0–2, 3–5, and 6–7 were analyzed to explore differences between the surviving (successfully weaned off the ventilator) and non-surviving groups. These data were further used to establish separate survival prediction models using random forest (RF). Results: The surviving group exhibited significantly lower mean C-reactive protein (CRP) levels and mean potential of hydrogen ions levels (pH) levels on days 0–2 compared to the non-surviving group (CRP: non-surviving group: 13.16 ± 5.15 ng/mL, surviving group: 10.23 ± 5.15 ng/mL; pH: non-surviving group: 7.32 ± 0.07, survival group: 7.37 ± 0.07). Regarding the survival prediction performanace, the RF model trained solely with data from days 0–2 outperformed models trained with data from days 3–5 and 6–7. Subsequently, CRP, the partial pressure of carbon dioxide in arterial blood (PaCO2), pH, and the arterial oxygen partial pressure to fractional inspired oxygen (P/F) ratio served as primary indicators in survival prediction in the day 0–2 model. Conclusions: The present developed models confirmed that early biochemical and ventilatory parameters—specifically, CRP levels, pH, PaCO2, and P/F ratio—were key predictors of survival for COVID-19 patients. Assessed during the initial two days, these indicators effectively predicted the likelihood of successful weaning of from ventilators, emphasizing their importance in early management and improved outcomes in COVID-19-related respiratory failure. Full article
(This article belongs to the Section Pulmonology)
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19 pages, 742 KiB  
Article
Retinopathy of Prematurity in Eight Portuguese Neonatal Intensive Care Units: Incidence, Risk Factors, and Progression—A Prospective Multicenter Study
by Mariza Fevereiro-Martins, Ana Carolina Santos, Carlos Marques-Neves, Manuel Bicho, Hercília Guimarães and on behalf of the GenE-ROP Study Group
Children 2024, 11(10), 1154; https://doi.org/10.3390/children11101154 - 24 Sep 2024
Cited by 3 | Viewed by 1301
Abstract
Background/Objectives: Retinopathy of prematurity (ROP) is a retinal neovascular disease affecting preterm infants. Identifying risk factors for its development and progression is critical for effective screening and prevention. This study aimed to analyze the incidence of ROP and identify key risk factors for [...] Read more.
Background/Objectives: Retinopathy of prematurity (ROP) is a retinal neovascular disease affecting preterm infants. Identifying risk factors for its development and progression is critical for effective screening and prevention. This study aimed to analyze the incidence of ROP and identify key risk factors for its development and progression. Methods: We conducted a prospective, observational cohort study on 455 neonates (gestational age [GA] < 32 weeks or birth weight < 1500 g) across eight Portuguese NICUs. Results: ROP incidence was 37.8%, with 4.6% requiring treatment. Multivariate analysis identified low GA and the number of red blood cell (RBC) transfusions as significant factors for ROP development and progression. After adjusting for these variables, platelet transfusions, high maximum fraction of inspired oxygen (FiO2) in the second week, and surfactant use remained significantly associated with ROP development, while early and late sepsis, maternal chronic hypertension, and delayed enteral nutrition were associated with progression to ROP requiring treatment. Conclusions: These findings underscore the importance of addressing low GAs and adult RBC transfusions in ROP risk management and suggest that maximum FiO2, platelet transfusions, and sepsis also play crucial roles. Larger studies are needed to validate these results and explore preventive interventions, particularly regarding the impact of multiple adult RBC transfusions on fetal hemoglobin percentages. Full article
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13 pages, 1605 KiB  
Article
Goal-Directed Fluid Therapy Using Pulse Pressure Variation in Thoracic Surgery Requiring One-Lung Ventilation: A Randomized Controlled Trial
by Giovanni Punzo, Giovanna Beccia, Chiara Cambise, Tiziana Iacobucci, Flaminio Sessa, Mauro Sgreccia, Teresa Sacco, Angela Leone, Maria Teresa Congedo, Elisa Meacci, Stefano Margaritora, Liliana Sollazzi and Paola Aceto
J. Clin. Med. 2024, 13(18), 5589; https://doi.org/10.3390/jcm13185589 - 20 Sep 2024
Cited by 2 | Viewed by 886
Abstract
Background: Intraoperative fluid management based on pulse pressure variation has shown potential to reduce postoperative pulmonary complications (PPCs) and improve clinical outcomes in various surgical settings. However, its efficacy and safety have not been assessed in patients undergoing thoracic surgery with one-lung [...] Read more.
Background: Intraoperative fluid management based on pulse pressure variation has shown potential to reduce postoperative pulmonary complications (PPCs) and improve clinical outcomes in various surgical settings. However, its efficacy and safety have not been assessed in patients undergoing thoracic surgery with one-lung ventilation. Methods: Patients scheduled for pulmonary lobectomy using uniportal video-assisted thoracic surgery approach were randomly assigned to two groups. In the PPV group, fluid administration was guided by the pulse pressure variation parameter, while in the near-zero group, it was guided by conventional hemodynamic parameters. The primary outcome was the partial pressure of oxygen (PaO2)/ fraction of inspired oxygen (FiO2) ratio 15 min after extubation. The secondary outcomes included extubation time, the incidence of postoperative pulmonary complications in the first three postoperative days, and the length of hospital stay. Results: The PaO2/FiO2 ratio did not differ between the two groups (364.48 ± 38.06 vs. 359.21 ± 36.95; p = 0.51), although patients in the PPV group (n = 44) received a larger amount of both crystalloids (1145 ± 470.21 vs. 890 ± 459.31, p = 0.01) and colloids (162.5 ± 278.31 vs 18.18 ± 94.68, p = 0.002) compared to the near-zero group (n = 44). No differences were found in extubation time, type and number of PPCs, and length of hospital stay. Conclusions: PPV-guided fluid management in thoracic surgery requiring one-lung ventilation does not improve pulmonary gas exchange as measured by the PaO2/FiO2 ratio and does not seem to offer clinical benefits. Additionally, it results in increased fluid administration compared to fluid management based on conventional hemodynamic parameters. Full article
(This article belongs to the Special Issue Thoracic Surgery: Current Practice and Future Directions)
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21 pages, 1546 KiB  
Article
Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO2 Requirements
by Fernando Carvalho Neuenschwander, Ofra Barnett-Griness, Stefania Piconi, Yasmin Maor, Eduardo Sprinz, Nimer Assy, Oleg Khmelnitskiy, Nikita V. Lomakin, Boris Mikhailovich Goloshchekin, Ewelina Nahorecka, Adilson Joaquim Westheimer Calvacante, Anastasia Ivanova, Sergey Vladimirovich Zhuravel, Galina Yurevna Trufanova, Stefano Bonora, Amer Saffoury, Ami Mayo, Yury G. Shvarts, Giuliano Rizzardini, Rogerio Sobroza de Mello, Janaina Pilau, Alexey Klinov, Benjamin Valente-Acosta, Oleg Olegovich Burlaka, Natalia Bakhtina, Maskit Bar-Meir, Ivan Nikolaevich Shishimorov, Jose Oñate-Gutierrez, Cristian Iván García Rincón, Tatiana Ivanovna Martynenko, Ludhmila Abrahão Hajjar, Ana Carolina Nazare de Mendonca Procopio, Krzysztof Simon, Walter Gabriel Chaves Santiago, Adam Fronczak, Conrado Roberto Hoffmann Filho, Osama Hussein, Vladimir Aleksandrovich Martynov, Guido Chichino, Piotr Blewaska, Jacek Wroblewski, Sergio Saul Irizar Santana, Andres Felipe Ocampo Agudelo, Adam Barczyk, Rachael lask Gerlach, Eppie Campbell, Aida Bibliowicz, Reza Fathi, Patricia Anderson, Gilead Raday, Michal Klein, Clara Fehrmann, Gina Eagle, Vered Katz Ben-Yair and Mark L. Levittadd Show full author list remove Hide full author list
Microorganisms 2024, 12(9), 1767; https://doi.org/10.3390/microorganisms12091767 - 26 Aug 2024
Cited by 3 | Viewed by 2381
Abstract
Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in [...] Read more.
Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation. Full article
(This article belongs to the Special Issue Recent Advances in Antivirals for Emerging Viruses (3rd Edition))
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13 pages, 1304 KiB  
Article
Analysis of Primary Graft Dysfunction (PGD) Risk Factors in Lung Transplantation (LuTx) Patients
by Michał Jan Kubisa, Małgorzata Edyta Wojtyś, Piotr Lisowski, Dawid Kordykiewicz, Maria Piotrowska, Janusz Wójcik, Jarosław Pieróg, Krzysztof Safranow, Tomasz Grodzki and Bartosz Kubisa
Clin. Pract. 2024, 14(4), 1571-1583; https://doi.org/10.3390/clinpract14040127 - 15 Aug 2024
Viewed by 1534
Abstract
Background: Primary graft dysfunction (PGD) is a form of acute lung injury (ALI) that occurs within 72 h after lung transplantation (LuTx) and is the most common early complication of the procedure. PGD is diagnosed and graded based on the ratio of the [...] Read more.
Background: Primary graft dysfunction (PGD) is a form of acute lung injury (ALI) that occurs within 72 h after lung transplantation (LuTx) and is the most common early complication of the procedure. PGD is diagnosed and graded based on the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen and chest X-ray results. PGD grade 3 increases recipient mortality and the chance of chronic lung allograft dysfunction (CLAD). Method: The aim of this retrospective study was to identify new PGD risk factors. The inclusion criteria were met by 59 patients, who all received transplants at the same center between 2010 and 2018. Donor data were taken from records provided by the Polish National Registry of Transplantation and analyzed in three variants: PGD 1–3 vs. PGD 0, PGD 3 vs. PGD 0 and PGD 3 vs. PGD 0–2. Results: A multiple-factor logistic regression model was used to identify decreasing recipient age; higher donor BMI and higher donor central venous pressure (CVP) for the PGD (of the 1–3 grade) risk factor. Conclusions: Longer cold ischemia time (CIT) and higher donor CVP proved to be independent risk factors of PGD 3. Full article
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11 pages, 2846 KiB  
Article
Safety and Tolerability of Continuous Inhaled Iloprost Therapy for Severe Pulmonary Hypertension in Neonates and Infants
by Amit V. Krishnan, Victoria Freniere, Rakesh Sahni, Diana P. Vargas Chaves, Sankaran S. Krishnan, Dimitrios Savva and Usha S. Krishnan
Children 2024, 11(6), 703; https://doi.org/10.3390/children11060703 - 7 Jun 2024
Viewed by 1896
Abstract
This is a single-center retrospective study to assess the safety and tolerability of continuous inhaled iloprost use as rescue therapy for refractory pulmonary hypertension (PH) in critically ill neonates and infants. A retrospective chart review was performed on 58 infants and data were [...] Read more.
This is a single-center retrospective study to assess the safety and tolerability of continuous inhaled iloprost use as rescue therapy for refractory pulmonary hypertension (PH) in critically ill neonates and infants. A retrospective chart review was performed on 58 infants and data were collected at baseline, 1, 6, 12, 24, 48 and 72 h of iloprost initiation. Primary outcomes were change in heart rate (HR), fraction of inspired oxygen (FiO2), mean airway pressures (MAP), blood pressure (BP) and oxygenation index (OI). Secondary outcomes were need for extracorporeal membrane oxygenation (ECMO) and death. 51 patients treated for >6 h were analyzed in 2 age groups, neonate (≤28 days: n = 32) and infant (29–365 days: n = 19). FiO2 (p < 0.001) and OI (p = 0.01) decreased, while there were no significant changes in MAP, BP and HR. Of the fifteen patients placed on ECMO, seven were bridged off ECMO on iloprost and eight died. Twenty-four out of fifty-one patients (47%) recovered without requiring ECMO, while twelve (23%) died. Iloprost as add-on therapy for refractory PH in critically ill infants in the NICU has an acceptable tolerability and safety profile. Large prospective multicenter studies using iloprost in the neonatal ICU are necessary to validate these results. Full article
(This article belongs to the Special Issue Pediatric Intensive Care – Practice and Research)
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15 pages, 878 KiB  
Article
Evaluation of a Lung Ultrasound Score in Hospitalized Adult Patients with COVID-19 in Barcelona, Spain
by Maria S. Lightowler, Julia Verena Sander, Gonzalo García de Casasola Sánchez, Maria Mateos González, Robert Güerri-Fernández, Maria Dolores Lorenzo Navarro, Fabienne Nackers, Erin Stratta, Candelaria Lanusse and Helena Huerga
J. Clin. Med. 2024, 13(11), 3282; https://doi.org/10.3390/jcm13113282 - 2 Jun 2024
Cited by 1 | Viewed by 1372
Abstract
Background/Objectives: During the COVID-19 pandemic and the burden on hospital resources, the rapid categorization of high-risk COVID-19 patients became essential, and lung ultrasound (LUS) emerged as an alternative to chest computed tomography, offering speed, non-ionizing, repeatable, and bedside assessments. Various LUS score [...] Read more.
Background/Objectives: During the COVID-19 pandemic and the burden on hospital resources, the rapid categorization of high-risk COVID-19 patients became essential, and lung ultrasound (LUS) emerged as an alternative to chest computed tomography, offering speed, non-ionizing, repeatable, and bedside assessments. Various LUS score systems have been used, yet there is no consensus on an optimal severity cut-off. We assessed the performance of a 12-zone LUS score to identify adult COVID-19 patients with severe lung involvement using oxygen saturation (SpO2)/fractional inspired oxygen (FiO2) ratio as a reference standard to define the best cut-off for predicting adverse outcomes. Methods: We conducted a single-centre prospective study (August 2020–April 2021) at Hospital del Mar, Barcelona, Spain. Upon admission to the general ward or intensive care unit (ICU), clinicians performed LUS in adult patients with confirmed COVID-19 pneumonia. Severe lung involvement was defined as a SpO2/FiO2 ratio <315. The LUS score ranged from 0 to 36 based on the aeration patterns. Results: 248 patients were included. The admission LUS score showed moderate performance in identifying a SpO2/FiO2 ratio <315 (area under the ROC curve: 0.71; 95%CI 0.64–0.77). After adjustment for COVID-19 risk factors, an admission LUS score ≥17 was associated with an increased risk of in-hospital death (OR 5.31; 95%CI: 1.38–20.4), ICU admission (OR 3.50; 95%CI: 1.37–8.94) and need for IMV (OR 3.31; 95%CI: 1.19–9.13). Conclusions: Although the admission LUS score had limited performance in identifying severe lung involvement, a cut-off ≥17 score was associated with an increased risk of adverse outcomes. and could play a role in the rapid categorization of COVID-19 pneumonia patients, anticipating the need for advanced care. Full article
(This article belongs to the Section Infectious Diseases)
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18 pages, 2929 KiB  
Article
Assessment of Autoregulation of the Cerebral Circulation during Acute Lung Injury in a Neonatal Porcine Model
by Asli Memisoglu, Martha Hinton, Yasser Elsayed, Ruth Graham and Shyamala Dakshinamurti
Children 2024, 11(5), 611; https://doi.org/10.3390/children11050611 - 20 May 2024
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Abstract
In neonates with acute lung injury (ALI), targeting lower oxygenation saturations is suggested to limit oxygen toxicity while maintaining vital organ function. Although thresholds for cerebral autoregulation are studied for the management of premature infants, the impact of hypoxia on hemodynamics, tissue oxygen [...] Read more.
In neonates with acute lung injury (ALI), targeting lower oxygenation saturations is suggested to limit oxygen toxicity while maintaining vital organ function. Although thresholds for cerebral autoregulation are studied for the management of premature infants, the impact of hypoxia on hemodynamics, tissue oxygen consumption and extraction is not well understood in term infants with ALI. We examined hemodynamics, cerebral autoregulation and fractional oxygen extraction, as measured by near-infrared spectroscopy (NIRS) and blood gases, in a neonatal porcine oleic acid injury model of moderate ALI. We hypothesized that in ALI animals, cerebral oxygen extraction would be increased to a greater degree than kidney or gut oxygen extraction as indicative of the brain’s adaptive efforts to increase cerebral oxygen extraction at the expense of splanchnic end organs. Fifteen anesthetized, ventilated 5-day-old neonatal piglets were divided into moderate lung injury by treatment with oleic acid or control (sham injection). The degree of lung injury was quantified at baseline and after establishment of ALI by blood gases, ventilation parameters and calculated oxygenation deficit, hemodynamic indices by echocardiography and lung injury score by ultrasound. PaCO2 was maintained constant during ventilation. Cerebral, renal and gut oxygenation was determined by NIRS during stepwise decreases in inspired oxygen from 50% to 21%, correlated with PaO2 and PvO2; changes in fractional oxygen extraction (ΔFOE) were calculated from NIRS and from regional blood gas samples. The proportion of cerebral autoregulation impairment attributable to blood pressure, and to hypoxemia, was calculated from autoregulation nomograms. ALI manifested as hypoxemia with increasing intrapulmonary shunt fraction, decreased lung compliance and increased resistance, and marked increase in lung ultrasound score. Brain, gut and renal NIRS, obtained from probes placed over the anterior skull, central abdomen and flank, respectively, correlated with concurrent SVC (brain) or IVC (gut, renal) PvO2 and SvO2. Cerebral autoregulation was impaired after ALI as a function of blood pressure at all FiO2 steps, but predominantly by hypoxemia at FiO2 < 40%. Cerebral ΔFOE was higher in ALI animals at all FiO2 steps. We conclude that in an animal model of neonatal ALI, cerebrovascular blood flow regulation is primarily dependent on oxygenation. There is not a defined oxygenation threshold below which cerebral autoregulation is impaired in ALI. Cerebral oxygen extraction is enhanced in ALI, reflecting compensation for exhausted cerebral autoregulation due to the degree of hypoxemia and/or hypotension, thereby protecting against tissue hypoxia. Full article
(This article belongs to the Section Pediatric Neonatology)
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13 pages, 1594 KiB  
Article
The Effects of Volatile Anesthetics on Renal Sympathetic and Phrenic Nerve Activity during Acute Intermittent Hypoxia in Rats
by Josip Krnić, Katarina Madirazza, Renata Pecotić, Benjamin Benzon, Mladen Carev and Zoran Đogaš
Biomedicines 2024, 12(4), 910; https://doi.org/10.3390/biomedicines12040910 - 19 Apr 2024
Viewed by 1711
Abstract
Coordinated activation of sympathetic and respiratory nervous systems is crucial in responses to noxious stimuli such as intermittent hypoxia. Acute intermittent hypoxia (AIH) is a valuable model for studying obstructive sleep apnea (OSA) pathophysiology, and stimulation of breathing during AIH is known to [...] Read more.
Coordinated activation of sympathetic and respiratory nervous systems is crucial in responses to noxious stimuli such as intermittent hypoxia. Acute intermittent hypoxia (AIH) is a valuable model for studying obstructive sleep apnea (OSA) pathophysiology, and stimulation of breathing during AIH is known to elicit long-term changes in respiratory and sympathetic functions. The aim of this study was to record the renal sympathetic nerve activity (RSNA) and phrenic nerve activity (PNA) during the AIH protocol in rats exposed to monoanesthesia with sevoflurane or isoflurane. Adult male Sprague-Dawley rats (n = 24; weight: 280–360 g) were selected and randomly divided into three groups: two experimental groups (sevoflurane group, n = 6; isoflurane group, n = 6) and a control group (urethane group, n = 12). The AIH protocol was identical in all studied groups and consisted in delivering five 3 min-long hypoxic episodes (fraction of inspired oxygen, FiO2 = 0.09), separated by 3 min recovery intervals at FiO2 = 0.5. Volatile anesthetics, isoflurane and sevoflurane, blunted the RSNA response to AIH in comparison to urethane anesthesia. Additionally, the PNA response to acute intermittent hypoxia was preserved, indicating that the respiratory system might be more robust than the sympathetic system response during exposure to acute intermittent hypoxia. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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